EUTECNIQ Sciences

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Sources and methodology Primary sources Peer-reviewed Regulations

Every external fact on this site traces to a dated source, and this page lists them all

How sources are chosen and checked, how regulatory status is dated, how superseded guidance is handled, and the full reference library, which can be filtered by author, title, agency or year.

Methodology

Primary records come first, and the library was reviewed for this version of the site on October 22, 2026

Regulatory statements on other pages say "as of October 2026" and name the status of each document. Market and trade figures carry their retrieval dates.

How sources are chosen

  1. Statutes and regulations from the official text (United States Code, Electronic Code of Federal Regulations, Federal Register).
  2. Agency guidance and records from the issuing agency (FDA, EFSA, WHO), marked final or draft.
  3. Peer-reviewed publications, cited with a DOI that resolves to the publisher's record.
  4. Government data and reference databases such as NIST, UN Comtrade and national health surveys.
  5. Standards and pharmacopeial texts (ICH, ISO, USP), cited by number and edition.
  6. Industry and market estimates, only with the publisher's definitions and scope, and labeled as third-party estimates.

How each source is checked

  • Every DOI is matched against its Crossref record: authors, title, journal, year, volume and pages.
  • Every web source is opened at its primary address; the access date is stated where content can change.
  • A fact that could not be confirmed from a fetched source is left out or stated as a limitation.
  • Numbers quoted from a source keep its definitions, units and basis (for example retail sales versus ingredient value, or CIF versus FOB trade values).
  • Each page keeps a claim manifest that maps its precise statements to these references.

Regulatory status and dates

Every regulatory reference carries its status: statute, final regulation, proposed rule, final guidance, draft guidance or withdrawn. Guidance is nonbinding and is described as a recommendation. Status is dated because it changes; statements on this site are current as of October 2026.

Superseded and updated guidance

When an agency finalizes part of a draft, the site cites the final document for those sections and keeps the draft only for what is still draft, naming both with their dates. For example, FDA's October 2026 final guidance on NDI identity and safety information finalizes Sections VI.A–C of the August 2016 revised draft; that draft's Section V was already replaced by a March 2024 final guidance, and its master-file questions by an April 2024 draft that remains draft. A December 2024 proposed rule on asbestos testing of talc cosmetics was withdrawn on November 28, 2025, and is cited only as withdrawn.

Sources for the examples: FDA final guidance, October 2026; 91 FR 66336 (October 20, 2026); 2016 revised draft, October 2026 version with document history; 90 FR 54603 (withdrawal, November 28, 2025).

Evidence types

Each claim on the site is labeled by the kind of evidence behind it

The same ten labels are used on every page. A full explanation, with how to read each one, is in the insights library.

  • Verified factPrimary source or government data
  • Peer-reviewedEstablished published evidence
  • Regulatory requirementStatute or regulation
  • Agency guidanceNonbinding recommendation, final or draft
  • Third-party estimateMarket research and other estimates
  • Founder-reportedA prior employer's result, reported by the founder
  • ProposalSomething EUTECNIQ would do; not yet done
  • SimulationEducational model output, not a measurement
  • External partnerWork a qualified partner would perform
  • RiskA stated way a plan or result could fail

Company projections and educational examples are never cited as evidence. Calculator methods and verification are listed in the model register.

Reference library

The complete list, grouped by topic

Type part of an author, title, agency, journal or year to narrow the list. Each reference has a permanent anchor on this page, and DOIs link to the publisher's record.

1640 references in 188 groups.

Regulatory and safety

Safety, interactions and bioavailability

  1. EFSA ANS Panel. Scientific opinion on the safety of green tea catechins. EFSA J. 2018;16(4):e05239. doi.org/10.2903/j.efsa.2018.5239
  2. EFSA CONTAM Panel. Risks for human health related to the presence of pyrrolizidine alkaloids in honey, tea, herbal infusions and food supplements. EFSA J. 2017;15(7):e04908. doi.org/10.2903/j.efsa.2017.4908
  3. Tucker J, Fischer T, Upjohn L, et al. Unapproved pharmaceutical ingredients included in dietary supplements associated with US Food and Drug Administration warnings. JAMA Netw Open. 2018;1(6):e183337. doi.org/10.1001/jamanetworkopen.2018.3337
  4. Moore LB, Goodwin B, Jones SA, et al. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA. 2000;97(13):7500–7502. doi.org/10.1073/pnas.130155097
  5. Misaka S, Yatabe J, Müller F, et al. Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects. Clin Pharmacol Ther. 2014;95(4):432–438. doi.org/10.1038/clpt.2013.241
  6. Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir concentrations and St John's wort. Lancet. 2000;355(9203):547–548. doi.org/10.1016/S0140-6736(99)05712-8
  7. Gurley BJ, Swain A, Hubbard MA, et al. Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo. Clin Pharmacol Ther. 2008;83(1):61–69. doi.org/10.1038/sj.clpt.6100222
  8. Bailey DG, Spence JD, Munoz C, Arnold JM. Interaction of citrus juices with felodipine and nifedipine. Lancet. 1991;337(8736):268–269. doi.org/10.1016/0140-6736(91)90872-m
  9. Paine MF, Shen DD, McCune JS. Recommended approaches for pharmacokinetic natural product–drug interaction research: a NaPDI Center commentary. Drug Metab Dispos. 2018;46(7):1041–1045. doi.org/10.1124/dmd.117.079962
  10. Schiborr C, Kocher A, Behnam D, et al. The oral bioavailability of curcumin from micronized powder and liquid micelles is significantly increased in healthy humans and differs between sexes. Mol Nutr Food Res. 2014;58(3):516–527. doi.org/10.1002/mnfr.201300724
  11. Jäger R, Lowery RP, Calvanese AV, et al. Comparative absorption of curcumin formulations. Nutr J. 2014;13:11. doi.org/10.1186/1475-2891-13-11
  12. Cuomo J, Appendino G, Dern AS, et al. Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation. J Nat Prod. 2011;74(4):664–669. doi.org/10.1021/np1007262
  13. Stohs SJ, Chen O, Ray SD, et al. Highly bioavailable forms of curcumin and promising avenues for curcumin-based research and application: a review. Molecules. 2020;25(6):1397. doi.org/10.3390/molecules25061397
  14. Minekus M, Alminger M, Alvito P, et al. A standardised static in vitro digestion method suitable for food—an international consensus. Food Funct. 2014;5(6):1113–1124. doi.org/10.1039/c3fo60702j
  15. Brodkorb A, Egger L, Alminger M, et al. INFOGEST static in vitro simulation of gastrointestinal food digestion. Nat Protoc. 2019;14(4):991–1014. doi.org/10.1038/s41596-018-0119-1
  16. McClements DJ. Nanoemulsions versus microemulsions: terminology, differences, and similarities. Soft Matter. 2012;8(6):1719–1729. doi.org/10.1039/C2SM06903B
  17. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification. Pharm Res. 1995;12(3):413–420. doi.org/10.1023/a:1016212804288
  18. Bos JD, Meinardi MM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000;9(3):165–169. doi.org/10.1034/j.1600-0625.2000.009003165.x Peer-reviewed
  19. Potts RO, Guy RH. Predicting skin permeability. Pharm Res. 1992;9(5):663–669. doi.org/10.1023/A:1015810312465 Peer-reviewed
  20. Bhujbal SV, Mitra B, Jain U, et al. Pharmaceutical amorphous solid dispersion: a review of manufacturing strategies. Acta Pharm Sin B. 2021;11(8):2505–2536. doi.org/10.1016/j.apsb.2021.05.014 Peer-reviewed
  21. Jamwal R. Bioavailable curcumin formulations: a review of pharmacokinetic studies in healthy volunteers. J Integr Med. 2018;16(6):367–374. doi.org/10.1016/j.joim.2018.07.001 Peer-reviewed
  22. Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and 'self-microemulsifying' drug delivery systems. Eur J Pharm Sci. 2000;11 Suppl 2:S93–S98. doi.org/10.1016/S0928-0987(00)00167-6 Peer-reviewed

Regulation and standards

  1. 21 CFR Part 111 — CGMP in manufacturing, packaging, labeling, or holding operations for dietary supplements (incl. 111.70 specifications; 111.75 identity testing and COA reliance). ecfr.gov/current/title-21/chapter-I/subchapter-B/part-111
  2. 21 CFR 117.5(e): exemption from Part 117 subparts C and G for dietary supplements made in compliance with Part 111. FDA declined to extend the exemption to dietary ingredients: Current Good Manufacturing Practice, Hazard Analysis, and Risk-Based Preventive Controls for Human Food, final rule, 80 FR 55908 (Sept 17, 2015), Response 196. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-117/su
  3. 21 CFR 190.6 — NDI notification at least 75 days before introduction into interstate commerce. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-190/su
  4. 21 CFR 101.93 — structure/function statements: notify FDA within 30 days of first marketing; mandatory disclaimer. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-101/su
  5. 21 CFR 170.30 (GRAS eligibility) and Part 170 subpart E (GRAS notification). ecfr.gov/current/title-21/chapter-I/subchapter-B/part-170
  6. 21 CFR Parts 210/211 (drug CGMP), 312 (IND), 314 (NDA). ecfr.gov/current/title-21/chapter-I/subchapter-C
  7. 21 CFR Part 58 — Good laboratory practice for nonclinical laboratory studies. ecfr.gov/current/title-21/chapter-I/subchapter-A/part-58
  8. 21 CFR 320.1 — definitions of bioavailability and bioequivalence. ecfr.gov/current/title-21/chapter-I/subchapter-D/part-320
  9. 21 CFR 314.80 — Postmarketing reporting of adverse drug experiences. ecfr.gov/current/title-21/chapter-I/subchapter-D/part-314/su
  10. 21 CFR 1.511 — Foreign Supplier Verification Programs for importers of dietary supplements and dietary supplement components. law.cornell.edu/cfr/text/21/1.511
  11. 21 U.S.C. 321(ff), definition of dietary supplement, including the drug exclusion at 201(ff)(3)(B). law.cornell.edu/uscode/text/21/321
  12. 21 U.S.C. 379aa-1 — serious adverse event reports within 15 business days; records retained 6 years. law.cornell.edu/uscode/text/21/379aa-1
  13. Federal Register. Substances Generally Recognized as Safe; Proposed Rule. 91 FR 51834; Docket FDA-2025-N-3262; comments due Dec 9, 2026. federalregister.gov/documents/2026/08/11/2026-16296/substanc
  14. Federal Register. Advancing Development of Botanical Drug Products; Request for Information. 91 FR 56887; Docket FDA-2026-N-9550; comments due Nov 3, 2026. federalregister.gov/documents/2026/09/04/2026-18133/advancin
  15. U.S. FDA. FDA seeks public input to advance development of botanical drug products (announces joint FDA/EMA workshop, Sep 25, 2026). Press release, Sep 3, 2026. fda.gov/news-events/press-announcements/fda-seeks-public-inp
  16. U.S. FDA. Botanical Drug Development: Guidance for Industry (Revision 1). December 2016. fda.gov/media/93113/download
  17. U.S. FDA. Botanical Drug Products (web page; approvals: Veregen NDA 021902, 2006; Fulyzaq/Mytesi NDA 202292, 2012; NexoBrid BLA 761192, 2022; Filsuvez NDA 215064, 2023). fda.gov/drugs/resources-drugs/botanical-drug-products
  18. FDA responses to citizen petitions concluding NMN is not excluded under 201(ff)(3)(B), Sep 29, 2025 (as reported by Venable LLP, Oct 2, 2025). venable.com/insights/publications/2025/10/fda-declares-nicot
  19. Natural Products Insider/SupplySide (Dec 18, 2020; FY2019, FY2022, FY2023 analyses of FDA NDI FOIA data): 1,166 NDINs received since 1995; 36.5% of FDA's 1,078 responses acknowledged without objection; FY22 71%, FY23 61%. supplysidesj.com/supplement-regulations/26-years-post-dshea-
  20. U.S. FDA. Dietary Supplements: New Dietary Ingredient Notification Master Files; Draft Guidance for Industry (April 2024); and NDI Notification Procedures and Timeframes; Final Guidance (March 2024). fda.gov/food/guidance-documents-regulatory-information-topic
  21. U.S. FDA. Inspection observations data, FY2025 (Foods tab): the six most frequent Part 111 citations (counts per FDA citation, each tied to a section) — 111.70(e) 188; 111.70(b) 177; 111.260 103; 111.210 93; 111.205(a) 75; 111.75(a)(1)(i) 66; 1,938 Part 111 citations in total. fda.gov/inspections-compliance-enforcement-and-criminal-inve
  22. Consumer Affairs Agency of Japan. GMP for Foods with Function Claims in supplement form (tablets, capsules and similar foods made from natural extracts), applicable from Sep 1, 2026. caa.go.jp/notice/assets/food_labeling_cms205_260703_01.pdf
  23. ICH. Q9(R1) Quality Risk Management. Step 4, January 2023 (with ICH Q8(R2) Pharmaceutical Development; Q10 Pharmaceutical Quality System). ich.org/page/quality-guidelines
  24. ICH M12 Drug Interaction Studies (2024); FDA In Vitro and Clinical Drug Interaction Studies guidances (January 2020). ich.org/page/multidisciplinary-guidelines
  25. ISO/IEC 17025:2017. General requirements for the competence of testing and calibration laboratories. iso.org/standard/66912.html
  26. United States Pharmacopeia–National Formulary general chapters: <467> Residual Solvents; <561> Articles of Botanical Origin; <563> Identification of Articles of Botanical Origin; <2021>–<2023> microbiological tests for nutritional and dietary supplements; <2040> Disintegration and Dissolution of Dietary Supplements; <2232> Elemental Contaminants in Dietary Supplements. usp.org/
  27. ISO 22412:2017 Particle size analysis — Dynamic light scattering; ISO 13320:2020 Particle size analysis — Laser diffraction methods. iso.org/
  28. USPTO. Revised Inventorship Guidance for AI-Assisted Inventions. 90 FR 54636, Nov 28, 2025 (rescinds and replaces Feb 13, 2024 guidance). federalregister.gov/documents/2025/11/28/2025-21457/revised-
  29. 21 U.S.C. 364a (FD&C Act § 605): serious adverse event reporting for cosmetics. Cornell LII. law.cornell.edu/uscode/text/21/364a Regulation or statute
  30. 21 U.S.C. 364b (FD&C Act § 606): cosmetic good manufacturing practice rulemaking. Cornell LII. law.cornell.edu/uscode/text/21/364b Regulation or statute
  31. 21 U.S.C. 364c (FD&C Act § 607): cosmetic facility registration and product listing. Cornell LII. law.cornell.edu/uscode/text/21/364c Regulation or statute
  32. 21 U.S.C. 364d (FD&C Act § 608): safety substantiation for cosmetics. Cornell LII. law.cornell.edu/uscode/text/21/364d Regulation or statute
  33. 21 U.S.C. 364e (FD&C Act § 609): cosmetic labeling, including contact information and fragrance allergens. Cornell LII. law.cornell.edu/uscode/text/21/364e Regulation or statute
  34. Consolidated Appropriations Act, 2023, Pub. L. 117-328, div. FF, title III, subtitle E (Modernization of Cosmetics Regulation Act of 2022), §§ 3503(b) and 3505. Enrolled text, govinfo. govinfo.gov/content/pkg/PLAW-117publ328/html/PLAW-117publ328 Regulation or statute
  35. U.S. FDA. Compliance Policy for Cosmetic Product Facility Registration and Cosmetic Product Listing; guidance availability. 88 FR 77323 (Nov 9, 2023). govinfo.gov/content/pkg/FR-2023-11-09/pdf/2023-24731.pdf Regulation or statute
  36. U.S. FDA. Testing Methods for Detecting and Identifying Asbestos in Talc-Containing Cosmetic Products; proposed rule. 89 FR 105490 (Dec 27, 2024). federalregister.gov/documents/2024/12/27/2024-30544/testing- Regulation or statute
  37. U.S. FDA. Testing Methods for Detecting and Identifying Asbestos in Talc-Containing Cosmetic Products; withdrawal of proposed rule. 90 FR 54603 (Nov 28, 2025). federalregister.gov/documents/2025/11/28/2025-21407/testing- Regulation or statute
  38. 21 CFR Part 700, Subpart B: Requirements for Specific Cosmetic Products (§§ 700.11–700.35). eCFR, current to Oct 21, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-G/part-700 Regulation or statute
  39. 15 U.S.C. 52 (FTC Act § 12): dissemination of false advertisements for food, drugs, devices, services or cosmetics. Cornell LII. law.cornell.edu/uscode/text/15/52 Regulation or statute
  40. ISO 22716:2007. Cosmetics — Good Manufacturing Practices (GMP) — Guidelines on Good Manufacturing Practices. Confirmed 2022. iso.org/standard/36437.html Primary source
  41. 21 CFR Part 210: Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of Drugs; General. eCFR, current to Oct 21, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-C/part-210 Regulation or statute
  42. 21 CFR Part 211: Current Good Manufacturing Practice for Finished Pharmaceuticals. eCFR, current to Oct 21, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-C/part-211 Regulation or statute
  43. 21 U.S.C. 348 (FD&C Act § 409): food additives; (a) use only in conformity with a regulation. Cornell LII. law.cornell.edu/uscode/text/21/348 Regulation or statute
  44. 21 CFR Part 171: Food Additive Petitions. eCFR, current to Oct 21, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-171 Regulation or statute
  45. U.S. HHS. HHS Secretary Kennedy Directs FDA to Explore Rulemaking to Eliminate Pathway for Companies to Self-Affirm Food Ingredients Are Safe. Press release, Mar 10, 2025. hhs.gov/about/news/2025/03/10/hhs-secretary-kennedy-directs- Primary source
  46. 21 CFR Part 113: Thermally Processed Low-Acid Foods Packaged in Hermetically Sealed Containers (§§ 113.3, 113.83). eCFR, current to Oct 21, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-113 Regulation or statute
  47. 21 CFR Part 114: Acidified Foods (§§ 114.3, 114.83). eCFR, current to Oct 21, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-114 Regulation or statute
  48. 21 CFR Part 120: Hazard Analysis and Critical Control Point (HACCP) Systems (juice), § 120.1. eCFR, current to Oct 21, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-120 Regulation or statute
  49. 35 U.S.C. 101: inventions patentable. Cornell LII. law.cornell.edu/uscode/text/35/101 Regulation or statute
  50. 21 U.S.C. 355h (FD&C Act § 505G): regulation of certain nonprescription drugs marketed without an approved application (OTC monographs). Cornell LII. law.cornell.edu/uscode/text/21/355h Regulation or statute
  51. U.S. FDA. Regulatory Perspectives on Herbal Medicinal/Botanical Drug Product Development – Joint FDA/EMA Workshop, Sep 25, 2026 (event page). fda.gov/drugs/news-events-human-drugs/regulatory-perspective Primary source
  52. Federal Register. Revised Inventorship Guidance for AI-Assisted Inventions. 90 FR 54636 (Nov 28, 2025). federalregister.gov/d/2025-21457 Primary source
  53. ICH M12 Drug Interaction Studies (Step 4, May 21, 2024), as reported by the Research Quality Association. therqa.com/news/ich-m12-guideline-reaches-step-4-ich-process Agency guidance
  54. U.S. FDA. New Dietary Ingredient Notification Master Files for Dietary Supplements: Draft Guidance for Industry (Apr 2024; Docket FDA-2024-D-0706). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  55. ILAC. ILAC-P8:11/2023, Supplementary requirements for the use of accreditation symbols and for claims of accreditation status. ilac.org/publications-and-resources/ilac-policy-series/ Primary source
  56. ANAB (ANSI National Accreditation Board). ISO/IEC 17025:2017 process requirements (summary of clause 7.4, handling of test or calibration items). blog.ansi.org/anab/iso-iec-17025-2017-process-requirements Primary source
  57. Long J. Most NDI notifications to FDA receive 'good day' letter in FY23. SupplySide, Dec 12, 2023 (FY22: 30 of 42; FY23: 27 of 44). supplysidesj.com/supplement-regulations/most-ndi-notificatio Third-party estimate

Ingredient safety, delivery and cross-category rules

  1. U.S. FDA. New Dietary Ingredient (NDI) Notifications and Related Issues; Identity and Safety Information About the NDI: guidance for industry (final). Constituent update Oct 19, 2026; 91 FR 66336 (Oct 20, 2026); Docket FDA-2025-D-6501. federalregister.gov/documents/2026/10/20/2026-21453/new-diet
  2. U.S. FDA. Draft guidance on new dietary ingredient notification master files for dietary supplements. Announced April 3, 2024; Docket FDA-2024-D-0706. Draft; not for implementation. fda.gov/food/hfp-constituent-updates/fda-issues-draft-guidan
  3. OECD Guidelines for the Testing of Chemicals, Section 4: Health Effects (including TG 407, 408, 414, 421/422, 443, 471, 474, 487, 489); OECD Principles of Good Laboratory Practice. oecd.org/en/topics/sub-issues/testing-of-chemicals/test-guid
  4. United States Pharmacopeia. General chapters <563> Identification of Articles of Botanical Origin and <565> Botanical Extracts. USP–NF.
  5. Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci. 2006;29(3–4):278–287. doi.org/10.1016/j.ejps.2006.04.016
  6. U.S. FDA. Modernization of Cosmetics Regulation Act of 2022 (MoCRA). fda.gov/cosmetics/cosmetics-laws-regulations/modernization-c
  7. U.S. FDA. Is It a Cosmetic, a Drug, or Both? (Or Is It Soap?). fda.gov/cosmetics/laws-regulations/it-cosmetic-drug-or-both-

Clinical research: rules, oversight and registration

  1. 21 CFR Part 50 — Protection of Human Subjects. ecfr.gov/current/title-21/chapter-I/subchapter-A/part-50 Regulation or statute
  2. 21 CFR Part 56 — Institutional Review Boards (including § 56.108(b)). ecfr.gov/current/title-21/chapter-I/subchapter-A/part-56 Regulation or statute
  3. 21 CFR Part 312 — Investigational New Drug Application (including § 312.32, IND safety reporting). ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312 Regulation or statute
  4. U.S. FDA. Investigational New Drug Applications (INDs) — Determining Whether Human Research Studies Can Be Conducted Without an IND. Final guidance, September 2013 (docket FDA-2010-D-0503); partial stay 80 FR 66907 (October 30, 2015). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  5. U.S. FDA. Investigational New Drug Applications; Exemptions for Clinical Investigations To Evaluate a Drug Use of a Product Lawfully Marketed as a Conventional Food, Dietary Supplement, or Cosmetic. Proposed rule, 87 FR 75536 (December 9, 2022). federalregister.gov/documents/2022/12/09/2022-26728/investig Regulation or statute
  6. U.S. FDA. E6(R3) Good Clinical Practice (GCP): Guidance for Industry (final, September 2025; docket FDA-2023-D-1955). ICH adoption of principles and Annex 1: January 6, 2025. fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  7. European Medicines Agency. ICH E6 Good clinical practice — scientific guideline (E6(R3) Annex 2 adopted by ICH on June 3, 2026). ema.europa.eu/en/scientific-guidelines/ich-e6-good-clinical- Primary source
  8. U.S. FDA. Establishment and Operation of Clinical Trial Data Monitoring Committees (guidance, March 2006); Use of Data Monitoring Committees in Clinical Trials (draft guidance, February 2024; docket FDA-2001-D-0219). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  9. 42 CFR Part 11 — Clinical Trials Registration and Results Information Submission (§§ 11.10, 11.22). ecfr.gov/current/title-42/chapter-I/subchapter-A/part-11 Regulation or statute
  10. International Committee of Medical Journal Editors. Clinical Trial Registration. icmje.org/recommendations/browse/publishing-and-editorial-is Primary source
  11. 21 CFR 314.126 — Adequate and well-controlled studies. ecfr.gov/current/title-21/chapter-I/subchapter-D/part-314/su Regulation or statute
  12. U.S. Federal Trade Commission. Health Products Compliance Guidance (December 20, 2022). ftc.gov/business-guidance/resources/health-products-complian Agency guidance
  13. Hopewell S, Chan AW, Collins GS, et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ. 2025;389:e081123. doi.org/10.1136/bmj-2024-081123 Peer-reviewed
  14. Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 Statement. BMJ. 2010;340:c332. doi.org/10.1136/bmj.c332 Peer-reviewed

Clinical research: design and sample size

  1. U.S. FDA. Adaptive Design Clinical Trials for Drugs and Biologics: Guidance for Industry (final, December 2019; docket FDA-2018-D-3124). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  2. U.S. FDA. Multiple Endpoints in Clinical Trials: Guidance for Industry (final, October 2022; docket FDA-2016-D-4460). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  3. ICH E9(R1). Statistical Principles for Clinical Trials: Addendum: Estimands and Sensitivity Analysis in Clinical Trials (FDA final guidance, May 2021). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  4. Guenther WC. Sample size formulas for normal theory t tests. Am Stat. 1981;35(4):243–244. doi.org/10.1080/00031305.1981.10479363 Peer-reviewed
  5. Julious SA. Sample sizes for clinical trials with Normal data. Stat Med. 2004;23(12):1921–1986. doi.org/10.1002/sim.1783 Peer-reviewed
  6. Borm GF, Fransen J, Lemmens WA. A simple sample size formula for analysis of covariance in randomized clinical trials. J Clin Epidemiol. 2007;60(12):1234–1238. doi.org/10.1016/j.jclinepi.2007.02.006 Peer-reviewed
  7. Lenth RV. Algorithm AS 243: cumulative distribution function of the non-central t distribution. Appl Stat. 1989;38(1):185–189. Peer-reviewed
  8. Fleiss JL, Levin B, Paik MC. Statistical Methods for Rates and Proportions, 3rd ed. Hoboken, NJ: Wiley; 2003. Peer-reviewed
  9. Fleiss JL, Tytun A, Ury HK. A simple approximation for calculating sample sizes for comparing independent proportions. Biometrics. 1980;36(2):343–346. Peer-reviewed
  10. Button KS, Ioannidis JPA, Mokrysz C, et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci. 2013;14(5):365–376. doi.org/10.1038/nrn3475 Peer-reviewed

Clinical research: dose–response, synergy and interactions

  1. Goutelle S, Maurin M, Rougier F, et al. The Hill equation: a review of its capabilities in pharmacological modelling. Fundam Clin Pharmacol. 2008;22(6):633–648. doi.org/10.1111/j.1472-8206.2008.00633.x Peer-reviewed
  2. Loewe S. The problem of synergism and antagonism of combined drugs. Arzneimittelforschung. 1953;3:285–290. Peer-reviewed
  3. Bliss CI. The toxicity of poisons applied jointly. Ann Appl Biol. 1939;26(3):585–615. doi.org/10.1111/j.1744-7348.1939.tb06990.x Peer-reviewed
  4. Berenbaum MC. What is synergy? Pharmacol Rev. 1989;41:93–141. Peer-reviewed
  5. Greco WR, Bravo G, Parsons JC. The search for synergy: a critical review from a response surface perspective. Pharmacol Rev. 1995;47:331–385. Peer-reviewed
  6. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984;22:27–55. doi.org/10.1016/0065-2571(84)90007-4 Peer-reviewed
  7. Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621–681. doi.org/10.1124/pr.58.3.10 Peer-reviewed
  8. Tang J, Wennerberg K, Aittokallio T. What is synergy? The Saariselkä agreement revisited. Front Pharmacol. 2015;6:181. doi.org/10.3389/fphar.2015.00181 Peer-reviewed
  9. Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine. 2009;16(2–3):97–110. doi.org/10.1016/j.phymed.2008.12.018 Peer-reviewed
  10. Caesar LK, Cech NB. Synergy and antagonism in natural product extracts: when 1 + 1 does not equal 2. Nat Prod Rep. 2019;36(6):869–888. doi.org/10.1039/c9np00011a Peer-reviewed
  11. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64(4):353–356. doi.org/10.1055/s-2006-957450 Peer-reviewed
  12. 21 CFR 300.50 — Fixed-combination prescription drugs for humans. ecfr.gov/current/title-21/chapter-I/subchapter-D/part-300/su Regulation or statute
  13. SupplySide Supplement Journal. USDA says ORAC tests useless, removes database for selected foods. June 12, 2012 (trade-press report of the USDA Nutrient Data Laboratory statement). supplysidesj.com/claims/usda-says-orac-tests-useless-removes

Evidence: grading, bias and effect sizes

  1. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–926. doi.org/10.1136/bmj.39489.470347.AD Peer-reviewed
  2. Balshem H, Helfand M, Schünemann HJ, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64(4):401–406. doi.org/10.1016/j.jclinepi.2010.07.015 Peer-reviewed
  3. Guyatt GH, Oxman AD, Sultan S, et al. GRADE guidelines: 9. Rating up the quality of evidence. J Clin Epidemiol. 2011;64(12):1311–1316. doi.org/10.1016/j.jclinepi.2011.06.004 Peer-reviewed
  4. GRADE Working Group. GRADE Handbook, Table 5.1: Quality of evidence grades. gdt.gradepro.org/app/handbook/handbook.html Primary source
  5. Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi.org/10.1136/bmj.l4898 Peer-reviewed

Evidence: botanical categories, harms and drug development

  1. U.S. FDA. What Is a Botanical Drug? (content current as of September 3, 2026). fda.gov/about-fda/cder-offices-and-divisions/what-botanical- Primary source
  2. U.S. FDA. Approval letter, BLA 761192 (NexoBrid, anacaulase-bcdb), December 28, 2022. accessdata.fda.gov/drugsatfda_docs/nda/2023/761192Orig1s000A Primary source
  3. BIO, Informa Pharma Intelligence, QLS Advisors. Clinical Development Success Rates and Contributing Factors 2011–2020 (February 2021). bio.org/clinical-development-success-rates-and-contributing- Third-party estimate

Evidence: absorption, exposure and herb–drug interactions

  1. 21 CFR 320.1 — Definitions (bioavailability). ecfr.gov/current/title-21/chapter-I/subchapter-D/part-320/su Regulation or statute

Toxicology: test guidelines, requirements and study quality

  1. OECD. Guidelines for the Testing of Chemicals, Section 4: Health Effects (TG 407, 408, 414, 420–425, 432, 437, 439, 442C–E, 443, 451–453, 471, 473, 474, 487, 489, 492, 497). oecd.org/en/publications/oecd-guidelines-for-the-testing-of- Primary source
  2. German Federal Institute for Risk Assessment (BfR). Alternative OECD test guidelines (summer 2021): in vitro and in chemico methods. bfr.bund.de/cm/349/alternative-oecd-test-guidelines-summer-2 Primary source
  3. U.S. FDA. Guidance for Industry: Summary Table of Recommended Toxicological Testing for Additives Used in Food (June 2006). fda.gov/food/guidance-documents-regulatory-information-topic Agency guidance
  4. European Commission. Ban on animal testing (cosmetics): testing ban on finished products since 11 September 2004 and on ingredients since 11 March 2009; marketing ban for all endpoints since 11 March 2013. single-market-economy.ec.europa.eu/sectors/cosmetics/ban-ani Regulation or statute
  5. ICH M3(R2). Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (FDA guidance). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  6. ICH S2(R1). Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use (FDA guidance). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  7. ICH S5(R3). Detection of Reproductive and Developmental Toxicity for Human Pharmaceuticals (FDA guidance). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  8. ICH S7B. The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals (FDA guidance). hhs.gov/guidance/document/s7b-nonclinical-evaluation-potenti Agency guidance
  9. ICH S1A. The Need for Long-term Rodent Carcinogenicity Studies of Pharmaceuticals (FDA guidance). hhs.gov/guidance/sites/default/files/hhs-guidance-documents/ Agency guidance
  10. ICH S10. Photosafety Evaluation of Pharmaceuticals (FDA guidance). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  11. ICH S3A. Toxicokinetics: The Assessment of Systemic Exposure in Toxicity Studies (FDA guidance, March 1995). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  12. Weaver RJ, Blomme EA, Chadwick AE, et al. Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models. Nat Rev Drug Discov. 2020;19(2):131–148. doi.org/10.1038/s41573-019-0048-x Peer-reviewed
  13. OECD. Principles of Good Laboratory Practice (as revised in 1997). ENV/MC/CHEM(98)17; Council Decision C(97)186/Final amending C(81)30(Final) on the Mutual Acceptance of Data. ntp.niehs.nih.gov/sites/default/files/iccvam/suppdocs/feddoc Primary source
  14. U.S. FDA. New Dietary Ingredient (NDI) Notifications and Related Issues; Identity and Safety Information About the NDI: Guidance for Industry (final, October 2026; docket FDA-2025-D-6501). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance

Toxicology: dose–response, reference points and interactions

  1. EFSA Scientific Committee; More SJ, Bampidis V, Benford D, et al. Guidance on the use of the benchmark dose approach in risk assessment. EFSA J. 2022;20(10):e07584. doi.org/10.2903/j.efsa.2022.7584 Peer-reviewed
  2. EFSA. Opinion of the Scientific Committee on a request from EFSA related to a harmonised approach for risk assessment of substances which are both genotoxic and carcinogenic. EFSA J. 2005;3(10):282. doi.org/10.2903/j.efsa.2005.282 Peer-reviewed
  3. EFSA Scientific Committee. Statement on the applicability of the Margin of Exposure approach for the safety assessment of impurities which are both genotoxic and carcinogenic in substances added to food/feed. EFSA J. 2012;10(3):2578. doi.org/10.2903/j.efsa.2012.2578 Peer-reviewed
  4. EFSA Scientific Committee. Guidance on selected default values to be used by the EFSA Scientific Committee, Scientific Panels and Units in the absence of actual measured data. EFSA J. 2012;10(3):2579. doi.org/10.2903/j.efsa.2012.2579 Peer-reviewed
  5. ICH M12. Drug Interaction Studies (FDA final guidance, August 2024; docket FDA-2022-D-1527). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance

Toxicology: test guideline texts, carcinogenicity and acute classification (October 2026 additions)

  1. OECD Guidelines for the Testing of Chemicals, Section 4: TG 407, 408 and 443 (adopted June 25, 2025); TG 414, 451, 452 and 453 (adopted June 25, 2018); TG 420 and 423 (adopted December 17, 2001); TG 425 (adopted October 16, 2008, corrected 2022); TG 471 (adopted 1997, corrected 2020); TG 487 (adopted 2016, corrected 2023). oecd.org/en/publications/test-no-451-carcinogenicity-studies Primary source
  2. OECD. Test No. 423: Acute Oral Toxicity – Acute Toxic Class Method (adopted December 17, 2001), paragraphs 9, 18–24 and Annex 2a–2d. oecd.org/content/dam/oecd/en/publications/reports/2002/02/te Primary source
  3. 29 CFR 1910.1200, Appendix A, Table A.1.1 (acute toxicity hazard categories). eCFR, current as of October 21, 2026. ecfr.gov/current/title-29/subtitle-B/chapter-XVII/part-1910/ Regulation or statute
  4. ICH S1B(R1) Testing for Carcinogenicity of Pharmaceuticals (addendum endorsed under Step 4 on August 4, 2022); EMA/774371/2022, in effect from March 16, 2023. consultations.tga.gov.au/tga/international-scientific-guidel Agency guidance
  1. 21 U.S.C. 360ee(b)(3): definition of medical food. Cornell LII. law.cornell.edu/uscode/text/21/360ee Regulation or statute
  2. U.S. FDA. Label Claims for Conventional Foods and Dietary Supplements. Content current as of March 28, 2024. fda.gov/food/nutrition-food-labeling-and-critical-foods/labe Agency guidance

Regulation and standards: international categories for botanicals

  1. Directive 2004/24/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC as regards traditional herbal medicinal products. OJ L 136, 30.4.2004. eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:32004 Regulation or statute
  2. Directive 2002/46/EC of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements. OJ L 183, 12.7.2002. eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:32002 Regulation or statute
  3. Natural Health Products Regulations, SOR/2003-196 (current to September 30, 2026). laws-lois.justice.gc.ca/eng/regulations/SOR-2003-196/FullTex Regulation or statute
  4. Health Canada. Product licensing (natural health products). canada.ca/en/health-canada/services/drugs-health-products/na Primary source
  5. Consumer Affairs Agency (Japan). Foods with Function Claims (機能性表示食品について). caa.go.jp/policies/policy/food_labeling/foods_with_function_ Primary source
  6. Therapeutic Goods Administration. Listed complementary medicines (page dated May 4, 2018). tga.gov.au/listed-complementary-medicines Primary source

Evidence: Persian heritage botanicals

  1. Hosseinzadeh H, Nassiri-Asl M. Avicenna's (Ibn Sina) the Canon of Medicine and saffron (Crocus sativus): a review. Phytother Res. 2013;27(4):475-83. doi:10.1002/ptr.4784. PMID 22815242. pubmed.ncbi.nlm.nih.gov/22815242/ Peer-reviewed
  2. Mollazadeh H, Emami SA, Hosseinzadeh H. Razi's Al-Hawi and saffron (Crocus sativus): a review. Iran J Basic Med Sci. 2015;18(12):1153-66. PMID 26877844. pubmed.ncbi.nlm.nih.gov/26877844/ Peer-reviewed
  3. Mahmoudi R, Mohammadi-Sartang M, Servatyari K, et al. Effect of saffron on depression, anxiety and mood disorder: a GRADE assessed systematic review and meta-analysis of 34 randomized controlled trials. Nutr Neurosci. 2026;29(7):816-837. doi:10.1080/1028415X.2025.2602153. PMID 41693488. pubmed.ncbi.nlm.nih.gov/41693488/ Peer-reviewed
  4. Amadieu C, Leyrolle Q, Farneti M, et al. Effect of saffron extract supplementation on mood in healthy adults with subclinical symptoms of depression: a randomized, double-blind placebo-controlled study. Am J Clin Nutr. 2025;122(6):1625-1635. doi:10.1016/j.ajcnut.2025.09.050. PMID 41047129. pubmed.ncbi.nlm.nih.gov/41047129/ Peer-reviewed
  5. Ahmad A, Husain A, Mujeeb M, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed. 2013;3(5):337-52. doi:10.1016/S2221-1691(13)60075-1. PMID 23646296. pubmed.ncbi.nlm.nih.gov/23646296/ Peer-reviewed
  6. Kavyani Z, Musazadeh V, Safaei E, et al. Antihypertensive effects of Nigella sativa supplementation: An updated systematic review and meta-analysis of randomized controlled trials. Phytother Res. 2023;37(8):3224-3238. doi:10.1002/ptr.7891. PMID 37341696. pubmed.ncbi.nlm.nih.gov/37341696/ Peer-reviewed
  7. Abolhassanzadeh Z, Ansari S, Lorigooini Z, et al. The nephrotoxicity of Aristolochia rotunda L. in rats: Mitochondrion as a target for renal toxicity of Aristolochic acids-containing plants. Heliyon. 2023;9(11):e21848. doi:10.1016/j.heliyon.2023.e21848. PMID 38027649. pubmed.ncbi.nlm.nih.gov/38027649/ Peer-reviewed

Regulatory: access, benefit-sharing and sanctions (heritage)

  1. OFAC. Iranian Transactions and Sanctions Regulations, final rule. 83 FR 30335 (June 28, 2018). federalregister.gov/documents/2018/06/28/2018-13939/iranian- Regulation or statute

Evidence: botanical atlas, human studies

  1. Jafari A, ParsiNezhad B, AhmadianMoghaddam M, et al. Sumac (Rhus coriaria L.) and Human Metabolic Health: A Systematic Review and Meta-Analysis. Endocrinol Diabetes Metab. 2026;9(1):e70135. doi:10.1002/edm2.70135. PMID 41329614. pubmed.ncbi.nlm.nih.gov/41329614/ Peer-reviewed
  2. Ghaemi F, Emadzadeh M, Atkin SL, et al. Impact of pomegranate juice on blood pressure: A systematic review and meta-analysis. Phytother Res. 2023;37(10):4429-4441. doi:10.1002/ptr.7952. PMID 37461211. pubmed.ncbi.nlm.nih.gov/37461211/ Peer-reviewed
  3. Penninkilampi R, Eslick EM, Eslick GD. The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis. J Hum Hypertens. 2017;31(11):699-707. doi:10.1038/jhh.2017.45. PMID 28660884. pubmed.ncbi.nlm.nih.gov/28660884/ Peer-reviewed
  4. Ursoniu S, Sahebkar A, Serban MC, et al. The impact of argan oil on plasma lipids in humans: Systematic review and meta-analysis of randomized controlled trials. Phytother Res. 2018;32(3):377-383. doi:10.1002/ptr.5959. PMID 29130532. pubmed.ncbi.nlm.nih.gov/29130532/ Peer-reviewed
  5. Li S, Duan F, Li S, et al. Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis. Ann Hepatol. 2024;29(2):101174. doi:10.1016/j.aohep.2023.101174. PMID 38579127. pubmed.ncbi.nlm.nih.gov/38579127/ Peer-reviewed
  6. Álvares AA, Garcêz A, Silva LT, et al. Olive leaf extract effect on cardiometabolic risk factors: a systematic review and meta-analysis of randomized clinical trials. Nutr Rev. 2024;82(12):1710-1725. doi:10.1093/nutrit/nuad164. PMID 38287654. pubmed.ncbi.nlm.nih.gov/38287654/ Peer-reviewed
  7. Dabos KJ, Sfika E, Vlatta LJ, et al. Is Chios mastic gum effective in the treatment of functional dyspepsia? A prospective randomised double-blind placebo controlled trial. J Ethnopharmacol. 2010;127(2):205-9. doi:10.1016/j.jep.2009.11.021. PMID 19961914. pubmed.ncbi.nlm.nih.gov/19961914/ Peer-reviewed
  8. Möller HJ, Volz HP, Dienel A, et al. Efficacy of Silexan in subthreshold anxiety: meta-analysis of randomised, placebo-controlled trials. Eur Arch Psychiatry Clin Neurosci. 2019;269(2):183-193. doi:10.1007/s00406-017-0852-4. PMID 29150713. pubmed.ncbi.nlm.nih.gov/29150713/ Peer-reviewed
  9. Zeng L, Yang T, Yang K, et al. Efficacy and Safety of Curcumin and Curcuma longa Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial. Front Immunol. 2022;13:891822. doi:10.3389/fimmu.2022.891822. PMID 35935936. pubmed.ncbi.nlm.nih.gov/35935936/ Peer-reviewed
  10. Akhgarjand C, Asoudeh F, Bagheri A, et al. Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trials. Phytother Res. 2022;36(11):4115-4124. doi:10.1002/ptr.7598. PMID 36017529. pubmed.ncbi.nlm.nih.gov/36017529/ Peer-reviewed
  11. Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, et al. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. J Ethnopharmacol. 2014;151(1):528-35. doi:10.1016/j.jep.2013.11.008. PMID 24252493. pubmed.ncbi.nlm.nih.gov/24252493/ Peer-reviewed
  12. Yu G, Xiang W, Zhang T, et al. Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis. BMC Complement Med Ther. 2020;20(1):225. doi:10.1186/s12906-020-02985-6. PMID 32680575. pubmed.ncbi.nlm.nih.gov/32680575/ Peer-reviewed
  13. Szapary PO, Wolfe ML, Bloedon LT, et al. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA. 2003;290(6):765-72. doi:10.1001/jama.290.6.765. PMID 12915429. pubmed.ncbi.nlm.nih.gov/12915429/ Peer-reviewed
  14. Hu XY, Wu RH, Logue M, et al. Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis. PLoS One. 2017;12(8):e0181780. doi:10.1371/journal.pone.0181780. PMID 28783743. pubmed.ncbi.nlm.nih.gov/28783743/ Peer-reviewed
  15. Wieland LS, Ludeman E, Chi Y, et al. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. 2026;2(2):CD013661. doi:10.1002/14651858.CD013661.pub2. PMID 41641880. pubmed.ncbi.nlm.nih.gov/41641880/ Peer-reviewed
  16. Shishtar E, Sievenpiper JL, Djedovic V, et al. The effect of ginseng (the genus panax) on glycemic control: a systematic review and meta-analysis of randomized controlled clinical trials. PLoS One. 2014;9(9):e107391. doi:10.1371/journal.pone.0107391. PMID 25265315. pubmed.ncbi.nlm.nih.gov/25265315/ Peer-reviewed
  17. Kim A, Chiu A, Barone MK, et al. Green tea catechins decrease total and low-density lipoprotein cholesterol: a systematic review and meta-analysis. J Am Diet Assoc. 2011;111(11):1720-9. doi:10.1016/j.jada.2011.08.009. PMID 22027055. pubmed.ncbi.nlm.nih.gov/22027055/ Peer-reviewed
  18. Yoshino S, Tagawa T, Awa R, et al. Polymethoxyflavone purified from Kaempferia parviflora reduces visceral fat in Japanese overweight individuals: a randomised, double-blind, placebo-controlled study. Food Funct. 2021;12(4):1603-1613. doi:10.1039/d0fo01217c. PMID 33475663. pubmed.ncbi.nlm.nih.gov/33475663/ Peer-reviewed
  19. Puttarak P, Dilokthornsakul P, Saokaew S, et al. Effects of Centella asiatica (L.) Urb. on cognitive function and mood related outcomes: A Systematic Review and Meta-analysis. Sci Rep. 2017;7(1):10646. doi:10.1038/s41598-017-09823-9. PMID 28878245. pubmed.ncbi.nlm.nih.gov/28878245/ Peer-reviewed
  20. Leisegang K, Finelli R, Sikka SC, et al. Eurycoma longifolia (Jack) Improves Serum Total Testosterone in Men: A Systematic Review and Meta-Analysis of Clinical Trials. Medicina (Kaunas). 2022;58(8). doi:10.3390/medicina58081047. PMID 36013514. pubmed.ncbi.nlm.nih.gov/36013514/ Peer-reviewed
  21. Penna EM, Harp A, Hack B, et al. Guarana (Paullinia cupana) but Not Low-Dose Caffeine Improves Cycling Time-Trial Performance Versus Placebo. Int J Sport Nutr Exerc Metab. 2024;34(1):30-37. doi:10.1123/ijsnem.2023-0148. PMID 37898479. pubmed.ncbi.nlm.nih.gov/37898479/ Peer-reviewed
  22. Kim H , Simbo SY , Fang C , et al. Açaí (Euterpe oleracea Mart.) beverage consumption improves biomarkers for inflammation but not glucose- or lipid-metabolism in individuals with metabolic syndrome in a randomized, double-blinded, placebo-controlled clinical trial. Food Funct. 2018;9(6):3097-3103. doi:10.1039/c8fo00595h. PMID 29850709. pubmed.ncbi.nlm.nih.gov/29850709/ Peer-reviewed
  23. Agrinier AL, Morissette A, Daoust L, et al. Camu-camu decreases hepatic steatosis and liver injury markers in overweight, hypertriglyceridemic individuals: A randomized crossover trial. Cell Rep Med. 2024;5(8):101682. doi:10.1016/j.xcrm.2024.101682. PMID 39168095. pubmed.ncbi.nlm.nih.gov/39168095/ Peer-reviewed
  24. Mur E, Hartig F, Eibl G, et al. Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of uncaria tomentosa for the treatment of rheumatoid arthritis. J Rheumatol. 2002;29(4):678-81. PMID 11950006. pubmed.ncbi.nlm.nih.gov/11950006/ Peer-reviewed
  25. Lee HW, Lee MS, Qu F, et al. Maca (Lepidium meyenii Walp.) on semen quality parameters: A systematic review and meta-analysis. Front Pharmacol. 2022;13:934740. doi:10.3389/fphar.2022.934740. PMID 36110519. pubmed.ncbi.nlm.nih.gov/36110519/ Peer-reviewed
  26. Machado AM, da Silva NBM, Chaves JBP, et al. Consumption of yacon flour improves body composition and intestinal function in overweight adults: A randomized, double-blind, placebo-controlled clinical trial. Clin Nutr ESPEN. 2019;29:22-29. doi:10.1016/j.clnesp.2018.12.082. PMID 30661690. pubmed.ncbi.nlm.nih.gov/30661690/ Peer-reviewed
  27. Macarthur RD, Hawkins TN, Brown SJ, et al. Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive individuals (ADVENT trial): a randomized, double-blind, placebo-controlled, two-stage study. HIV Clin Trials. 2013;14(6):261-73. doi:10.1310/hct1406-261. PMID 24334179. pubmed.ncbi.nlm.nih.gov/24334179/ Peer-reviewed
  28. DailyMed. MYTESI (crofelemer) delayed-release tablets, label, Napo Pharmaceuticals (version published August 14, 2026): "a botanical drug substance that is derived from the red latex of Croton lechleri Müll. Arg." dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=45584fba-8081 Primary source
  29. Gagnier JJ, Chrubasik S, Manheimer E. Harpgophytum procumbens for osteoarthritis and low back pain: a systematic review. BMC Complement Altern Med. 2004;4:13. doi:10.1186/1472-6882-4-13. PMID 15369596. pubmed.ncbi.nlm.nih.gov/15369596/ Peer-reviewed
  30. Wilt T, Ishani A, Mac Donald R, et al. Pygeum africanum for benign prostatic hyperplasia. Cochrane Database Syst Rev. 2002;1998(1):CD001044. doi:10.1002/14651858.CD001044. PMID 11869585. pubmed.ncbi.nlm.nih.gov/11869585/ Peer-reviewed
  31. Blom WA, Abrahamse SL, Bradford R, et al. Effects of 15-d repeated consumption of Hoodia gordonii purified extract on safety, ad libitum energy intake, and body weight in healthy, overweight women: a randomized controlled trial. Am J Clin Nutr. 2011;94(5):1171-81. doi:10.3945/ajcn.111.020321. PMID 21993434. pubmed.ncbi.nlm.nih.gov/21993434/ Peer-reviewed
  32. Hartnick MD, Marnewick JL, Engel-Hills P, et al. Impact of Chronic Consumption of Herbal Rooibos on Cardiovascular Function in Adults with Cardiovascular Risk. J Med Food. 2024;27(10):905-911. doi:10.1089/jmf.2024.0012. PMID 38958559. pubmed.ncbi.nlm.nih.gov/38958559/ Peer-reviewed
  33. Ellis LR, Zulfiqar S, Holmes M, et al. A systematic review and meta-analysis of the effects of Hibiscus sabdariffa on blood pressure and cardiometabolic markers. Nutr Rev. 2022;80(6):1723-1737. doi:10.1093/nutrit/nuab104. PMID 34927694. pubmed.ncbi.nlm.nih.gov/34927694/ Peer-reviewed

Ingredient safety: botanical atlas

  1. Khaikin E, Chrubasik-Hausmann S, Kaya S, et al. Screening of Thymoquinone Content in Commercial Nigella sativa Products to Identify a Promising and Safe Study Medication. Nutrients. 2022;14(17). doi:10.3390/nu14173501. PMID 36079759. pubmed.ncbi.nlm.nih.gov/36079759/ Peer-reviewed
  2. National Center for Complementary and Integrative Health. Pomegranate. Herb fact sheet, last updated April 2025. nccih.nih.gov/health/pomegranate Primary source
  3. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Licorice. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2023 Mar 20. PMID 37043593. ncbi.nlm.nih.gov/books/NBK590484/ Primary source
  4. National Center for Complementary and Integrative Health. Licorice Root. Herb fact sheet, last updated April 2025. nccih.nih.gov/health/licorice-root Primary source
  5. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Milk Thistle. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2020 Jan 21. PMID 31644124. ncbi.nlm.nih.gov/books/NBK548817/ Primary source
  6. National Center for Complementary and Integrative Health. Milk Thistle. Herb fact sheet, last updated February 2025. nccih.nih.gov/health/milk-thistle Primary source
  7. National Center for Complementary and Integrative Health. Lavender. Herb fact sheet, last updated February 2025. nccih.nih.gov/health/lavender Primary source
  8. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Turmeric. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2025 Jun 16. PMID 31643876. ncbi.nlm.nih.gov/books/NBK548561/ Primary source
  9. Halegoua-DeMarzio D, Navarro V, Ahmad J, et al. Liver Injury Associated with Turmeric-A Growing Problem: Ten Cases from the Drug-Induced Liver Injury Network [DILIN]. Am J Med. 2023;136(2):200-206. doi:10.1016/j.amjmed.2022.09.026. PMID 36252717. pubmed.ncbi.nlm.nih.gov/36252717/ Peer-reviewed
  10. National Center for Complementary and Integrative Health. Turmeric. Herb fact sheet, last updated April 2025. nccih.nih.gov/health/turmeric Primary source
  11. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Ashwagandha. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2024 Dec 3. PMID 31643854. ncbi.nlm.nih.gov/books/NBK548536/ Primary source
  12. Björnsson HK, Björnsson ES, Avula B, et al. Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network. Liver Int. 2020;40(4):825-829. doi:10.1111/liv.14393. PMID 31991029. pubmed.ncbi.nlm.nih.gov/31991029/ Peer-reviewed
  13. National Center for Complementary and Integrative Health. Ashwagandha. Herb fact sheet, last updated March 2023. nccih.nih.gov/health/ashwagandha Primary source
  14. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bacopa monnieri. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2024 Apr 24. PMID 38718157. ncbi.nlm.nih.gov/books/NBK603563/ Primary source
  15. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Boswellia Serrata. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2020 Nov 4. PMID 33151656. ncbi.nlm.nih.gov/books/NBK563692/ Primary source
  16. National Center for Complementary and Integrative Health. Boswellia. Herb fact sheet, last updated April 2025. nccih.nih.gov/health/boswellia Primary source
  17. Worakunphanich W, Thavorncharoensap M, Youngkong S, et al. Safety of Andrographis paniculata: A systematic review and meta-analysis. Pharmacoepidemiol Drug Saf. 2021;30(6):727-739. doi:10.1002/pds.5190. PMID 33372366. pubmed.ncbi.nlm.nih.gov/33372366/ Peer-reviewed
  18. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Ginkgo. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2018 Mar 14. PMID 31644154. ncbi.nlm.nih.gov/books/NBK548847/ Primary source
  19. National Center for Complementary and Integrative Health. Ginkgo. Herb fact sheet, last updated February 2025. nccih.nih.gov/health/ginkgo Primary source
  20. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Ginseng. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2018 Mar 14. PMID 31643526. ncbi.nlm.nih.gov/books/NBK548200/ Primary source
  21. National Center for Complementary and Integrative Health. Asian Ginseng. Herb fact sheet, last updated February 2025. nccih.nih.gov/health/asian-ginseng Primary source
  22. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Green Tea. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2020 Nov 20. PMID 31643260. ncbi.nlm.nih.gov/books/NBK547925/ Primary source
  23. Hu J, Webster D, Cao J, et al. The safety of green tea and green tea extract consumption in adults - Results of a systematic review. Regul Toxicol Pharmacol. 2018;95:412-433. doi:10.1016/j.yrtph.2018.03.019. PMID 29580974. pubmed.ncbi.nlm.nih.gov/29580974/ Peer-reviewed
  24. DailyMed. VEREGEN (sinecatechins) ointment 15%, label (version published November 15, 2022): "a partially purified fraction of the water extract of green tea leaves from Camellia sinensis". dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=f0fc1e21-e3cf Primary source
  25. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Centella asiatica. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2024 Apr 24. PMID 38718155. ncbi.nlm.nih.gov/books/NBK603561/ Primary source
  26. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Guarana. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2023 Jan 28. PMID 36753599. ncbi.nlm.nih.gov/books/NBK589113/ Primary source
  27. National Center for Complementary and Integrative Health. Acai. Herb fact sheet, last updated November 2024. nccih.nih.gov/health/acai Primary source
  28. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Cat's Claw. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2019 Feb 18. PMID 31643645. ncbi.nlm.nih.gov/books/NBK548323/ Primary source
  29. National Center for Complementary and Integrative Health. Cat's Claw. Herb fact sheet, last updated November 2024. nccih.nih.gov/health/cats-claw Primary source
  30. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Maca. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2019 Apr 10. PMID 31643869. ncbi.nlm.nih.gov/books/NBK548552/ Primary source
  31. Vlachojannis J, Roufogalis BD, Chrubasik S. Systematic review on the safety of Harpagophytum preparations for osteoarthritic and low back pain. Phytother Res. 2008;22(2):149-52. doi:10.1002/ptr.2314. PMID 18236448. pubmed.ncbi.nlm.nih.gov/18236448/ Peer-reviewed
  32. National Center for Complementary and Integrative Health. Hoodia. Herb fact sheet, last updated April 2025. nccih.nih.gov/health/hoodia Primary source
  33. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Hoodia. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Updated 2018 Mar 28. PMID 31644014. ncbi.nlm.nih.gov/books/NBK548704/ Primary source

Regulatory: U.S. import route for botanicals

  1. 16 U.S.C. 3371(g): definition of plant and its exclusions (Lacey Act). Cornell LII. law.cornell.edu/uscode/text/16/3371 Regulation or statute
  2. 16 U.S.C. 3372(f): plant import declarations (Lacey Act). Cornell LII. law.cornell.edu/uscode/text/16/3372 Regulation or statute
  3. USDA APHIS. Lacey Act (plant imports): Phase VII from December 1, 2024; ACE and LAWGS filing; paper PPQ 505 not accepted from January 1, 2026. Last modified October 19, 2026. aphis.usda.gov/plant-imports/lacey-act Primary source
  4. USDA APHIS. CITES (Endangered Plant Species): Protected Plant Permit under 7 CFR 355; designated ports. Last modified September 9, 2026. aphis.usda.gov/plant-imports/cites Primary source
  5. 50 CFR 23.13 (what is prohibited) and 23.20 (CITES documents required for international trade). eCFR, current as of October 2026. ecfr.gov/current/title-50/chapter-I/subchapter-B/part-23 Regulation or statute
  6. OFAC. Iranian Transactions and Sanctions Regulations. 91 FR 54957 (August 26, 2026): five general licenses suspended indefinitely. federalregister.gov/documents/2026/08/26/2026-17426/iranian- Regulation or statute

Safety, interactions and combination science (opened in PubMed, NIH ODS or NCCIH, October 22, 2026)

  1. Hallberg L, Brune M, Rossander L. Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate. Am J Clin Nutr. 1989;49(1):140–144. PMID 2911999. doi.org/10.1093/ajcn/49.1.140 Peer-reviewed
  2. Cook JD, Reddy MB. Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet. Am J Clin Nutr. 2001;73(1):93–98. PMID 11124756. doi.org/10.1093/ajcn/73.1.93 Peer-reviewed
  3. Hurrell RF, Reddy M, Cook JD. Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages. Br J Nutr. 1999;81(4):289–295. PMID 10999016. pubmed.ncbi.nlm.nih.gov/10999016/ Peer-reviewed
  4. Tuntipopipat S, Judprasong K, Zeder C, et al. Chili, but not turmeric, inhibits iron absorption in young women from an iron-fortified composite meal. J Nutr. 2006;136(12):2970–2974. PMID 17116705. doi.org/10.1093/jn/136.12.2970 Peer-reviewed
  5. Hallberg L, Brune M, Erlandsson M, Sandberg AS, Rossander-Hultén L. Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans. Am J Clin Nutr. 1991;53(1):112–119. PMID 1984335. doi.org/10.1093/ajcn/53.1.112 Peer-reviewed
  6. Brown MJ, Ferruzzi MG, Nguyen ML, et al. Carotenoid bioavailability is higher from salads ingested with full-fat than with fat-reduced salad dressings as measured with electrochemical detection. Am J Clin Nutr. 2004;80(2):396–403. PMID 15277161. doi.org/10.1093/ajcn/80.2.396 Peer-reviewed
  7. Peters CM, Green RJ, Janle EM, Ferruzzi MG. Formulation with ascorbic acid and sucrose modulates catechin bioavailability from green tea. Food Res Int. 2010;43(1):95–102. PMID 20161530. doi.org/10.1016/j.foodres.2009.08.016 Peer-reviewed
  8. Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003;290(11):1500–1504. PMID 13129991. doi.org/10.1001/jama.290.11.1500 Peer-reviewed
  9. Hursel R, Viechtbauer W, Westerterp-Plantenga MS. The effects of green tea on weight loss and weight maintenance: a meta-analysis. Int J Obes (Lond). 2009;33(9):956–961. PMID 19597519. doi.org/10.1038/ijo.2009.135 Peer-reviewed
  10. Haroyan A, Mukuchyan V, Mkrtchyan N, et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. 2018;18(1):7. PMID 29316908. doi.org/10.1186/s12906-017-2062-z Peer-reviewed
  11. NIH Office of Dietary Supplements. Iron: Fact Sheet for Health Professionals. Updated September 4, 2025. Retrieved October 22, 2026. ods.od.nih.gov/factsheets/Iron-HealthProfessional/ Primary source
  12. National Center for Complementary and Integrative Health. St. John's Wort. Last updated May 2025. Retrieved October 22, 2026. nccih.nih.gov/health/st-johns-wort Primary source

Evidence: synergy reference models and factorial trials

  1. Greco WR, Bravo G, Parsons JC. The search for synergy: a critical review from a response surface perspective. Pharmacol Rev. 1995;47(2):331–385. PMID 7568331. pubmed.ncbi.nlm.nih.gov/7568331/ Peer-reviewed
  2. Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70(2):440–446. PMID 20068163. doi.org/10.1158/0008-5472.CAN-09-1947 Peer-reviewed
  3. Montgomery AA, Peters TJ, Little P. Design, analysis and presentation of factorial randomised controlled trials. BMC Med Res Methodol. 2003;3:26. PMID 14633287. doi.org/10.1186/1471-2288-3-26 Peer-reviewed

Evidence: PubChem structure records

  1. National Center for Biotechnology Information. PubChem Compound Summary for CID 3520, Guanidine. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/3520 Primary source
  2. National Center for Biotechnology Information. PubChem Compound Summary for CID 4091, Metformin. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/4091 Primary source
  3. National Center for Biotechnology Information. PubChem Compound Summary for CID 36314, Paclitaxel. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/36314 Primary source
  4. National Center for Biotechnology Information. PubChem Compound Summary for CID 3828, Khellin. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/3828 Primary source
  5. National Center for Biotechnology Information. PubChem Compound Summary for CID 2882, Cromolyn. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/2882 Primary source
  6. National Center for Biotechnology Information. PubChem Compound Summary for CID 2157, Amiodarone. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/2157 Primary source
  7. National Center for Biotechnology Information. PubChem Compound Summary for CID 14888, Arsenic trioxide. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/14888 Primary source
  8. National Center for Biotechnology Information. PubChem Compound Summary for CID 5978, Vincristine. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/5978 Primary source

Regulation and standards: quality by design and control strategy

  1. ICH Q9(R1) Quality Risk Management, adopted 18 January 2023 (section 3 principles; glossary; Annex I.1 and I.5). database.ich.org/sites/default/files/ICH_Q9%28R1%29_Guidelin Agency guidance
  2. ICH Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management, adopted 20 November 2019 (section 3.2.1; chapters 4 and 5). database.ich.org/sites/default/files/Q12_Guideline_Step4_201 Agency guidance
  3. Yu LX, Amidon G, Khan MA, Hoag SW, Polli J, Raju GK, Woodcock J. Understanding pharmaceutical quality by design. AAPS J. 2014;16(4):771–783 (control strategy levels; CMA definition). doi.org/10.1208/s12248-014-9598-3 Peer-reviewed
  4. FDA. Guidance for Industry: PAT, a Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance. September 2004. fda.gov/media/71012/download Agency guidance
  5. Pan X, Li Y, Wu Z, Zhang Q, Zheng Z, Shi X, Qiao Y. A online NIR sensor for the pilot-scale extraction process in Fructus aurantii coupled with single and ensemble methods. Sensors. 2015;15(4):8749–8763. doi.org/10.3390/s150408749 Peer-reviewed
  6. Delueg S, Kirchler CG, Meischl F, Ozaki Y, Popp MA, Bonn GK, Huck CW. At-line monitoring of the extraction process of Rosmarini folium via wet chemical assays, UHPLC analysis, and newly developed near-infrared spectroscopic analysis methods. Molecules. 2019;24(13):2480. doi.org/10.3390/molecules24132480 Peer-reviewed
  7. FAO and WHO. General Principles of Food Hygiene, CXC 1-1969 (adopted 1969; amended 1999; revised 1997, 2003, 2020, 2022): sections 3, 17 and 19 and Annex IV, Figure 1. English text read in the FAO/WHO/Japan Food Hygiene Association bilingual edition (2024). n-shokuei.jp/eisei/pdf/ippangensoku_2022.pdf Primary source
  8. Current Good Manufacturing Practice, Hazard Analysis, and Risk-Based Preventive Controls for Human Food; final rule. 80 FR 55908 (September 17, 2015). govinfo.gov/content/pkg/FR-2015-09-17/pdf/2015-21920.pdf Regulation or statute
  9. United States Pharmacopeia. General chapter titles ⟨203⟩, ⟨233⟩, ⟨401⟩, ⟨429⟩, ⟨430⟩, ⟨467⟩, ⟨561⟩, ⟨563⟩, ⟨616⟩, ⟨621⟩, ⟨731⟩, ⟨791⟩, ⟨891⟩, ⟨921⟩, ⟨922⟩, ⟨941⟩, ⟨1174⟩, ⟨2021⟩, ⟨2022⟩, ⟨2023⟩, ⟨2040⟩, ⟨2091⟩, ⟨2232⟩ as registered in USP–NF DOI records (Crossref prefix 10.31003), checked October 23, 2026. doi.org/10.31003/uspnf_m99970_04_01 Primary source
  10. ISO 13099-2 Colloidal systems — Methods for zeta-potential determination — Part 2: Optical methods (2012 edition withdrawn August 2025; replaced by ISO 13099-2:2025). iso.org/standard/52832.html Primary source
  11. IUPAC Compendium of Chemical Terminology (Gold Book): Arrhenius equation. Arrhenius S. Z Phys Chem. 1889;4U:226–248. doi.org/10.1351/goldbook.A00446 Peer-reviewed

Clinical research: endpoint definitions

  1. FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource: Glossary. Silver Spring (MD): Food and Drug Administration (US); co-published by National Institutes of Health (US). Updated January 16, 2025. ncbi.nlm.nih.gov/books/NBK338448/ Agency guidance

Regulatory: cosmetics and MoCRA

  1. 21 U.S.C. 364h (FD&C Act § 612), Small businesses. Cornell LII. law.cornell.edu/uscode/text/21/364h Regulation or statute
  2. 21 U.S.C. 364i (FD&C Act § 613), Exemption for certain products and facilities. Cornell LII. law.cornell.edu/uscode/text/21/364i Regulation or statute
  3. U.S. FDA. FDA Authority Over Cosmetics: How Cosmetics Are Not FDA-Approved, but Are FDA-Regulated. Content current as of Nov 18, 2025. fda.gov/cosmetics/cosmetics-laws-regulations/fda-authority-o Primary source
  4. 21 CFR Part 701, Cosmetic Labeling (§§ 701.3, 701.11, 701.12, 701.13). eCFR, current to Oct 21, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-G/part-701 Regulation or statute
  5. 21 CFR Part 740, Cosmetic Product Warning Statements (§ 740.10). eCFR, current to Oct 21, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-G/part-740 Regulation or statute
  6. 21 U.S.C. 379e (FD&C Act § 721), Listing and certification of color additives for foods, drugs, devices, and cosmetics. Cornell LII. law.cornell.edu/uscode/text/21/379e Regulation or statute
  7. 21 U.S.C. 364f (FD&C Act § 610), Records: access to and copying of records of a cosmetic product, including safety substantiation data, when statutory conditions are met. Cornell LII, read October 24, 2026. law.cornell.edu/uscode/text/21/364f Regulation or statute

Regulatory: GRAS and food ingredients

  1. 21 CFR Parts 70, 73 and 74, Color additives and their listings. eCFR, current to Oct 21, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-A Regulation or statute
  2. U.S. FDA. Guidance for Industry: New Dietary Ingredient Notification Procedures and Timeframes. Final guidance, March 2024; docket FDA-2023-D-5280; 89 FR 16003 (Mar 6, 2024). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance

Regulatory: international market access

  1. European Parliament Legislative Observatory. Summary of Commission report COM(2008) 824 on substances other than vitamins and minerals in food supplements (Dec 5, 2008). oeil.europarl.europa.eu/oeil/en/document-summary?id=1060078 Primary source
  2. Australian Government. Therapeutic Goods (Permissible Ingredients) Determination (No. 1) 2026, F2026L00162, Explanatory Statement (registered Feb 26, 2026). Federal Register of Legislation. legislation.gov.au/F2026L00162/asmade/2026-02-26/es/original Regulation or statute
  3. Australian Government. Therapeutic Goods (Permissible Ingredients) Determination (No. 2) 2026, F2026L00707 (version from Jun 11, 2026). Federal Register of Legislation. legislation.gov.au/F2026L00707/asmade Regulation or statute
  4. Therapeutic Goods Administration. Three-tiered risk-based framework for complementary medicines, factsheet (Mar 19, 2018). tga.gov.au/sites/default/files/three-tiered-risk-based-frame Primary source
  5. Consumer Affairs Agency, Japan. Outline of Food Labelling Systems for Nutrition and Health Claims (English summary, PDF). caa.go.jp/en/policy/food_labeling/assets/food_labeling_cms20 Primary source
  6. OECD. Decision of the Council concerning the Mutual Acceptance of Data in the Assessment of Chemicals. OECD/LEGAL/0194, adopted May 12, 1981. legalinstruments.oecd.org/public/doc/263/263.en.pdf Primary source
  7. Australian Government, Federal Register of Legislation. Therapeutic Goods (Permissible Ingredients) Determination titles and status: No. 3 of 2026, F2026L01382 (registered October 13, 2026, in force); Amendment (Removal of Andrographis Paniculata) Determination 2026, F2026L01211 (registered September 14, 2026); No. 2 of 2026 and No. 1 of 2026 repealed. Read October 24, 2026. legislation.gov.au/F2026L01382/asmade Primary source

Regulatory: new dietary ingredient notifications

  1. OECD Guidelines for the Testing of Chemicals, Section 4: Health Effects (test guideline titles as listed by Germany's Federal Institute for Risk Assessment, BfR). bfr.bund.de/chemikaliensicherheit/internationale-massnahmen- Primary source
  2. U.S. FDA. Guidance for Industry: Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology. June 2014. fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance

Technologies

Engineering equations used in the calculators

  1. Crank J. The Mathematics of Diffusion. 2nd ed. Oxford: Clarendon Press; 1975 (diffusion in a sphere).
  2. Stokes GG. On the effect of the internal friction of fluids on the motion of pendulums. Trans Camb Philos Soc. 1851;9(Part II):8–106.
  3. Einstein A. Über die von der molekularkinetischen Theorie der Wärme geforderte Bewegung von in ruhenden Flüssigkeiten suspendierten Teilchen. Ann Phys. 1905;17:549–560. doi.org/10.1002/andp.19053220806
  4. Murphy DM, Koop T. Review of the vapour pressures of ice and supercooled water for atmospheric applications. Q J R Meteorol Soc. 2005;131(608):1539–1565. doi.org/10.1256/qj.04.94
  5. Arrhenius S. Über die Reaktionsgeschwindigkeit bei der Inversion von Rohrzucker durch Säuren. Z Phys Chem. 1889;4:226–248.
  6. Purnell JH. The correlation of separating power and efficiency of gas-chromatographic columns. J Chem Soc. 1960:1268–1274. pubs.rsc.org/en/content/articlelanding/1960/jr/jr9600001268
  7. Snyder LR, Kirkland JJ, Dolan JW. Introduction to Modern Liquid Chromatography. 3rd ed. Hoboken: Wiley; 2010.

Computational science & AI: methods, evaluation and reporting

  1. Lewis P, Perez E, Piktus A, et al. Retrieval-augmented generation for knowledge-intensive NLP tasks. Advances in Neural Information Processing Systems 33 (NeurIPS 2020):9459–9474. papers.nips.cc/paper/2020/hash/6b493230205f780e1bc26945df748
  2. Mitchell M, Wu S, Zaldivar A, et al. Model cards for model reporting. Proceedings of the Conference on Fairness, Accountability, and Transparency (FAT* 2019):220–229. doi.org/10.1145/3287560.3287596
  3. Gebru T, Morgenstern J, Vecchione B, et al. Datasheets for datasets. Commun ACM. 2021;64(12):86–92. doi.org/10.1145/3458723
  4. Gilmer J, Schoenholz SS, Riley PF, Vinyals O, Dahl GE. Neural message passing for quantum chemistry. Proceedings of the 34th International Conference on Machine Learning, PMLR 70:1263–1272; 2017. proceedings.mlr.press/v70/gilmer17a.html
  5. Dührkop K, Fleischauer M, Ludwig M, et al. SIRIUS 4: a rapid tool for turning tandem mass spectra into metabolite structure information. Nat Methods. 2019;16(4):299–302. doi.org/10.1038/s41592-019-0344-8
  6. Radford A, Kim JW, Hallacy C, et al. Learning transferable visual models from natural language supervision. Proceedings of the 38th International Conference on Machine Learning, PMLR 139:8748–8763; 2021. proceedings.mlr.press/v139/radford21a.html
  7. Guo C, Pleiss G, Sun Y, Weinberger KQ. On calibration of modern neural networks. Proceedings of the 34th International Conference on Machine Learning, PMLR 70:1321–1330; 2017. proceedings.mlr.press/v70/guo17a.html
  8. Angelopoulos AN, Bates S. A gentle introduction to conformal prediction and distribution-free uncertainty quantification. arXiv:2107.07511 (v6, December 2022). arxiv.org/abs/2107.07511
  9. OECD. OECD Principles for the Validation, for Regulatory Purposes, of (Quantitative) Structure-Activity Relationship Models. Agreed November 2004. www2.oecd.org/chemicalsafety/risk-assessment/37849783.pdf
  10. Chen S, Yao H, Han J, et al. Validation of the ITS2 region as a novel DNA barcode for identifying medicinal plant species. PLoS ONE. 2010;5(1):e8613. doi.org/10.1371/journal.pone.0008613
  11. Kapoor S, Narayanan A. Leakage and the reproducibility crisis in machine-learning-based science. Patterns. 2023;4(9):100804. doi.org/10.1016/j.patter.2023.100804 Peer-reviewed
  12. Schymanski EL, Ruttkies C, Krauss M, et al. Critical Assessment of Small Molecule Identification 2016: automated methods. J Cheminform. 2017;9:22. doi.org/10.1186/s13321-017-0207-1 Peer-reviewed
  13. Sheridan RP. Time-split cross-validation as a method for estimating the goodness of prospective prediction. J Chem Inf Model. 2013;53(4):783–790. doi.org/10.1021/ci400084k Peer-reviewed
  14. Wu Z, Ramsundar B, Feinberg EN, et al. MoleculeNet: a benchmark for molecular machine learning. Chem Sci. 2018;9(2):513–530. doi.org/10.1039/C7SC02664A Peer-reviewed
  15. Wold S, Sjöström M, Eriksson L. PLS-regression: a basic tool of chemometrics. Chemom Intell Lab Syst. 2001;58(2):109–130. doi.org/10.1016/S0169-7439(01)00155-1 Peer-reviewed

Computational science & AI: public scientific data resources (counts and terms checked October 22, 2026)

  1. Kim S, Chen J, Cheng T, et al. PubChem 2025 update. Nucleic Acids Res. 2025;53(D1):D1516–D1525 (119 million compounds, 322 million substances, 295 million bioactivities). doi.org/10.1093/nar/gkae1059
  2. EMBL-EBI. ChEMBL 36 is live. October 15, 2025 (2.8 million distinct compounds; 17,803 targets). ebi.ac.uk/about/news/updates-from-data-resources/chembl-36/
  3. Zdrazil B, Felix E, Hunter F, et al. The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res. 2024;52(D1):D1180–D1192. doi.org/10.1093/nar/gkad1004
  4. ChEMBL interface documentation, general questions: license (CC BY-SA 3.0 Unported) and use of commercially derived calculations. chembl.gitbook.io/chembl-interface-documentation/frequently-
  5. Chandrasekhar V, Rajan K, Kanakam SRS, et al. COCONUT 2.0: a comprehensive overhaul and curation of the collection of open natural products database. Nucleic Acids Res. 2025;53(D1):D634–D643. doi.org/10.1093/nar/gkae1063
  6. COCONUT statistics page (738,795 unique molecules) and About page (data CC0, code MIT). Accessed October 22, 2026. coconut.naturalproducts.net/stats
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Computational science & AI: regulatory and governance frameworks

  1. U.S. FDA. Considerations for the Use of Artificial Intelligence to Support Regulatory Decision-Making for Drug and Biological Products. Draft guidance, January 2025; Docket FDA-2024-D-4689. Not for implementation. fda.gov/regulatory-information/search-fda-guidance-documents
  2. NIST. Artificial Intelligence Risk Management Framework (AI RMF 1.0), NIST AI 100-1, January 26, 2023; Generative AI Profile, NIST AI 600-1, July 26, 2024. nist.gov/itl/ai-risk-management-framework
  3. 21 CFR Part 11 — Electronic records; electronic signatures. ecfr.gov/current/title-21/chapter-I/subchapter-A/part-11
  4. 21 CFR 111.605 — Requirements for records, including (c): all electronic records must comply with part 11. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-111/su

Colloids & emulsions: formation, ripening and devices

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  2. McClements DJ. Critical review of techniques and methodologies for characterization of emulsion stability. Crit Rev Food Sci Nutr. 2007;47(7):611–649. doi.org/10.1080/10408390701289292 Peer-reviewed
  3. McClements DJ. Food Emulsions: Principles, Practices, and Techniques. 3rd ed. Boca Raton: CRC Press; 2015 (Stokes creaming, sedimentation–diffusion equilibrium, instability mechanisms). doi.org/10.1201/b18868 Peer-reviewed
  4. Pátek J, Hrubý J, Klomfar J, Součková M, Harvey AH. Reference correlations for thermophysical properties of liquid water at 0.1 MPa. J Phys Chem Ref Data. 2009;38(1):21–29 (water viscosity 0.890 mPa·s at 25 °C). doi.org/10.1063/1.3043575 Peer-reviewed
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  6. Pavoni L, Perinelli DR, Bonacucina G, Cespi M, Palmieri GF. An overview of micro- and nanoemulsions as vehicles for essential oils: formulation, preparation and stability. Nanomaterials. 2020;10(1):135 (50–200 MPa, passes, sonication damage, PIT method, LSW ripening rate, ripening inhibitors). Full text read via Europe PMC, PMC7023169, October 2026. doi.org/10.3390/nano10010135
  7. Choi SJ, McClements DJ. Nanoemulsions as delivery systems for lipophilic nutraceuticals: strategies for improving their formulation, stability, functionality and bioavailability. Food Sci Biotechnol. 2020;29(2):149–168 (valve homogenizer, microfluidizer, ultrasonication and low-energy methods). Full text read via Europe PMC, PMC6992823, October 2026. doi.org/10.1007/s10068-019-00731-4
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  9. Romano E, Netti PA, Torino E. A high throughput approach based on dynamic high pressure for the encapsulation of active compounds in exosomes for precision medicine. Int J Mol Sci. 2021;22(18):9896 (temperature rise about 2.5 °C per 10 MPa). doi.org/10.3390/ijms22189896
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Extraction: methods and conditions

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  2. Nayak A, Shah A, Bhatt S, Bhushan B, Kumar A, Gaur R, Tyagi I. Ultrasound and microwave assisted extraction of bioactives from food wastes: an overview on their comparative analysis towards commercialization. Ultrason Sonochem. 2026;124:107712 (Table 1). doi.org/10.1016/j.ultsonch.2025.107712
  3. Kumar K, Srivastav S, Sharanagat VS. Ultrasound assisted extraction (UAE) of bioactive compounds from fruit and vegetable processing by-products: a review. Ultrason Sonochem. 2021;70:105325. doi.org/10.1016/j.ultsonch.2020.105325
  4. Tzima S, Georgiopoulou I, Louli V, Magoulas K. Recent advances in supercritical CO2 extraction of pigments, lipids and bioactive compounds from microalgae. Molecules. 2023;28(3):1410. doi.org/10.3390/molecules28031410
  5. U.S. Environmental Protection Agency. SW-846 Method 3545A: Pressurized Fluid Extraction (PFE), Revision 1. February 2007. Accessed October 22, 2026. archive.epa.gov/epawaste/hazard/testmethods/web/pdf/3545a.pd
  6. Cheng Y, Xue F, Yu S, Du S, Yang Y. Subcritical water extraction of natural products. Molecules. 2021;26(13):4004. doi.org/10.3390/molecules26134004 Peer-reviewed
  7. Puri M, Sharma D, Barrow CJ. Enzyme-assisted extraction of bioactives from plants. Trends Biotechnol. 2012;30(1):37–44. doi.org/10.1016/j.tibtech.2011.06.014 Peer-reviewed
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Extraction: supercritical CO2 thermodynamics and kinetics

  1. Span R, Wagner W. A new equation of state for carbon dioxide covering the fluid region from the triple-point temperature to 1100 K at pressures up to 800 MPa. J Phys Chem Ref Data. 1996;25(6):1509–1596. doi.org/10.1063/1.555991
  2. Bell IH, Wronski J, Quoilin S, Lemort V. Pure and pseudo-pure fluid thermophysical property evaluation and the open-source thermophysical property library CoolProp. Ind Eng Chem Res. 2014;53(6):2498–2508 (CoolProp 8.0.0 used to evaluate Span–Wagner). doi.org/10.1021/ie4033999
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  5. Bawazeer S. Measurement and modeling of rizatriptan in supercritical CO2 for pharmaceutical processing. Sci Rep. 2025;15:42267 (association-number interpretation of the Chrastil model). doi.org/10.1038/s41598-025-26435-w
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  7. Sovová H. Mathematical model for supercritical fluid extraction of natural products and extraction curve evaluation. J Supercrit Fluids. 2005;33(1):35–52. doi.org/10.1016/j.supflu.2004.03.005
  8. Mouahid A, Claeys-Bruno M, Clercq S. A new methodology based on experimental design and Sovová's broken and intact cells model for the prediction of supercritical CO2 extraction kinetics. Processes. 2024;12(9):1865. doi.org/10.3390/pr12091865

Extraction: solvents

  1. U.S. Food and Drug Administration. Q3C—Tables and List: Guidance for Industry, Revision 3. June 2017. Accessed October 22, 2026. fda.gov/media/71737/download
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  3. Hansen CM. Hansen Solubility Parameters: A User's Handbook. 2nd ed. CRC Press; 2007. Values for water and heptane as tabulated by Accu Dyne Test, accessed October 22, 2026. accudynetest.com/solubility_table_print.html
  4. Hansen Solubility Parameters (official site). HSP Basics: blend rule and HSP distance. Accessed October 22, 2026. hansen-solubility.com/HSP-science/basics.php
  5. Dai Y, van Spronsen J, Witkamp G-J, Verpoorte R, Choi YH. Natural deep eutectic solvents as new potential media for green technology. Anal Chim Acta. 2013;766:61–68. doi.org/10.1016/j.aca.2012.12.019 Peer-reviewed
  6. Passos H, Freire MG, Coutinho JAP. Ionic liquid solutions as extractive solvents for value-added compounds from biomass. Green Chem. 2014;16(12):4786–4815. doi.org/10.1039/c4gc00236a Peer-reviewed
  7. Electronic Code of Federal Regulations. 21 CFR Part 173, Subpart C—Solvents, Lubricants, Release Agents and Related Substances (including § 173.270 Hexane). Up to date as of October 15, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-173/su Regulation or statute

Extraction: fractionation and purification

  1. Ito Y. Golden rules and pitfalls in selecting optimum conditions for high-speed counter-current chromatography. J Chromatogr A. 2005;1065(2):145–168. doi.org/10.1016/j.chroma.2004.12.044 Peer-reviewed
  2. Friesen JB, Pauli GF. G.U.E.S.S.—A generally useful estimate of solvent systems for CCC. J Liq Chromatogr Relat Technol. 2005;28(17):2777–2806. doi.org/10.1080/10826070500225234 Peer-reviewed
  3. Soto ML, Moure A, Domínguez H, Parajó JC. Recovery, concentration and purification of phenolic compounds by adsorption: a review. J Food Eng. 2011;105(1):1–27. doi.org/10.1016/j.jfoodeng.2011.02.010 Peer-reviewed
  4. Cassano A, Conidi C, Ruby-Figueroa R, Castro-Muñoz R. Nanofiltration and tight ultrafiltration membranes for the recovery of polyphenols from agro-food by-products. Int J Mol Sci. 2018;19(2):351. doi.org/10.3390/ijms19020351 Peer-reviewed

Extraction: process safety

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  3. NIOSH Pocket Guide to Chemical Hazards: Acetone. Retrieved October 22, 2026. cdc.gov/niosh/npg/npgd0004.html Primary source
  4. NIOSH Pocket Guide to Chemical Hazards: Ethyl acetate. Retrieved October 22, 2026. cdc.gov/niosh/npg/npgd0260.html Primary source
  5. NIOSH Pocket Guide to Chemical Hazards: n-Heptane. Retrieved October 22, 2026. cdc.gov/niosh/npg/npgd0312.html Primary source
  6. NIOSH Pocket Guide to Chemical Hazards: Methyl alcohol. Retrieved October 22, 2026. cdc.gov/niosh/npg/npgd0397.html Primary source
  7. NIOSH Pocket Guide to Chemical Hazards: Isopropyl alcohol. Retrieved October 22, 2026. cdc.gov/niosh/npg/npgd0359.html Primary source
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  11. 2025 California Fire Code (California Code of Regulations Title 24, Part 9), Chapter 39 Processing and Extraction Facilities, § 3904 Systems and equipment, as published by GoCodeBook (accessed October 22, 2026); confirm with the authority having jurisdiction. gocodebook.com/library/us/ca/ca-fire-code/chapter-39-process Regulation or statute

Analytical methods: principles, compendial chapters and validation

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  6. United States Pharmacopeia. ⟨761⟩ Nuclear Magnetic Resonance Spectroscopy. doi.usp.org/USPNF/USPNF_M99550_40101_01.html
  7. United States Pharmacopeia. ⟨1761⟩ Nuclear Magnetic Resonance Spectroscopy—Theory and Practice. doi.usp.org/USPNF/USPNF_M4348_02_01.html
  8. United States Pharmacopeia. ⟨891⟩ Thermal Analysis (harmonized standard). usp.org/node/10461
  9. United States Pharmacopeia. ⟨941⟩ Characterization of Crystalline and Partially Crystalline Solids by X-Ray Powder Diffraction (XRPD). doi.usp.org/USPNF/USPNF_M99730_02_01.html
  10. United States Pharmacopeia. ⟨1724⟩ Semisolid Drug Products—Performance Tests (vertical diffusion cell). gmp-compliance.org/gmp-news/major-revision-of-usp-chapter-17
  11. United States Pharmacopeia. ⟨2040⟩ Disintegration and Dissolution of Dietary Supplements. doi.usp.org/USPNF/USPNF_M99970_04_01.html
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  13. OECD. Test No. 428: Skin Absorption: In Vitro Method. OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD; 2004. oecd.org/en/publications/test-no-428-skin-absorption-in-vitr
  14. ISO 22412:2017. Particle size analysis — Dynamic light scattering (DLS). webstore.ansi.org/standards/iso/iso224122017
  15. ISO 13320:2020. Particle size analysis — Laser diffraction methods. scc-ccn.ca/standardsdb/standards/8168933
  16. NIST Chemistry WebBook, SRD 69. Carbon dioxide: phase-change data (Tc 304.18 K, Pc 73.80 bar, triple point 216.58 K and 5.185 bar). Accessed October 22, 2026. webbook.nist.gov/cgi/cbook.cgi?ID=C124389&Mask=4
  17. Bragg WH, Bragg WL. The reflection of X-rays by crystals. Proc R Soc Lond A. 1913;88(605):428–438. doi.org/10.1098/rspa.1913.0040
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  21. Houk RS, Fassel VA, Flesch GD, Svec HJ, Gray AL, Taylor CE. Inductively coupled argon plasma as an ion source for mass spectrometric determination of trace elements. Anal Chem. 1980;52(14):2283–2289. doi.org/10.1021/ac50064a012
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Drying & particle engineering: spray drying and powder stickiness

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  2. Kashiwakura Y, Sogabe T, Anantawittayanon S, Mochizuki T, Kawai K. Water sorption isotherm and critical water activity of amorphous water-soluble carbohydrates characterized by the glass transition temperature. J Appl Glycosci. 2024;71(1):15–21 (Table 1: GAB and Gordon–Taylor parameters for mango solids, maltodextrin and blends). Full text read via Europe PMC, PMC11117189, October 2026. doi.org/10.5458/jag.jag.JAG-2023_0015
  3. Fongin S, Kawai K, Harnkarnsujarit N, Hagura Y. Effects of water and maltodextrin on the glass transition temperature of freeze-dried mango pulp and an empirical model to predict plasticizing effect of water on dried fruits. J Food Eng. 2017;210:91–97. doi.org/10.1016/j.jfoodeng.2017.04.025
  4. Fongin S, Alvino Granados AE, Harnkarnsujarit N, Hagura Y, Kawai K. Effects of maltodextrin and pulp on the water sorption, glass transition, and caking properties of freeze-dried mango powder. J Food Eng. 2019;247:95–103. doi.org/10.1016/j.jfoodeng.2018.11.027
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Drying & particle engineering: freeze-drying

  1. Bhatta S, Stevanovic Janezic T, Ratti C. Freeze-drying of plant-based foods. Foods. 2020;9(1):87 (three stages, collapse temperature practice, triple point, condenser conditions, guava vitamin C retention 63% versus 25%). Full text read via Europe PMC, PMC7022747, October 2026. doi.org/10.3390/foods9010087

Drying & particle engineering: water, packaging and stability

  1. U.S. FDA. Inspection Technical Guide No. 39: Water Activity (aw) in Foods. April 16, 1984 (content current as of August 27, 2014). fda.gov/inspections-compliance-enforcement-and-criminal-inve Primary source
  2. ASTM F1249. Standard Test Method for Water Vapor Transmission Rate Through Plastic Film and Sheeting Using a Modulated Infrared Sensor. ASTM International (method summary by AMETEK MOCON, accessed October 22, 2026). ametekmocon.com/servicessupport/astm-f1249 Primary source
  3. ICH Q1A(R2) Stability Testing of New Drug Substances and Products. Step 4, February 6, 2003 (storage conditions, testing frequency, three primary batches, significant change). database.ich.org/sites/default/files/Q1A%28R2%29%20Guideline Agency guidance
  4. ICH Q1E Evaluation of Stability Data. Step 4, February 6, 2003 (one-sided 95% confidence limit; extrapolation up to twice, but not more than 12 months beyond, the long-term data). database.ich.org/sites/default/files/Q1E%20Guideline.pdf Agency guidance
  5. U.S. FDA. Q1 Stability Testing of Drug Substances and Drug Products. Draft guidance, June 24, 2025; Docket FDA-2025-D-1106 (consolidated revision of Q1A(R2), Q1B, Q1C, Q1D, Q1E and Q5C; not for implementation). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  6. Consumer Healthcare Products Association. Summary of key differences between FDA drug and dietary supplement GMPs (March 4, 2015): Part 111 has no expiration-date requirement; the Part 111 preamble (72 FR 34752, June 25, 2007) says a firm using an expiration date should have data to support it. CHPA.org/sites/default/files/media/docs/2020-10/Summary-of-K Primary source

Process engineering: transport, unit operations, scale-up and transfer

  1. Bird RB, Stewart WE, Lightfoot EN. Transport Phenomena. 2nd ed. New York: Wiley; 2002.
  2. Bergman TL, Lavine AS, Incropera FP, DeWitt DP. Fundamentals of Heat and Mass Transfer. 7th ed. Hoboken: Wiley; 2011 (effectiveness–NTU method, ch. 11).
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  4. Geankoplis CJ. Transport Processes and Separation Process Principles (Includes Unit Operations). 4th ed. Upper Saddle River: Prentice Hall; 2003 (drying of process materials).
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  8. ASHRAE Handbook—Fundamentals (SI). Atlanta: ASHRAE; 2017. Chapter 1, Psychrometrics (moist-air enthalpy h = 1.006t + W(2501 + 1.86t); W = 0.621945 p_w/(p − p_w)).
  9. NIST Chemistry WebBook, SRD 69. Thermophysical properties of water (isobaric data at 101.325 kPa, 20 °C: 998.21 kg/m³, c_p 4.1841 kJ/kg·K, 1.0016 mPa·s; saturation at 200 kPa ≈ 120.2 °C). Retrieved October 22, 2026. webbook.nist.gov/cgi/fluid.cgi?ID=C7732185&Action=Page
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  15. Montgomery DC. Design and Analysis of Experiments. 10th ed. Hoboken: Wiley; 2020.
  16. ICH Q8(R2) Pharmaceutical Development. Step 4, August 2009 (definitions of design space, CPP and CQA). database.ich.org/sites/default/files/Q8%28R2%29%20Guideline.
  17. ICH Q10 Pharmaceutical Quality System. Step 4, 4 June 2008 (technology transfer; knowledge management). database.ich.org/sites/default/files/Q10%20Guideline.pdf
  18. U.S. FDA. Process Validation: General Principles and Practices. Guidance for industry, January 2011 (Revision 1). fda.gov/media/71021/download
  19. World Health Organization. WHO guidelines on technology transfer in pharmaceutical manufacturing. WHO Technical Report Series 1044, Annex 4; 2022. who.int/publications/m/item/trs1044-annex4
  20. United States Pharmacopeia. General chapter <1224> Transfer of Analytical Procedures. USP–NF.
  21. 21 CFR 111.205 (master manufacturing record) and 111.255 (batch production record). law.cornell.edu/cfr/text/21/111.205
  22. ANSI/ISA-5.1-2024. Instrumentation and Control Symbols and Identification. International Society of Automation; 2024. isa.org/standards-and-publications/isa-standards/isa-5-stand
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  24. Grenville RK, Nienow AW. Blending of miscible liquids. In: Paul EL, Atiemo-Obeng VA, Kresta SM, eds. Handbook of Industrial Mixing. Wiley; 2003:507–542 (turbulent blend time; as cited by Fořt I, Jirout T. Chem Process Eng. 2011;32(4):311–319). journals.pan.pl//Content/84632/PDF/07-paper-Fort.pdf Peer-reviewed
  25. Danckwerts PV. Continuous flow systems: distribution of residence times. Chem Eng Sci. 1953;2(1):1–13. doi.org/10.1016/0009-2509(53)80001-1 Peer-reviewed
  26. Levenspiel O. Chemical Reaction Engineering. 3rd ed. New York: Wiley; 1999 (tanks-in-series and dispersion models). Peer-reviewed
  27. NIST Chemistry WebBook, SRD 69. Ethanol: enthalpy of vaporization 38.56 kJ/mol at 351.5 K (Majer and Svoboda, 1985). Retrieved October 22, 2026. webbook.nist.gov/cgi/cbook.cgi?ID=C64175&Mask=4 Primary source
  28. NFPA 30, Flammable and Combustible Liquids Code. National Fire Protection Association. nfpa.org/codes-and-standards/nfpa-30-standard-development/30 Primary source
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Analytical methods: botanical atlas

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  2. Li J, He X, Li M, et al. Chemical fingerprint and quantitative analysis for quality control of polyphenols extracted from pomegranate peel by HPLC. Food Chem. 2015;176:7-11. doi:10.1016/j.foodchem.2014.12.040. PMID 25624199. pubmed.ncbi.nlm.nih.gov/25624199/ Peer-reviewed
  3. Gantait A, Pandit S, Nema NK, et al. Quantification of glycyrrhizin in Glycyrrhiza glabra extract by validated HPTLC densitometry. J AOAC Int. 2010;93(2):492-5. PMID 20480894. pubmed.ncbi.nlm.nih.gov/20480894/ Peer-reviewed
  4. Miklavčič MB, Taous F, Valenčič V, et al. Fatty Acid Composition of Cosmetic Argan Oil: Provenience and Authenticity Criteria. Molecules. 2020;25(18). doi:10.3390/molecules25184080. PMID 32906680. pubmed.ncbi.nlm.nih.gov/32906680/ Peer-reviewed
  5. Mudge E, Paley L, Schieber A, et al. Optimization and single-laboratory validation of a method for the determination of flavonolignans in milk thistle seeds by high-performance liquid chromatography with ultraviolet detection. Anal Bioanal Chem. 2015;407(25):7657-66. doi:10.1007/s00216-015-8925-6. PMID 26229030. pubmed.ncbi.nlm.nih.gov/26229030/ Peer-reviewed
  6. Martínez-Navarro EM, Cebrián-Tarancón C, Moratalla-López N, et al. Development and validation of an HPLC-DAD method for determination of oleuropein and other bioactive compounds in olive leaf by-products. J Sci Food Agric. 2021;101(4):1447-1453. doi:10.1002/jsfa.10758. PMID 32839982. pubmed.ncbi.nlm.nih.gov/32839982/ Peer-reviewed
  7. Paraschos S, Magiatis P, Gikas E, et al. Quality profile determination of Chios mastic gum essential oil and detection of adulteration in mastic oil products with the application of chiral and non-chiral GC-MS analysis. Fitoterapia. 2016;114:12-17. doi:10.1016/j.fitote.2016.08.003. PMID 27514656. pubmed.ncbi.nlm.nih.gov/27514656/ Peer-reviewed
  8. García-Rodríguez MV, López-Córcoles H, Alonso GL, et al. Comparative evaluation of an ISO 3632 method and an HPLC-DAD method for safranal quantity determination in saffron. Food Chem. 2017;221:838-843. doi:10.1016/j.foodchem.2016.11.089. PMID 27979282. pubmed.ncbi.nlm.nih.gov/27979282/ Peer-reviewed
  9. Beale DJ, Morrison PD, Karpe AV, et al. Chemometric Analysis of Lavender Essential Oils Using Targeted and Untargeted GC-MS Acquired Data for the Rapid Identification and Characterization of Oil Quality. Molecules. 2017;22(8). doi:10.3390/molecules22081339. PMID 28800104. pubmed.ncbi.nlm.nih.gov/28800104/ Peer-reviewed
  10. Mudge EM, Brown PN. Determination of Curcuminoids in Turmeric Raw Materials and Dietary Supplements by HPLC: Single-Laboratory Validation, First Action 2016.16. J AOAC Int. 2018;101(1):203-207. doi:10.5740/jaoacint.17-0111. PMID 28707614. pubmed.ncbi.nlm.nih.gov/28707614/ Peer-reviewed
  11. Girme A, Saste G, Pawar S, et al. Investigating 11 Withanosides and Withanolides by UHPLC-PDA and Mass Fragmentation Studies from Ashwagandha (Withania somnifera). ACS Omega. 2020;5(43):27933-27943. doi:10.1021/acsomega.0c03266. PMID 33163776. pubmed.ncbi.nlm.nih.gov/33163776/ Peer-reviewed
  12. Murthy PB, Raju VR, Ramakrisana T, et al. Estimation of twelve bacopa saponins in Bacopa monnieri extracts and formulations by high-performance liquid chromatography. Chem Pharm Bull (Tokyo). 2006;54(6):907-11. doi:10.1248/cpb.54.907. PMID 16755069. pubmed.ncbi.nlm.nih.gov/16755069/ Peer-reviewed
  13. Brusač E, Jeličić ML, Nigović B, et al. Determination of Curcuminoids, Piperine, Boswellic Acids and Andrographolides in Food and Dietary Supplements by HPLC. Food Technol Biotechnol. 2022;60(4):434-448. doi:10.17113/ftb.60.04.22.7560. PMID 36816876. pubmed.ncbi.nlm.nih.gov/36816876/ Peer-reviewed
  14. Ahmed R, Wang YH, Ali Z, et al. HPLC Method for Chemical Fingerprinting of Guggul (Commiphora wightii)--Quantification of E- and Z-Guggulsterones and Detection of Possible Adulterants. Planta Med. 2016;82(4):356-61. doi:10.1055/s-0035-1558211. PMID 26669677. pubmed.ncbi.nlm.nih.gov/26669677/ Peer-reviewed
  15. Karioti A, Timoteo P, Bergonzi MC, et al. A Validated Method for the Quality Control of Andrographis paniculata Preparations. Planta Med. 2017;83(14-15):1207-1213. doi:10.1055/s-0043-113827. PMID 28651289. pubmed.ncbi.nlm.nih.gov/28651289/ Peer-reviewed
  16. Croom E, Pace R, Paletti A, et al. Single-laboratory validation for the determination of terpene lactones in Ginkgo biloba dietary supplement crude materials and finished products by high-performance liquid chromatography with evaporative light-scattering detection. J AOAC Int. 2007;90(3):647-58. PMID 17580616. pubmed.ncbi.nlm.nih.gov/17580616/ Peer-reviewed
  17. Brown PN, Yu R, Cain T, et al. Determination of ginsenoside content in Panax ginseng C.A. Meyer and Panax quinquefolius L. root materials and finished products by high-performance liquid chromatography with ultraviolet absorbance detection: interlaboratory study. J AOAC Int. 2013;96(1):12-9. doi:10.5740/jaoacint.12-153. PMID 23513950. pubmed.ncbi.nlm.nih.gov/23513950/ Peer-reviewed
  18. Roman MC. Determination of catechins and caffeine in camillia sinensis raw materials, extracts, and dietary supplements by HPLC-uv: single-laboratory validation. J AOAC Int. 2013;96(5):933-41. doi:10.5740/jaoacint.10-488. PMID 24282928. pubmed.ncbi.nlm.nih.gov/24282928/ Peer-reviewed
  19. Ninomiya K, Matsumoto T, Chaipech S, et al. Simultaneous quantitative analysis of 12 methoxyflavones with melanogenesis inhibitory activity from the rhizomes of Kaempferia parviflora. J Nat Med. 2016;70(2):179-89. doi:10.1007/s11418-015-0955-z. PMID 26711832. pubmed.ncbi.nlm.nih.gov/26711832/ Peer-reviewed
  20. Sabaragamuwa R, Perera CO, Fedrizzi B. Ultrasound assisted extraction and quantification of targeted bioactive compounds of Centella asiatica (Gotu Kola) by UHPLC-MS/MS MRM tandem mass spectroscopy. Food Chem. 2022;371:131187. doi:10.1016/j.foodchem.2021.131187. PMID 34592625. pubmed.ncbi.nlm.nih.gov/34592625/ Peer-reviewed
  21. Chaingam J, Juengwatanatrakul T, Yusakul G, et al. HPLC-UV-Based Simultaneous Determination of Canthin-6-One Alkaloids, Quassinoids, and Scopoletin: The Active Ingredients in Eurycoma Longifolia Jack and Eurycoma Harmandiana Pierre, and Their Anti-Inflammatory Activities. J AOAC Int. 2021;104(3):802-810. doi:10.1093/jaoacint/qsaa141. PMID 33064798. pubmed.ncbi.nlm.nih.gov/33064798/ Peer-reviewed
  22. Machado KN, Freitas AA, Cunha LH, et al. A rapid simultaneous determination of methylxanthines and proanthocyanidins in Brazilian guaraná (Paullinia cupana Kunth.). Food Chem. 2018;239:180-188. doi:10.1016/j.foodchem.2017.06.089. PMID 28873557. pubmed.ncbi.nlm.nih.gov/28873557/ Peer-reviewed
  23. Fibigr J, Šatínský D, Solich P. A UHPLC method for the rapid separation and quantification of anthocyanins in acai berry and dry blueberry extracts. J Pharm Biomed Anal. 2017;143:204-213. doi:10.1016/j.jpba.2017.05.045. PMID 28605682. pubmed.ncbi.nlm.nih.gov/28605682/ Peer-reviewed
  24. Zanatta CF, Cuevas E, Bobbio FO, et al. Determination of anthocyanins from camu-camu (Myrciaria dubia) by HPLC-PDA, HPLC-MS, and NMR. J Agric Food Chem. 2005;53(24):9531-5. doi:10.1021/jf051357v. PMID 16302773. pubmed.ncbi.nlm.nih.gov/16302773/ Peer-reviewed
  25. Ganzera M, Muhammad I, Khan RA, et al. Improved method for the determination of oxindole alkaloids in Uncaria tomentosa by high performance liquid chromatography. Planta Med. 2001;67(5):447-50. doi:10.1055/s-2001-15824. PMID 11488460. pubmed.ncbi.nlm.nih.gov/11488460/ Peer-reviewed
  26. Xu YQ, Qiao SY, Wang ZQ, et al. Quantitative Determination of 15 Active Components in Lepidium meyenii with UHPLC-PDA and GC-MS. J Anal Methods Chem. 2021;2021:6333989. doi:10.1155/2021/6333989. PMID 34513111. pubmed.ncbi.nlm.nih.gov/34513111/ Peer-reviewed
  27. Zhu ZY, Lian HY, Si CL, et al. The chromatographic analysis of oligosaccharides and preparation of 1-kestose and nystose in yacon. Int J Food Sci Nutr. 2012;63(3):338-42. doi:10.3109/09637486.2011.627847. PMID 22013906. pubmed.ncbi.nlm.nih.gov/22013906/ Peer-reviewed
  28. Günther M, Schmidt PC. Comparison between HPLC and HPTLC-densitometry for the determination of harpagoside from Harpagophytum procumbens CO(2)-extracts. J Pharm Biomed Anal. 2005;37(4):817-21. doi:10.1016/j.jpba.2004.11.037. PMID 15797807. pubmed.ncbi.nlm.nih.gov/15797807/ Peer-reviewed
  29. You Y, Cheng G. [Determination of docosyl ferulate in extract of Pygeum africanton Hook. by high performance liquid chromatography (HPLC)]. Se Pu. 1997;15(3):259-60. PMID 15739376. pubmed.ncbi.nlm.nih.gov/15739376/ Peer-reviewed
  30. Avula B, Wang YH, Pawar RS, et al. Determination of the appetite suppressant P57 in Hoodia gordonii plant extracts and dietary supplements by liquid chromatography/electrospray ionization mass spectrometry (LC-MSD-TOF) and LC-UV methods. J AOAC Int. 2006;89(3):606-11. PMID 16792058. pubmed.ncbi.nlm.nih.gov/16792058/ Peer-reviewed
  31. Bramati L, Aquilano F, Pietta P. Unfermented rooibos tea: quantitative characterization of flavonoids by HPLC-UV and determination of the total antioxidant activity. J Agric Food Chem. 2003;51(25):7472-4. doi:10.1021/jf0347721. PMID 14640601. pubmed.ncbi.nlm.nih.gov/14640601/ Peer-reviewed
  32. Li N, Simon JE, Wu Q. Determination of anthocyanins, organic acids, and phenolic acids in hibiscus market products using LC/UV/MS. J Food Sci. 2024;89(2):1098-1113. doi:10.1111/1750-3841.16909. PMID 38235990. pubmed.ncbi.nlm.nih.gov/38235990/ Peer-reviewed

Process engineering: design space and optimization

  1. Box GEP, Behnken DW. Some new three level designs for the study of quantitative variables. Technometrics. 1960;2(4):455–475. doi.org/10.1080/00401706.1960.10489912 Peer-reviewed
  2. Blank J, Deb K. pymoo: multi-objective optimization in Python. IEEE Access. 2020;8:89497–89509 (software version 0.6.2 used for the reference runs). doi.org/10.1109/ACCESS.2020.2990567 Peer-reviewed
  3. Zitzler E, Thiele L. Multiobjective evolutionary algorithms: a comparative case study and the strength Pareto approach. IEEE Trans Evol Comput. 1999;3(4):257–271. doi.org/10.1109/4235.797969 Peer-reviewed
  4. While L, Hingston P, Barone L, Huband S. A faster algorithm for calculating hypervolume. IEEE Trans Evol Comput. 2006;10(1):29–38. doi.org/10.1109/TEVC.2005.851275 Peer-reviewed
  5. Peterson JJ. A posterior predictive approach to multiple response surface optimization. J Qual Technol. 2004;36(2):139–153 (bibliographic record verified; full text not accessed). doi.org/10.1080/00224065.2004.11980261 Peer-reviewed
  6. Peterson JJ. A Bayesian approach to the ICH Q8 definition of design space. J Biopharm Stat. 2008;18(5):959–975 (abstract verified; full text not accessed). doi.org/10.1080/10543400802278197 Peer-reviewed
  7. van de Berg D, Kis Z, Behmer CF, et al. Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases. NPJ Vaccines. 2021;6:65 (Monte Carlo probabilistic design space). doi.org/10.1038/s41541-021-00322-7 Peer-reviewed

Analytical method development: ICH, USP, FDA and AOAC documents

  1. ICH Q14. Analytical Procedure Development. Final version adopted November 1, 2023. database.ich.org/sites/default/files/ICH_Q14_Guideline_2023_ Agency guidance
  2. Food and Drug Administration. Q2(R2) Validation of Analytical Procedures and Q14 Analytical Procedure Development; International Council for Harmonisation; Guidances for Industry; Availability. Federal Register 89(46), March 7, 2024; docket FDA-2022-D-1503. govinfo.gov/content/pkg/FR-2024-03-07/html/2024-04834.htm Agency guidance
  3. 21 CFR 111.320, What requirements apply to laboratory methods for testing and examination? eCFR; accessed October 23, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-111/su Regulation or statute
  4. United States Pharmacopeia. Introduction to new General Chapter <1220> Analytical Procedure Life Cycle (stages 1–3). USP user forum presentation, 2022. usp.org/sites/default/files/usp/document/user-forums/04-intr Primary source
  5. Pappa H. USP general chapters on validation, verification and transfer of analytical procedures (<1225>, <1226>, <1224>, <1220>, <1210>). Presentation, Association for Accessible Medicines. accessiblemeds.org/wp-content/uploads/2024/09/Horacio-Pappa- Primary source
  6. ECA Academy. Proposed revision of USP <1225> published in the Pharmacopeial Forum (PF 51(6); comment deadline January 31, 2026). November 13, 2025. gmp-compliance.org/gmp-news/proposed-revision-of-usp-1225-pu Primary source
  7. United States Pharmacopeia. <621> Chromatography, Stage 4 harmonized text, official December 1, 2022. usp.org/sites/default/files/usp/document/harmonization/gen-c Primary source
  8. Brown P, Solyom AM, Betz JM, et al. AOAC SMPR 2016.003: Standard method performance requirements for quantitation of curcuminoids. J AOAC Int. 2016. doi.org/10.5740/jaoacint.SMPR2016.003 Primary source

Analytical method development: chromatographic retention theory

  1. Guillarme D, Bouvarel T, Rouvière F, Heinisch S. A simple mathematical treatment for predicting linear solvent strength behavior in gradient elution: application to biomolecules. J Sep Sci. 2022;45(17):3276–3285 (open access). doi.org/10.1002/jssc.202200161 Peer-reviewed
  2. den Uijl MJ, Schoenmakers PJ, Pirok BWJ, van Bommel MR. Recent applications of retention modelling in liquid chromatography. J Sep Sci. 2021;44(1):88–114 (open access). doi.org/10.1002/jssc.202000905 Peer-reviewed
  3. Tanase M, Soare A, David V, Moldoveanu SC. Sources of nonlinear van't Hoff temperature dependence in high-performance liquid chromatography. ACS Omega. 2019;4(22):19808–19817 (open access). doi.org/10.1021/acsomega.9b02689 Peer-reviewed
  4. Zhu PL, Snyder LR, Dolan JW, Djordjevic NM, Hill DW, Sander LC, Waeghe TJ. Combined use of temperature and solvent strength in reversed-phase gradient elution. I. Predicting separation as a function of temperature and gradient conditions. J Chromatogr A. 1996;756:21–39. doi.org/10.1016/S0021-9673(96)00721-2 Peer-reviewed
  5. Dolan JW, Snyder LR, Djordjevic NM, Hill DW, Saunders DL, Van Heukelem L, Waeghe TJ. Simultaneous variation of temperature and gradient steepness for reversed-phase high-performance liquid chromatography method development. I. Application to 14 different samples using computer simulation. J Chromatogr A. 1998;803:1–31. doi.org/10.1016/S0021-9673(97)01293-4 Peer-reviewed
  6. Harvey D. Analytical Chemistry 2.1, section 12.2: General Theory of Column Chromatography (eq 12.1). LibreTexts open textbook; accessed October 22, 2026. chem.libretexts.org/Bookshelves/Analytical_Chemistry/Analyti Book

Analytical method development: chromatography definitions used in the figures

  1. Advanced Chromatography Technologies (ACT Ltd). How to Determine System Dwell Volume: Theory and Practice. ACE Knowledge Note #0001. 2016. theanalyticalscientist.com/media/ucag0iwd/14_-_akn0001_how_t Primary source
  2. Agilent Technologies. OpenLab CDS Data Analysis help: Signal-to-noise calculation (S/N = 2H/h according to the definition of the European Pharmacopoeia). Accessed October 23, 2026. openlab.help.agilent.com/en/mergedProjects/DataAnalysis/2702 Primary source
  3. EDQM. FAQ on Ph. Eur. general chapter 2.2.46 Chromatographic separation techniques: signal-to-noise ratio (noise as the range of the noise in a chromatogram obtained after injection of a blank). Accessed October 23, 2026. faq.edqm.eu/x/FgAjAw Primary source

Delivery and bioavailability: definitions, biopharmaceutics numbers and absorbable dose

  1. Salvia-Trujillo L, Martín-Belloso O, McClements DJ. Excipient nanoemulsions for improving oral bioavailability of bioactives. Nanomaterials (Basel). 2016;6(1):17 (eq 1, Table 2). doi.org/10.3390/nano6010017 Peer-reviewed
  2. McClements DJ, Li F, Xiao H. The nutraceutical bioavailability classification scheme: classifying nutraceuticals according to factors limiting their oral bioavailability. Annu Rev Food Sci Technol. 2015;6:299–327. doi.org/10.1146/annurev-food-032814-014043 Peer-reviewed
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  4. Abuhassan Q, Khadra I, Pyper K, Augustijns P, Brouwers J, Halbert GW. Fasted intestinal solubility limits and distributions applied to the biopharmaceutics and developability classification systems. Eur J Pharm Biopharm. 2022;170:160–169 (open access). doi.org/10.1016/j.ejpb.2021.12.006 Peer-reviewed
  5. Curatolo W. Physical chemical properties of oral drug candidates in the discovery and exploratory development settings. Pharm Sci Technol Today. 1998;1(9):387–393 (MAD equation as given by Abuhassan et al. 2022). doi.org/10.1016/S1461-5347(98)00097-2 Peer-reviewed
  6. Ding X, Rose JP, Van Gelder J. Developability assessment of clinical drug products with maximum absorbable doses. Int J Pharm. 2012;427(2):260–269. doi.org/10.1016/j.ijpharm.2012.02.003 Peer-reviewed

Delivery and bioavailability: curcumin pharmacokinetics, interactions and safety

  1. Jamwal R. Corrigendum to “Bioavailable curcumin formulations: a review of pharmacokinetic studies in healthy volunteers” [J Integr Med. 2018;16(6):367–374]. J Integr Med. 2019;17(4):310. doi.org/10.1016/j.joim.2019.05.002 Peer-reviewed
  2. UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. Discussion paper on novel formulations of supplement compounds designed to increase oral bioavailability, Annex A, case study 2: curcuminoids (TOX/2025/09), Table 5; last updated March 19, 2025. cot.food.gov.uk/Case%20study%202%3A%20Curcuminoids Primary source
  3. Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J Agric Food Chem. 2010;58:2095–2099. doi.org/10.1021/jf9024807 Peer-reviewed
  4. Purpura M, Lowery RP, Wilson JM, Mannan H, Münch G, Razmovski-Naumovski V. Analysis of different innovative formulations of curcumin for improved relative oral bioavailability in human subjects. Eur J Nutr. 2018;57:929–938. doi.org/10.1007/s00394-016-1376-9 Peer-reviewed
  5. Sasaki H, Sunagawa Y, Takahashi K, et al. Innovative preparation of curcumin for improved oral bioavailability. Biol Pharm Bull. 2011;34:660–665. doi.org/10.1248/bpb.34.660 Peer-reviewed
  6. Madhavi D, Kagan D. Bioavailability of a sustained release formulation of curcumin. Integr Med (Encinitas). 2014;13:24–30. ncbi.nlm.nih.gov/pmc/articles/PMC4684130/ Peer-reviewed
  7. Antony B, Merina B, Iyer VS, Judy N, Lennertz K, Joyal S. A pilot cross-over study to evaluate human oral bioavailability of BCM-95CG (Biocurcumax), a novel bioenhanced preparation of curcumin. Indian J Pharm Sci. 2008;70:445–449. doi.org/10.4103/0250-474X.44591 Peer-reviewed
  8. Bučević Popović V, Karahmet Farhat E, Banjari I, Jeličić Kadić A, Puljak L. Bioavailability of oral curcumin in systematic reviews: a methodological study. Pharmaceuticals (Basel). 2024;17(2):164. doi.org/10.3390/ph17020164 Peer-reviewed

Delivery: lipid and self-emulsifying systems

  1. Alskär LC, Bergström CAS. Models for predicting drug absorption from oral lipid-based formulations. Curr Mol Biol Rep. 2015;1(4):141–147 (Table 1 reproduces the LFCS from Pouton 2006). doi.org/10.1007/s40610-015-0023-1 Peer-reviewed
  2. Kollipara S, Gandhi RK. Pharmacokinetic aspects and in vitro–in vivo correlation potential for lipid-based formulations. Acta Pharm Sin B. 2014;4(5):333–349. doi.org/10.1016/j.apsb.2014.09.001 Peer-reviewed
  3. Gao P, Morozowich W. Development of supersaturatable self-emulsifying drug delivery system formulations for improving the oral absorption of poorly soluble drugs. Expert Opin Drug Deliv. 2006;3(1):97–110. doi.org/10.1517/17425247.3.1.97 Peer-reviewed
  4. Trevaskis NL, Charman WN, Porter CJH. Lipid-based delivery systems and intestinal lymphatic drug transport: a mechanistic update. Adv Drug Deliv Rev. 2008;60(6):702–716. doi.org/10.1016/j.addr.2007.09.007 Peer-reviewed
  5. Porter CJH, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007;6(3):231–248. doi.org/10.1038/nrd2197 Peer-reviewed
  6. Williams HD, Sassene P, Kleberg K, et al. Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3: understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations. Pharm Res. 2013;30(12):3059–3076. doi.org/10.1007/s11095-013-1038-z Peer-reviewed
  7. Oketch-Rabah HA, Roe AL, Rider CV, et al. United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts. Toxicol Rep. 2020;7:386–402. doi.org/10.1016/j.toxrep.2020.02.008 Peer-reviewed
  8. U.S. FDA. Assessing the Effects of Food on Drugs in INDs and NDAs—Clinical Pharmacology Considerations. Final guidance; docket FDA-2018-D-4368; content current as of May 20, 2026. fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance

Delivery: colloidal, vesicular and solid-state systems

  1. Akbarzadeh A, Rezaei-Sadabady R, Davaran S, et al. Liposome: classification, preparation, and applications. Nanoscale Res Lett. 2013;8(1):102. doi.org/10.1186/1556-276X-8-102 Peer-reviewed
  2. Uchegbu IF, Vyas SP. Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm. 1998;172(1–2):33–70. doi.org/10.1016/S0378-5173(98)00169-0 Peer-reviewed
  3. Müller RH, Radtke M, Wissing SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev. 2002;54 Suppl 1:S131–S155. doi.org/10.1016/S0169-409X(02)00118-7 Peer-reviewed
  4. Müller RH, Gohla S, Keck CM. State of the art of nanocrystals—special features, production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm. 2011;78(1):1–9. doi.org/10.1016/j.ejpb.2011.01.007 Peer-reviewed
  5. Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins: basic science and product development. J Pharm Pharmacol. 2010;62(11):1607–1621. doi.org/10.1111/j.2042-7158.2010.01030.x Peer-reviewed
  6. Lu M, Qiu Q, Luo X, et al. Phyto-phospholipid complexes (phytosomes): a novel strategy to improve the bioavailability of active constituents. Asian J Pharm Sci. 2019;14(3):265–274. doi.org/10.1016/j.ajps.2018.05.011 Peer-reviewed

Delivery: characterization, skin and selection tools

  1. Bhattacharjee S. DLS and zeta potential—what they are and what they are not? J Control Release. 2016;235:337–351. doi.org/10.1016/j.jconrel.2016.06.017 Peer-reviewed
  2. Hubatsch I, Ragnarsson EGE, Artursson P. Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nat Protoc. 2007;2(9):2111–2119. doi.org/10.1038/nprot.2007.303 Peer-reviewed
  3. Evans MV, Moxon TE, Lian G, et al. A regression analysis using simple descriptors for multiple dermal datasets: going from individual membranes to the full skin. J Appl Toxicol. 2023;43:940–950 (Equation 1 reproduces Potts and Guy 1992). doi.org/10.1002/jat.4435 Peer-reviewed
  4. OECD. Test No. 428: Skin Absorption: In Vitro Method. OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing; 2004. oecd.org/en/publications/test-no-428-skin-absorption-in-vitr Primary source
  5. ICH M9 guideline on biopharmaceutics classification system-based biowaivers. EMA/CHMP/ICH/493213/2018, Step 5, 10 February 2020 (Section 2.1: 250 mL, pH 1.2–6.8, 37 °C). ema.europa.eu/en/documents/scientific-guideline/ich-m9-bioph Agency guidance
  6. Jain N, Yalkowsky SH. Estimation of the aqueous solubility I: application to organic nonelectrolytes. J Pharm Sci. 2001;90(2):234–252. doi.org/10.1002/1520-6017(200102)90:2<234::AID-JPS14>3.0.CO; Peer-reviewed
  7. Avdeef A, Kansy M. Trends in PhysChem properties of newly approved drugs over the last six years; predicting solubility of drugs approved in 2021. J Solution Chem. 2022;51(12):1455–1481 (Eq. 1 gives the general solubility equation). doi.org/10.1007/s10953-022-01199-3 Peer-reviewed
  8. Bergström CAS, Wassvik CM, Johansson K, Hubatsch I. Poorly soluble marketed drugs display solvation limited solubility. J Med Chem. 2007;50(23):5858–5862. doi.org/10.1021/jm0706416 Peer-reviewed
  9. Butler JM, Dressman JB. The developability classification system: application of biopharmaceutics concepts to formulation development. J Pharm Sci. 2010;99(12):4940–4954. doi.org/10.1002/jps.22217 Peer-reviewed

Delivery: regulatory status of carriers and excipients

  1. U.S. FDA. Inactive Ingredients in Approved Drug Products Search: Frequently Asked Questions. Content current as of January 26, 2022. fda.gov/drugs/drug-approvals-and-databases/inactive-ingredie Primary source

Discovery: identity, variability and markers

  1. United States Pharmacopeia. General chapter <203> High-Performance Thin-Layer Chromatography Procedure for Identification of Articles of Botanical Origin. USP–NF (title verified October 22, 2026). doi.usp.org/USPNF/USPNF_M9134_02_01.html Primary source
  2. Wolfender J-L, Marti G, Thomas A, Bertrand S. Current approaches and challenges for the metabolite profiling of complex natural extracts. J Chromatogr A. 2015;1382:136–164. doi.org/10.1016/j.chroma.2014.10.091 Peer-reviewed
  3. EMA Committee on Herbal Medicinal Products. Reflection paper on markers used for quantitative and qualitative analysis of herbal medicinal products and traditional herbal medicinal products. EMEA/HMPC/253629/2007, 15 July 2008. ema.europa.eu/en/documents/scientific-guideline/reflection-p Agency guidance

Discovery: adulteration and contamination

  1. Perini M, Pianezze S, Ziller L, Larcher R, Pace R. Stable isotope ratio analysis for the authentication of natural antioxidant curcuminoids from Curcuma longa (turmeric). Antioxidants. 2023;12(2):498. doi.org/10.3390/antiox12020498 Peer-reviewed
  2. United States Pharmacopeia. General chapter <561> Articles of Botanical Origin. USP–NF (title verified October 22, 2026). doi.usp.org/USPNF/USPNF_M99320_60101_01.html Primary source
  3. United States Pharmacopeia. General Chapter 〈2232〉 Elemental Contaminants in Dietary Supplements. USP–NF (DOI landing page, 2022): limits elemental contaminants in finished dietary supplement dosage forms labeled as conforming to USP or NF; limits for dietary ingredients are set in their monographs. doi.usp.org/USPNF/USPNF_M5291_02_01.html Primary source
  4. Ałtyn I, Twarużek M. Mycotoxin contamination concerns of herbs and medicinal plants. Toxins. 2020;12(3):182. doi.org/10.3390/toxins12030182 Peer-reviewed
  5. Holland J, Rose M, Petch S. Occurrence of Polycyclic Aromatic Hydrocarbons in Herbs, Spices, Supplements and Tea. FERA for the UK Food Standards Agency; 2015. food.gov.uk/sites/default/files/media/document/pahs-in-herbs Primary source

Discovery: botanical explorer sources

  1. EMA. Hyperici herba (St. John's wort), herbal medicinal product page; EU herbal monograph revision 1 (EMA/HMPC/7695/2021). Accessed October 22, 2026. ema.europa.eu/en/medicines/herbal/hyperici-herba-0 Primary source
  2. EMA HMPC. Assessment report on Hypericum perforatum L., herba. EMA/HMPC/244315/2016 Rev. 1, 23 November 2022. ema.europa.eu/en/documents/herbal-report/final-assessment-re Primary source
  3. Nahrstedt A, Butterweck V. Lessons learned from herbal medicinal products: the example of St. John's wort. J Nat Prod. 2010;73(5):1015–1021. doi.org/10.1021/np1000329 Peer-reviewed
  4. EMA. Ginkgo folium (ginkgo leaf), herbal medicinal product page; EU herbal monograph (2015). Accessed October 22, 2026. ema.europa.eu/en/medicines/herbal/ginkgo-folium Primary source
  5. van Beek TA, Montoro P. Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals. J Chromatogr A. 2009;1216(11):2002–2032. doi.org/10.1016/j.chroma.2009.01.013 Peer-reviewed
  6. National Toxicology Program. TR-578: Toxicology and Carcinogenesis Studies of Ginkgo Biloba Extract (CASRN 90045-36-6) in F344/N Rats and B6C3F1/N Mice (Gavage Studies), levels of evidence. ntp.niehs.nih.gov/data/tr/500s/tr578levels Primary source
  7. NIST. Certificate of Analysis, Standard Reference Material 3246 Ginkgo biloba (Leaves). tsapps.nist.gov/srmext/certificates/3246.pdf Primary source
  8. EMA. Curcumae longae rhizoma (turmeric), herbal medicinal product page; EU herbal monograph revision 1 (2019). Accessed October 22, 2026. ema.europa.eu/en/medicines/herbal/curcumae-longae-rhizoma Primary source
  9. EMA HMPC. Assessment report on Curcuma longa L., rhizoma. EMA/HMPC/329745/2017, 25 September 2018. ema.europa.eu/documents/herbal-report/final-assessment-repor Primary source
  10. Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA. The essential medicinal chemistry of curcumin. J Med Chem. 2017;60(5):1620–1637. doi.org/10.1021/acs.jmedchem.6b00975 Peer-reviewed
  11. EMA. Camelliae sinensis non fermentatum folium (green tea), herbal medicinal product page; EU herbal monograph (2014). Accessed October 22, 2026. ema.europa.eu/en/medicines/herbal/camelliae-sinensis-non-fer Primary source
  12. NCCIH. Green Tea: Usefulness and Safety. Last updated February 2025. nccih.nih.gov/health/green-tea Primary source
  13. NIST. Certificate of Analysis, Standard Reference Material 3254 Green Tea (Camellia sinensis) Leaves. tsapps.nist.gov/srmext/certificates/3254.pdf Primary source

Drying & particle engineering: figures

  1. IAPWS R14-08(2011). Revised Release on the Pressure along the Melting and Sublimation Curves of Ordinary Water Substance. International Association for the Properties of Water and Steam; September 2011 (triple point 273.16 K, 611.657 Pa). iapws.org/documents/release/MeltSub Primary source

Colloids & emulsions: measurement standards (figures)

  1. ISO 22412:2025. Particle size analysis — Dynamic light scattering (DLS). Edition 3, September 2025 (replaces the withdrawn ISO 22412:2017). iso.org/standard/85505.html Primary source
  2. ISO 13320:2020. Particle size analysis — Laser diffraction methods. Edition 2, January 2020; applicable to particle sizes from approximately 0.1 µm to 3 mm. iso.org/standard/69111.html Primary source

Extraction: hazardous (classified) locations

  1. Electronic Code of Federal Regulations. 29 CFR 1910.307, Hazardous (classified) locations, § (a)(1), (b) and (c). Up to date as of October 21, 2026. ecfr.gov/current/title-29/section-1910.307 Regulation or statute
  2. Electronic Code of Federal Regulations. 29 CFR 1910.399, Definitions applicable to Subpart S: Class I, Division 1 and Class I, Division 2 locations, with notes. Up to date as of October 21, 2026. ecfr.gov/current/title-29/section-1910.399 Regulation or statute

Process engineering: process safety (figures)

  1. U.S. OSHA. Combustible Dust in Industry: Preventing and Mitigating the Effects of Fire and Explosions. Safety and Health Information Bulletin SHIB 07-31-2005, updated November 12, 2014 (dust explosion pentagon; dust-control, ignition-control and protection recommendations of NFPA 654; NFPA 69). Accessed October 23, 2026. osha.gov/publications/shib073105 Agency guidance

Extraction, purification and standardization: separation equations and published purification data

  1. Harvey D. Analytical Chemistry 2.1, section 7.7: Liquid–Liquid Extractions (eqs 7.1, 7.6, 7.7). LibreTexts open textbook; accessed October 22, 2026. chem.libretexts.org/Bookshelves/Analytical_Chemistry/Analyti Book
  2. Harvey D. Analytical Chemistry 2.1, sections 12.2–12.3: General Theory of Column Chromatography; Optimizing Chromatographic Separations (eqs 12.1, 12.3). LibreTexts open textbook; accessed October 22, 2026. chem.libretexts.org/Bookshelves/Analytical_Chemistry/Analyti Book
  3. Langmuir I. The adsorption of gases on plane surfaces of glass, mica and platinum. J Am Chem Soc. 1918;40:1361–1403. doi.org/10.1021/ja02242a004 Peer-reviewed
  4. Hou M, Hu W, Xiu Z, Jiang A, Men L, Hao K, Sun X, Cao D. Preparative purification of total flavonoids from Sophora tonkinensis Gagnep. by macroporous resin column chromatography and comparative analysis of flavonoid profiles by HPLC-PAD. Molecules. 2019;24(17):3200. doi.org/10.3390/molecules24173200 Peer-reviewed
  5. Fu R, Yan X, Zeng Z, Yang Y, Zhang P, Lin Y, Gong D, Yu P. Enrichment of alkaloids from Cinnamomum camphora seed kernels using macroporous resin: adsorption/desorption behavior, process optimization and scale-up study. Foods. 2026;15(6):1054. doi.org/10.3390/foods15061054 Peer-reviewed
  6. Aranda-García E, Cristiani-Urbina E. Hexavalent chromium removal and total chromium biosorption from aqueous solution by Quercus crassipes acorn shell in a continuous up-flow fixed-bed column: influencing parameters, kinetics, and mechanism. PLoS One. 2020;15(1):e0227953 (Thomas model, eq 5). doi.org/10.1371/journal.pone.0227953 Peer-reviewed
  7. Juela DM. Comments on “Dynamic adsorption of sulfamethoxazole from aqueous solution by lignite activated coke”. Materials (Basel). 2021;14(4):848 (equivalence of the Bohart–Adams, Thomas and Yoon–Nelson models). doi.org/10.3390/ma14040848 Peer-reviewed
  8. Xiao H, Feng Y, Goundry WRF, Karlsson S. Organic solvent nanofiltration in pharmaceutical applications. Org Process Res Dev. 2024;28(4):891–923. doi.org/10.1021/acs.oprd.3c00470 Peer-reviewed
  9. Urwin SJ, Levilain G, Marziano I, Merritt JM, Houson I, Ter Horst JH. A structured approach to cope with impurities during industrial crystallization development. Org Process Res Dev. 2020;24:1443–1456. doi.org/10.1021/acs.oprd.0c00166 Peer-reviewed
  10. Guiochon G. Preparative liquid chromatography. J Chromatogr A. 2002;965:129–161. doi.org/10.1016/S0021-9673(01)01471-6 Peer-reviewed
  11. Chen L, Zhao F, Li W, Chen Z, Pan J, Xiong D, Li B, Zhang Q, Qu H. Evaluation of a multiple and global analytical indicator of batch consistency: traditional Chinese medicine injection as a case study. RSC Adv. 2020;10:10338–10351. doi.org/10.1039/c9ra10065b Peer-reviewed
  12. Gan F, Ye R. New approach on similarity analysis of chromatographic fingerprint of herbal medicine. J Chromatogr A. 2006;1104:100–105. doi.org/10.1016/j.chroma.2005.11.099 Peer-reviewed

Extraction, purification and standardization: regulatory definitions and reference materials

  1. European Medicines Agency. Draft guideline on declaration of herbal substances and herbal preparations, EMA/HMPC/CHMP/CVMP/287539/2005 Rev. 2, dated March 4, 2026; public consultation April 1–June 30, 2026 (draft). ema.europa.eu/en/documents/scientific-guideline/draft-guidel Agency guidance
  2. 21 CFR 117.110, Defect action levels (paragraph (b) on mixing of adulterated food). Electronic Code of Federal Regulations; accessed October 23, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-117/su Regulation or statute

Process engineering: processability, scale-up and technology transfer

  1. United States Pharmacopeia. General chapter <1174> Powder Flow (USP 38–NF 33 text): four methods; Table 1, flow properties and angles of repose; Table 2, scale of flowability (compressibility index and Hausner ratio). Read October 24, 2026. Primary source
  2. Allada R. Hygroscopicity categorization of pharmaceutical solids by gravimetric sorption analysis: a systematic approach. Asian J Pharm. 2016;10(4) (European Pharmacopoeia method: 24 h at 25 ± 1 °C and 80 ± 2% RH; Table 1 classes). doi.org/10.22377/ajp.v10i04.867 Peer-reviewed
  3. Grau Baquero G, Sorolla S, Casas C, Bacardit A. Life cycle assessment of polyphenolic extracts derived from pine by-products. Materials. 2025;18(5):1000 (Tables 1 and 2: extraction and atomization inventories). doi.org/10.3390/ma18051000 Peer-reviewed
  4. Withouck H, Paelinck A, Foubert I, Fraeye I. Ultrasound-assisted extraction of applewood polyphenols at lab and pilot scales. Foods. 2023;12(17):3142. doi.org/10.3390/foods12173142 Peer-reviewed
  5. Prado JM, Dalmolin I, Carareto NDD, Basso RC, Meirelles AJA, Oliveira JV, Batista EAC, Meireles MAA. Supercritical fluid extraction of grape seed: process scale-up, extract chemical composition and economic evaluation. J Food Eng. 2012;109(2):249–257. doi.org/10.1016/j.jfoodeng.2011.10.007 Peer-reviewed
  6. Poozesh S, Bilgili E. Scale-up of pharmaceutical spray drying using scale-up rules: a review. Int J Pharm. 2019;562:271–292. doi.org/10.1016/j.ijpharm.2019.03.047 Peer-reviewed
  7. Thybo P, Hovgaard L, Lindeløv JS, Brask A, Andersen SK. Scaling up the spray drying process from pilot to production scale using an atomized droplet size criterion. Pharm Res. 2008;25(7):1610–1620. doi.org/10.1007/s11095-008-9565-8 Peer-reviewed
  8. Tye CK, Sun CC, Amidon GE. Evaluation of the effects of tableting speed on the relationships between compaction pressure, tablet tensile strength, and tablet solid fraction. J Pharm Sci. 2005;94(3):465–472. doi.org/10.1002/jps.20262 Peer-reviewed
  9. Fell JT, Newton JM. Determination of tablet strength by the diametral-compression test. J Pharm Sci. 1970;59(5):688–691. doi.org/10.1002/jps.2600590523 Peer-reviewed
  10. United States Pharmacopeia. General chapter <1062> Tablet Compression Characterization (USP 40–NF 35, Second Supplement; official December 1, 2017), as reported by ECA Academy GMP news. Accessed October 24, 2026. gmp-compliance.org/gmp-news/new-usp-chapter-1062-tablet-comp Primary source
  11. O'Donoghue LT. Compositional and analytical factors affecting the stickiness of dairy powders. MRes thesis, University College Cork; 2019 (section 1.2.1.2: T − Tg in stickiness determination). cora.ucc.ie/bitstreams/4b372ab5-6aa8-4c55-aeeb-e19dd3c7751e/ Primary source
  12. ICH Q5E Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process. Step 4, 18 November 2004. database.ich.org/sites/default/files/Q5E%20Guideline.pdf Agency guidance

Applications and commercialization

Commercialization, intellectual property and licensing

  1. Cooper RG. Stage-gate systems: a new tool for managing new products. Business Horizons. 1990;33(3):44–54. doi.org/10.1016/0007-6813(90)90040-I
  2. 35 U.S.C. 154(a)(2)–(3) — patent term of 20 years from the filing date; priority under 119/365(a)/365(b)/386 not counted (accessed Oct 22, 2026). law.cornell.edu/uscode/text/35/154
  3. 35 U.S.C. 111(b)(5) and 119(e) — provisional application abandoned 12 months after filing; non-provisional must be filed within 12 months to claim it (accessed Oct 22, 2026). law.cornell.edu/uscode/text/35/119
  4. 35 U.S.C. 156 — patent term extension for products subject to regulatory review (drug products, medical devices, food additives, color additives); 5-year and 14-year caps (accessed Oct 22, 2026). law.cornell.edu/uscode/text/35/156
  5. 35 U.S.C. 271(a) and 271(g) — infringement, including importing or selling in the U.S. a product made by a U.S.-patented process (accessed Oct 22, 2026). law.cornell.edu/uscode/text/35/271
  6. 18 U.S.C. 1836 — civil action for trade-secret misappropriation; subsections (b)–(d) added by Pub. L. 114-153 (Defend Trade Secrets Act of 2016), effective May 11, 2016; 3-year limitation (accessed Oct 22, 2026). law.cornell.edu/uscode/text/18/1836
  7. Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66 (2012), decided March 20, 2012. govinfo.gov/app/details/USREPORTS-566/USREPORTS-566-66
  8. Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013), decided June 13, 2013. govinfo.gov/content/pkg/USREPORTS-569/pdf/USREPORTS-569-576.
  9. USPTO. Manual of Patent Examining Procedure § 2106.04(c), The Markedly Different Characteristics Analysis (nature-based products). uspto.gov/web/offices/pac/mpep/s2106.html
  10. WIPO. PCT frequently asked questions: 12-month priority period, international publication after 18 months, national phase generally at 30 months, grant by national or regional offices (accessed Oct 22, 2026). wipo.int/en/web/pct-system/faqs/faqs
  11. Uniloc USA, Inc. v. Microsoft Corp., 632 F.3d 1292, 1315 (Fed. Cir. Jan. 4, 2011): the 25 percent rule of thumb is 'a fundamentally flawed tool for determining a baseline royalty rate in a hypothetical negotiation' (quoted in Amundson, Boston Univ. J. Sci. & Tech. Law, 2016). bu.edu/jostl/files/2016/05/AMUNDSON_ART_MACROD_FINALWEB.pdf
  12. Lemley MA, Shapiro C. Patent Holdup and Royalty Stacking. Texas Law Review. 2007;85(7):1991–2049. law.stanford.edu/publications/patent-holdup-and-royalty-stac
  13. U.S. FDA. Over-the-Counter (OTC) Drug Review | OTC Monograph Reform in the CARES Act. fda.gov/drugs/over-counter-otc-nonprescription-drugs/over-co
  14. U.S. FDA. Contract Manufacturing Arrangements for Drugs: Quality Agreements. Guidance for Industry. November 2016. fda.gov/regulatory-information/search-fda-guidance-documents
  15. United States Pharmacopeia. General chapter <1224> Transfer of Analytical Procedures (comparative testing, covalidation, revalidation, transfer waiver; pre-approved protocol with acceptance criteria).
  16. 35 U.S.C. 261 — patents and applications assignable by an instrument in writing; exclusive rights for the whole or a specified part of the United States (accessed Oct 22, 2026). law.cornell.edu/uscode/text/35/261
  17. 35 U.S.C. 262 — joint owners: absent agreement, each may make, use, offer to sell, sell or import without consent of and without accounting to the others (accessed Oct 22, 2026). law.cornell.edu/uscode/text/35/262

Applications: terms used for botanical products

  1. Kalra EK. Nutraceutical--definition and introduction. AAPS PharmSci. 2003;5(3):E25. doi:10.1208/ps050325. PMID 14621960. pubmed.ncbi.nlm.nih.gov/14621960/ Peer-reviewed
  2. Arai S. Studies on functional foods in Japan--state of the art. Biosci Biotechnol Biochem. 1996;60(1):9-15. doi:10.1271/bbb.60.9. PMID 8824819. pubmed.ncbi.nlm.nih.gov/8824819/ Peer-reviewed

Applications: FDA, FTC and USPTO guidance

  1. U.S. FDA. Is It a Cosmetic, a Drug, or Both? (Or Is It Soap?). Content current as of Sep 11, 2024. fda.gov/cosmetics/cosmetics-laws-regulations/it-cosmetic-dru Primary source
  2. U.S. FDA. "Cosmeceutical." Content current as of Feb 25, 2022. fda.gov/cosmetics/cosmetics-labeling-claims/cosmeceutical Primary source
  3. U.S. FDA. Guidance for Industry: Safety of Nanomaterials in Cosmetic Products. Final, June 2014; docket FDA-2011-D-0489. fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  4. U.S. FDA. Questions and Answers on Dietary Supplements. Content current as of Aug 27, 2026. fda.gov/food/information-consumers-using-dietary-supplements Primary source
  5. U.S. FDA. Guidance for Industry: Substantiation for Dietary Supplement Claims Made Under Section 403(r)(6) of the Federal Food, Drug, and Cosmetic Act. Final, January 2009; docket FDA-2004-D-0303. fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  6. U.S. FDA. Guidance for Industry: Distinguishing Liquid Dietary Supplements from Beverages. Final, January 2014; docket FDA-2009-D-0542. fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  7. U.S. FDA. Guidance for Industry: Assessing the Effects of Significant Manufacturing Process Changes, Including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact Substances, Including Food Ingredients that Are Color Additives. Final, June 2014; docket FDA-2011-D-0490. fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  8. U.S. FDA. Structure/Function Claims. Content current as of Mar 28, 2024. fda.gov/food/nutrition-food-labeling-and-critical-foods/stru Primary source
  9. U.S. FDA. Brominated Vegetable Oil (BVO). Content current as of Jul 2, 2024 (final rule issued Jul 3, 2024; effective Aug 2, 2024). fda.gov/food/food-additives-petitions/brominated-vegetable-o Primary source
  10. U.S. FDA. Dietary Supplements: New Dietary Ingredient Notifications and Related Issues. Revised draft guidance (2016; October 2026 version with document history); docket FDA-2011-D-0376. fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  11. U.S. FDA. Botanical Drug Development: Guidance for Industry. Revision 1, final, December 2016; docket FDA-2000-D-0103. fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  12. U.S. FDA. Small Entity Compliance Guide: Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements. December 2010; docket FDA-2010-D-0605. fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  13. U.S. FDA, CDER. What Is a Botanical Drug? Undated page, read Oct 22, 2026. fda.gov/about-fda/center-drug-evaluation-and-research-cder/w Primary source

Global ingredient development and distribution: U.S. import and supplier rules

  1. 21 CFR Part 1, Subpart L (§§ 1.500–1.514), Foreign Supplier Verification Programs for Food Importers, including § 1.511 (dietary supplements) and § 1.500 (definition of importer); eCFR, up to date as of 10/20/2026 (accessed Oct 22, 2026). ecfr.gov/current/title-21/chapter-I/subchapter-A/part-1/subp Regulation or statute
  2. U.S. FDA. Foreign Supplier Verification Programs for Importers of Food for Humans and Animals. Final rule. 80 FR 74226 (November 27, 2015). federalregister.gov/documents/2015/11/27/2015-28158/foreign- Regulation or statute
  3. 21 CFR Part 1, Subpart I, Prior Notice of Imported Food: § 1.277 (scope, including quality-assurance and trade samples) and § 1.279 (timing: 2, 4 and 8 hours; 30 or 15 days); eCFR, up to date as of 10/20/2026. ecfr.gov/current/title-21/chapter-I/subchapter-A/part-1/subp Regulation or statute
  4. 21 CFR Part 1, Subpart H, Registration of Food Facilities: §§ 1.225, 1.226(a), 1.227, 1.230(b); eCFR, up to date as of 10/20/2026. ecfr.gov/current/title-21/chapter-I/subchapter-A/part-1/subp Regulation or statute
  5. 21 CFR 111.70 (specifications) and 111.75 (identity testing of dietary ingredients; reliance on certificates of analysis); eCFR, up to date as of 10/20/2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-111/su Regulation or statute
  6. 21 CFR 117.405, Requirement to establish and implement a supply-chain program; eCFR, up to date as of 10/20/2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-117/su Regulation or statute
  7. 19 CFR 142.3 (entry documentation required) and 142.12 (entry summary within 10 working days); eCFR, up to date as of 10/20/2026. ecfr.gov/current/title-19/chapter-I/part-142 Regulation or statute
  8. 21 U.S.C. 381(a), Imports: refusal of admission of articles that appear adulterated, misbranded, made under insanitary conditions or restricted in sale in the country of production or export (Cornell LII, accessed Oct 22, 2026). law.cornell.edu/uscode/text/21/381 Regulation or statute
  9. 19 U.S.C. 1401a, Value: transaction value as the primary basis of appraisal; price actually paid or payable excludes international transportation and insurance (Cornell LII, accessed Oct 22, 2026). law.cornell.edu/uscode/text/19/1401a Regulation or statute
  10. U.S. FDA. Import Alerts (detention without physical examination). Content current as of 03/03/2025 (accessed Oct 22, 2026). fda.gov/industry/actions-enforcement/import-alerts Primary source
  11. International Chamber of Commerce. Incoterms® 2020: eleven three-letter trade terms allocating costs, risks and obligations; CIF reserved for maritime trade (accessed Oct 22, 2026). iccwbo.org/business-solutions/incoterms-rules/incoterms-2020 Primary source
  12. CITES Secretariat. How CITES works: Appendix II trade requires an export permit or re-export certificate from the Management Authority of the exporting State (accessed Oct 22, 2026). cites.org/eng/disc/how.php Primary source

Applications: international market entry

  1. Regulation (EU) 2015/2283 of the European Parliament and of the Council of 25 November 2015 on novel foods. OJ L 327, 11.12.2015, p. 1. eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:32015 Regulation or statute
  2. European Commission. Food supplements (harmonised list of vitamins and minerals). food.ec.europa.eu/food-safety/labelling-and-nutrition/food-s Primary source
  3. Regulation (EC) No 1223/2009 of 30 November 2009 on cosmetic products (recast). OJ L 342, 22.12.2009, p. 59. eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:32009 Regulation or statute

Applications: demand and international regulation data

  1. American Public Health Association. WHO launches traditional and complementary medicine report. Public Health Newswire, September 3, 2019 (earlier survey values: national policy 79, herbal-medicine regulation 116, registration 109, national office 89 in 2012; research institute 58 in 2005). Checked October 24, 2026. apha.org/publications/public-health-newswire/public-health-n Primary source

Scientific insights and data

Machine learning and optimization

  1. Psichogios DC, Ungar LH. A hybrid neural network–first principles approach to process modeling. AIChE J. 1992;38(10):1499–1511. doi.org/10.1002/aic.690381003
  2. Shields BJ, Stevens J, Li J, et al. Bayesian reaction optimization as a tool for chemical synthesis. Nature. 2021;590(7844):89–96. doi.org/10.1038/s41586-021-03213-y
  3. Jones DR, Schonlau M, Welch WJ. Efficient global optimization of expensive black-box functions. J Glob Optim. 1998;13:455–492. doi.org/10.1023/A:1008306431147
  4. Rasmussen CE, Williams CKI. Gaussian Processes for Machine Learning. Cambridge, MA: MIT Press; 2006. gaussianprocess.org/gpml/

Markets, demand and industry

  1. Grand View Research. Botanical Supplements Market report GVR-4-68039-086-6 (updated Jul 2026): $38.2B (2024) to $67.0B (2030), 9.9% CAGR 2025–2030. grandviewresearch.com/industry-analysis/botanical-supplement
  2. Grand View Research. Plant Extracts Market report (Sep 2026): $45.9B (2025) to $86.1B (2033), 8.3% CAGR 2026–2033. grandviewresearch.com/industry-analysis/plant-extracts-marke
  3. MarketsandMarkets. Dietary Supplements Testing Market (Aug 2025): $2.40B (2025) to $3.65B (2030), 8.8% CAGR. marketsandmarkets.com/Market-Reports/dietary-supplements-tes
  4. Grand View Research Horizon outlook. Dietary supplements contract manufacturing: $22.6B (2025) to $58.9B (2033), 12.75% CAGR 2026–2033. grandviewresearch.com/horizon/outlook/dietary-supplements-co
  5. Global Growth Insights, dietary supplement contract manufacturing ($9.7B, 2025); Research and Markets (Nov 2025, $68.02B, 2025); Value Market Research ($72.02B, 2025). Publisher pages accessed October 2026; methods undisclosed. researchandmarkets.com/reports/6184199/dietary-supplements-c
  6. Precedence Research. Contract Research Organization Services Market (updated Sep 16, 2026): $77.0B (2025) to $158.6B (2035), 7.49% CAGR 2026–2035. precedenceresearch.com/contract-research-organization-servic
  7. Fortune Business Insights. Pharmaceutical CDMO Market (updated Sep 21, 2026): $169.25B (2025) to $324.18B (2034), 7.49% CAGR. fortunebusinessinsights.com/pharmaceutical-cdmo-market-11801
  8. Grand View Research. AI in Drug Discovery Market (updated Jun 2026): $2.3B (2025) to $13.8B (2033), 24.8% CAGR 2026–2033 (Precedence Research estimates $6.93B for 2025). grandviewresearch.com/industry-analysis/artificial-intellige
  9. Precedence Research. Artificial intelligence in drug discovery market (Report 1875, updated Sep 21, 2026): $6.93B (2025) to $17.81B (2035). precedenceresearch.com/artificial-intelligence-in-drug-disco
  10. Smith T, et al. US sales of herbal supplements increase by 5.4% in 2024. HerbalGram. 2025;144 (data: SPINS, Nutrition Business Journal): $13.231B in 2024. umb.herbalgram.org/media/gqkbi0gy/hg144-hmr.pdf
  11. Stierman B, Couch CA, Gahche JJ, Mishra S. Dietary supplement use among adults and youth: United States, August 2021–August 2023. NCHS Data Brief No. 561. 2026. cdc.gov/nchs/products/databriefs/db561.htm
  12. NCHS Data Brief No. 399. Dietary supplement use among adults: United States, 2017–2018. 2021. cdc.gov/nchs/data/databriefs/db399-H.pdf
  13. BIO, Informa Pharma Intelligence, QLS Advisors. Clinical Development Success Rates and Contributing Factors 2011–2020. February 2021. go.bio.org/rs/490-EHZ-999/images/ClinicalDevelopmentSuccessR
  14. Enveda Biosciences. Series E $311M (Sep 23, 2026; total >$845M); ENV-294 open-label Phase 1b (n=9) results Jul 23, 2026 (secondary reports). hlth.com/insights/news/enveda-raises-311-million-to-advance-

Global trade data: customs categories, valuation and botanical origins

  1. United Nations. UN Comtrade Database, public API (preview endpoint): HS 1211 exports and imports by reporter 2015–2024; bilateral importer-reported flows 2024; U.S. imports by partner for HS 1211, 1301, 1302, 0904–0910 and 3301, and 1302 subheadings, 2024; exporter-reported exports to the United States, 2024. Retrieved October 22, 2026. comtradeplus.un.org/ Primary source
  2. UN Statistics Division. Methodology Guide for UN Comtrade User on UN Comtrade Upgrade 2019 (CIF, FOB and primary trade values). comtradeapi.un.org/files/v1/app/wiki/MethodologyGuideforComt Primary source
  3. United Nations, Department of Economic and Social Affairs, Statistics Division. International Merchandise Trade Statistics: Concepts and Definitions 2010. Statistical Papers Series M No. 52/Rev.3. New York; 2011 (paras. 4.7–4.8 valuation; 6.25–6.26 partner attribution). unstats.un.org/unsd/trade/eg-imts/IMTS%202010%20(English).pd Primary source
  4. U.S. Census Bureau, Foreign Trade. Definitions: customs value, CIF import value, general imports. census.gov/foreign-trade/reference/definitions/index.html Primary source
  5. World Customs Organization. HS Nomenclature 2022 Edition, Chapter 9: Coffee, tea, maté and spices (headings 09.04–09.10). wcoomd.org/-/media/wco/public/global/pdf/topics/nomenclature Primary source
  6. World Customs Organization. HS Nomenclature 2022 Edition, Chapter 12, heading 12.11 and Chapter Note 4. wcoomd.org/-/media/wco/public/global/pdf/topics/nomenclature Primary source
  7. World Customs Organization. HS Nomenclature 2022 Edition, Chapter 13: Lac; gums, resins and other vegetable saps and extracts (headings 13.01, 13.02; Chapter Note 1). wcoomd.org/-/media/wco/public/global/pdf/topics/nomenclature Primary source
  8. World Customs Organization. HS Nomenclature 2022 Edition, Chapter 21, heading 21.06. wcoomd.org/-/media/wco/public/global/pdf/topics/nomenclature Primary source
  9. World Customs Organization. HS Nomenclature 2022 Edition, Chapter 33, heading 33.01. wcoomd.org/-/media/wco/public/global/pdf/topics/nomenclature Primary source
  10. National Center for Complementary and Integrative Health. Herb fact sheets: Turmeric (updated April 2025), Ashwagandha (March 2023), Asian Ginseng (February 2025), Kava (April 2025), Echinacea (November 2024), European Elder (November 2024), Saw Palmetto (April 2025), Cranberry (November 2024), Milk Thistle (February 2025), Black Cohosh (November 2024). Retrieved October 22, 2026. nccih.nih.gov/health/herbsataglance Primary source
  11. U.S. Fish and Wildlife Service, Division of Scientific Authority. General advice for the export of wild and wild-simulated American ginseng (Panax quinquefolius) roots. Memorandum, September 1, 2022. cites.org/sites/default/files/ndf_material/USA%20NDF%20for%2 Primary source
  12. Baeg IH, So SH. The world ginseng market and the ginseng (Korea). J Ginseng Res. 2013;37(1):1–7. doi.org/10.5142/jgr.2013.37.1 Peer-reviewed
  13. Gohari AR, Saeidnia S, Mahmoodabadi MK. An overview on saffron, phytochemicals, and medicinal properties. Pharmacogn Rev. 2013;7(13):61–66. doi.org/10.4103/0973-7847.112850 Peer-reviewed
  14. Gonzales GF. Ethnobiology and ethnopharmacology of Lepidium meyenii (maca), a plant from the Peruvian highlands. Evid Based Complement Alternat Med. 2012;2012:193496. doi.org/10.1155/2012/193496 Peer-reviewed
  15. Schimpl FC, da Silva JF, Gonçalves JF, Mazzafera P. Guarana: revisiting a highly caffeinated plant from the Amazon. J Ethnopharmacol. 2013;150(1):14–31. doi.org/10.1016/j.jep.2013.08.023 Peer-reviewed
  16. South African Rooibos Council. Application for the registration of 'Rooibos / Red Bush' as a protected designation of origin under Regulation (EU) No 1151/2012 (ZA/PDO/0005/02427), 21 August 2018. EU eAmbrosia register attachment. ec.europa.eu/geographical-indications-register/eambrosia-pub Primary source
  17. Kotwal S, Kaul S, Sharma P, et al. De novo transcriptome analysis of medicinally important Plantago ovata using RNA-Seq. PLoS One. 2016;11(3):e0150273. doi.org/10.1371/journal.pone.0150273 Peer-reviewed
  18. Feng Z, Yao Z, Wang Q, et al. Single-nucleus sequencing and spatial metabolomics analysis reveal the regulatory mechanism of ginkgolic acid biosynthesis in the episperm of Ginkgo biloba. Hortic Res. 2026;13:uhag064. doi.org/10.1093/hr/uhag064 Peer-reviewed
  19. Bostock M. world-atlas 2.0.2 (countries-110m TopoJSON derived from Natural Earth, public domain). github.com/topojson/world-atlas

Botanical Intelligence: hybrid models, optimization and model reporting

  1. Box GEP, Wilson KB. On the experimental attainment of optimum conditions. J R Stat Soc Series B. 1951;13(1):1–38 (response-surface methodology). doi.org/10.1111/j.2517-6161.1951.tb00067.x Peer-reviewed
  2. Crank J. The Mathematics of Diffusion. 2nd ed. Oxford: Clarendon Press; 1975 (diffusion from a sphere with constant surface concentration). Peer-reviewed
  3. Gneiting T, Balabdaoui F, Raftery AE. Probabilistic forecasts, calibration and sharpness. J R Stat Soc Series B. 2007;69(2):243–268. doi.org/10.1111/j.1467-9868.2007.00587.x Peer-reviewed
  4. Angelopoulos AN, Bates S. Conformal prediction: a gentle introduction. Found Trends Mach Learn. 2023;16(4):494–591. doi.org/10.1561/2200000101 Peer-reviewed
  5. Wilkinson MD, Dumontier M, Aalbersberg IJ, et al. The FAIR guiding principles for scientific data management and stewardship. Sci Data. 2016;3:160018. doi.org/10.1038/sdata.2016.18 Peer-reviewed
  6. Mehrkesh AH, Hajimirzaee S, Hatamipour MS, Tavakoli T. Artificial neural network for modeling the extraction of aromatic hydrocarbons from lube oil cuts. Chem Eng Technol. 2011;34(3):459–464. doi.org/10.1002/ceat.201000361 Peer-reviewed
  7. Mehrkesh A, Tavakoli T, Hatamipour MS, Karunanithi AT. Modeling and simulation of a rotating-disk contactor for the extraction of aromatic hydrocarbons from a lube-oil cut. Ind Eng Chem Res. 2013;52(27):9422–9432. doi.org/10.1021/ie303427m Peer-reviewed
  8. Karunanithi AT, Mehrkesh A. Computer-aided design of tailor-made ionic liquids. AIChE J. 2013;59(12):4627–4640. doi.org/10.1002/aic.14228 Peer-reviewed
  9. Mehrkesh A, Karunanithi AT. Optimal design of ionic liquids for thermal energy storage. Comput Chem Eng. 2016;93:402–412. doi.org/10.1016/j.compchemeng.2016.04.008 Peer-reviewed

Science lab: equations, constants and standards

  1. Crank J. The Mathematics of Diffusion, 2nd ed. Oxford: Clarendon Press; 1975. Peer-reviewed
  2. Stokes GG. On the effect of the internal friction of fluids on the motion of pendulums. Trans Camb Philos Soc. 1851;9(2):8–106. Peer-reviewed
  3. Wagner W, Pruß A. The IAPWS formulation 1995 for the thermodynamic properties of ordinary water substance for general and scientific use. J Phys Chem Ref Data. 2002;31(2):387–535. doi.org/10.1063/1.1461829 Peer-reviewed
  4. Huber ML, Perkins RA, Laesecke A, et al. New international formulation for the viscosity of H2O. J Phys Chem Ref Data. 2009;38(2):101–125. doi.org/10.1063/1.3088050 Peer-reviewed
  5. Tiesinga E, Mohr PJ, Newell DB, Taylor BN. CODATA recommended values of the fundamental physical constants: 2018. Rev Mod Phys. 2021;93(2):025010. doi.org/10.1103/RevModPhys.93.025010 Peer-reviewed
  6. Wagner W, Riethmann T, Feistel R, Harvey AH. New equations for the sublimation pressure and melting pressure of H2O ice Ih. J Phys Chem Ref Data. 2011;40(4):043103. doi.org/10.1063/1.3657937 Peer-reviewed
  7. Tang X, Pikal MJ. Design of freeze-drying processes for pharmaceuticals: practical advice. Pharm Res. 2004;21(2):191–200. doi.org/10.1023/B:PHAM.0000016234.73023.75 Peer-reviewed
  8. Arrhenius S. Über die Reaktionsgeschwindigkeit bei der Inversion von Rohrzucker durch Säuren. Z Phys Chem. 1889;4U(1):226–248. doi.org/10.1515/zpch-1889-0416 Peer-reviewed
  9. ICH Q1A(R2). Stability Testing of New Drug Substances and Products (FDA guidance, November 2003). fda.gov/media/71707/download Agency guidance
  10. ICH Q1E. Evaluation of Stability Data (FDA guidance, June 2004). fda.gov/media/71722/download Agency guidance
  11. ICH Q1 Expert Working Group. Work plan (March 18, 2026): Step 2 April 2025; Step 4 adoption planned for November 2026. database.ich.org/sites/default/files/ICH52_Q1_EWG_WorkPlan_2 Primary source
  12. Purnell JH. The correlation of separating power and efficiency of gas-chromatographic columns. J Chem Soc. 1960:1268–1274. doi.org/10.1039/JR9600001268 Peer-reviewed
  13. Snyder LR, Kirkland JJ, Dolan JW. Introduction to Modern Liquid Chromatography, 3rd ed. Hoboken, NJ: Wiley; 2010. Peer-reviewed

Market data: botanical sales, consumer use, publishers' estimates, listed peers and policy

  1. U.S. Bureau of Labor Statistics. Consumer Price Index for All Urban Consumers (CPI-U), all items, U.S. city average, not seasonally adjusted, series CUUR0000SA0, annual averages 2015–2025. Retrieved October 22, 2026. download.bls.gov/pub/time.series/cu/cu.data.1.AllItems Primary source
  2. Europe PMC REST API, search endpoint. Query TITLE_ABS:(terms) AND SRC:MED AND PUB_YEAR:year for eight botanicals, 2000–2025. Queried October 22, 2026. europepmc.org/RestfulWebService Primary source
  3. World Health Organization. WHO global report on traditional and complementary medicine 2019. Geneva: WHO; 2019. ISBN 978-92-4-151543-6 (pp. 10, 15, 18, 21, 25, 29, 39). who.int/publications/i/item/978924151536 Primary source
  4. Grand View Research. Dietary supplements contract manufacturing market (global; 2025 USD 22.6 billion; 2033 USD 58.9 billion; CAGR 12.8%, 2026–2033). August 2026. grandviewresearch.com/industry-analysis/dietary-supplement-c Third-party estimate
  5. Fortune Business Insights. Dietary supplement contract manufacturing market (global; 2025 USD 68.18 billion; 2034 USD 201.41 billion; CAGR 12.79%, 2026–2034). Page updated October 5, 2026. fortunebusinessinsights.com/dietary-supplement-contract-manu Third-party estimate
  6. MarketsandMarkets. Supplement testing market, global forecast to 2030 (2025 USD 2,400.0 million; 2030 USD 3,652.2 million; CAGR 8.8%). Published August 2025. marketsandmarkets.com/Market-Reports/dietary-supplement-test Third-party estimate
  7. Natural Alternatives International, Inc. Form 10-K for the fiscal year ended June 30, 2026, filed September 28, 2026 (SEC EDGAR, CIK 0000787253). sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=000078725 Primary source
  8. Global Market Insights. Botanical extracts market (global; 2024 USD 30 billion; 2025 USD 32.3 billion; 2034 USD 64.6 billion; CAGR 8%, 2025–2034). Published November 2025. Read October 22, 2026. gminsights.com/industry-analysis/botanical-extracts-market Third-party estimate
  9. Market Research Future. Botanical extracts market (global; 2024 USD 6.592 billion; 2025 USD 7.218 billion; 2035 USD 17.89 billion; CAGR 9.5%). Last updated September 15, 2026. Read October 22, 2026. marketresearchfuture.com/reports/botanical-extracts-market-4 Third-party estimate
  10. MarketsandMarkets. Plant extracts market (global; 2024 USD 42.52 billion; 2025 USD 47.54 billion; 2030 USD 85.28 billion; CAGR 12.4%, 2025–2030). Published December 2025. Read October 22, 2026. marketsandmarkets.com/Market-Reports/plant-extracts-market-9 Third-party estimate
  11. Fortune Business Insights. Botanical supplements market (global; 2025 USD 60.02 billion; 2034 USD 143.44 billion; CAGR 10.15%, 2026–2034). Last updated August 31, 2026. Read October 22, 2026. fortunebusinessinsights.com/botanical-supplements-market-106 Third-party estimate
  12. Grand View Research, Horizon Databook. Dietary supplements market size, global (2025 USD 209,523.5 million; 2033 USD 431,687.5 million; CAGR 9.5%, 2026–2033). Page modified August 26, 2026. Read October 22, 2026. grandviewresearch.com/horizon/outlook/dietary-supplements-ma Third-party estimate
  13. Grand View Research, Horizon Databook. Dietary supplements market, United States (2025 USD 68,744.8 million; 2033 USD 129,391.3 million; CAGR 8.3%, 2026–2033). Published May 14, 2026. Read October 22, 2026. grandviewresearch.com/horizon/outlook/dietary-supplements-ma Third-party estimate
  14. Burleson G. Watch now! How to navigate the $75 billion supplement market. New Hope Network. June 10, 2026 (summarizes Nutrition Business Journal's 2026 Supplement Business Report: U.S. supplement sales $74.15 billion in 2025, +7.1%; the article prints 'million'). Read October 24, 2026. newhope.com/industry-insights/register-now-navigating-the-75 Third-party estimate
  15. U.S. Census Bureau. U.S. population projected to begin declining in second half of century (press release). November 9, 2023. Read October 24, 2026. census.gov/newsroom/press-releases/2023/population-projectio Primary source
  16. Board of Governors of the Federal Reserve System. Foreign exchange rates, G.5A annual release, January 5, 2026 (2025 averages: US$1.1306 per euro, US$1.3192 per pound, CHF 0.8305 per US$). Read October 24, 2026. federalreserve.gov/releases/g5a/current/default.htm Primary source
  17. Fortune Business Insights. Dietary supplements market (global; 2025 USD 100.92 billion; 2034 USD 219.31 billion; CAGR 9.11%, 2026–2034). Last updated October 5, 2026. Read October 24, 2026. fortunebusinessinsights.com/dietary-supplements-market-10208 Third-party estimate
  18. The Business Research Company, via Research and Markets. Dietary supplement testing services market report 2026 (2025 USD 3.18 billion; 2026 USD 3.49 billion; 2030 USD 4.85 billion; CAGR 8.6%, 2026–2030). February 2026. Read October 24, 2026. researchandmarkets.com/report/dietary-supplement-testing-ser Third-party estimate
  19. Precedence Research. Pharmaceutical CDMO market size worth USD 368.70 Bn by 2034 (press release via BioSpace; 2024 USD 184.90 billion; 2025 USD 197.40 billion; CAGR 7.15%, 2025–2034). December 1, 2025. Read October 24, 2026. biospace.com/press-releases/pharmaceutical-cdmo-market-size- Third-party estimate
  20. Natural Alternatives International, Inc. Natural Alternatives International, Inc. announces fiscal 2026 Q4 and YTD results (GlobeNewswire release, Carlsbad, CA, September 28, 2026; loss from operations $(18,752) thousand). Read October 24, 2026. finviz.com/news/396165/natural-alternatives-international-in Primary source
  21. Eurofins Scientific SE. Eurofins delivers FY 2025 objectives (press release, preliminary unaudited results). January 29, 2026. Read October 24, 2026. echanges.dila.gouv.fr/OPENDATA/AMF/BWR/2026/01/FCBWR166349_2 Primary source
  22. SGS SA. 2025 full year results (press release). February 11, 2026. Read October 24, 2026. sgs.com/-/media/sgscorp/documents/corporate/reports-and-pres Primary source
  23. Intertek Group plc. Full year 2025 results (RNS). March 3, 2026. Read October 24, 2026. data.fca.org.uk/artefacts/NSM/RNS/9671dd2f-592d-4f1e-b21b-20 Primary source
  24. Bureau Veritas SA. Sector-leading organic revenue growth of 6.5% in FY 2025 (Business Wire). February 24, 2026. Read October 24, 2026. businesswire.com/news/home/20260224846309/en/Bureau-Veritas- Primary source
  25. Givaudan SA. 2025 full year results (media release). January 29, 2026. Read October 24, 2026. givaudan.com/media/media-releases/2026/2025-full-year-result Primary source
  26. dsm-firmenich AG. dsm-firmenich reports full year 2025 results (press release). February 12, 2026. Read October 24, 2026. dsm-firmenich.com/content/dam/dsm-firmenich/investors/docume Primary source
  27. International Flavors & Fragrances Inc. IFF reports fourth quarter and full year 2025 results (Business Wire). February 11, 2026. Read October 24, 2026. businesswire.com/news/home/20260211509419/en/IFF-Reports-Fou Primary source
  28. Glanbia plc. Annual Report 2025 (52 weeks ended January 3, 2026). Read October 24, 2026. glanbia.com/sites/glanbia-plc/files/glanbia/investors/annual Primary source
  29. Symrise AG. Symrise delivered solid organic sales growth and strong profitability improvement for 2025 (release). March 4, 2026. Read October 24, 2026. symrise.com/newsroom/article/symrise-delivered-solid-organic Primary source
  30. Kerry Group plc. Preliminary statement of results for the year ended 31 December 2025. February 17, 2026. Read October 24, 2026. kerry.com/about/news-and-media/2026/kerry-group-preliminary- Primary source
  31. Balchem Corporation. Fourth quarter and full year 2025 financial results (earnings release). February 20, 2026. Read October 24, 2026. balchem.com/wp-content/uploads/2026/02/Balchem-Q4-2025-Earni Primary source
  32. Lonza Group AG. Full-year 2025 results. January 28, 2026. Read October 24, 2026. lonza.com/news/2026-01-28-06-30 Primary source
  33. Siegfried Holding AG. Full-year 2025 results (media release). February 20, 2026. Read October 24, 2026. siegfried.ch/app/uploads/2026/02/20260220_Siegfried_Media-Re Primary source

Operational excellence: lean, Six Sigma, statistical quality and risk management

  1. Rother M, Shook J. Learning to See: Value-Stream Mapping to Create Value and Eliminate Muda. Cambridge, MA: Lean Enterprise Institute; 1999 (ISBN 0-9667843-0-8). lean.org/store/book/learning-to-see/ Peer-reviewed
  2. Montgomery DC. Introduction to Statistical Quality Control. 8th ed. Hoboken, NJ: Wiley; 2019 (control-chart constants d2, A2, D4; DMAIC). Peer-reviewed
  3. Western Electric Company. Statistical Quality Control Handbook. Indianapolis, IN: Western Electric Co.; 1956. Peer-reviewed
  4. NIST/SEMATECH e-Handbook of Statistical Methods, section 6.1.6: What is process capability? (Cp, Cpk, Pp, Ppk; approximate confidence interval for Cpk, valid for n ≥ 25 and 0.75 ≤ Cpk ≤ 4; reject rates 0.27% at Cp = 1.00 and 64 ppm at Cp = 1.33 for a centered normal process; sample-size and non-normal-data guidance). Retrieved October 22, 2026. itl.nist.gov/div898/handbook/pmc/section1/pmc16.htm Primary source
  5. Bissell AF. How reliable is your capability index? J R Stat Soc Ser C Appl Stat. 1990;39(3):331–340. doi.org/10.2307/2347383 Peer-reviewed
  6. Harry MJ, Lawson JR. Six Sigma Producibility Analysis and Process Characterization. Reading, MA: Addison-Wesley; 1992. Peer-reviewed
  7. Coskun A, Ialongo C. Six Sigma revisited: we need evidence to include a 1.5 SD shift in the extraanalytical phase of the total testing process. Biochem Med (Zagreb). 2020;30(1):010901. doi.org/10.11613/BM.2020.010901 Peer-reviewed
  8. Ishikawa K. Guide to Quality Control. 2nd rev. ed. Tokyo: Asian Productivity Organization; 1982. Peer-reviewed
  9. Nakajima S. Introduction to TPM: Total Productive Maintenance. Cambridge, MA: Productivity Press; 1988. Peer-reviewed
  10. ICH Q9(R1) Quality Risk Management. Adopted by the ICH Assembly (Step 4) on 18 January 2023. health.ec.europa.eu/system/files/2023-10/mp_ich_q9guideline- Agency guidance
  11. AIAG and VDA. FMEA Handbook. 1st ed. 2019 (introduces Action Priority tables to address limitations of the risk priority number). Peer-reviewed
  12. 21 CFR 117.130, Hazard analysis; 21 CFR 117.5(e), exemption from subparts C and G for the manufacturing of dietary supplements in compliance with Part 111 and FD&C Act § 761. eCFR, current. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-117 Regulation or statute
  13. AIAG. AIAG and VDA release new automotive FMEA handbook (June 3, 2019): seven-step approach; Action Priority methodology and tables to replace RPN. aiag.org/about/news/2019/06/03/aiag-and-vda-release-new-auto Primary source

Quantum chemistry and COSMO-type solvation models

  1. Klamt A, Schüürmann G. COSMO: a new approach to dielectric screening in solvents with explicit expressions for the screening energy and its gradient. J Chem Soc Perkin Trans 2. 1993;(5):799–805. doi.org/10.1039/P29930000799 Peer-reviewed
  2. Klamt A. Conductor-like screening model for real solvents: a new approach to the quantitative calculation of solvation phenomena. J Phys Chem. 1995;99(7):2224–2235. doi.org/10.1021/j100007a062 Peer-reviewed
  3. Klamt A, Jonas V, Bürger T, Lohrenz JCW. Refinement and parametrization of COSMO-RS. J Phys Chem A. 1998;102(26):5074–5085 (atomic cavity radii used here). doi.org/10.1021/jp980017s Peer-reviewed
  4. Klamt A. COSMO-RS: From Quantum Chemistry to Fluid Phase Thermodynamics and Drug Design. Amsterdam: Elsevier; 2005. ISBN 0-444-51994-7 (σ-moment descriptors; definitions as documented by SCM, accessed October 22, 2026). scm.com/doc/COSMO-RS/Examples/Sigma_moments.html Peer-reviewed
  5. Lin S-T, Sandler SI. A priori phase equilibrium prediction from a segment contribution solvation model. Ind Eng Chem Res. 2002;41(5):899–913 (COSMO-SAC). doi.org/10.1021/ie001047w Peer-reviewed
  6. Mullins E, Oldland R, Liu YA, et al. Sigma-profile database for using COSMO-based thermodynamic methods. Ind Eng Chem Res. 2006;45(12):4389–4415 (cited for the averaging, binning and COSMO-SAC 2002 constants only; the database itself is not used on this site). doi.org/10.1021/ie060370h Peer-reviewed
  7. Hsieh C-M, Sandler SI, Lin S-T. Improvements of COSMO-SAC for vapor–liquid and liquid–liquid equilibrium predictions. Fluid Phase Equilib. 2010;297(1):90–97. doi.org/10.1016/j.fluid.2010.06.011 Peer-reviewed
  8. Hsieh C-M, Lin S-T, Vrabec J. Considering the dispersive interactions in the COSMO-SAC model for more accurate predictions of fluid phase behavior. Fluid Phase Equilib. 2014;367:109–116 (COSMO-SAC-dsp; not used here). doi.org/10.1016/j.fluid.2014.01.032 Peer-reviewed
  9. Bell IH, Mickoleit E, Hsieh C-M, et al. A benchmark open-source implementation of COSMO-SAC. J Chem Theory Comput. 2020;16(4):2635–2646. doi.org/10.1021/acs.jctc.9b01016 Peer-reviewed
  10. National Institute of Standards and Technology. COSMOSAC: benchmark open-source implementation of COSMO-SAC (source code), commit 1b82456 of July 3, 2026. MIT-style license; the UD and VT-2005 profile databases in the repository carry separate, non-commercial terms. Constants checked October 22, 2026. github.com/usnistgov/COSMOSAC Primary source
  11. Sun Q, Berkelbach TC, Blunt NS, et al. PySCF: the Python-based simulations of chemistry framework. WIREs Comput Mol Sci. 2018;8(1):e1340. doi.org/10.1002/wcms.1340 Peer-reviewed
  12. Sun Q, Zhang X, Banerjee S, et al. Recent developments in the PySCF program package. J Chem Phys. 2020;153(2):024109. doi.org/10.1063/5.0006074 Peer-reviewed
  13. Becke AD. Density-functional exchange-energy approximation with correct asymptotic behavior. Phys Rev A. 1988;38(6):3098–3100. doi.org/10.1103/PhysRevA.38.3098 Peer-reviewed
  14. Perdew JP. Density-functional approximation for the correlation energy of the inhomogeneous electron gas. Phys Rev B. 1986;33(12):8822–8824. doi.org/10.1103/PhysRevB.33.8822 Peer-reviewed
  15. Weigend F, Ahlrichs R. Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn. Phys Chem Chem Phys. 2005;7(18):3297–3305 (def2-SVP). doi.org/10.1039/b508541a Peer-reviewed
  16. York DM, Karplus M. A smooth solvation potential based on the conductor-like screening model. J Phys Chem A. 1999;103(50):11060–11079. doi.org/10.1021/jp992097l Peer-reviewed
  17. Riniker S, Landrum GA. Better informed distance geometry: using what we know to improve conformation generation. J Chem Inf Model. 2015;55(12):2562–2574 (ETKDG, RDKit). doi.org/10.1021/acs.jcim.5b00654 Peer-reviewed
  18. Halgren TA. Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J Comput Chem. 1996;17(5–6):490–519. doi.org/10.1002/(SICI)1096-987X(199604)17:5/6<490::AID-JCC1> Peer-reviewed
  19. NIST Chemistry WebBook, SRD 69. Salicylic acid (CAS 69-72-7), phase-change data: ΔfusH = 24.6 kJ/mol at 431.8 K. Accessed October 2026. webbook.nist.gov/cgi/cbook.cgi?ID=C69727&Mask=4 Primary source
  20. NIST Chemistry WebBook, SRD 69. Caffeine (CAS 58-08-2), phase-change data: ΔfusH = 21.9 kJ/mol at 510.2 K (Pinto and Diogo 2006); reported values 18.3–24.8 kJ/mol. Accessed October 2026. webbook.nist.gov/cgi/cbook.cgi?ID=C58082&Mask=4 Primary source
  21. Shalmashi A, Eliassi A. Solubility of salicylic acid in water, ethanol, carbon tetrachloride, ethyl acetate, and xylene. J Chem Eng Data. 2008;53(1):199–200. Data via the NIST TRC ThermoML archive. trc.nist.gov/ThermoML/10.1021/je7004962.html Peer-reviewed
  22. Shalmashi A, Golmohammad F. Solubility of caffeine in water, ethyl acetate, ethanol, carbon tetrachloride, methanol, chloroform, dichloromethane, and acetone between 298 and 323 K. Lat Am Appl Res. 2010;40(3):283–285 (record in US EPA HERO). hero.epa.gov/hero/index.cfm/reference/details/reference_id/1 Peer-reviewed
  23. Mehrkesh A, Karunanithi AT. New quantum chemistry-based descriptors for better prediction of melting point and viscosity of ionic liquids. Fluid Phase Equilib. 2016;427:498–503. doi.org/10.1016/j.fluid.2016.07.006 Peer-reviewed

Thermodynamics: phase-equilibrium models and methods (original papers)

  1. Raoult FM. Loi générale des tensions de vapeur des dissolvants. C R Acad Sci. 1887;104:1430–1433. web.lemoyne.edu/Giunta/classicalcs/raoultvapnote.html Peer-reviewed
  2. Margules M. Über die Zusammensetzung der gesättigten Dämpfe von Mischungen. Sitzungsber Akad Wiss Wien. 1895;104 (equation form as implemented in NIST TRC ThermoData Engine). trc.nist.gov/TDE/TDE_Help/Margules-AC-Model.htm Peer-reviewed
  3. van Laar JJ. The vapor pressure of binary mixtures. Z Phys Chem. 1910;72:723 (equation form as implemented in NIST TRC ThermoData Engine). trc.nist.gov/TDE/TDE_Help/VanLaar-AC-Model.htm Peer-reviewed
  4. Wilson GM. Vapor-liquid equilibrium. XI. A new expression for the excess free energy of mixing. J Am Chem Soc. 1964;86(2):127–130. doi.org/10.1021/ja01056a002 Peer-reviewed
  5. Renon H, Prausnitz JM. Local compositions in thermodynamic excess functions for liquid mixtures. AIChE J. 1968;14(1):135–144. doi.org/10.1002/aic.690140124 Peer-reviewed
  6. Abrams DS, Prausnitz JM. Statistical thermodynamics of liquid mixtures: a new expression for the excess Gibbs energy of partly or completely miscible systems. AIChE J. 1975;21(1):116–128. doi.org/10.1002/aic.690210115 Peer-reviewed
  7. Fredenslund A, Jones RL, Prausnitz JM. Group-contribution estimation of activity coefficients in nonideal liquid mixtures. AIChE J. 1975;21(6):1086–1099. doi.org/10.1002/aic.690210607 Peer-reviewed
  8. Magnussen T, Rasmussen P, Fredenslund A. UNIFAC parameter table for prediction of liquid-liquid equilibriums. Ind Eng Chem Process Des Dev. 1981;20(2):331–339. doi.org/10.1021/i200013a024 Peer-reviewed
  9. Weidlich U, Gmehling J. A modified UNIFAC model. 1. Prediction of VLE, hE, and γ∞. Ind Eng Chem Res. 1987;26(7):1372–1381. doi.org/10.1021/ie00067a018 Peer-reviewed
  10. Gross J, Sadowski G. Perturbed-chain SAFT: an equation of state based on a perturbation theory for chain molecules. Ind Eng Chem Res. 2001;40(4):1244–1260. doi.org/10.1021/ie0003887 Peer-reviewed
  11. McCabe WL, Thiele EW. Graphical design of fractionating columns. Ind Eng Chem. 1925;17(6):605–611. doi.org/10.1021/ie50186a023 Peer-reviewed
  12. McGarry J. Correlation and prediction of the vapor pressures of pure liquids over large pressure ranges. Ind Eng Chem Process Des Dev. 1983;22(2):313–322 (Wagner-equation vapor pressures for ethanol and water). doi.org/10.1021/i200021a023 Peer-reviewed
  13. Mullin JW. Crystallization. 4th ed. Oxford: Butterworth-Heinemann; 2001 (supersaturation and the metastable zone). Peer-reviewed

Thermodynamics: measured phase-equilibrium data (retrieved from the NIST TRC ThermoML Archive, October 2026)

  1. Lai H-S, Lin Y-F, Tu C-H. Isobaric (vapor + liquid) equilibria for the ternary system of (ethanol + water + 1,3-propanediol) and three constituent binary systems at P = 101.3 kPa. J Chem Thermodyn. 2014;68:13–19 (ethanol + water VLE and azeotrope). doi.org/10.1016/j.jct.2013.08.020 Peer-reviewed
  2. Toikka M, Samarov A, Trofimova M, et al. Solubility, liquid–liquid equilibrium and critical states for the quaternary system acetic acid–ethanol–ethyl acetate–water at 303.15 K and 313.15 K. Fluid Phase Equilib. 2014;373:72–79 (water + ethanol + ethyl acetate tie lines). doi.org/10.1016/j.fluid.2014.04.013 Peer-reviewed
  3. Grande MdC, Marschoff CM. Liquid–liquid equilibria for water + benzonitrile + ethyl acetate or + butyl acetate. J Chem Eng Data. 2005;50(4):1324–1327 (water + ethyl acetate mutual solubility, 298–333 K). doi.org/10.1021/je050051h Peer-reviewed
  4. Zhong J, Tang N, Asadzadeh B, Yan W. Measurement and correlation of solubility of theobromine, theophylline, and caffeine in water and organic solvents at various temperatures. J Chem Eng Data. 2017;62(9):2570–2577. doi.org/10.1021/acs.jced.7b00065 Peer-reviewed
  5. Dabir TO, Gaikar VG, Jayaraman S, Mukherjee S. Thermodynamic modeling studies of aqueous solubility of caffeine, gallic acid and their cocrystal in the temperature range of 303 K–363 K. Fluid Phase Equilib. 2018;456:65–76. doi.org/10.1016/j.fluid.2017.09.021 Peer-reviewed
  6. Cesari L, Namysl S, Canabady-Rochelle L, Mutelet F. Phase equilibria of phenolic compounds in water or ethanol. Fluid Phase Equilib. 2017;453:58–66 (vanillin in water). doi.org/10.1016/j.fluid.2017.09.008 Peer-reviewed
  7. Nordström FL, Rasmuson ÅC. Solubility and melting properties of salicylic acid. J Chem Eng Data. 2006;51(5):1668–1671. doi.org/10.1021/je060134d Peer-reviewed
  8. Shalmashi A, Eliassi A. Solubility of salicylic acid in water, ethanol, carbon tetrachloride, ethyl acetate, and xylene. J Chem Eng Data. 2008;53(1):199–200. doi.org/10.1021/je7004962 Peer-reviewed
  9. Lim J, Jang S, Cho HK, Shin MS, et al. Solubility of salicylic acid in pure alcohols at different temperatures. J Chem Thermodyn. 2013;57:295–300. doi.org/10.1016/j.jct.2012.09.006 Peer-reviewed
  10. Matsuda H, Kaburagi K, Matsumoto S, Kurihara K, et al. Solubilities of salicylic acid in pure solvents and binary mixtures containing cosolvent. J Chem Eng Data. 2009;54(2):480–484 (ethanol + water at 298.15 K). doi.org/10.1021/je800475d Peer-reviewed
  11. Riccardi D, Trautt Z, Bazyleva A, et al. Towards improved FAIRness of the ThermoML Archive. J Comput Chem. 2022;43(12):879–887. doi.org/10.1002/jcc.26842 Peer-reviewed
  12. Linstrom PJ, Mallard WG, eds. NIST Chemistry WebBook, NIST Standard Reference Database 69: phase-change data for caffeine (C58082), vanillin (C121335) and salicylic acid (C69727). Accessed October 22, 2026. doi.org/10.18434/T4D303 Primary source
  13. National Center for Biotechnology Information. PubChem Compound Summary for CID 8857, Ethyl acetate: solubility in water, 8.0 × 10⁴ mg/L at 25 °C (from HSDB). Accessed October 22, 2026. pubchem.ncbi.nlm.nih.gov/compound/8857 Primary source

Thermodynamics: parameter tables and software used in our calculations

  1. Kooijman HA, Taylor R. ChemSep interaction-parameter data, NRTL file labeled 'DECHEMA NRTL data @ 1 atm' (2008; Artistic License 2.0), as distributed with the thermo library. chemsep.org/ Primary source
  2. DDBST GmbH. Published parameters, modified UNIFAC (Dortmund). Accessed October 22, 2026. ddbst.com/PublishedParametersUNIFACDO.html Primary source
  3. Bell C, and contributors. thermo: Chemical Engineering Design Library (ChEDL) thermodynamics package, version 0.6.1 (UNIFAC, Dortmund UNIFAC, UNIFAC-LLE and ChemSep parameter tables; vapor pressures). github.com/CalebBell/thermo Primary source
  4. Crossref REST API, works records for every DOI cited on the Thermodynamics page (authors, title, journal, year, volume, pages), queried October 22, 2026. api.crossref.org/ Primary source

Global trade: botanical atlas, accepted names (POWO)

  1. Plants of the World Online. Nigella sativa L. (Ranunculaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:711687-1 Primary source
  2. Plants of the World Online. Rhus coriaria L. (Anacardiaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:70477-1 Primary source
  3. Plants of the World Online. Punica granatum L. (Lythraceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:554129-1 Primary source
  4. Plants of the World Online. Glycyrrhiza glabra L. (Fabaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:496941-1 Primary source
  5. Plants of the World Online. Sideroxylon spinosum L. (Sapotaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:789863-1 Primary source
  6. Plants of the World Online. Silybum marianum (L.) Gaertn. (Asteraceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:249211-1 Primary source
  7. Plants of the World Online. Olea europaea L. (Oleaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:610675-1 Primary source
  8. Plants of the World Online. Pistacia lentiscus L. (Anacardiaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:70253-1 Primary source
  9. Plants of the World Online. Crocus sativus L. (Iridaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:436688-1 Primary source
  10. Plants of the World Online. Lavandula angustifolia Mill. (Lamiaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:449008-1 Primary source
  11. Plants of the World Online. Curcuma longa L. (Zingiberaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:796451-1 Primary source
  12. Plants of the World Online. Withania somnifera (L.) Dunal (Solanaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:821709-1 Primary source
  13. Plants of the World Online. Bacopa monnieri (L.) Wettst. (Plantaginaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:1072674-2 Primary source
  14. Plants of the World Online. Boswellia serrata Roxb. (Burseraceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:127067-1 Primary source
  15. Plants of the World Online. Commiphora wightii (Arn.) Bhandari (Burseraceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:127856-1 Primary source
  16. Plants of the World Online. Andrographis paniculata (Burm.f.) Wall. ex Nees (Acanthaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:45226-1 Primary source
  17. Plants of the World Online. Ginkgo biloba L. (Ginkgoaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:262125-1 Primary source
  18. Plants of the World Online. Panax ginseng C.A.Mey. (Araliaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:91472-1 Primary source
  19. Plants of the World Online. Camellia sinensis (L.) Kuntze (Theaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:828548-1 Primary source
  20. Plants of the World Online. Kaempferia parviflora Wall. ex Baker (Zingiberaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:797188-1 Primary source
  21. Plants of the World Online. Centella asiatica (L.) Urb. (Apiaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:1197718-2 Primary source
  22. Plants of the World Online. Eurycoma longifolia Jack (Simaroubaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:813715-1 Primary source
  23. Plants of the World Online. Paullinia cupana Kunth (Sapindaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:784110-1 Primary source
  24. Plants of the World Online. Euterpe oleracea Mart. (Arecaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:666941-1 Primary source
  25. Plants of the World Online. Myrciaria dubia (Kunth) McVaugh (Myrtaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:166146-2 Primary source
  26. Plants of the World Online. Uncaria tomentosa (Willd. ex Schult.) DC. (Rubiaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:768322-1 Primary source
  27. Plants of the World Online. Lepidium meyenii Walp. (Brassicaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:286286-1 Primary source
  28. Plants of the World Online. Smallanthus sonchifolius (Poepp.) H.Rob. (Asteraceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:237510-2 Primary source
  29. Plants of the World Online. Croton lechleri Müll.Arg. (Euphorbiaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:342842-1 Primary source
  30. Plants of the World Online. Harpagophytum procumbens (Burch.) DC. (Pedaliaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:675824-1 Primary source
  31. Plants of the World Online. Prunus africana (Hook.f.) Kalkman (Rosaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:729417-1 Primary source
  32. Plants of the World Online. Hoodia gordonii (Masson) Sweet ex Decne. (Apocynaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:98342-1 Primary source
  33. Plants of the World Online. Aspalathus linearis (Burm.f.) R.Dahlgren (Fabaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:475647-1 Primary source
  34. Plants of the World Online. Sabdariffa gossypiifolia (Mill.) M.M.Hanes & R.L.Barrett (Malvaceae). Royal Botanic Gardens, Kew. Accessed October 22, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:77361038- Primary source

Global trade: botanical atlas, CITES, customs and market

  1. CITES Species+ (UNEP-WCMC and CITES Secretariat), taxon concept search under the CITES taxonomy, checked October 22, 2026. A species with no record has no CITES listing. speciesplus.net/ Primary source
  2. U.S. Customs and Border Protection. NY ruling N351895, 2025-08-29: black seed oil (with peanut and pumpkin seed oils) from Canada; HTSUS 1515.90.8190. rulings.cbp.gov/ruling/N351895 Primary source
  3. U.S. Customs and Border Protection. NY ruling N158315, 2011-04-21: argan oil from Morocco; HTSUS 1515.90.8090. rulings.cbp.gov/ruling/N158315 Primary source
  4. U.S. Customs and Border Protection. NY ruling N236981, 2013-05-01: milk thistle extract from China; HTSUS 1302.19.4040. rulings.cbp.gov/ruling/N236981 Primary source
  5. U.S. Customs and Border Protection. HQ ruling 967971, 2006-03-02: silymarin 80% (milk thistle standardized extract); revokes HQ 964338; HTSUS 2932.99.6100. rulings.cbp.gov/ruling/967971 Primary source
  6. U.S. Customs and Border Protection. HQ ruling 088327, 1991-01-29: saffron; HTSUS 0910.20.0000. rulings.cbp.gov/ruling/088327 Primary source
  7. U.S. Customs and Border Protection. HQ ruling H322257, 2023-10-20: granulated turmeric extract / standardized curcumin 95% (protest denied); HTSUS 2106.90.99. rulings.cbp.gov/ruling/H322257 Primary source
  8. U.S. Customs and Border Protection. NY ruling R04280, 2006-07-02: powdered ashwagandha, bacopa, banaba and 'asiatica' extracts from India; HTSUS 1302.19.9040. rulings.cbp.gov/ruling/R04280 Primary source
  9. CITES Species+. Boswellia serrata, taxon concept 99841: not currently listed. Checked October 22, 2026. speciesplus.net/species#/taxon_concepts/99841/legal Primary source
  10. U.S. Customs and Border Protection. NY ruling N359039, 2026-03-11: frankincense resins from Oman; HTSUS 1301.90.9190. rulings.cbp.gov/ruling/N359039 Primary source
  11. CITES Species+. Commiphora wightii, taxon concept 104877: Appendix II, effective March 5, 2026, annotation #19. Checked October 22, 2026. speciesplus.net/species#/taxon_concepts/104877/legal Primary source
  12. U.S. Customs and Border Protection. NY ruling N253401, 2014-06-02: Andrographis paniculata extract from China; HTSUS 1302.19.4040. rulings.cbp.gov/ruling/N253401 Primary source
  13. U.S. Customs and Border Protection. NY ruling d85468, 1998-12-09: dried whole Ginkgo biloba leaves from China; HTSUS 1211.90.8090. rulings.cbp.gov/ruling/d85468 Primary source
  14. U.S. Customs and Border Protection. NY ruling b80155, 1996-12-17: Ginkgo biloba extract from China; HTSUS 1302.19.4040. rulings.cbp.gov/ruling/b80155 Primary source
  15. CITES Species+. Panax ginseng, taxon concept 19207: Appendix II, only the population of the Russian Federation. Checked October 22, 2026. speciesplus.net/species#/taxon_concepts/19207/legal Primary source
  16. U.S. Customs and Border Protection. NY ruling N046674, 2008-12-16: green tea extract 95% polyphenols from China; HTSUS 2101.20.2000. rulings.cbp.gov/ruling/N046674 Primary source
  17. U.S. Customs and Border Protection. NY ruling M80570, 2006-02-28: tongkat ali powder extract from Malaysia, bulk and capsules; HTSUS 1302.19.9040 (bulk); 2106.90.9998 (capsules). rulings.cbp.gov/ruling/M80570 Primary source
  18. U.S. Customs and Border Protection. NY ruling N042120, 2009-03-01: açaí juice from Brazil; HTSUS 2009.80.6035. rulings.cbp.gov/ruling/N042120 Primary source
  19. U.S. Customs and Border Protection. NY ruling N106022, 2010-05-25: frozen camu camu fruit from Brazil; HTSUS 0811.90.8080. rulings.cbp.gov/ruling/N106022 Primary source
  20. U.S. Customs and Border Protection. NY ruling N356055, 2025-12-10: camu camu fruit powder from Brazil; HTSUS 1106.30.4000. rulings.cbp.gov/ruling/N356055 Primary source
  21. U.S. Customs and Border Protection. NY ruling a89824, 1996-12-11: cat's claw (una de gato) extract; HTSUS 1302.19.4040. rulings.cbp.gov/ruling/a89824 Primary source
  22. U.S. Customs and Border Protection. NY ruling N309185, 2020-02-11: maca powder from Peru; HTSUS 2106.90.9898. rulings.cbp.gov/ruling/N309185 Primary source
  23. CITES Species+. Harpagophytum procumbens, taxon concept 21493: not currently listed. Checked October 22, 2026. speciesplus.net/species#/taxon_concepts/21493/legal Primary source
  24. U.S. Customs and Border Protection. NY ruling c86018, 1998-04-06: liquid devil's claw from the United Kingdom; HTSUS 1302.19.4040. rulings.cbp.gov/ruling/c86018 Primary source
  25. CITES Species+. Prunus africana, taxon concept 22086: Appendix II, annotation #4 (amended, effective March 5, 2026). Checked October 22, 2026. speciesplus.net/species#/taxon_concepts/22086/legal Primary source
  26. CITES Species+. Hoodia gordonii, taxon concept 16793: Appendix II (Hoodia spp.), annotation #9. Checked October 22, 2026. speciesplus.net/species#/taxon_concepts/16793/legal Primary source
  27. U.S. Customs and Border Protection. NY ruling L86868, 2005-08-11: Hoodia gordonii powder from South Africa; HTSUS 1211.90.9090. rulings.cbp.gov/ruling/L86868 Primary source
  28. U.S. Customs and Border Protection. HQ ruling H320527, 2021-11-12: rooibos tea from South Africa; modifies NY N280540; HTSUS 1211.90.9280. rulings.cbp.gov/ruling/H320527 Primary source
  29. U.S. Fish and Wildlife Service, Office of Law Enforcement. Public Bulletin PB 26-001: CITES CoP20 Amendments to Appendices I and II (January 13, 2026; effective March 5, 2026). fws.gov/sites/default/files/documents/2026-01/ole-public-bul Primary source

Market: competitive landscape (company filings, releases and websites, read October 22, 2026)

  1. Givaudan SA. Givaudan completes the acquisition and delisting of Naturex (media release). September 18, 2018. givaudan.com/print/15531 Primary source
  2. dsm-firmenich AG. Integrated Annual Report 2025, Note 4 Segment information (published February 20, 2026). Net sales 2025: Perfumery & Beauty €3,760M; Taste, Texture & Health €3,146M; Health, Nutrition & Care €2,102M; continuing operations €9,034M; discontinued operations €3,487M. annualreport.dsm-firmenich.com/2025/financial-statements/con Primary source
  3. dsm-firmenich AG. Integrated Annual Report 2025, About us (dual headquarters in Kaiseraugst, Switzerland, and Maastricht, the Netherlands; listed on Euronext Amsterdam). annualreport.dsm-firmenich.com/2025/our-company/about-us.htm Primary source
  4. International Flavors & Fragrances Inc. Form 10-K for the fiscal year ended December 31, 2025, filed February 27, 2026 (SEC EDGAR, accession 0000051253-26-000006). Net sales $10,890 million; Health & Biosciences segment net sales $2,283 million. sec.gov/Archives/edgar/data/51253/000005125326000006/iff-202 Primary source
  5. 桂林莱茵生物科技股份有限公司 (Guilin Layn Natural Ingredients Corp.). 2025年年度报告 (2025 Annual Report), Shenzhen Stock Exchange stock code 002166, disclosed March 31, 2026. Operating revenue RMB 2,043,836,317.70 (+15.36%); plant-extract products RMB 1,967,015,301.88 (96.24%). disc.static.szse.cn/disc/disk03/finalpage/2026-03-31/636043e Primary source
  6. Martin Bauer Group. Company website, home page (family business; botanical products since 1930). martin-bauer.com/en/ Primary source
  7. Martin Bauer Group. Imprint (MB-Holding GmbH & Co. KG, Dutendorfer Straße 5-7, 91487 Vestenbergsgreuth). martin-bauer.com/en/imprint Primary source
  8. Indena S.p.A. About us (since 1921; main production site in Settala, near Milan). indena.com/about-us/ Primary source
  9. Sabinsa Corporation. About us (founded 1988; East Windsor, NJ; self-reported patents and company-funded clinical studies). sabinsa.com/about-us/ Primary source
  10. Lonza Group AG. Lonza to divest Capsules & Health Ingredients business to Lone Star Funds (release). Basel, March 6, 2026. Enterprise value CHF 2.3 billion (USD 3 billion); Lonza retains a 40% stake. capsugel.com/news/2026-03-06-18-05 Primary source
  11. Lonza Group AG. Q3 2026 business update. Basel, October 14, 2026 (CHI transaction expected to close before the end of 2026). lonza.com/news/2026-10-14-06-30 Primary source
  12. Lonza Capsules & Health Ingredients (Capsugel). Company website, home page. capsugel.com/ Primary source
  13. SGS SA. 2025 full year results (ad hoc announcement). February 11, 2026. Sales CHF 6,945 million; organic growth 5.6%. sgs.com/news/2026/02/2025-full-year-results Primary source
  14. SGS SA. About SGS (company description; Baar, Switzerland address). sgs.com/en/our-company/about-sgs Primary source
  15. Alkemist Labs. About (founded 1997; Garden Grove, CA; identity by HPTLC and microscopy; ISO/IEC 17025 flexible scope). alkemist.com/about/ Primary source
  16. A2LA. Growth Through Accreditation: Alkemist Labs case study (Garden Grove, California; ISO/IEC 17025). 2023. Certificate number 3851.01 from the laboratory's published A2LA scope. a2la.org/wp-content/uploads/2024/01/A2LA-Case-Study-Alkemist Primary source
  17. Enveda. Enveda raises $311 million from leading AI and biotech investors … (press release). September 23, 2026. Series E led by Catalio Capital Management; more than $845 million raised since inception; three candidates in human trials. enveda.com/news/enveda-raises-311-million/ Primary source
  18. Enveda. Press page (Series D, $150 million, September 4, 2025). enveda.com/press/ Primary source
  19. Brightseed. Company website, home page (Forager and Hummingbird AI). brightseedbio.com/ Primary source
  20. Nuritas. Company website, home page (Magnifier AI platform; Dublin). nuritas.com/ Primary source

Market: documented quality gaps (FDA citations, adulteration)

  1. Gafner S, Upton R, Blumenthal M, Khan I. Fifteen years of the ABC-AHP-NCNPR Botanical Adulterants Prevention Program: what have we learned? Oxford International Conference on the Science of Botanicals (ICSB), April 23, 2026. Abstract. egrove.olemiss.edu/icsb/2026_ICSB/Schedule/29/ Primary source

Quantum chemistry: PubChem structure records

  1. National Center for Biotechnology Information. PubChem Compound Summary for CID 962, Water. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/962 Primary source
  2. National Center for Biotechnology Information. PubChem Compound Summary for CID 702, Ethanol. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/702 Primary source
  3. National Center for Biotechnology Information. PubChem Compound Summary for CID 180, Acetone. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/180 Primary source
  4. National Center for Biotechnology Information. PubChem Compound Summary for CID 8058, Hexane. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/8058 Primary source
  5. National Center for Biotechnology Information. PubChem Compound Summary for CID 6344, Dichloromethane. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/6344 Primary source
  6. National Center for Biotechnology Information. PubChem Compound Summary for CID 6212, Chloroform. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/6212 Primary source
  7. National Center for Biotechnology Information. PubChem Compound Summary for CID 5943, Carbon Tetrachloride. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/5943 Primary source
  8. National Center for Biotechnology Information. PubChem Compound Summary for CID 16666, (-)-Menthol. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/16666 Primary source
  9. National Center for Biotechnology Information. PubChem Compound Summary for CID 440917, (+)-Limonene. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/440917 Primary source

Company and founder

Companies and accreditation records

  1. Givaudan. Full-year 2025 results: group sales CHF 7,472M. givaudan.com/print/2745501
  2. Indena. Company Profile 2025: 900+ employees; 4 production sites. indena.com/indena_files/2025/05/Indena_CompanyProfile_2025.p
  3. Martin Bauer Group. Company website: consolidated turnover of more than €600 million (undated). martin-bauer.com/en/martin-bauer/
  4. Natural Alternatives International. Form 10-K for FY ended Jun 30, 2026: net sales $142.5M; gross margin ~6.3%. sec.gov/Archives/edgar/data/787253/000143774926031343/naii20
  5. A2LA. Eurofins Botanical Testing US (Brea, CA) certificate 2918.07, valid to Dec 31, 2027; Alkemist Labs (Garden Grove, CA) certificate 3851.01 (accredited since 2015). a2la.org/accreditation-case-study-alkemist-labs/

Founder public record

  1. Mehrkesh A. Optimization-based design and analysis of tailor-made ionic liquids. Ph.D. dissertation, Civil Engineering, University of Colorado (Denver), 2015. arXiv:1612.06407. arxiv.org/abs/1612.06407
  2. US 10,168,080 B2 and US 10,465,950 B2 (Expired – Fee Related); US 11,608,460 B2 (Active); JP7189322B2 (Active); JP6898355B2 (Expired – Fee Related); EP3810578B1 (in force only in DE per event log). All assigned to Yazaki Corp. patents.google.com/patent/US11608460B2/en
  3. Semantic Scholar profile A. Mehrkesh (author 3470516): 18 indexed items (including preprints, the dissertation and one 2010 article-in-press withdrawn under Elsevier policy), 403 citations, h-index 9. Retrieved October 22, 2026. semanticscholar.org/author/3470516

Facilities, safety codes and sourcing

  1. NFPA 70, National Electrical Code (hazardous classified locations, Articles 500–505) (NFPA codes and standards page). nfpa.org/codes-and-standards/nfpa-70-standard-development/70 Primary source
  2. NFPA 652, Standard on the Fundamentals of Combustible Dust (dust hazard analysis) (NFPA codes and standards page). nfpa.org/codes-and-standards/nfpa-652-standard-development/6 Primary source
  3. CDC and NIH. Biosafety in Microbiological and Biomedical Laboratories (BMBL), 6th edition. 2020. cdc.gov/labs/bmbl/index.html Primary source
  4. Los Angeles Fire Department CUPA. Hazardous Materials: Hazardous Materials Business Plan thresholds (55 gal, 500 lb, 200 cu ft; Health and Safety Code § 25507) and CERS submission. lafd.org/hazardous-materials Primary source
  5. CalEPA. California Environmental Reporting System (CERS). cers.calepa.ca.gov/ Primary source
  6. CITES Secretariat. What is CITES? (Convention on International Trade in Endangered Species of Wild Fauna and Flora). cites.org/eng/disc/what.php Primary source
  7. Convention on Biological Diversity. The Nagoya Protocol on Access and Benefit-sharing. cbd.int/abs/ Primary source

Founder: degree and research profiles

  1. Google Scholar. Profile of Amirhossein Mehrkesh: 534 citations, h-index 10. Retrieved October 22, 2026. scholar.google.com/citations?user=_EsxTqMAAAAJ Primary source

Founder: peer-reviewed publications

  1. Mehrkesh A, Karunanithi AT. Life-cycle perspectives on aquatic ecotoxicity of common ionic liquids. Environ Sci Technol. 2016;50:6814–6821. doi.org/10.1021/acs.est.5b04721 Peer-reviewed
  2. Farahipour R, Mehrkesh A, Karunanithi AT. A systematic screening methodology towards exploration of ionic liquids for CO2 capture processes. Chem Eng Sci. 2016;145:126–132. doi.org/10.1016/j.ces.2015.12.015 Peer-reviewed
  3. Mehrkesh A, Tavakoli T, Hatamipour MS. Effect of operating conditions of the extraction process on the physical properties of lubricating oil. J Appl Solution Chem Model. 2015;4:1–6. doi.org/10.6000/1929-5030.2015.04.01.1 Peer-reviewed
  4. Mehrkesh A, Karunanithi AT. New perspective on computer aided molecular design. Comput Aided Chem Eng. 2014;34:369–374. doi.org/10.1016/B978-0-444-63433-7.50046-8 Peer-reviewed
  5. Mehrkesh A, Karunanithi AT. Energetic ionic materials: how green are they? A comparative life cycle assessment study. ACS Sustain Chem Eng. 2013;1:448–455. doi.org/10.1021/sc3001383 Peer-reviewed
  6. FakhrHoseini SM, Tavakkoli T, Hatamipour MS, Mehrkesh AH. Mathematical modeling of RDC column in extraction of base oil and computing of the energy saving. J Chem Technol Biotechnol. 2013;88:1289–1294. doi.org/10.1002/jctb.3974 Peer-reviewed
  7. Mehrkesh AH, Hajimirzaee S, Hatamipour MS. A generalized correlation for characterization of lubricating base-oils from their viscosities. Chin J Chem Eng. 2010;18:642–647. doi.org/10.1016/S1004-9541(10)60269-8 Peer-reviewed
  8. Hatamipour MS, Fakhr Hoseini SM, Tavakkoli T, Mehrkesh AH. An energy-saving opportunity in producing lubricating oil using mixed-solvent in simulated rotary disc contacting (RDC) extraction tower. Energy. 2010;35:2130–2133. doi.org/10.1016/j.energy.2010.01.031 Peer-reviewed

Founder: granted patents (assigned to Yazaki Corporation)

  1. Mehrkesh A, Maat S, Tamas GG. Eutectic mixtures of ionic liquids in absorption chillers. US Patent 10,168,080 B2, granted January 1, 2019. Assignee: Yazaki Corporation. Google Patents status (October 22, 2026): expired, fee related. patents.google.com/patent/US10168080B2/en Primary source
  2. Mehrkesh A, Maat S, Tamas GG. Guanidinium-based ionic liquids in absorption chillers. US Patent 10,465,950 B2, granted November 5, 2019. Assignee: Yazaki Corporation. Google Patents status (October 22, 2026): expired, fee related. patents.google.com/patent/US10465950B2/en Primary source
  3. Mehrkesh A, Maat S, Tamas GG. A eutectic mixture of ionic liquids in an absorption chiller. JP Patent 6898355 B2, granted July 7, 2021. Assignee: Yazaki Corporation. Google Patents status (October 22, 2026): expired, fee related. patents.google.com/patent/JP6898355B2/en Primary source
  4. Raychaudhuri S, Mehrkesh A, Tamas GG, Maat S, Coronas Salcedo A, Salavera Muñoz D, Prieto Gonzalez J. Ionic liquid additive for use as absorbent in absorption chillers. JP Patent 7189322 B2, granted December 13, 2022. Assignee: Yazaki Corporation. Google Patents status (October 22, 2026): active. patents.google.com/patent/JP7189322B2/en Primary source
  5. Raychaudhuri S, Mehrkesh A, Tamas GG, Maat S, Coronas Salcedo A, Salavera Muñoz D, Prieto Gonzalez J. Ionic liquid additives for use as an absorbent in absorption chillers. EP 3810578 B1, granted January 4, 2023. Proprietor: Yazaki Corporation. Google Patents status (October 22, 2026): active; event log records a 2026 renewal fee in Germany and lapses in most other designated states. patents.google.com/patent/EP3810578B1/en Primary source

Founder: Persian medical heritage, history of medicine

  1. Richter-Bernburg L. Gondēšāpur ii. History and medical school. Encyclopaedia Iranica, vol. XI, fasc. 2, pp. 131–135; published December 15, 2002, last updated September 25, 2018. iranicaonline.org/articles/gondesapur/gondesapur-ii-history- Book
  2. Shahbazi AS. Gondēšāpur i. The city. Encyclopaedia Iranica, published December 15, 2002; last updated September 25, 2018. Locates the site at the ruins south of Šāhābād, 14 km southeast of Dezful, Khuzestan. iranicaonline.org/articles/gondesapur-i Book
  3. Shoja MM, Tubbs RS. The history of anatomy in Persia. J Anat. 2007;210(4):359-78. doi:10.1111/j.1469-7580.2007.00711.x. PMID 17428200. pubmed.ncbi.nlm.nih.gov/17428200/ Peer-reviewed
  4. Daneshfard B, Naseri M, Ghaffari F. Medical education in the first university of the world, the Jundishapur Academy. J Family Med Prim Care. 2022;11(8):4267-4272. doi:10.4103/jfmpc.jfmpc_2449_21. PMID 36353031. pubmed.ncbi.nlm.nih.gov/36353031/ Peer-reviewed
  5. Nasser M, Tibi A, Savage-Smith E. Ibn Sina's Canon of Medicine: 11th century rules for assessing the effects of drugs. James Lind Library (reprint of J R Soc Med 2009;102:78–80). jameslindlibrary.org/articles/ibn-sinas-canon-of-medicine-11 Peer-reviewed
  6. Shoja MM, Tubbs RS, Ardalan MR, et al. Anatomy of the cranial nerves in medieval Persian literature: Esmail Jorjani (AD 1042-1137) and The treasure of the Khwarazm shah. Neurosurgery. 2007;61(6):1325-30; discussion 1330-1. doi:10.1227/01.neu.0000306113.00916.7d. PMID 18162914. pubmed.ncbi.nlm.nih.gov/18162914/ Peer-reviewed
  7. Moattar F, Shams Ardekani MR, Ghannadi A. The life of jorjani: one of the persian pioneers of medical encyclopedia compiling: on the occasion of his 1000th birthday anniversary (434, a.h. - 1434, a.h.). Iran Red Crescent Med J. 2013;15(9):763-6. doi:10.5812/ircmj.8080. PMID 24616781. pubmed.ncbi.nlm.nih.gov/24616781/ Peer-reviewed
  8. Abdel-Halim RE. The role of Ibn Sina (Avicenna)'s medical poem in the transmission of medical knowledge to medieval Europe. Urol Ann. 2014;6(1):1-12. doi:10.4103/0974-7796.127010. PMID 24669114. pubmed.ncbi.nlm.nih.gov/24669114/ Peer-reviewed
  9. Mosaffa-Jahromi M. Properties Related to Bile as Viewed in Makhzan ol-Adviya. Iran J Med Sci. 2016;41(3 Suppl):S50. PMID 27840516. pubmed.ncbi.nlm.nih.gov/27840516/ Peer-reviewed
  10. Parsa E, Mokaberinejad R, Khodadoost M, et al. Appetite Reducing Herbal Drugs from the Perspective of Avicenna and Aghili in Iranian Traditional Medicine (Persian medicine). Curr Drug Discov Technol. 2019;16(4):400-405. doi:10.2174/1570163815666180704093151. PMID 29972103. pubmed.ncbi.nlm.nih.gov/29972103/ Peer-reviewed
  11. Natural Earth. 1:110m physical vectors, Land (version 4.0.0), public domain; used through the world-atlas land-110m TopoJSON file for the map of places on this page. naturalearthdata.com/downloads/110m-physical-vectors/ Primary source

Investor information: industry benchmark

  1. Natural Alternatives International, Inc. Annual report on Form 10-K for the fiscal year ended June 30, 2026, filed September 28, 2026 (accession 0001437749-26-031343). Gross profit $8,997,000; net sales $142,515,000 (SEC XBRL company facts). sec.gov/Archives/edgar/data/787253/000143774926031343/ Primary source

Privacy notice: service providers

  1. Cloudflare. Cloudflare cookies (developer documentation). Retrieved October 22, 2026. developers.cloudflare.com/fundamentals/reference/policies-co Primary source
  2. Cloudflare, Inc. Privacy policy. Retrieved October 22, 2026. cloudflare.com/privacypolicy/ Primary source
  3. Resend. Privacy policy. Retrieved October 22, 2026. resend.com/legal/privacy-policy Primary source

Academy courses

Academy: COA science, regulations and harmonised guidelines

  1. ICH. Q3D(R2) Guideline for Elemental Impurities. Final version adopted April 26, 2022 (Tables A.2.1, A.2.2, 5.1; Appendices 1 and 4). database.ich.org/sites/default/files/Q3D-R2_Guideline_Step4_ Agency guidance
  2. ICH. Q3C(R9) Impurities: Guideline for Residual Solvents. Current Step 4 version dated January 24, 2024 (copy hosted by PMDA). pmda.go.jp/files/000268163.pdf Agency guidance
  3. ICH. Q3C(R10) EWG Work Plan, July 25, 2026 (revised monographs for DMF, dichloromethane and ethylene glycol; Step 4 planned March 2027). database.ich.org/sites/default/files/ICH53_Q3C%28R10%29_EWG_ Agency guidance
  4. Commission Regulation (EU) 2023/915 of 25 April 2023 on maximum levels for certain contaminants in food, Annex I (entries 1.1.14–1.1.15, 1.2.17–1.2.19, 2.4.4–2.4.10, 3.1.28, 3.2.21, 3.3.2, 5.1.16). EUR-Lex, read October 23, 2026. eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32023R0915 Regulation or statute
  5. Commission Implementing Regulation (EU) 2023/2782 of 14 December 2023 laying down the methods of sampling and analysis for the control of the levels of mycotoxins in food. EUR-Lex. eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32023R2782 Regulation or statute
  6. 40 CFR 180.151, Ethylene oxide; tolerances for residues. eCFR, read October 23, 2026. ecfr.gov/current/title-40/chapter-I/subchapter-E/part-180/su Regulation or statute
  7. U.S. FDA. Guidance for Industry: Action Levels for Poisonous or Deleterious Substances in Human Food and Animal Feed (August 2000; content current as of September 20, 2018). Aflatoxin, foods: 20 ppb (CPG Sec. 555.400). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  8. California OEHHA. Proposition 65: Lead. Safe harbor levels: NSRL 15 µg/day (oral); MADL 0.5 µg/day. oehha.ca.gov/proposition-65/chemicals/lead Regulation or statute
  9. WHO Expert Committee on Specifications for Pharmaceutical Preparations. Model certificate of analysis. WHO Technical Report Series No. 1010 (2018), Annex 4. extranet.who.int/prequal/sites/default/files/document_files/ Agency guidance

Academy: COA science, USP general chapters (USP 38–NF 33 Second Supplement text)

  1. USP. ⟨561⟩ Articles of Botanical Origin (Pesticide Residue Analysis, Table 4; Test for Aflatoxins; Table 5 elemental limits). USP 38–NF 33 2S text as mirrored; confirm in the current USP–NF. drugfuture.com/Pharmacopoeia/usp38/data/v38332/usp38nf33s2_c Primary source
  2. USP. ⟨565⟩ Botanical Extracts (Residual Solvents; Pesticide Residues). USP 38–NF 33 2S text as mirrored. drugfuture.com/Pharmacopoeia/usp38/data/v38332/usp38nf33s2_c Primary source
  3. USP. ⟨467⟩ Residual Solvents (classes; Options 1 and 2; headspace GC procedures). USP 38–NF 33 2S text as mirrored. drugfuture.com/Pharmacopoeia/usp38/data/v38332/usp38nf33s2_c Primary source
  4. USP. ⟨233⟩ Elemental Impurities—Procedures (ICP-OES and ICP-MS; validation criteria). USP 38–NF 33 2S text as mirrored. drugfuture.com/Pharmacopoeia/usp38/data/v38332/usp38nf33s2_c Primary source
  5. USP. ⟨232⟩ Elemental Impurities—Limits (introduction: dietary supplements addressed in ⟨2232⟩). USP 38–NF 33 2S text as mirrored. drugfuture.com/Pharmacopoeia/usp38/data/v38332/usp38nf33s2_c Primary source
  6. Marles R. Pesticide residues (USP stakeholder forum presentation, slides dated 2018–2019): limit formulas AM/100B and AME/100B. usp.org/sites/default/files/usp/document/stakeholder-forum/2 Primary source
  7. GMP Platform. USP revised Chapter ⟨561⟩ Articles of Botanical Origin published in Pharmacopeial Forum 51(4) (news item). gmp-platform.com/article_detail.html?id=32631 Third-party estimate

Academy: COA science, measurement, structures and laboratory practice

  1. ILAC. ILAC-G8:09/2019 Guidelines on Decision Rules and Statements of Conformity (Sections 1–5; Table 1). Quotes ISO/IEC 17025:2017 clauses 7.1.3, 7.8.3.1 and 7.8.6. ilac.org/?ddownload=122722 Agency guidance
  2. JCGM 106:2012 Evaluation of measurement data: the role of measurement uncertainty in conformity assessment (published as OIML G 1-106, 2012). Expression (9); Example 1; ISO 14253-1 guard band example. oiml.org/en/files/pdf_g/g001-106-e12.pdf Agency guidance
  3. PubChem. Aflatoxin B1 (CID 186907), B2 (CID 2724360), G1 (CID 2724361), G2 (CID 2724362) and ochratoxin A (CID 442530): isomeric SMILES. Read October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/186907 Primary source
  4. Eurofins US. Multiresidue pesticides analysis (USP ⟨561⟩): "The majority of the pesticides listed in USP <561> are analyzed by GC-MS/MS and LC-MS/MS." Read October 23, 2026. eurofinsus.com/food-testing/resources/multiresidue-pesticide Third-party estimate
  5. Finnish Food Authority. Maximum residue levels for ethylene oxide (residue definition: sum of ethylene oxide and 2-chloroethanol expressed as ethylene oxide; Regulation (EC) No 396/2005). Page updated October 22, 2021. ruokavirasto.fi/en/foodstuffs/food-sector/contaminants-and-r Primary source

Academy: genomes and species — species and genome size

  1. Govaerts R, Nic Lughadha E, Black N, Turner R, Paton A. The World Checklist of Vascular Plants, a continuously updated resource for exploring global plant diversity. Sci Data. 2021;8:215. doi.org/10.1038/s41597-021-00997-6 Peer-reviewed
  2. Royal Botanic Gardens, Kew. Plant DNA C-values database, release 7.1 (April 2019): 12,273 species, 10,770 angiosperms (landing page accessed October 23, 2026). cvalues.science.kew.org/ Primary source
  3. Pellicer J, Leitch IJ. The Plant DNA C-values database (release 7.1): an updated online repository of plant genome size data for comparative studies. New Phytol. 2020;226(2):301–305. doi.org/10.1111/nph.16261 Peer-reviewed
  4. Marks RA, Hotaling S, Frandsen PB, VanBuren R. Representation and participation across 20 years of plant genome sequencing. Nat Plants. 2021;7(12):1571–1578. doi.org/10.1038/s41477-021-01031-8 Peer-reviewed
  5. Greilhuber J, Doležel J, Lysák MA, Bennett MD. The origin, evolution and proposed stabilization of the terms 'genome size' and 'C-value' to describe nuclear DNA contents. Ann Bot. 2005;95(1):255–260. doi.org/10.1093/aob/mci019 Peer-reviewed
  6. Doležel J, Bartoš J, Voglmayr H, Greilhuber J. Nuclear DNA content and genome size of trout and human. Cytometry A. 2003;51(2):127–128 (1 pg = 978 Mbp). doi.org/10.1002/cyto.a.10013 Peer-reviewed
  7. Pellicer J, Fay MF, Leitch IJ. The largest eukaryotic genome of them all? Bot J Linn Soc. 2010;164(1):10–15. doi.org/10.1111/j.1095-8339.2010.01072.x Peer-reviewed
  8. Fernández P, Amice R, Bruy D, et al. A 160 Gbp fork fern genome shatters size record for eukaryotes. iScience. 2024;27(6):109889. doi.org/10.1016/j.isci.2024.109889 Peer-reviewed
  9. Fleischmann A, Michael TP, Rivadavia F, et al. Evolution of genome size and chromosome number in the carnivorous plant genus Genlisea (Lentibulariaceae), with a new estimate of the minimum genome size in angiosperms. Ann Bot. 2014;114(8):1651–1663. doi.org/10.1093/aob/mcu189 Peer-reviewed
  10. Charalambous I, Ioannou N, Kyratzis AC, Kourtellarides D, et al. Genome size variation across a Cypriot Fabeae tribe germplasm collection. Plants (Basel). 2023;12(7):1469 (internal standards and their 1C values). doi.org/10.3390/plants12071469 Peer-reviewed
  11. Al-Qurainy F, Gaafar AZ, Khan S, Nadeem M, et al. Estimation of genome size in the endemic species Reseda pentagyna and the locally rare species Reseda lutea using comparative analyses of flow cytometry and k-mer approaches. Plants (Basel). 2021;10(7):1362 (2C formula; 1 pg = 978 Mbp). doi.org/10.3390/plants10071362 Peer-reviewed

Academy: genomes and species — polyploidy and Acorus

  1. Wood TE, Takebayashi N, Barker MS, Mayrose I, Greenspoon PB, Rieseberg LH. The frequency of polyploid speciation in vascular plants. PNAS. 2009;106(33):13875–13879. doi.org/10.1073/pnas.0811575106 Peer-reviewed
  2. Jiao Y, Wickett NJ, Ayyampalayam S, et al. Ancestral polyploidy in seed plants and angiosperms. Nature. 2011;473(7345):97–100. doi.org/10.1038/nature09916 Peer-reviewed
  3. Sokoloff DD, Degtjareva GV, Valiejo-Roman CM, et al. Kazakhstan has an unexpected diversity of medicinal plants of the genus Acorus (Acoraceae) and could be a cradle of the triploid species A. calamus. Plants (Basel). 2024;13(14):1978. doi.org/10.3390/plants13141978 Peer-reviewed
  4. European Medicines Agency, HMPC. Public statement on the use of herbal medicinal products containing asarone. EMEA/HMPC/139215/2005, November 23, 2005. ema.europa.eu/en/documents/scientific-guideline/public-state Agency guidance
  5. Electronic Code of Federal Regulations. 21 CFR 189.110, Calamus and its derivatives. Current as of October 20, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-189/su Regulation or statute
  6. Plants of the World Online (POWO). Acorus americanus (Raf.) Raf., Acorus calamus L. and Acorus verus (L.) Raf., accepted; API search accessed October 23, 2026. powo.science.kew.org/ Primary source
  7. PubChem. β-Asarone, CID 5281758; α-asarone, CID 636822 (isomeric SMILES retrieved October 23, 2026). pubchem.ncbi.nlm.nih.gov/compound/5281758 Primary source

Academy: genomes and species — chloroplast genomes and barcodes

  1. Daniell H, Lin CS, Yu M, Chang WJ. Chloroplast genomes: diversity, evolution, and applications in genetic engineering. Genome Biol. 2016;17:134. doi.org/10.1186/s13059-016-1004-2 Peer-reviewed
  2. NCBI RefSeq chloroplast genome records NC_006290.1, NC_027456.1, NC_026447.1, NC_028703.1, NC_016430.1, NC_024038.1, NC_034683.1, NC_021423.1, NC_029434.1, NC_020019.1, NC_016986.1, NC_007407.1, NC_010093.1, NC_042886.1, NC_047245.1, NC_083133.1, NC_000932.1 and NC_001879.2 (efetch, October 23, 2026); statistics computed by src/modules/acidn/compute/plastome_stats.py. ncbi.nlm.nih.gov/nuccore/NC_006290.1 Primary source
  3. CBOL Plant Working Group. A DNA barcode for land plants. PNAS. 2009;106(31):12794–12797. doi.org/10.1073/pnas.0905845106 Peer-reviewed
  4. Nguyen VB, Linh Giang VN, Waminal NE, et al. Comprehensive comparative analysis of chloroplast genomes from seven Panax species and development of an authentication system based on species-unique single nucleotide polymorphism markers. J Ginseng Res. 2020;44(1):135–144. doi.org/10.1016/j.jgr.2018.06.003 Peer-reviewed

Academy: genomes and species — genome assemblies and sequencing

  1. Mochida K, Sakurai T, Seki H, et al. Draft genome assembly and annotation of Glycyrrhiza uralensis, a medicinal legume. Plant J. 2017;89(2):181–194. doi.org/10.1111/tpj.13385 Peer-reviewed
  2. Xu Z, Wang G, Wang Q, et al. A near-complete genome assembly of Catharanthus roseus and insights into its vinblastine biosynthesis and high susceptibility to the Huanglongbing pathogen. Plant Commun. 2023;4(6):100661. doi.org/10.1016/j.xplc.2023.100661 Peer-reviewed
  3. Shen Q, Zhang L, Liao Z, et al. The genome of Artemisia annua provides insight into the evolution of Asteraceae family and artemisinin biosynthesis. Mol Plant. 2018;11(6):776–788. doi.org/10.1016/j.molp.2018.03.015 Peer-reviewed
  4. Liao B, Shen X, Xiang L, et al. Allele-aware chromosome-level genome assembly of Artemisia annua reveals the correlation between ADS expansion and artemisinin yield. Mol Plant. 2022;15(8):1310–1328. doi.org/10.1016/j.molp.2022.05.013 Peer-reviewed
  5. Guo L, Winzer T, Yang X, et al. The opium poppy genome and morphinan production. Science. 2018;362(6412):343–347. doi.org/10.1126/science.aat4096 Peer-reviewed
  6. Kim NH, Jayakodi M, Lee SC, et al. Genome and evolution of the shade-requiring medicinal herb Panax ginseng. Plant Biotechnol J. 2018;16(11):1904–1917. doi.org/10.1111/pbi.12926 Peer-reviewed
  7. Xia EH, Zhang HB, Sheng J, et al. The tea tree genome provides insights into tea flavor and independent evolution of caffeine biosynthesis. Mol Plant. 2017;10(6):866–877. doi.org/10.1016/j.molp.2017.04.002 Peer-reviewed
  8. Wei C, Yang H, Wang S, et al. Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality. PNAS. 2018;115(18):E4151–E4158. doi.org/10.1073/pnas.1719622115 Peer-reviewed
  9. Guan R, Zhao Y, Zhang H, et al. Draft genome of the living fossil Ginkgo biloba. GigaScience. 2016;5:49. doi.org/10.1186/s13742-016-0154-1 Peer-reviewed
  10. Liu H, Wang X, Wang G, et al. The nearly complete genome of Ginkgo biloba illuminates gymnosperm evolution. Nat Plants. 2021;7(6):748–756. doi.org/10.1038/s41477-021-00933-x Peer-reviewed
  11. Lander ES, Waterman MS. Genomic mapping by fingerprinting random clones: a mathematical analysis. Genomics. 1988;2(3):231–239. doi.org/10.1016/0888-7543(88)90007-9 Peer-reviewed

Academy: genomes and species — biosynthetic pathways

  1. Mercke P, Bengtsson M, Bouwmeester HJ, Posthumus MA, Brodelius PE. Molecular cloning, expression, and characterization of amorpha-4,11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L. Arch Biochem Biophys. 2000;381(2):173–180. doi.org/10.1006/abbi.2000.1962 Peer-reviewed
  2. Teoh KH, Polichuk DR, Reed DW, Nowak G, Covello PS. Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a cytochrome P450 with a key role in the biosynthesis of the antimalarial sesquiterpene lactone artemisinin. FEBS Lett. 2006;580(5):1411–1416. doi.org/10.1016/j.febslet.2006.01.065 Peer-reviewed
  3. Ro DK, Paradise EM, Ouellet M, et al. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature. 2006;440(7086):940–943. doi.org/10.1038/nature04640 Peer-reviewed
  4. Zhang Y, Teoh KH, Reed DW, et al. The molecular cloning of artemisinic aldehyde Δ11(13) reductase and its role in glandular trichome-dependent biosynthesis of artemisinin in Artemisia annua. J Biol Chem. 2008;283(31):21501–21508. doi.org/10.1074/jbc.M803090200 Peer-reviewed
  5. Teoh KH, Polichuk DR, Reed DW, Covello PS. Molecular cloning of an aldehyde dehydrogenase implicated in artemisinin biosynthesis in Artemisia annua. Botany. 2009;87(6):635–642. doi.org/10.1139/b09-032 Peer-reviewed
  6. Olsson ME, Olofsson LM, Lindahl AL, et al. Localization of enzymes of artemisinin biosynthesis to the apical cells of glandular secretory trichomes of Artemisia annua L. Phytochemistry. 2009;70(9):1123–1128. doi.org/10.1016/j.phytochem.2009.07.009 Peer-reviewed
  7. Czechowski T, Larson TR, Catania TM, Harvey D, Brown GD, Graham IA. Artemisia annua mutant impaired in artemisinin synthesis demonstrates importance of nonenzymatic conversion in terpenoid metabolism. PNAS. 2016;113(52):15150–15155. doi.org/10.1073/pnas.1611567113 Peer-reviewed
  8. Paddon CJ, Westfall PJ, Pitera DJ, et al. High-level semi-synthetic production of the potent antimalarial artemisinin. Nature. 2013;496(7446):528–532. doi.org/10.1038/nature12051 Peer-reviewed
  9. Winzer T, Gazda V, He Z, et al. A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapine. Science. 2012;336(6089):1704–1708. doi.org/10.1126/science.1220757 Peer-reviewed
  10. Li Y, Smolke CD. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast. Nat Commun. 2016;7:12137. doi.org/10.1038/ncomms12137 Peer-reviewed
  11. Thompson JD, Chalchat JC, Michet A, Linhart YB, Ehlers B. Qualitative and quantitative variation in monoterpene co-occurrence and composition in the essential oil of Thymus vulgaris chemotypes. J Chem Ecol. 2003;29(4):859–880. doi.org/10.1023/A:1022927615442 Peer-reviewed
  12. PubChem isomeric SMILES (retrieved October 23, 2026): farnesyl diphosphate CID 445713; amorpha-4,11-diene CID 11052747; artemisinic alcohol CID 15983960; artemisinic aldehyde CID 15983961; artemisinic acid CID 10922465; dihydroartemisinic aldehyde CID 10857031; dihydroartemisinic acid CID 11020893; artemisinin CID 68827; (S)-scoulerine CID 439654; noscapine CID 275196. pubchem.ncbi.nlm.nih.gov/compound/68827 Primary source

Academy: History of botanical medicine, records and catalogues

  1. Penn Museum. Medical Tablet, object CBS14221, Nippur, ca. 2200 BCE (Early Dynastic IIIB per the record). Collections database. Accessed October 23, 2026. penn.museum/collections/object.php?irn=218008 Primary source
  2. Geller MJ. An apothecary's handbook. Le Journal des Médecines Cunéiformes. 2020;35:1–33. discovery-pp.ucl.ac.uk/10118275/1/GELLER%20JMC%2035%20p.%201 Peer-reviewed
  3. British Museum. Reconstructing a 2,500-year-old medical encyclopaedia (research project page). Accessed October 23, 2026. britishmuseum.org/research/projects/reconstructing-2500-year Primary source
  4. Simko K. Ancient healthcare fit for a king. British Museum blog, November 30, 2021. britishmuseum.org/blog/ancient-healthcare-fit-king Primary source
  5. Leipzig University Library. Ebers Papyrus (permanent exhibition: contents, date, acquisition). Accessed October 23, 2026. ub.uni-leipzig.de/en/about-us/exhibitions/permanent-exhibiti Primary source
  6. Dias DA, Urban S, Roessner U. A historical overview of natural products in drug discovery. Metabolites. 2012;2(2):303–336. doi:10.3390/metabo2020303. doi.org/10.3390/metabo2020303 Peer-reviewed
  7. Zhao Z, Guo P, Brand E. A concise classification of bencao (materia medica). Chin Med. 2018;13:18. doi:10.1186/s13020-018-0176-y. doi.org/10.1186/s13020-018-0176-y Peer-reviewed
  8. UNESCO Memory of the World, Asia-Pacific register: Ben Cao Gang Mu (Compendium of Materia Medica), Library of China Academy of Chinese Medical Sciences; inscribed on the International Register in 2011. mowcaparchives.org/mwc/inct/detl/11 Primary source
  9. Kobayashi A, Uefuji M, Yasumo W. History and progress of Japanese acupuncture. Evid Based Complement Alternat Med. 2010;7(3):359. doi:10.1093/ecam/nem155. doi.org/10.1093/ecam/nem155 Peer-reviewed
  10. Kwon CY, Shen C, Yoshino T, et al. Integrating east Asian traditional medicine into national dementia care: a comparative policy analysis of China, Japan, and South Korea. Integr Med Res. 2026;15:101290. doi:10.1016/j.imr.2026.101290. doi.org/10.1016/j.imr.2026.101290 Peer-reviewed
  11. Uneda K, Kawai Y, Kaneko A, et al. Analysis of clinical factors associated with Kampo formula-induced pseudoaldosteronism based on self-reported information from the Japanese Adverse Drug Event Report database. PLoS One. 2024;19:e0296450. doi:10.1371/journal.pone.0296450. doi.org/10.1371/journal.pone.0296450 Peer-reviewed
  12. Encyclopaedia Britannica. Charaka. Last updated June 22, 2026. britannica.com/biography/Charaka Peer-reviewed
  13. Encyclopaedia Britannica. Sushruta (flourished c. 6th century BCE). britannica.com/biography/Sushruta Peer-reviewed
  14. Wujastyk D, et al. The Suśruta Project: the Suśrutasaṃhitā, a medical encyclopedia composed in Sanskrit two millennia ago. Accessed October 23, 2026. sushrutaproject.github.io/ Peer-reviewed
  15. Totelin L. When foods become remedies in ancient Greece: the curious case of garlic and other substances. J Ethnopharmacol. 2015;167:30–37. doi:10.1016/j.jep.2014.08.018. doi.org/10.1016/j.jep.2014.08.018 Peer-reviewed
  16. Encyclopaedia Britannica. Theophrastus (c. 372–c. 287 BCE). britannica.com/biography/Theophrastus Peer-reviewed
  17. Encyclopaedia Britannica. Pedanius Dioscorides (De materia medica, five books, about 77 CE). britannica.com/biography/Pedanius-Dioscorides Peer-reviewed
  18. Encyclopaedia Britannica. Pliny the Elder. Last updated October 1, 2026. britannica.com/biography/Pliny-the-Elder Peer-reviewed
  19. Encyclopaedia Britannica. Galen. Last updated September 1, 2026. britannica.com/biography/Galen Peer-reviewed
  20. Austrian Commission for UNESCO. Vienna Dioscurides Manuscript, Austrian National Library; Memory of the World, inscribed 1997. unesco.at/en/communication/documentary-heritage/memory-of-th Primary source
  21. Edriss H, Rosales BN, Nugent C, et al. Islamic medicine in the Middle Ages. Am J Med Sci. 2017;354(3):223–229. doi:10.1016/j.amjms.2017.03.021. pubmed.ncbi.nlm.nih.gov/28918826/ Peer-reviewed
  22. Compier AH. Rhazes in the renaissance of Andreas Vesalius. Med Hist. 2012;56(1):3–25. doi:10.1017/S0025727300000259. pubmed.ncbi.nlm.nih.gov/23752981/ Peer-reviewed
  23. Nasser M, Tibi A, Savage-Smith E. Ibn Sina's Canon of Medicine: 11th century rules for assessing the effects of drugs. J R Soc Med. 2009;102(2):78–80. doi:10.1258/jrsm.2008.08k040. pubmed.ncbi.nlm.nih.gov/19208873/ Peer-reviewed
  24. Arráez-Aybar LA, Bueno-López JL, Raio N. Toledo School of Translators and their influence on anatomical terminology. Ann Anat. 2015;198:21–33. doi:10.1016/j.aanat.2014.12.003. pubmed.ncbi.nlm.nih.gov/25667112/ Peer-reviewed
  25. Botanical Research Institute of Texas. Native American Ethnobotany Database (D. E. Moerman): filtered searches by group and use category, queried October 23, 2026; history page for earlier editions. naeb.brit.org/about Primary source

Academy: History of botanical medicine, from plant to drug

  1. Tu Y. Artemisinin: a gift from traditional Chinese medicine to the world. Nobel Lecture, December 7, 2015. In: Les Prix Nobel 2015. nobelprize.org/prizes/medicine/2015/tu/lecture/ Primary source
  2. Nobel Prize Outreach. The Nobel Prize in Physiology or Medicine 2015 (one half to Tu Youyou; one half jointly to William C. Campbell and Satoshi Ōmura). nobelprize.org/prizes/medicine/2015/summary/ Primary source
  3. Krishnamurti C, Rao SSCC. The isolation of morphine by Serturner. Indian J Anaesth. 2016;60(11):861–862. doi:10.4103/0019-5049.193696. doi.org/10.4103/0019-5049.193696 Peer-reviewed
  4. Achan J, Talisuna AO, Erhart A, et al. Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malar J. 2011;10:144. doi:10.1186/1475-2875-10-144. doi.org/10.1186/1475-2875-10-144 Peer-reviewed
  5. Bowman WC. Neuromuscular block. Br J Pharmacol. 2006;147(Suppl 1):S277–S286. doi:10.1038/sj.bjp.0706404. doi.org/10.1038/sj.bjp.0706404 Peer-reviewed
  6. King H. Curare alkaloids. Part I. Tubocurarine. J Chem Soc. 1935:1381. doi:10.1039/JR9350001381. doi.org/10.1039/JR9350001381 Peer-reviewed
  7. Holmstedt B, Wassén SH, Schultes RE. Jaborandi: an interdisciplinary appraisal. J Ethnopharmacol. 1979;1(1):3–21. doi:10.1016/0378-8741(79)90014-x. doi.org/10.1016/0378-8741(79)90014-x Peer-reviewed
  8. Proudfoot A. The early toxicology of physostigmine: a tale of beans, great men and egos. Toxicol Rev. 2006;25(2):99–138. doi:10.2165/00139709-200625020-00004. doi.org/10.2165/00139709-200625020-00004 Peer-reviewed
  9. Ramsay RR, Tipton KF. Assessment of enzyme inhibition: a review with examples from the development of monoamine oxidase and cholinesterase inhibitory drugs. Molecules. 2017;22(7):1192. doi:10.3390/molecules22071192. doi.org/10.3390/molecules22071192 Peer-reviewed
  10. Noble RL. The discovery of the vinca alkaloids: chemotherapeutic agents against cancer. Biochem Cell Biol. 1990;68(12):1344–1351. doi:10.1139/o90-197. doi.org/10.1139/o90-197 Peer-reviewed
  11. Talib WH, Daoud S, Mahmod AI, et al. Plants as a source of anticancer agents: from bench to bedside. Molecules. 2022;27(15):4818. doi:10.3390/molecules27154818. doi.org/10.3390/molecules27154818 Peer-reviewed
  12. Plants of the World Online, Royal Botanic Gardens, Kew. Catharanthus roseus (L.) G.Don, Apocynaceae: native to eastern and southern Madagascar. Accessed October 23, 2026. powo.science.kew.org/taxon/urn:lsid:ipni.org:names:77880-1 Primary source
  13. Brendler T, van Wyk BE. A historical, scientific and commercial perspective on the medicinal use of Pelargonium sidoides (Geraniaceae). J Ethnopharmacol. 2008;119(3):420–433. doi:10.1016/j.jep.2008.07.037. doi.org/10.1016/j.jep.2008.07.037 Peer-reviewed
  14. Reihling HCW. Bioprospecting the African Renaissance: the new value of muthi in South Africa. J Ethnobiol Ethnomed. 2008;4:9. doi:10.1186/1746-4269-4-9. doi.org/10.1186/1746-4269-4-9 Peer-reviewed
  15. Blom WA, Abrahamse SL, Bradford R, et al. Effects of 15-d repeated consumption of Hoodia gordonii purified extract on safety, ad libitum energy intake, and body weight in healthy, overweight women: a randomized controlled trial. Am J Clin Nutr. 2011;94(5):1171–1181. doi:10.3945/ajcn.111.020321. doi.org/10.3945/ajcn.111.020321 Peer-reviewed
  16. Stone E. An account of the success of the bark of the willow in the cure of agues. Philos Trans R Soc Lond. 1763:195–200. doi:10.1098/rstl.1763.0033. doi.org/10.1098/rstl.1763.0033 Peer-reviewed
  17. Wood JN. From plant extract to molecular panacea: a commentary on Stone (1763) 'An account of the success of the bark of the willow in the cure of the agues'. Philos Trans R Soc B. 2015;370:20140317. doi:10.1098/rstb.2014.0317. doi.org/10.1098/rstb.2014.0317 Peer-reviewed
  18. Smith S. Digoxin, a new digitalis glucoside. J Chem Soc. 1930:508–510. doi:10.1039/JR9300000508. doi.org/10.1039/JR9300000508 Peer-reviewed
  19. Khandelwal R, Vagha JD, Meshram RJ, Patel A. A comprehensive review on unveiling the journey of digoxin: past, present, and future perspectives. Cureus. 2024;16(3):e56755. doi:10.7759/cureus.56755. doi.org/10.7759/cureus.56755 Peer-reviewed
  20. Heinrich M, Teoh HL. Galanthamine from snowdrop: the development of a modern drug against Alzheimer's disease from local Caucasian knowledge. J Ethnopharmacol. 2004;92(2–3):147–162. doi:10.1016/j.jep.2004.02.012. doi.org/10.1016/j.jep.2004.02.012 Peer-reviewed
  21. Singh A, Choudhary R, Ganguly S. Podophyllin in dermatology: revisiting a historical drug. Indian Dermatol Online J. 2022;13(1):167–171. doi:10.4103/idoj.idoj_225_21. doi.org/10.4103/idoj.idoj_225_21 Peer-reviewed
  22. Stähelin HF, von Wartburg A. The chemical and biological route from podophyllotoxin glucoside to etoposide: ninth Cain memorial Award lecture. Cancer Res. 1991;51(1):5–15. pubmed.ncbi.nlm.nih.gov/1988106/ Peer-reviewed
  23. Roy P. Global pharma and local science: the untold tale of reserpine. Indian J Psychiatry. 2018;60(Suppl 2):S277–S283. doi:10.4103/psychiatry.IndianJPsychiatry_444_17. doi.org/10.4103/psychiatry.IndianJPsychiatry_444_17 Peer-reviewed
  24. U.S. FDA, Drugs@FDA data (openFDA): NDA 022268, Coartem (artemether and lumefantrine), original approval April 7, 2009. api.fda.gov/drug/drugsfda.json?search=application_number:NDA Primary source
  25. U.S. FDA, Drugs@FDA data (openFDA): NDA 018768, VePesid (etoposide), original approval November 10, 1983. api.fda.gov/drug/drugsfda.json?search=application_number:NDA Primary source
  26. U.S. FDA, Drugs@FDA data (openFDA): NDA 020262, Taxol (paclitaxel), original approval December 29, 1992. api.fda.gov/drug/drugsfda.json?search=application_number:NDA Primary source
  27. U.S. FDA, Drugs@FDA data (openFDA): NDA 021169, Razadyne (galantamine hydrobromide), original approval February 28, 2001. api.fda.gov/drug/drugsfda.json?search=application_number:NDA Primary source
  28. U.S. FDA, Drugs@FDA data (openFDA): NDA 020357, Glucophage (metformin hydrochloride), original approval March 3, 1995. api.fda.gov/drug/drugsfda.json?search=application_number:NDA Primary source
  29. National Toxicology Program. Report on Carcinogens, Fifteenth Edition: Aristolochic Acids (known to be human carcinogens; first listed in 2011). ntp.niehs.nih.gov/sites/default/files/ntp/roc/content/profil Primary source

Academy: History of botanical medicine, statistics, policy and law

  1. Sarbadhikary P, George BP. A review on traditionally used African medicinal plant Annickia chlorantha, its phytochemistry, and anticancer potential. Plants (Basel). 2022;11(17):2293 (reproduces Newman and Cragg's category shares). doi:10.3390/plants11172293. doi.org/10.3390/plants11172293 Peer-reviewed
  2. World Health Organization. WHO global report on traditional and complementary medicine 2019. Geneva: WHO; 2019. ISBN 978-92-4-151543-6. Tables 5.1–5.6. iris.who.int/items/0dc0d605-b1c3-4350-b62e-984b47688442 Primary source
  3. Secretariat of the Convention on Biological Diversity. History of the Convention (opened for signature June 5, 1992; in force December 29, 1993). Accessed October 23, 2026. cbd.int/history/ Regulation or statute
  4. Secretariat of the Convention on Biological Diversity. Parties to the Nagoya Protocol (adopted October 29, 2010; in force October 12, 2014; 143 Parties). Accessed October 23, 2026. cbd.int/abs/nagoya-protocol/signatories/ Regulation or statute
  5. World Intellectual Property Organization. WIPO Treaty on Intellectual Property, Genetic Resources and Associated Traditional Knowledge, adopted in Geneva on May 24, 2024. wipo.int/treaties/en/ip/gratk/ Regulation or statute
  6. 31 CFR 560.201: Prohibited importation of goods or services from Iran. eCFR, current as of October 2026. ecfr.gov/current/title-31/subtitle-B/chapter-V/part-560/subp Regulation or statute

Academy: History of botanical medicine, PubChem structure records

  1. PubChem Compound Summary for CID 439503, Salicin. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/439503 Primary source
  2. PubChem Compound Summary for CID 2244, Aspirin. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/2244 Primary source
  3. PubChem Compound Summary for CID 5288826, Morphine. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/5288826 Primary source
  4. PubChem Compound Summary for CID 3034034, Quinine. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/3034034 Primary source
  5. PubChem Compound Summary for CID 68911, Artemether. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/68911 Primary source
  6. PubChem Compound Summary for CID 10607, Podophyllotoxin. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/10607 Primary source
  7. PubChem Compound Summary for CID 36462, Etoposide. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/36462 Primary source
  8. PubChem Compound Summary for CID 5983, Physostigmine. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/5983 Primary source
  9. PubChem Compound Summary for CID 9651, (-)-Galantamine. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/9651 Primary source
  10. PubChem Compound Summary for CID 6000, Tubocurarine. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/6000 Primary source
  11. PubChem Compound Summary for CID 5910, Pilocarpine. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/5910 Primary source
  12. PubChem Compound Summary for CID 5770, Reserpine. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/5770 Primary source
  13. PubChem Compound Summary for CID 13342, Vinblastine. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/13342 Primary source
  14. PubChem Compound Summary for CID 2724385, Digoxin. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/2724385 Primary source

Academy: Microbiology of botanicals, pharmacopeial and regulatory sources

  1. United States Pharmacopeia. General Chapter ⟨2021⟩ Microbial Enumeration Tests—Nutritional and Dietary Supplements. USP 38–NF 33 (2015), Second Supplement; Pharmacopeial Forum 38(2). A 2025 version is retitled “—Dietary Ingredients and Dietary Supplements” (DOI landing page). doi.org/10.31003/USPNF_M99965_02_01 Primary source
  2. United States Pharmacopeia. General Chapter ⟨2022⟩ Microbiological Procedures for Absence of Specified Microorganisms—Nutritional and Dietary Supplements. USP 38–NF 33 (2015), Second Supplement. 2025 version: DOI landing page. doi.org/10.31003/USPNF_M99966_03_01 Primary source
  3. United States Pharmacopeia. General Chapter ⟨2023⟩ Microbiological Attributes of Nonsterile Nutritional and Dietary Supplements, Tables 2 and 3. USP 38–NF 33 (2015), Second Supplement; earlier text USP 35–NF 30 (official May 1, 2012). 2025 version: DOI landing page. doi.org/10.31003/USPNF_M99967_02_01 Primary source
  4. United States Pharmacopeia. General Chapters ⟨61⟩ Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests; ⟨62⟩ Tests for Specified Microorganisms; ⟨1111⟩ Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use. USP 38–NF 33 (2015). Primary source
  5. United States Pharmacopeia. Commentary, USP–NF 2025 Issue 2 (February 3, 2025): ⟨72⟩ Respiration-Based and ⟨73⟩ ATP Bioluminescence-Based Microbiological Methods for the Detection of Contamination in Short-Life Products; ⟨1071⟩ Rapid Microbiological Methods for the Detection of Contamination in Short-Life Products—A Risk-Based Approach. uspnf.com/sites/default/files/usp_pdf/EN/USPNF/usp-nf-commen Primary source
  6. American Herbal Products Association. Recommended Microbial Limits for Botanical Ingredients and Finished Botanical Products, comparison table (June 2022). ahpa.org/Files/Document%20Library/AHPAGuidancePolicies/AHPA_ Third-party estimate
  7. U.S. FDA. Bacteriological Analytical Manual, Chapter 3: Aerobic Plate Count (January 2026 edition). Zhang G, Ferguson M, Blodgett RJ. fda.gov/food/laboratory-methods-food/bam-chapter-3-aerobic-p Primary source
  8. U.S. FDA. Bacteriological Analytical Manual, Chapter 5: Salmonella (October 2026 edition), section C.10, Spices. Andrews WH, Wang H, Jacobson A, Ge B, Zhang G, Hammack T. fda.gov/food/laboratory-methods-food/bam-chapter-5-salmonell Primary source
  9. U.S. FDA, Center for Food Safety and Applied Nutrition. Draft Risk Profile: Pathogens and Filth in Spices (2013). Executive Summary and Table 4.3. fda.gov/media/86724/download Primary source
  10. U.S. FDA. Updated FDA Risk Profile: Pathogens and Filth in Spices (2017), Retail Survey Key Findings, Tables 1 and 2. fda.gov/media/108126/download Primary source
  11. U.S. FDA. Fish and Fishery Products Hazards and Controls Guidance, Appendix 4: Bacterial Pathogen Growth and Inactivation, Tables A-1, A-3 and A-4. fda.gov/media/80390/download Agency guidance
  12. 21 CFR 179.26, Ionizing radiation for the treatment of food. eCFR, current as of October 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-179/su Regulation or statute
  13. U.S. EPA. News release: EPA finalizes protections for workers and communities from cancer-causing ethylene oxide (Interim Decision for Ethylene Oxide), January 14, 2025. epa.gov/newsreleases/epa-finalizes-protections-workers-and-c Primary source
  14. European Commission, DG SANTE. Food and Feed Crisis Coordinators meeting of 9 October 2020 on high levels of ethylene oxide detected in sesame seeds imported from India: summary record. ec.europa.eu/food/system/files/2021-01/rasff_ethylene-oxide- Primary source
  15. EFSA BIOHAZ Panel. Guidance on the requirements for the development of microbiological criteria. EFSA J. 2017;15(11):e05052. doi.org/10.2903/j.efsa.2017.5052 Agency guidance

Academy: Microbiology of botanicals, peer-reviewed studies

  1. Faliarizao NT, Fanfan J, Randriamiarintsoa N, Siddiq M, Bergholz TM, Dolan KD. Modeling the combined impact of water activity and temperature on Salmonella Montevideo thermal inactivation on dried chili peppers. J Food Sci. 2025;90:e70201. doi.org/10.1111/1750-3841.70201 Peer-reviewed
  2. Alvarenga VO, Campagnollo FB, Pia AKR, et al. Quantifying the responses of three Bacillus cereus strains in isothermal conditions and during spray drying of different carrier agents. Front Microbiol. 2018;9:1113. doi.org/10.3389/fmicb.2018.01113 Peer-reviewed
  3. Stevenson A, Cray JA, Williams JP, et al. Is there a common water-activity limit for the three domains of life? ISME J. 2015;9:1333–1351. doi.org/10.1038/ismej.2014.219 Peer-reviewed
  4. Setlow P. Spores of Bacillus subtilis: their resistance to and killing by radiation, heat and chemicals. J Appl Microbiol. 2006;101:514–525. doi.org/10.1111/j.1365-2672.2005.02736.x Peer-reviewed
  5. Setlow P. Germination of spores of Bacillus species: what we know and do not know. J Bacteriol. 2014;196:1297–1305. doi.org/10.1128/jb.01455-13 Peer-reviewed
  6. Foster JW, Hall HK. Adaptive acidification tolerance response of Salmonella typhimurium. J Bacteriol. 1990;172:771–778. doi.org/10.1128/jb.172.2.771-778.1990 Peer-reviewed
  7. Leyer GJ, Johnson EA. Acid adaptation induces cross-protection against environmental stresses in Salmonella typhimurium. Appl Environ Microbiol. 1993;59:1842–1847. doi.org/10.1128/aem.59.6.1842-1847.1993 Peer-reviewed
  8. Lin J, Smith MP, Chapin KC, Baik HS, Bennett GN, Foster JW. Mechanisms of acid resistance in enterohemorrhagic Escherichia coli. Appl Environ Microbiol. 1996;62:3094–3100. doi.org/10.1128/aem.62.9.3094-3100.1996 Peer-reviewed
  9. Li Z, Huang Z, Gu P. Response of Escherichia coli to acid stress: mechanisms and applications—a narrative review. Microorganisms. 2024;12:1774. doi.org/10.3390/microorganisms12091774 Peer-reviewed
  10. Flemming HC, Wingender J. The biofilm matrix. Nat Rev Microbiol. 2010;8:623–633. doi.org/10.1038/nrmicro2415 Peer-reviewed
  11. Ceri H, Olson ME, Stremick C, Read RR, Morck D, Buret A. The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol. 1999;37:1771–1776. doi.org/10.1128/jcm.37.6.1771-1776.1999 Peer-reviewed
  12. Mah TF, O'Toole GA. Mechanisms of biofilm resistance to antimicrobial agents. Trends Microbiol. 2001;9:34–39. doi.org/10.1016/s0966-842x(00)01913-2 Peer-reviewed
  13. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999;284:1318–1322. doi.org/10.1126/science.284.5418.1318 Peer-reviewed
  14. Joseph B, Otta SK, Karunasagar I, Karunasagar I. Biofilm formation by Salmonella spp. on food contact surfaces and their sensitivity to sanitizers. Int J Food Microbiol. 2001;64:367–372. doi.org/10.1016/s0168-1605(00)00466-9 Peer-reviewed
  15. Li L, Mendis N, Trigui H, Oliver JD, Faucher SP. The importance of the viable but non-culturable state in human bacterial pathogens. Front Microbiol. 2014;5:258. doi.org/10.3389/fmicb.2014.00258 Peer-reviewed
  16. Oliver JD. The viable but nonculturable state in bacteria. J Microbiol. 2005;43(Spec No):93–100. PMID 15765062. pubmed.ncbi.nlm.nih.gov/15765062/ Peer-reviewed
  17. Oliver JD. Recent findings on the viable but nonculturable state in pathogenic bacteria. FEMS Microbiol Rev. 2010;34:415–425. doi.org/10.1111/j.1574-6976.2009.00200.x Peer-reviewed
  18. Wesche AM, Gurtler JB, Marks BP, Ryser ET. Stress, sublethal injury, resuscitation, and virulence of bacterial foodborne pathogens. J Food Prot. 2009;72:1121–1138. doi.org/10.4315/0362-028x-72.5.1121 Peer-reviewed
  19. Balaban NQ, Merrin J, Chait R, Kowalik L, Leibler S. Bacterial persistence as a phenotypic switch. Science. 2004;305:1622–1625. doi.org/10.1126/science.1099390 Peer-reviewed
  20. Lewis K. Persister cells, dormancy and infectious disease. Nat Rev Microbiol. 2007;5:48–56. doi.org/10.1038/nrmicro1557 Peer-reviewed
  21. Emerson JB, Adams RI, Román CMB, et al. Schrödinger's microbes: tools for distinguishing the living from the dead in microbial ecosystems. Microbiome. 2017;5:86. doi.org/10.1186/s40168-017-0285-3 Peer-reviewed
  22. Nocker A, Cheung CY, Camper AK. Comparison of propidium monoazide with ethidium monoazide for differentiation of live vs. dead bacteria by selective removal of DNA from dead cells. J Microbiol Methods. 2006;67:310–320. doi.org/10.1016/j.mimet.2006.04.015 Peer-reviewed
  23. Berney M, Hammes F, Bosshard F, Weilenmann HU, Egli T. Assessment and interpretation of bacterial viability by using the LIVE/DEAD BacLight Kit in combination with flow cytometry. Appl Environ Microbiol. 2007;73:3283–3290. doi.org/10.1128/aem.02750-06 Peer-reviewed
  24. Singhal N, Kumar M, Kanaujia PK, Virdi JS. MALDI-TOF mass spectrometry: an emerging technology for microbial identification and diagnosis. Front Microbiol. 2015;6:791. doi.org/10.3389/fmicb.2015.00791 Peer-reviewed
  25. Janda JM, Abbott SL. 16S rRNA gene sequencing for bacterial identification in the diagnostic laboratory: pluses, perils, and pitfalls. J Clin Microbiol. 2007;45:2761–2764. doi.org/10.1128/jcm.01228-07 Peer-reviewed
  26. D'Oca MC, Di Noto AM, Bartolotta A, et al. Assessment of contamination of Salmonella spp. in imported black pepper and sesame seed and salmonella inactivation by gamma irradiation. Ital J Food Saf. 2021;10:8914. doi.org/10.4081/ijfs.2021.8914 Peer-reviewed
  27. Gonzales-Barron U, Zwietering MH, Butler F. A novel derivation of a within-batch sampling plan based on a Poisson-gamma model characterising low microbial counts in foods. Int J Food Microbiol. 2013;161:84–96. doi.org/10.1016/j.ijfoodmicro.2012.11.026 Peer-reviewed

Academy: multi-objective ingredient design (methods)

  1. Derringer G, Suich R. Simultaneous optimization of several response variables. J Qual Technol. 1980;12(4):214–219. doi.org/10.1080/00224065.1980.11980968 Peer-reviewed
  2. NIST/SEMATECH e-Handbook of Statistical Methods, section 5.5.3.2.2, Multiple responses: the desirability approach (accessed October 23, 2026). itl.nist.gov/div898/handbook/pri/section5/pri5322.htm Primary source
  3. Deb K, Pratap A, Agarwal S, Meyarivan T. A fast and elitist multiobjective genetic algorithm: NSGA-II. IEEE Trans Evol Comput. 2002;6(2):182–197. doi.org/10.1109/4235.996017 Peer-reviewed
  4. Zitzler E, Deb K, Thiele L. Comparison of multiobjective evolutionary algorithms: empirical results. Evol Comput. 2000;8(2):173–195 (test functions T1–T3, Eq. 7–9). doi.org/10.1162/106365600568202 Peer-reviewed
  5. Das I, Dennis JE. A closer look at drawbacks of minimizing weighted sums of objectives for Pareto set generation in multicriteria optimization problems. Struct Optim. 1997;14(1):63–69. doi.org/10.1007/BF01197559 Peer-reviewed
  6. Das I, Dennis JE. Normal-boundary intersection: a new method for generating the Pareto surface in nonlinear multicriteria optimization problems. SIAM J Optim. 1998;8(3):631–657. doi.org/10.1137/S1052623496307510 Peer-reviewed
  7. Haimes YY, Lasdon LS, Wismer DA. On a bicriterion formulation of the problems of integrated system identification and system optimization. IEEE Trans Syst Man Cybern. 1971;SMC-1(3):296–297. doi.org/10.1109/TSMC.1971.4308298 Peer-reviewed
  8. Kennedy MC, O'Hagan A. Predicting the output from a complex computer code when fast approximations are available. Biometrika. 2000;87(1):1–13. doi.org/10.1093/biomet/87.1.1 Peer-reviewed
  9. Le Gratiet L. Recursive co-kriging model for design of computer experiments with multiple levels of fidelity. arXiv:1210.0686 (states the Kennedy–O'Hagan autoregressive model). arxiv.org/abs/1210.0686 Peer-reviewed
  10. Settles B. Active Learning Literature Survey. Computer Sciences Technical Report 1648, University of Wisconsin–Madison; 2009. minds.wisconsin.edu/handle/1793/60660 Peer-reviewed

Academy: multi-objective ingredient design (data, models and their limits)

  1. Gueffai A, Gonzalez-Serrano DJ, Christodoulou MC, et al. Phenolics from defatted black cumin seeds (Nigella sativa L.): ultrasound-assisted extraction optimization, comparison, and antioxidant activity. Biomolecules. 2022;12(9):1311 (Table 1). doi.org/10.3390/biom12091311 Peer-reviewed
  2. Brookes ST, Whitely E, Egger M, Smith GD, Mulheran PA, Peters TJ. Subgroup analyses in randomized trials: risks of subgroup-specific analyses; power and sample size for the interaction test. J Clin Epidemiol. 2004;57(3):229–236. doi.org/10.1016/j.jclinepi.2003.08.009 Peer-reviewed
  3. Walters WH, Wilder EI. Fabrication and errors in the bibliographic citations generated by ChatGPT. Sci Rep. 2023;13:14045. doi.org/10.1038/s41598-023-41032-5 Peer-reviewed

Academy: multi-objective ingredient design (regulation)

  1. CITES Secretariat. The CITES Appendices (Appendix I: trade in specimens prohibited except when the purpose of the import is not commercial; Appendix II: trade controlled through export permits). Accessed October 23, 2026. cites.org/eng/app/index.php Primary source

Academy: Other ingredients, U.S. regulations and FDA guidance

  1. 21 CFR 101.4 (Food; designation of ingredients), paragraphs (a)(1), (a)(2), (g) and (h); 21 CFR 101.36 (Nutrition labeling of dietary supplements), paragraphs (b)(3), (d) and (g). eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-101 Regulation or statute
  2. 21 CFR 172.410 (calcium silicate), 172.480 (silicon dioxide), 172.863 (salts of fatty acids), 172.868 (ethyl cellulose), 172.870 (hydroxypropyl cellulose), 172.874 (hydroxypropyl methylcellulose); 173.55 (polyvinylpyrrolidone). eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-172 Regulation or statute
  3. 21 CFR 182.1217 (calcium phosphate), 182.1745 (sodium carboxymethylcellulose); 184.1090 (stearic acid), 184.1191 (calcium carbonate), 184.1229 (calcium stearate), 184.1330 (acacia), 184.1400 (lecithin), 184.1440 (magnesium stearate), 184.1444 (maltodextrin), 184.1978 (carnauba wax); 168.122 (lactose). eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-184 Regulation or statute
  4. 21 CFR 73.200 (synthetic iron oxide) and 73.575 (titanium dioxide), color additives exempt from certification. eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-A/part-73 Regulation or statute
  5. FDA. Guidance for Industry: Considerations Regarding Substances Added to Foods, Including Beverages and Dietary Supplements. January 2014; docket FDA-2009-D-0542; section III.B and footnote 2. fda.gov/media/87680/download Agency guidance
  6. FDA. Dietary Supplement Labeling Guide, Chapter IV: Nutrition Labeling (April 2005). fda.gov/food/dietary-supplements/dietary-supplement-labeling Agency guidance
  7. FDA. Food Allergies: What You Need to Know (major food allergens; FASTER Act; labeling examples). Content current as of March 11, 2026. fda.gov/food/nutrition-food-labeling-and-critical-foods/food Primary source
  8. Federal Register. Filing of Color Additive Petition From Environmental Defense Fund, et al.; Request To Revoke Color Additive Listing for Use of Titanium Dioxide in Food. 88 FR 27818, May 3, 2023 (FR Doc. 2023-09366). federalregister.gov/documents/2023/05/03/2023-09366/filing-o Regulation or statute

Academy: Other ingredients, EPA pesticide inert ingredients

  1. 40 CFR 152.3 (definitions: active ingredient, inert ingredient). eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-40/chapter-I/subchapter-E/part-152/su Regulation or statute
  2. 40 CFR 180 Subpart D, 180.910–180.960 (exemptions from the requirement of a tolerance). eCFR XML, up to date as of October 22, 2026; table rows counted October 24, 2026. ecfr.gov/current/title-40/chapter-I/subchapter-E/part-180/su Regulation or statute
  3. U.S. EPA. Pesticide Registration Notice 97-6: Use of Term “Inert” in the Label Ingredients Statement. epa.gov/pesticide-registration/prn-97-6-use-term-inert-label Agency guidance

Academy: Other ingredients, pharmacopeias, international guidance and data

  1. Pharmacopoeial Discussion Group. Powder Flow, harmonized text (003-2003PDG), corresponding to USP <1174>, Ph. Eur. 2.9.36 and JP; Tables 1 and 2. Published by PMDA. pmda.go.jp/files/000233963.pdf Primary source
  2. EDQM. Harmonisation status for excipient monographs (PDG), as of September 1, 2026. edqm.eu/harmonisation-status-for-excipient-monographs-pdg- Primary source
  3. EMA. Guideline on declaration of herbal substances and herbal preparations in herbal medicinal products/traditional herbal medicinal products. EMA/HMPC/CHMP/CVMP/287539/2005 Rev.1, March 11, 2010. ema.europa.eu/en/documents/scientific-guideline/guideline-de Agency guidance
  4. Food Safety Authority of Ireland. Titanium Dioxide is No Longer Authorised as a Food Additive in the EU (Commission Regulation (EU) 2022/63). News, July 15, 2022. fsai.ie/news-and-alerts/latest-news/titanium-dioxide-is-no-l Primary source
  5. NIH Office of Dietary Supplements. Dietary Supplement Label Database (DSLD), API v9 (version 9.5.0, May 2026; index of September 25, 2025). Random sample of 600 on-market labels retrieved October 24, 2026. dsld.od.nih.gov/ Primary source
  6. Li J, Wu Y. Lubricants in pharmaceutical solid dosage forms. Lubricants. 2014;2(1):21–43. doi.org/10.3390/lubricants2010021 Peer-reviewed
  7. Desai PM, Liew CV, Heng PWS. Review of disintegrants and the disintegration phenomena. J Pharm Sci. 2016;105(9):2545–2555. doi.org/10.1016/j.xphs.2015.12.019 Peer-reviewed

Academy: botanical identity — U.S. law and FDA data

  1. Electronic Code of Federal Regulations. 21 CFR 111.75(a)(1)(i)–(ii), identity testing of dietary ingredients and the exemption petition. Current as of October 20, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-111/su Regulation or statute
  2. Electronic Code of Federal Regulations. 21 CFR 101.4(h), names of botanical ingredients (Herbs of Commerce, 1992; part of the plant; Latin binomial and author). Current as of October 20, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-101/su Regulation or statute
  3. Electronic Code of Federal Regulations. 21 CFR 101.36(d)(1), source ingredients; the listing of botanicals shall specify the part of the plant. Current as of October 20, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-101/su Regulation or statute
  4. 21 U.S.C. 343(s)(2)(C) and 343(u) (Federal Food, Drug, and Cosmetic Act § 403); paragraph (u) added by Pub. L. 107-171, title X, § 10806(b)(2), May 13, 2002. Legal Information Institute text, accessed October 23, 2026. law.cornell.edu/uscode/text/21/343 Regulation or statute
  5. FDA. Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements; final rule. 72 FR 34752, June 25, 2007 (compliance dates June 25, 2008, 2009 and 2010 by firm size). federalregister.gov/documents/2007/06/25/07-3039/current-goo Regulation or statute

Academy: botanical identity — names and standards

  1. National Library of Medicine. MeSH descriptor D028001, Eleutherococcus (entry terms include Siberian Ginseng). meshb.nlm.nih.gov/record/ui?ui=D028001 Primary source
  2. European Medicines Agency, Herbal Medicinal Products Working Party. Position paper on the risks associated with the use of herbal products containing Aristolochia species. EMEA/HMPWP/23/00 Rev. 3, October 31, 2000. ema.europa.eu/en/documents/position/position-paper-risks-ass Agency guidance
  3. United States Pharmacopeia. General chapter <563> Identification of Articles of Botanical Origin and <203> High-Performance Thin-Layer Chromatography Procedure for Identification of Articles of Botanical Origin; USP course description 'Botanical ID Methodology Tests' (macroscopic and microscopic assessment highlighted), accessed October 23, 2026. usp.org/node/485716 Primary source
  4. Chinese Medicine Regulatory Office, Department of Health, Hong Kong SAR. Hong Kong Chinese Materia Medica Standards: Vol. 1, Radix Ginseng; Vol. 3, Radix Panacis Quinquefolii; Vol. 6, Acanthopanacis Senticosi Radix et Rhizoma seu Caulis (PDF monographs, accessed October 23, 2026). cmro.gov.hk/files/hkcmms/vol1/pdf_e/Radix_Ginseng_v1_e.pdf Primary source

Academy: botanical identity — microscopy and HPTLC

  1. Lawrie NS, et al. Systematic review on raphide morphotype calcium oxalate crystals in angiosperms. AoB Plants. 2023;15:plad031. doi.org/10.1093/aobpla/plad031 Peer-reviewed
  2. Franceschi VR, Nakata PA. Calcium oxalate in plants: formation and function. Annu Rev Plant Biol. 2005;56:41–71. doi.org/10.1146/annurev.arplant.56.032604.144106 Peer-reviewed
  3. Gray A, Liu L, Facette M. Flanking support: how subsidiary cells contribute to stomatal form and function. Front Plant Sci. 2020;11:881. doi.org/10.3389/fpls.2020.00881 Peer-reviewed
  4. Reich E. HPTLC for polyherbal formulations. USP workshop presentation (usp.org), slide 2: standardized parameters per USP <203>. usp.org/sites/default/files/usp/document/events-training/wor Primary source
  5. HPTLC Association. White paper: High-Performance Thin-Layer Chromatography in Practice (CAMAG website, accessed October 23, 2026). camag.com/article/whitepaper/high-performance-thin-layer-chr Primary source
  6. Do TKT, Schmid M, Phanse M, Charegaonkar A, Sprecher H, Obkircher M, Reich E. Development of the first universal mixture for use in system suitability tests for high-performance thin layer chromatography. J Chromatogr A. 2021;1638:461830. doi.org/10.1016/j.chroma.2020.461830 Peer-reviewed
  7. Ettre LS. Nomenclature for chromatography (IUPAC Recommendations 1993). Pure Appl Chem. 1993;65(4):819–872 (R_F p. 845; retardation factor R p. 843; peak resolution p. 847), as given in the IUPAC Gold Book. doi.org/10.1351/pac199365040819 Primary source
  8. Goodarzi M, Russell PJ, Vander Heyden Y. Similarity analyses of chromatographic herbal fingerprints: a review. Anal Chim Acta. 2013;804:16–28. doi.org/10.1016/j.aca.2013.09.017 Peer-reviewed
  9. Noviana E, Indrayanto G, Rohman A. Advances in fingerprint analysis for standardization and quality control of herbal medicines. Front Pharmacol. 2022;13:853023. doi.org/10.3389/fphar.2022.853023 Peer-reviewed
  10. PubChem. Ginsenoside Rf, CID 441922; pseudoginsenoside F11, CID 21633072 (isomeric SMILES retrieved October 23, 2026). pubchem.ncbi.nlm.nih.gov/compound/441922 Primary source

Academy: botanical identity — DNA and adulteration

  1. China Plant BOL Group, Li DZ, Gao LM, et al. Comparative analysis of a large dataset indicates that internal transcribed spacer (ITS) should be incorporated into the core barcode for seed plants. PNAS. 2011;108(49):19641–19646. doi.org/10.1073/pnas.1104551108 Peer-reviewed
  2. Parveen I, Gafner S, Techen N, Murch SJ, Khan IA. DNA barcoding for the identification of botanicals in herbal medicine and dietary supplements: strengths and limitations. Planta Med. 2016;82(14):1225–1235. doi.org/10.1055/s-0042-111208 Peer-reviewed
  3. Raclariu AC, Heinrich M, Ichim MC, de Boer H. Benefits and limitations of DNA barcoding and metabarcoding in herbal product authentication. Phytochem Anal. 2018;29(2):123–128. doi.org/10.1002/pca.2732 Peer-reviewed
  4. Raclariu AC, Paltinean R, Vlase L, et al. Comparative authentication of Hypericum perforatum herbal products using DNA metabarcoding, TLC and HPLC-MS. Sci Rep. 2017;7:1291. doi.org/10.1038/s41598-017-01389-w Peer-reviewed
  5. Raclariu AC, Țebrencu CE, Ichim MC, Ciupercǎ OT, Brysting AK, de Boer H. What's in the box? Authentication of Echinacea herbal products using DNA metabarcoding and HPTLC. Phytomedicine. 2018;44:32–38. doi.org/10.1016/j.phymed.2018.03.058 Peer-reviewed
  6. Gafner S, Blumenthal M, Foster S, Cardellina JH 2nd, Khan IA, Upton R. Botanical ingredient forensics: detection of attempts to deceive commonly used analytical methods for authenticating herbal dietary and food ingredients and supplements. J Nat Prod. 2023;86(2):460–472. doi.org/10.1021/acs.jnatprod.2c00929 Peer-reviewed
  7. Gafner S, Orhan N, Kahraman Ç, Blumenthal M. A scoping review of turmeric adulteration based on data from six continents. Pharm Biol. 2026;64(1):87–107 (online December 26, 2025). doi.org/10.1080/13880209.2025.2606229 Peer-reviewed
  8. Villani TS, Reichert W, Ferruzzi MG, Pasinetti GM, Simon JE, Wu Q. Chemical investigation of commercial grape seed derived products to assess quality and detect adulteration. Food Chem. 2015;170:271–280. doi.org/10.1016/j.foodchem.2014.08.084 Peer-reviewed
  9. Frommenwiler DA, Reich E, Sudberg S, Sharaf MHM, Bzhelyansky A, Lucas B. St. John's wort versus counterfeit St. John's wort: an HPTLC study. J AOAC Int. 2016;99(5):1204–1212. doi.org/10.5740/jaoacint.16-0170 Peer-reviewed
  10. Jiang B, Kronenberg F, Nuntanakorn P, Qiu MH, Kennelly EJ. Evaluation of the botanical authenticity and phytochemical profile of black cohosh products by high-performance liquid chromatography with selected ion monitoring liquid chromatography-mass spectrometry. J Agric Food Chem. 2006;54(9):3242–3253. doi.org/10.1021/jf0606149 Peer-reviewed

Academy: Soil and cultivation, soil chemistry and uptake

  1. Wade J, Ac-Pangan M, Favoretto VR, Taylor AJ, Engeseth N, Margenot AJ. Drivers of cadmium accumulation in Theobroma cacao L. beans: a quantitative synthesis of soil-plant relationships across the Cacao Belt. PLoS One. 2022;17(2):e0261989. doi.org/10.1371/journal.pone.0261989 Peer-reviewed
  2. Wade J. Cacao-cadmium-meta-analysis: Extracted and finalized data.csv (dataset and code accompanying PLoS One 2022;17(2):e0261989), commit b16cd1d, August 22, 2021. github.com/jordon-wade/Cacao-cadmium-meta-analysis Peer-reviewed
  3. Argüello D, Chavez E, Lauryssen F, Vanderschueren R, Smolders E, Montalvo D. Soil properties and agronomic factors affecting cadmium concentrations in cacao beans: a nationwide survey in Ecuador. Sci Total Environ. 2019;649:120–127. doi.org/10.1016/j.scitotenv.2018.08.292 Peer-reviewed
  4. Zhou T, Wang Y, Qin J, Zhao S, Cao D, Zhu M, Jiang Y. Potential risk, spatial distribution, and soil identification of potentially toxic elements in Lycium barbarum L. (wolfberry) fruits and soil system in Ningxia, China. Int J Environ Res Public Health. 2022;19(23):16186. doi.org/10.3390/ijerph192316186 Peer-reviewed
  5. U.S. Environmental Protection Agency. Guidance for Developing Ecological Soil Screening Levels (Eco-SSLs), Attachment 4-1: Exposure Factors and Bioaccumulation Models for Derivation of Wildlife Eco-SSLs. OSWER Directive 9285.7-55, revised April 2007. Table 4a. epa.gov/sites/production/files/2015-09/documents/ecossl_atta Primary source
  6. Efroymson RA, Sample BE, Suter GW. Uptake of inorganic chemicals from soil by plant leaves: regressions of field data. Environ Toxicol Chem. 2001;20(11):2561–2571. doi.org/10.1897/1551-5028(2001)020<2561:uoicfs>2.0.co;2 Peer-reviewed
  7. Sasaki A, Yamaji N, Yokosho K, Ma JF. Nramp5 is a major transporter responsible for manganese and cadmium uptake in rice. Plant Cell. 2012;24(5):2155–2167. doi.org/10.1105/tpc.112.096925 Peer-reviewed
  8. Ma JF, Yamaji N, Mitani N, Xu XY, Su YH, McGrath SP, Zhao FJ. Transporters of arsenite in rice and their role in arsenic accumulation in rice grain. Proc Natl Acad Sci U S A. 2008;105(29):9931–9935. doi.org/10.1073/pnas.0802361105 Peer-reviewed
  9. Clemens S, Ma JF. Toxic heavy metal and metalloid accumulation in crop plants and foods. Annu Rev Plant Biol. 2016;67:489–512. doi.org/10.1146/annurev-arplant-043015-112301 Peer-reviewed

Academy: Soil and cultivation, contamination cases and limits

  1. Forsyth JE, Nurunnahar S, Islam SS, et al. Turmeric means "yellow" in Bengali: lead chromate pigments added to turmeric threaten public health across Bangladesh. Environ Res. 2019;179(Pt A):108722. doi.org/10.1016/j.envres.2019.108722 Peer-reviewed
  2. Troeschel AN, Buser MC, Winquist A, et al. Investigation of lead and chromium exposure after consumption of contaminated cinnamon-containing applesauce, United States, November 2023–April 2024. MMWR Morb Mortal Wkly Rep. 2025;74(14):239–244. doi.org/10.15585/mmwr.mm7414a2 Primary source
  3. Commission Regulation (EU) 2023/915 of 25 April 2023 on maximum levels for certain contaminants in food and repealing Regulation (EC) No 1881/2006. OJ L 119, 5.5.2023. Annex I, entries 3.1.28, 3.2.12.3, 3.2.15.1–3.2.15.4. eur-lex.europa.eu/eli/reg/2023/915/oj/eng Regulation or statute
  4. Regulation (EU) 2019/1009 of the European Parliament and of the Council of 5 June 2019 laying down rules on the making available on the market of EU fertilising products. Article 42(8) and Article 49(b) (cadmium limit values in phosphate fertilisers). eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:32019R1009 Regulation or statute
  5. U.S. Food and Drug Administration. Action Level for Inorganic Arsenic in Rice Cereals for Infants: Guidance for Industry. August 2020 (docket FDA-2016-D-1099); and FDA constituent update, August 5, 2020. fda.gov/food/hfp-constituent-updates/fda-issues-final-guidan Agency guidance

Academy: Soil and cultivation, harvest, drying and collection practice

  1. Stefanakis MK, Papaioannou C, Lianopoulou V, Philotheou-Panou E, Giannakoula AE, Lazari DM. Seasonal variation of aromatic plants under cultivation conditions. Plants (Basel). 2022;11(16):2083. doi.org/10.3390/plants11162083 Peer-reviewed
  2. Caputo L, Amato G, de Bartolomeis P, De Martino L, Manna F, Nazzaro F, De Feo V, Barba AA. Impact of drying methods on the yield and chemistry of Origanum vulgare L. essential oil. Sci Rep. 2022;12:3845. doi.org/10.1038/s41598-022-07841-w Peer-reviewed
  3. Santana ACM, Pereira GS, Boaventura CM, Uetenabaro APT, Costa LCB, Oliveira RA. Rupture of glandular trichomes in Ocimum gratissimum leaves influences the content of essential oil during the drying method. Rev Bras Farmacogn. 2014;24(5):524–530. doi.org/10.1016/j.bjp.2014.10.006 Peer-reviewed
  4. Ferreira JF, Simon JE, Janick J. Developmental studies of Artemisia annua: flowering and artemisinin production under greenhouse and field conditions. Planta Med. 1995;61(2):167–170. doi.org/10.1055/s-2006-958040 Peer-reviewed
  5. Ferreira JFS, Benedito VA, Sandhu D, Marchese JA, Liu S. Seasonal and differential sesquiterpene accumulation in Artemisia annua suggest selection based on both artemisinin and dihydroartemisinic acid may increase artemisinin in planta. Front Plant Sci. 2018;9:1096. doi.org/10.3389/fpls.2018.01096 Peer-reviewed
  6. Xenophontos M, Stavropoulos E, Avramakis E, Navakoudis E, Dörnemann D, Kotzabasis K. Influence of the developmental stage on the (proto)-hypericin and (proto)pseudohypericin levels of Hypericum plants from Crete. Planta Med. 2007;73(12):1309–1315. doi.org/10.1055/s-2007-990222 Peer-reviewed
  7. Xiao D, Yue H, Xiu Y, Sun X, Wang Y, Liu S. Accumulation characteristics and correlation analysis of five ginsenosides with different cultivation ages from different regions. J Ginseng Res. 2015;39(4):338–344. doi.org/10.1016/j.jgr.2015.03.004 Peer-reviewed
  8. World Health Organization. WHO guidelines on good agricultural and collection practices (GACP) for medicinal plants. Geneva: WHO; 2003. ISBN 92 4 154627 1. who.int/publications/i/item/9241546271 Agency guidance
  9. 50 CFR 23.68, How can I trade internationally in roots of American ginseng? (eCFR, up to date as of October 21, 2026). ecfr.gov/current/title-50/chapter-I/subchapter-B/part-23/sub Regulation or statute
  10. Secretariat of the Convention on Biological Diversity. List of Parties (United States of America: signature June 4, 1993; not a Party). cbd.int/information/parties.shtml Primary source

Academy: solubility, pH and the body · gut physiology, solubility and dissolution

  1. Evans DF, Pye G, Bramley R, Clark AG, Dyson TJ, Hardcastle JD. Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut. 1988;29(8):1035–1041. doi.org/10.1136/gut.29.8.1035 Peer-reviewed
  2. Fallingborg J, Christensen LA, Ingeman-Nielsen M, Jacobsen BA, Abildgaard K, Rasmussen HH. pH-profile and regional transit times of the normal gut measured by a radiotelemetry device. Aliment Pharmacol Ther. 1989;3(6):605–613. doi.org/10.1111/j.1365-2036.1989.tb00254.x Peer-reviewed
  3. Fallingborg J. Intraluminal pH of the human gastrointestinal tract. Dan Med Bull. 1999;46(3):183–196. pubmed.ncbi.nlm.nih.gov/10421978/ Peer-reviewed
  4. Dressman JB, Berardi RR, Dermentzoglou LC, Russell TL, Schmaltz SP, Barnett JL, Jarvenpaa KM. Upper gastrointestinal (GI) pH in young, healthy men and women. Pharm Res. 1990;7(7):756–761. doi.org/10.1023/A:1015827908309 Peer-reviewed
  5. Davis SS, Hardy JG, Fara JW. Transit of pharmaceutical dosage forms through the small intestine. Gut. 1986;27(8):886–892. doi.org/10.1136/gut.27.8.886 Peer-reviewed
  6. Mudie DM, Murray K, Hoad CL, Pritchard SE, Garnett MC, Amidon GL, Gowland PA, Spiller RC, Amidon GE, Marciani L. Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state. Mol Pharm. 2014;11(9):3039–3047. doi.org/10.1021/mp500210c Peer-reviewed
  7. Schiller C, Fröhlich CP, Giessmann T, Siegmund W, Mönnikes H, Hosten N, Weitschies W. Intestinal fluid volumes and transit of dosage forms as assessed by magnetic resonance imaging. Aliment Pharmacol Ther. 2005;22(10):971–979. doi.org/10.1111/j.1365-2036.2005.02683.x Peer-reviewed
  8. Avdeef A. Solubility of sparingly-soluble ionizable drugs. Adv Drug Deliv Rev. 2007;59(7):568–590. doi.org/10.1016/j.addr.2007.05.008 Peer-reviewed
  9. Avdeef A. Absorption and Drug Development: Solubility, Permeability, and Charge State. 2nd ed. Hoboken, NJ: Wiley; 2012. doi.org/10.1002/9781118286067 Book
  10. Bergström CAS, Avdeef A. Perspectives in solubility measurement and interpretation. ADMET DMPK. 2019;7(2):88–105. doi.org/10.5599/admet.686 Peer-reviewed
  11. Scherrer RA, Howard SM. Use of distribution coefficients in quantitative structure-activity relationships. J Med Chem. 1977;20(1):53–58. doi.org/10.1021/jm00211a010 Peer-reviewed
  12. Shore PA, Brodie BB, Hogben CA. The gastric secretion of drugs: a pH partition hypothesis. J Pharmacol Exp Ther. 1957;119(3):361–369. pubmed.ncbi.nlm.nih.gov/13417090/ Peer-reviewed
  13. ICH M9. Biopharmaceutics Classification System-Based Biowaivers. Adopted November 20, 2019 (sections 1, 2.1 and 2.2; Table 2). database.ich.org/sites/default/files/M9_Guideline_Step4_2019 Agency guidance
  14. Noyes AA, Whitney WR. The rate of solution of solid substances in their own solutions. J Am Chem Soc. 1897;19(12):930–934. doi.org/10.1021/ja02086a003 Peer-reviewed
  15. Dokoumetzidis A, Macheras P. A century of dissolution research: from Noyes and Whitney to the biopharmaceutics classification system. Int J Pharm. 2006;321(1–2):1–11. doi.org/10.1016/j.ijpharm.2006.07.011 Peer-reviewed
  16. Brouwers J, Brewster ME, Augustijns P. Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability? J Pharm Sci. 2009;98(8):2549–2572. doi.org/10.1002/jps.21650 Peer-reviewed
  17. Guzmán HR, Tawa M, Zhang Z, Ratanabanangkoon P, Shaw P, Gardner CR, Chen H, Moreau JP, Almarsson O, Remenar JF. Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations. J Pharm Sci. 2007;96(10):2686–2702. doi.org/10.1002/jps.20906 Peer-reviewed

Academy: solubility, pH and the body · compound constants and structures

  1. PubChem Compound Summary, CID 338, salicylic acid (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/338 Primary source
  2. PubChem Compound Summary, CID 370, gallic acid (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/370 Primary source
  3. PubChem Compound Summary, CID 445858, ferulic acid (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/445858 Primary source
  4. PubChem Compound Summary, CID 689043, caffeic acid (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/689043 Primary source
  5. PubChem Compound Summary, CID 5280343, quercetin (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/5280343 Primary source
  6. PubChem Compound Summary, CID 969516, curcumin (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/969516 Primary source
  7. PubChem Compound Summary, CID 9294, ephedrine (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/9294 Primary source
  8. PubChem Compound Summary, CID 2519, caffeine (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/2519 Primary source
  9. PubChem Compound Summary, CID 2353, berberine (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/2353 Primary source
  10. PubChem Compound Summary, CID 638024, piperine (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/638024 Primary source
  11. PubChem Compound Summary, CID 5281855, ellagic acid (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/5281855 Primary source
  12. PubChem Compound Summary, CID 5488186, urolithin A (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/5488186 Primary source
  13. PubChem Compound Summary, CID 5281708, daidzein (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/5281708 Primary source
  14. PubChem Compound Summary, CID 91469, (3S)-equol (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/91469 Primary source
  15. PubChem Compound Summary, CID 10217, dihydroberberine (structure SMILES; Dissociation Constants and LogP sections citing HSDB, CRC, Serjeant & Dempsey 1979, Hansch et al. 1995, Sangster 1993, Avdeef 2012 or Svorc 2013 where listed). National Library of Medicine; accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/10217 Primary source
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  17. Rothwell JA, Day AJ, Morgan MRA. Experimental determination of octanol–water partition coefficients of quercetin and related flavonoids. J Agric Food Chem. 2005;53(11):4355–4360. doi.org/10.1021/jf0483669 Peer-reviewed
  18. Bernabé-Pineda M, Ramírez-Silva MT, Romero-Romo M, González-Vergara E, Rojas-Hernández A. Determination of acidity constants of curcumin in aqueous solution and apparent rate constant of its decomposition. Spectrochim Acta A Mol Biomol Spectrosc. 2004;60(5):1091–1097. doi.org/10.1016/S1386-1425(03)00342-1 Peer-reviewed
  19. Battu SK, Repka MA, Maddineni S, Chittiboyina AG, Avery MA, Majumdar S. Physicochemical characterization of berberine chloride: a perspective in the development of a solution dosage form for oral delivery. AAPS PharmSciTech. 2010;11(3):1466–1475. doi.org/10.1208/s12249-010-9520-y Peer-reviewed
  20. Wang YJ, Pan MH, Cheng AL, Lin LI, Ho YS, Hsieh CY, Lin JK. Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal. 1997;15(12):1867–1876. doi.org/10.1016/S0731-7085(96)02024-9 Peer-reviewed

Academy: solubility, pH and the body · absorption, metabolism, microbes and dose

  1. Varma MV, Obach RS, Rotter C, Miller HR, Chang G, Steyn SJ, El-Kattan A, Troutman MD. Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination. J Med Chem. 2010;53(3):1098–1108. doi.org/10.1021/jm901371v Peer-reviewed
  2. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci U S A. 1987;84(21):7735–7738. doi.org/10.1073/pnas.84.21.7735 Peer-reviewed
  3. Ireson CR, Jones DJ, Orr S, Coughtrie MW, Boocock DJ, Williams ML, Farmer PB, Steward WP, Gescher AJ. Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomarkers Prev. 2002;11(1):105–111. pubmed.ncbi.nlm.nih.gov/11815407/ Peer-reviewed
  4. Vareed SK, Kakarala M, Ruffin MT, Crowell JA, Normolle DP, Djuric Z, Brenner DE. Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiol Biomarkers Prev. 2008;17(6):1411–1417. doi.org/10.1158/1055-9965.EPI-07-2693 Peer-reviewed
  5. Liu YT, Hao HP, Xie HG, Lai L, Wang Q, Liu CX, Wang GJ. Extensive intestinal first-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats. Drug Metab Dispos. 2010;38(10):1779–1784. doi.org/10.1124/dmd.110.033936 Peer-reviewed
  6. Pan GY, Wang GJ, Liu XD, Fawcett JP, Xie YY. The involvement of P-glycoprotein in berberine absorption. Pharmacol Toxicol. 2002;91(4):193–197. doi.org/10.1034/j.1600-0773.2002.t01-1-910403.x Peer-reviewed
  7. Fança-Berthon P, Tenon M, Le Bouter-Banon S, Manfré A, Maudet C, Dion A, Chevallier H, Laval J, van Breemen RB. Pharmacokinetics of a single dose of turmeric curcuminoids depends on formulation: results of a human crossover study. J Nutr. 2021;151(7):1802–1816. doi.org/10.1093/jn/nxab087 Peer-reviewed
  8. UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. Statement on the potential risk to human health of turmeric and curcumin supplements (COT/2024/07): Toxicokinetics, paragraphs 26–30. Last updated December 9, 2024. cot.food.gov.uk/%20Turmeric%20and%20Curcumin%20Supplements%2 Agency guidance
  9. Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther. 2002;302(2):645–650. doi.org/10.1124/jpet.102.034728 Peer-reviewed
  10. Tomás-Barberán FA, García-Villalba R, González-Sarrías A, Selma MV, Espín JC. Ellagic acid metabolism by human gut microbiota: consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age, and health status. J Agric Food Chem. 2014;62(28):6535–6538. doi.org/10.1021/jf5024615 Peer-reviewed
  11. Setchell KDR, Clerici C. Equol: history, chemistry, and formation. J Nutr. 2010;140(7):1355S–1362S. doi.org/10.3945/jn.109.119776 Peer-reviewed
  12. Setchell KDR, Cole SJ. Method of defining equol-producer status and its frequency among vegetarians. J Nutr. 2006;136(8):2188–2193. doi.org/10.1093/jn/136.8.2188 Peer-reviewed
  13. Feng R, Shou JW, Zhao ZX, et al. Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci Rep. 2015;5:12155. doi.org/10.1038/srep12155 Peer-reviewed
  14. Ludden TM. Nonlinear pharmacokinetics: clinical implications. Clin Pharmacokinet. 1991;20(6):429–446. doi.org/10.2165/00003088-199120060-00001 Peer-reviewed
  15. Chow HH, Cai Y, Alberts DS, Hakim I, Dorr R, Shahi F, Crowell JA, Yang CS, Hara Y. Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol Biomarkers Prev. 2001;10(1):53–58. pubmed.ncbi.nlm.nih.gov/11205489/ Peer-reviewed
  16. Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21(4B):2895–2900. pubmed.ncbi.nlm.nih.gov/11712783/ Peer-reviewed

Academy: toxicology and dose, dose–response and acute toxicity

  1. Grandjean P. Paracelsus revisited: the dose concept in a complex world. Basic Clin Pharmacol Toxicol. 2016;119(2):126–132. doi:10.1111/bcpt.12622. doi.org/10.1111/bcpt.12622 Peer-reviewed
  2. Trevan JW. The error of determination of toxicity. Proc R Soc Lond B. 1927;101:483–514. doi:10.1098/rspb.1927.0030. doi.org/10.1098/rspb.1927.0030 Peer-reviewed
  3. OECD. Test No. 401: Acute Oral Toxicity (1987). Deleted on December 17, 2002, following an OECD Council decision. oecd.org/en/publications/test-no-401-acute-oral-toxicity_978 Primary source
  4. OECD. C(2001)282: Note by the Secretary-General with a draft Council Decision deleting Test Guideline 401 and adopting updated Test Guidelines 420, 423 and 425 (2001). one.oecd.org/document/C(2001)282/en Primary source
  5. OECD. Guidance Document on Acute Oral Toxicity Testing. Series on Testing and Assessment No. 24. ENV/JM/MONO(2001)4. Paris: OECD; 2001. ntp.niehs.nih.gov/sites/default/files/iccvam/suppdocs/feddoc Agency guidance
  6. OECD. Test No. 420: Acute Oral Toxicity – Fixed Dose Procedure (published February 7, 2002). oecd.org/en/publications/test-no-420-acute-oral-toxicity-fix Primary source
  7. OECD. Test No. 425: Acute Oral Toxicity – Up-and-Down Procedure (adopted 2008; corrected version published June 29, 2022). oecd.org/en/publications/test-no-425-acute-oral-toxicity-up- Primary source
  8. U.S. EPA Risk Assessment Forum. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Washington, DC; June 2012 (section 2.3.8; Appendices B and C). archive.epa.gov/raf/web/pdf/benchmark_dose_guidance.pdf Agency guidance
  9. Crump KS. A new method for determining allowable daily intakes. Fundam Appl Toxicol. 1984;4(5):854–871. doi:10.1016/0272-0590(84)90107-6. doi.org/10.1016/0272-0590(84)90107-6 Peer-reviewed

Academy: toxicology and dose, study guidelines

  1. OECD. Test No. 471: Bacterial Reverse Mutation Test (adopted July 21, 1997; corrected June 26, 2020). oecd.org/content/dam/oecd/en/publications/reports/2020/06/te Primary source
  2. OECD. Test No. 487: In Vitro Mammalian Cell Micronucleus Test (adopted July 19, 2016; corrected July 4, 2023). oecd.org/content/dam/oecd/en/publications/reports/2023/07/te Primary source
  3. OECD. Test No. 474: Mammalian Erythrocyte Micronucleus Test (adopted July 29, 2016). oecd.org/content/dam/oecd/en/publications/reports/2016/07/te Primary source
  4. OECD. Test No. 407: Repeated Dose 28-day Oral Toxicity Study in Rodents (adopted June 25, 2025). oecd.org/content/dam/oecd/en/publications/reports/2008/10/te Primary source
  5. OECD. Test No. 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents (adopted June 25, 2025), paragraphs 3, 16 and 17. oecd.org/content/dam/oecd/en/publications/reports/2018/06/te Primary source
  6. OECD. Test No. 414: Prenatal Developmental Toxicity Study (published June 26, 2018). oecd.org/en/publications/test-no-414-prenatal-development-to Primary source
  7. OECD. Test No. 443: Extended One-Generation Reproductive Toxicity Study (adopted June 25, 2025). oecd.org/content/dam/oecd/en/publications/reports/2018/06/te Primary source
  8. OECD. Test No. 451: Carcinogenicity Studies (2018), paragraphs 5, 19–22. oecd.org/content/dam/oecd/en/publications/reports/2018/06/te Primary source
  9. OECD. Test No. 452: Chronic Toxicity Studies (2018). oecd.org/content/dam/oecd/en/publications/reports/2018/06/te Primary source
  10. OECD. Test No. 453: Combined Chronic Toxicity/Carcinogenicity Studies (2018). oecd.org/content/dam/oecd/en/publications/reports/2018/06/te Primary source

Academy: toxicology and dose, guidance values, margins and TTC

  1. IPCS. Chemical-specific adjustment factors for interspecies differences and human variability: guidance document for use of data in dose/concentration–response assessment. Harmonization Project Document No. 2. Geneva: WHO; 2005. archive.epa.gov/scipoly/sap/meetings/web/pdf/ipcs2005csaf.pd Agency guidance
  2. Renwick AG. Data-derived safety factors for the evaluation of food additives and environmental contaminants. Food Addit Contam. 1993;10(3):275–305. doi:10.1080/02652039309374152. doi.org/10.1080/02652039309374152 Peer-reviewed
  3. U.S. EPA. Integrated Risk Information System (IRIS) Chemical Assessment Summary: Boron and Compounds. Oral RfD, last revised August 5, 2004 (sections I.A.1–I.A.3). iris.epa.gov/static/pdfs/0410_summary.pdf Primary source
  4. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Scientific Opinion on the safety of steviol glycosides for the proposed uses as a food additive. EFSA J. 2010;8(4):1537. doi:10.2903/j.efsa.2010.1537. doi.org/10.2903/j.efsa.2010.1537 Agency guidance
  5. EFSA Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC). Opinion on coumarin (adopted October 6, 2004). EFSA J. 2004;104. efsa.europa.eu/en/efsajournal/pub/104 Agency guidance
  6. EFSA AFC Panel. Coumarin in flavourings and other food ingredients with flavouring properties. EFSA J. 2008;793:1–15. doi:10.2903/j.efsa.2008.793. doi.org/10.2903/j.efsa.2008.793 Agency guidance
  7. German Federal Institute for Risk Assessment (BfR). Cassia cinnamon with high coumarin contents to be consumed in moderation. Press release, September 27, 2012. bfr.bund.de/en/press-release/cassia-cinnamon-with-high-couma Primary source
  8. U.S. FDA CDER. Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. July 2005 (sections I–III, V and VII; Tables 1 and 3; Appendices B–D). fda.gov/media/72309/download Agency guidance
  9. Fu PP, Xia Q, Lin G, Chou MW. Pyrrolizidine alkaloids: genotoxicity, metabolism enzymes, metabolic activation, and mechanisms. Drug Metab Rev. 2004;36(1):1–55. doi:10.1081/DMR-120028426. doi.org/10.1081/DMR-120028426 Peer-reviewed
  10. PubChem. Riddelliine, CID 5281744 (C18H23NO6; isomeric SMILES used for the structure drawing). pubchem.ncbi.nlm.nih.gov/compound/5281744 Primary source
  11. EFSA Scientific Committee; More SJ, Bampidis V, Benford D, et al. Guidance on the use of the Threshold of Toxicological Concern approach in food safety assessment. EFSA J. 2019;17(6):5708. doi:10.2903/j.efsa.2019.5708. doi.org/10.2903/j.efsa.2019.5708 Agency guidance
  12. Munro IC, Ford RA, Kennepohl E, Sprenger JG. Correlation of structural class with no-observed-effect levels: a proposal for establishing a threshold of concern. Food Chem Toxicol. 1996;34:829–867. doi:10.1016/S0278-6915(96)00049-X. doi.org/10.1016/S0278-6915(96)00049-X Peer-reviewed

Academy: toxicology and dose, NTP bioassays and botanical organ toxicity

  1. National Toxicology Program. Toxicology and Carcinogenesis Studies of Turmeric Oleoresin (CAS No. 8024-37-1) (Major Component 79%–85% Curcumin) in F344/N Rats and B6C3F1 Mice (Feed Studies). NTP TR 427. August 1993. ntp.niehs.nih.gov/sites/default/files/ntp/htdocs/lt_rpts/tr4 Primary source
  2. National Toxicology Program. Toxicology and Carcinogenesis Studies of Riddelliine (CAS No. 23246-96-0) in F344/N Rats and B6C3F1 Mice (Gavage Studies). NTP TR 508. May 2003. ntp.niehs.nih.gov/sites/default/files/ntp/htdocs/lt_rpts/tr5 Primary source
  3. National Toxicology Program. Toxicology and Carcinogenesis Studies of Goldenseal Root Powder (Hydrastis canadensis) in F344/N Rats and B6C3F1 Mice (Feed Studies). NTP TR 562. August 2010. ntp.niehs.nih.gov/sites/default/files/ntp/htdocs/lt_rpts/tr5 Primary source
  4. National Toxicology Program. Toxicology and Carcinogenesis Studies of Pulegone (CAS No. 89-82-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies). NTP TR 563. August 2011. ntp.niehs.nih.gov/sites/default/files/ntp/htdocs/lt_rpts/tr5 Primary source
  5. National Toxicology Program. Toxicology and Carcinogenesis Studies of Milk Thistle Extract (CAS No. 84604-20-6) in F344/N Rats and B6C3F1 Mice (Feed Studies). NTP TR 565. May 2011. ntp.niehs.nih.gov/sites/default/files/ntp/htdocs/lt_rpts/tr5 Primary source
  6. National Toxicology Program. Toxicology and Carcinogenesis Studies of Ginseng (CAS No. 50647-08-0) in F344/N Rats and B6C3F1 Mice (Gavage Studies). NTP TR 567. September 2011. ntp.niehs.nih.gov/sites/default/files/ntp/htdocs/lt_rpts/tr5 Primary source
  7. National Toxicology Program. Toxicology and Carcinogenesis Studies of Kava Kava Extract (CAS No. 9000-38-8) in F344/N Rats and B6C3F1 Mice (Gavage Studies). NTP TR 571. March 2012. ntp.niehs.nih.gov/sites/default/files/ntp/htdocs/lt_rpts/tr5 Primary source
  8. National Toxicology Program. Toxicology and Carcinogenesis Studies of a Nondecolorized Whole Leaf Extract of Aloe barbadensis Miller (Aloe vera) in F344/N Rats and B6C3F1 Mice (Drinking Water Studies). NTP TR 577. August 2013. ntp.niehs.nih.gov/sites/default/files/ntp/htdocs/lt_rpts/tr5 Primary source
  9. National Toxicology Program. Toxicology and Carcinogenesis Studies of Ginkgo biloba Extract (CAS No. 90045-36-6) in F344/N Rats and B6C3F1/N Mice (Gavage Studies). NTP TR 578. March 2013. ntp.niehs.nih.gov/sites/default/files/ntp/htdocs/lt_rpts/tr5 Primary source
  10. Commission Regulation (EU) 2022/2340 of 30 November 2022 amending Annex III to Regulation (EC) No 1925/2006 as regards green tea extracts containing (−)-epigallocatechin-3-gallate. OJ L 310, 1.12.2022. eur-lex.europa.eu/eli/reg/2022/2340/oj Regulation or statute

Academy: the untapped botanicals, plants and counts

  1. Allkin B. Useful plants – medicines: at least 28,187 plant species are currently recorded as being of medicinal use. In: Willis KJ, editor. State of the World's Plants 2017. London: Royal Botanic Gardens, Kew; 2017. NCBI Bookshelf NBK464488. ncbi.nlm.nih.gov/books/NBK464488/ Primary source
  2. CITES Secretariat. The CITES species (counts as of February 23, 2023). Read October 23, 2026. cites.org/eng/disc/species.php Primary source
  3. Secretariat of the Convention on Biological Diversity. About the Nagoya Protocol. Read October 23, 2026. cbd.int/abs/about Primary source

Academy: the untapped botanicals, FDA records and law

  1. U.S. FDA. Submitted 75-Day Premarket Notifications for New Dietary Ingredients; spreadsheet “List of NDINs 1995 to the Present” (downloaded October 23, 2026). fda.gov/food/new-dietary-ingredient-ndi-notification-process Primary source
  2. U.S. FDA. New Dietary Ingredients in Dietary Supplements – Background for Industry (“There is no authoritative list…”). fda.gov/food/new-dietary-ingredient-ndi-notification-process Agency guidance
  3. U.S. FDA. New Dietary Ingredient (NDI) Notification Process (public meeting on pre-DSHEA ingredients, October 3, 2017). Content current as of October 19, 2026. fda.gov/food/dietary-supplements/new-dietary-ingredient-ndi- Primary source
  4. Federal Register. Agency Information Collection Activities; Premarket Notification for a New Dietary Ingredient. 89 FR 2957, January 17, 2024 (OMB 0910-0330). federalregister.gov/documents/2024/01/17/2024-00732/agency-i Founder-reported
  5. Federal Register. Agency Information Collection Activities; Notification Procedures for Statements of Dietary Supplements. 90 FR 35694, July 29, 2025. federalregister.gov/documents/2025/07/29/2025-14222/agency-i Founder-reported
  6. Federal Register. Substances Generally Recognized as Safe; proposed rule. 91 FR 51834, August 11, 2026 (paperwork estimate of 180 hours per GRAS notice). govinfo.gov/content/pkg/FR-2026-08-11/pdf/2026-16296.pdf Founder-reported
  7. 21 CFR 312.40, General requirements for use of an investigational new drug in a clinical investigation (eCFR). ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312/su Regulation or statute
  8. 21 U.S.C. 350b (FD&C Act § 413), new dietary ingredients. Cornell LII. law.cornell.edu/uscode/text/21/350b Regulation or statute
  9. Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013). Cornell LII. law.cornell.edu/supremecourt/text/12-398 Regulation or statute
  10. U.S. FDA. Guidance for Industry: New Dietary Ingredient (NDI) Notifications and Related Issues; Identity and Safety Information About the NDI (final, October 2026), Section VI. fda.gov/media/195770/download Agency guidance

Academy: the untapped botanicals, drugs and evidence costs

  1. Park JK, Lee D, Rui L, Gao X, Furness MS, Wu C. Analysis of regulatory botanical submission profile for cancer management from the U.S. FDA perspectives. Ther Innov Regul Sci. 2025;59(5):1129–1137. doi.org/10.1007/s43441-025-00786-y Peer-reviewed
  2. Drugs@FDA. NDA 021902, Veregen (sinecatechins) ointment, 15%; approved October 31, 2006; label section 11. accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview Primary source
  3. Drugs@FDA. NDA 202292, crofelemer delayed-release tablets 125 mg (Fulyzaq, now Mytesi); approved December 31, 2012; label section 11. accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview Primary source
  4. Drugs@FDA. BLA 761192, NexoBrid (anacaulase-bcdb); approved December 28, 2022; label section 11. accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview Primary source
  5. Drugs@FDA. NDA 215064, Filsuvez (birch triterpenes) topical gel, 10%; approved December 18, 2023; label section 11. accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview Primary source
  6. Moore TJ, Zhang H, Anderson G, Alexander GC. Estimated costs of pivotal trials for novel therapeutic agents approved by the US Food and Drug Administration, 2015–2016. JAMA Intern Med. 2018;178(11):1451–1457. doi.org/10.1001/jamainternmed.2018.3931 Peer-reviewed
  7. DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20–33. doi.org/10.1016/j.jhealeco.2016.01.012 Peer-reviewed

Academy: why no disease claims, statute and regulations

  1. 21 U.S.C. 355(a), (d) (FD&C Act § 505): new drugs; “substantial evidence” defined. Cornell LII. law.cornell.edu/uscode/text/21/355 Regulation or statute
  2. 21 U.S.C. 301 and notes: enactment dates of Pub. L. 87-781 (1962), 101-535 (1990), 103-417 (1994) and 109-462 (2006). Cornell LII. law.cornell.edu/uscode/text/21/301 Regulation or statute
  3. 21 CFR 101.14, Health claims: general requirements (eCFR). ecfr.gov/current/title-21/chapter-I/subchapter-B/part-101/su Regulation or statute
  4. 21 CFR Part 101, Subpart E, Specific requirements for health claims, 101.70–101.83 (eCFR). ecfr.gov/current/title-21/chapter-I/subchapter-B/part-101/su Regulation or statute
  5. FDA Food Safety Modernization Act, Pub. L. 111-353, approved January 4, 2011, § 113. govinfo.gov/content/pkg/PLAW-111publ353/html/PLAW-111publ353 Regulation or statute
  6. Dietary Supplement and Nonprescription Drug Consumer Protection Act, Pub. L. 109-462, approved December 22, 2006. govinfo.gov/content/pkg/PLAW-109publ462/html/PLAW-109publ462 Regulation or statute

Academy: why no disease claims, FDA and FTC documents

  1. Federal Register. Regulations on Statements Made for Dietary Supplements Concerning the Effect of the Product on the Structure or Function of the Body; final rule. 65 FR 1000–1050, January 6, 2000 (Docket 98N-0044). govinfo.gov/content/pkg/FR-2000-01-06/pdf/00-53.pdf Founder-reported
  2. U.S. FDA. Small Entity Compliance Guide on Structure/Function Claims. January 2002 (issued January 9, 2002); docket FDA-1998-N-0071. fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance
  3. U.S. FDA. Qualified Health Claims: Letters of Enforcement Discretion. Content current as of March 28, 2024. fda.gov/food/food-labeling-nutrition/qualified-health-claims Primary source
  4. Federal Register. Experimental Study of Consumer Response to Health Claims and Disclaimers; information collection. 77 FR 4329, January 27, 2012 (describes Pearson v. Shalala, 164 F.3d 650 (D.C. Cir. 1999)). govinfo.gov/content/pkg/FR-2012-01-27/html/2012-1692.htm Founder-reported
  5. HHS Office of Inspector General. Dietary Supplements: Structure/Function Claims Fail To Meet Federal Requirements. OEI-01-11-00210, October 2, 2012. oig.hhs.gov/reports/all/2012/dietary-supplements-structurefu Primary source
  6. U.S. FDA. Fraudulent Coronavirus Disease 2019 (COVID-19) Products, warning letter table. Content current as of April 22, 2026. fda.gov/consumers/health-fraud-scams/fraudulent-coronavirus- Primary source
  7. U.S. FDA and FTC. Warning letter MARCS-CMS 604813, March 6, 2020: unapproved and misbranded products related to COVID-19. fda.gov/inspections-compliance-enforcement-and-criminal-inve Primary source
  8. U.S. FDA. About Warning and Close-Out Letters. fda.gov/inspections-compliance-enforcement-and-criminal-inve Primary source
  9. U.S. FDA. Milestones in U.S. Food and Drug Law. fda.gov/about-fda/fda-history/milestones-us-food-and-drug-la Primary source

Academy: how EUTECNIQ differs (company documents, read October 22–23, 2026)

  1. JiaHerb Inc. Company website, home page (address 1 Chapin Road, Unit 1, Pine Brook, NJ 07058; more than 500 ingredients). Read October 23, 2026. jiaherbinc.com/ Primary source
  2. JiaHerb Inc. History (2000 founded in Xi'an; 2008 New Jersey; 2010 California; 2015 U.S. operations over 100,000 sq ft; 2018 1.5 million sq ft campus; 2023 organic farm; 2024 laboratory and R&D center). Read October 23, 2026. jiaherbinc.com/html/history/index.html Primary source
  3. JiaHerb Inc. Manufacturing Capabilities (over 1.5 million sq ft NSF-GMP registered manufacturing facilities in Xi'an, China). Read October 23, 2026. jiaherbinc.com/html/manufacturingcapabilities/index.html Primary source
  4. JiaHerb Inc. Quality (in-house 22,000 sq ft ISO 17025 laboratory; HPLC, GC, UV, FTIR, HP-TLC, LC/GC/ICP-MS). Read October 23, 2026. jiaherbinc.com/html/quality42/index.html Primary source
  5. JiaHerb Inc. Sourcing & Traceability (HerbaLink chain-of-custody program; DNA, HPTLC and HPLC testing). Read October 23, 2026. jiaherbinc.com/html/sourcingtraceability/index.html Primary source
  6. Krawiec S. Jiaherb partners with USP to validate monograph of feverfew extract. Nutritional Outlook, October 9, 2019. nutritionaloutlook.com/view/jiaherb-partners-usp-validate-mo Primary source
  7. McEvoy E. Jiaherb celebrates 25 years in the industry, highlighting innovations and growth. Nutritional Outlook, January 15, 2025 (founded August 24, 2000, in Xi'an). nutritionaloutlook.com/view/jiaherb-celebrates-25-years-in-t Primary source
  8. Nutrasource. Company website, home page (contract research organization; now part of SGS; regulatory consulting, clinical trials, analytical testing). Read October 23, 2026. nutrasource.ca/ Primary source

Academy: how EUTECNIQ differs (regulation and standards)

  1. 21 CFR 111.1, Who is subject to this part? ((a) manufacture, package, label or hold a dietary supplement; (b) retail holding exemption). eCFR, current to October 21, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-111/su Regulation or statute
  2. SADCAS F 60a, Management requirements of ISO/IEC 17025:2017 (Issue 3), checklist summarizing clause 4.1 impartiality (4.1.4 risks to impartiality, including those arising from relationships). Accessed October 23, 2026. sadcas.org/sites/default/files/2024-09/SADCAS%20F%2060a%20-% Primary source

General and cross-cutting

Natural products, history and cautions

  1. Newman DJ, Cragg GM. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod. 2020;83(3):770–803. doi.org/10.1021/acs.jnatprod.9b01285
  2. Tu Y. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat Med. 2011;17(10):1217–1220. doi.org/10.1038/nm.2471
  3. Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood. 2008;111(5):2505–2515. doi.org/10.1182/blood-2007-07-102798
  4. Bailey CJ. Metformin: historical overview. Diabetologia. 2017;60(9):1566–1576. doi.org/10.1007/s00125-017-4318-z
  5. Edwards AM. Chromones. Chem Immunol Allergy. 2014;100:317–322. doi.org/10.1159/000359986
  6. Shah RP, Bharate SS. Analytical methods for furanochromone natural product, khellin and its inspired drug candidates, amiodarone and sodium cromoglycate. Crit Rev Anal Chem. 2024;54(4):691–706. doi.org/10.1080/10408347.2022.2094198
  7. Noble RL. The discovery of the vinca alkaloids—chemotherapeutic agents against cancer. Biochem Cell Biol. 1990;68(12):1344–1351. pubmed.ncbi.nlm.nih.gov/2085431/
  8. Wani MC, Taylor HL, Wall ME, et al. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc. 1971;93(9):2325–2327. doi.org/10.1021/ja00738a045
  9. Vanherweghem JL, Depierreux M, Tielemans C, et al. Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet. 1993;341(8842):387–391. doi.org/10.1016/0140-6736(93)92984-2
  10. Nortier JL, Martinez MC, Schmeiser HH, et al. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N Engl J Med. 2000;342(23):1686–1692. doi.org/10.1056/NEJM200006083422301
  11. Saper RB, Phillips RS, Sehgal A, et al. Lead, mercury, and arsenic in US- and Indian-manufactured Ayurvedic medicines sold via the Internet. JAMA. 2008;300(8):915–923. doi.org/10.1001/jama.300.8.915
  12. Halegoua-DeMarzio D, Navarro V, Ahmad J, et al. Liver injury associated with turmeric—a growing problem: ten cases from the Drug-Induced Liver Injury Network [DILIN]. Am J Med. 2023;136(2):200–206. doi.org/10.1016/j.amjmed.2022.09.026
  13. Li Y, Kong D, Fu Y, Sussman MR, Wu H. The effect of developmental and environmental factors on secondary metabolites in medicinal plants. Plant Physiol Biochem. 2020;148:80–89. doi.org/10.1016/j.plaphy.2020.01.006
  14. Wohlmuth H, Savage K, Dowell A, Mouatt P. Adulteration of Ginkgo biloba products and a simple method to improve its detection. Phytomedicine. 2014;21(6):912–918. doi.org/10.1016/j.phymed.2014.01.010
  15. Bhandari BR, Datta N, Howes T. Problems associated with spray drying of sugar-rich foods. Drying Technol. 1997;15(2):671–684. doi.org/10.1080/07373939708917253
  16. Wu C, Lee SL, Taylor C, et al. Scientific and regulatory approach to botanical drug development: a U.S. FDA perspective. J Nat Prod. 2020;83(2):552–562. doi.org/10.1021/acs.jnatprod.9b00949

Research activity (v14, retrieved Oct 24, 2026)

  1. National Center for Biotechnology Information. PubMed, searched through the E-utilities esearch service (rettype=count) by publication year; query strings are listed under the chart. Retrieved Oct 24, 2026. ncbi.nlm.nih.gov/books/NBK25499/ Primary source

Elemental contaminants (dose-to-limit calculator)

  1. United States Pharmacopeia. General Chapter ⟨2232⟩ Elemental Contaminants in Dietary Supplements. Table 1 (PDE), Table 2 (individual component limits, based on a maximum daily intake of 10 g) and options for compliance, as published in USP 38–NF 33; current official text on USP–NF. drugfuture.com/Pharmacopoeia/usp38/data/v38332/usp38nf33s2_c Primary source
  2. United States Pharmacopeia. General Chapter ⟨2232⟩ Elemental Contaminants in Dietary Supplements. USP–NF DOI landing page. doi.org/10.31003/USPNF_M5291_01_01 Primary source

Marker structures and recorded chemistry

  1. COCONUT downloads, October 2026 release, full CSV with organism field (CC0). Downloaded October 24, 2026; counts computed by EUTECNIQ (src/modules/ana_nta/compute/coco_species.py). coconut.naturalproducts.net/download Primary source
  2. Kim HW, Wang M, Leber CA, et al. NPClassifier: a deep neural network-based structural classification tool for natural products. J Nat Prod. 2021;84(11):2795–2807. doi.org/10.1021/acs.jnatprod.1c00399 Peer-reviewed
  3. PubChem compound records: hyperforin (CID 441298), ginkgolide B (CID 11973122), curcumin (CID 969516), epigallocatechin gallate (CID 65064); SMILES and formula checked October 24, 2026. 3D: one RDKit ETKDGv3 + MMFF94 conformer each (Wang S, et al. J Chem Inf Model. 2020;60(4):2044–2058; Halgren TA. J Comput Chem. 1996;17:490–519). pubchem.ncbi.nlm.nih.gov/ Primary source

Water properties

  1. National Institute of Standards and Technology. NIST Chemistry WebBook, SRD 69: Thermophysical Properties of Fluid Systems, water, isobaric data at 0.101325 MPa, 5–80 °C (density and viscosity). Retrieved October 24, 2026. webbook.nist.gov/chemistry/fluid/ Primary source

Reference-material comparison and control charts

  1. Linsinger T. ERM Application Note 1: Comparison of a measurement result with the certified value. European Commission, Joint Research Centre, Institute for Reference Materials and Measurements; January 2010. crm.jrc.ec.europa.eu/sites/default/files/2025-03/erm1_englis Primary source
  2. National Institute of Standards and Technology. Certificate of Analysis, Standard Reference Material 3247, Ginkgo biloba (Extract), Table 1 (certified mass fractions of flavonoid aglycones and terpene lactones, dry-mass basis, U95). Issued February 10, 2021; certification valid until October 30, 2029. tsapps.nist.gov/srmext/certificates/3247.pdf Primary source
  3. Nelson LS. The Shewhart control chart—tests for special causes. J Qual Technol. 1984;16(4):237–239. doi.org/10.1080/00224065.1984.11978921 Peer-reviewed
  4. Western Electric Company. Statistical Quality Control Handbook. Indianapolis: Western Electric; 1956 (zone rules for control charts). Peer-reviewed

Design of experiments and calibration checks (v14, Oct 24, 2026)

  1. NIST/SEMATECH e-Handbook of Statistical Methods. Section 5.3.3.6.3, Comparisons of response surface designs (Tables 3.24 and 3.28). National Institute of Standards and Technology. itl.nist.gov/div898/handbook/pri/section3/pri3363.htm Primary source

Data sets behind the charts (read October 24, 2026)

  1. Office of the Federal Register. eCFR versioner API, structure endpoint: sections per CFR part, titles 21 and 42 up to date as of Oct 21, 2026; applicability as mapped on EUTECNIQ's CFR atlas. ecfr.gov/developers/documentation/api/v1 Primary source
  2. Porter M, Mills R, Weinstein R. Industry norms and reasonable royalty rate determination. les Nouvelles (Licensing Executives Society International). March 2008:47–64, Table 1 and Appendix B. law.shu.edu/documents/industry-notes-mb1018.pdf Peer-reviewed
  3. U.S. FDA. Registration & Listing of Cosmetic Product Facilities and Products (content current as of Sep 9, 2026), and its facility metrics by state and country, data as of Jun 30, 2026. fda.gov/cosmetics/registration-listing-cosmetic-product-faci Primary source
  4. U.S. FDA, Human Foods Program. GRAS Notice Inventory, downloaded file (last updated Oct 21, 2026; downloaded Oct 24, 2026). hfpappexternal.fda.gov/scripts/fdcc/?set=GRASNotices Primary source
  5. U.S. FDA. openFDA drugsfda endpoint (Drugs@FDA original approvals: NDA 021902, NDA 202292, BLA 761192, NDA 215064) and drug label endpoint (Description sections). Read Oct 24, 2026. open.fda.gov/apis/drug/drugsfda/ Primary source

Heritage: structures and research counts

  1. Wang S, Witek J, Landrum GA, Riniker S. Improving conformer generation for small rings and macrocycles based on distance geometry and experimental torsional-angle preferences. J Chem Inf Model. 2020;60(4):2044–2058. doi.org/10.1021/acs.jcim.0c00025 Peer-reviewed

Company: regulatory activity data

  1. Federal Register API (federalregister.gov/developers), documents/facets/yearly with full-text term "dietary supplement", agency Food and Drug Administration, document types Rule, Proposed Rule and Notice, 1994–2026. Retrieved October 24, 2026 by src/modules/front_maps/compute/fr_dietary_supplement.py. federalregister.gov/developers/documentation/api/v1 Primary source

Ab initio reactivity: bond dissociation enthalpies of phenols

  1. Mulder P, Korth HG, Pratt DA, DiLabio GA, Valgimigli L, Pedulli GF, Ingold KU. Critical re-evaluation of the O–H bond dissociation enthalpy in phenol. J Phys Chem A. 2005;109(11):2647–2655. doi.org/10.1021/jp047148f Peer-reviewed
  2. Lucarini M, Pedulli GF, Guerra M. A critical evaluation of the factors determining the effect of intramolecular hydrogen bonding on the O–H bond dissociation enthalpy of catechol and of flavonoid antioxidants. Chem Eur J. 2004;10(4):933–939. doi.org/10.1002/chem.200305311 Peer-reviewed
  3. Wright JS, Johnson ER, DiLabio GA. Predicting the activity of phenolic antioxidants: theoretical method, analysis of substituent effects, and application to major families of antioxidants. J Am Chem Soc. 2001;123(6):1173–1183. doi.org/10.1021/ja002455u Peer-reviewed
  4. Litwinienko G, Ingold KU. Solvent effects on the rates and mechanisms of reaction of phenols with free radicals. Acc Chem Res. 2007;40(3):222–230. doi.org/10.1021/ar0682029 Peer-reviewed
  5. Amorati R, Ferroni F, Lucarini M, Pedulli GF, Valgimigli L. A quantitative approach to the recycling of α-tocopherol by coantioxidants. J Org Chem. 2002;67(26):9295–9303. doi.org/10.1021/jo026501f Peer-reviewed
  6. National Center for Complementary and Integrative Health. Antioxidant supplements: what you need to know. Last updated July 2023. nccih.nih.gov/health/antioxidant-supplements-what-you-need-t Agency guidance
  7. Brigati G, Lucarini M, Mugnaini V, Pedulli GF. Determination of the substituent effect on the O–H bond dissociation enthalpies of phenolic antioxidants by the EPR radical equilibration technique. J Org Chem. 2002;67(14):4828–4832. doi.org/10.1021/jo025755y Peer-reviewed

Ab initio reactivity: methods and software

  1. Becke AD. Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys. 1993;98(7):5648–5652. doi.org/10.1063/1.464913 Peer-reviewed
  2. Lee C, Yang W, Parr RG. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B. 1988;37(2):785–789. doi.org/10.1103/PhysRevB.37.785 Peer-reviewed
  3. Weigend F. Hartree–Fock exchange fitting basis sets for H to Rn. J Comput Chem. 2008;29(2):167–175. doi.org/10.1002/jcc.20702 Peer-reviewed
  4. Mulliken RS. Electronic population analysis on LCAO–MO molecular wave functions. I. J Chem Phys. 1955;23(10):1833–1840. doi.org/10.1063/1.1740588 Peer-reviewed

Ab initio reactivity: PubChem structure records

  1. National Center for Biotechnology Information. PubChem Compound Summary for CID 996, Phenol. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/996 Primary source
  2. National Center for Biotechnology Information. PubChem Compound Summary for CID 123143, Phenoxy radical. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/123143 Primary source
  3. National Center for Biotechnology Information. PubChem Compound Summary for CID 289, Catechol. Accessed October 23, 2026. pubchem.ncbi.nlm.nih.gov/compound/289 Primary source

Molecule identity (v14)

  1. National Center for Biotechnology Information. PubChem Compound Summary for CID 460, Guaiacol. Accessed October 24, 2026. pubchem.ncbi.nlm.nih.gov/compound/460 Primary source
  2. National Center for Biotechnology Information. PubChem Compound Summary for CID 1183, Vanillin. Accessed October 24, 2026. pubchem.ncbi.nlm.nih.gov/compound/1183 Primary source
  3. National Center for Biotechnology Information. PubChem Compound Summary for CID 3314, Eugenol. Accessed October 24, 2026. pubchem.ncbi.nlm.nih.gov/compound/3314 Primary source

Assay reference molecules (v14)

  1. National Center for Biotechnology Information. PubChem Compound Summary for CID 2735032, 1,1-Diphenyl-2-picrylhydrazyl (free radical). Accessed October 24, 2026. pubchem.ncbi.nlm.nih.gov/compound/2735032 Primary source

v14 published-data charts (checked October 24, 2026)

  1. Chow HH, Cai Y, Hakim IA, et al. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clin Cancer Res. 2003;9(9):3312–3319 (abstract). PMID 12960117. pubmed.ncbi.nlm.nih.gov/12960117/ Peer-reviewed
  2. Chow HH, Hakim IA, Vining DR, et al. Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals. Clin Cancer Res. 2005;11(12):4627–4633 (abstract). doi.org/10.1158/1078-0432.CCR-04-2549 Peer-reviewed
  3. Lao CD, Ruffin MT, Normolle D, et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med. 2006;6:10 (Table 2; open access). doi.org/10.1186/1472-6882-6-10 Peer-reviewed
  4. Boocock DJ, Faust GE, Patel KR, et al. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev. 2007;16(6):1246–1252 (abstract). doi.org/10.1158/1055-9965.EPI-07-0022 Peer-reviewed
  5. Walle T, Hsieh F, DeLegge MH, Oatis JE, Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004;32(12):1377–1382 (abstract). doi.org/10.1124/dmd.104.000885 Peer-reviewed
  6. Czank C, Cassidy A, Zhang Q, Morrison DJ, Preston T, Kroon PA, Botting NP, Kay CD. Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study. Am J Clin Nutr. 2013;97(5):995–1003 (abstract; NCT01106729). doi.org/10.3945/ajcn.112.049247 Peer-reviewed
  7. PubChem Compound Summary, Resveratrol (CID 445154): C14H12O3, MW 228.24 g/mol, XLogP3 3.1 (computed); melting point 253–255 °C (HSDB) as listed in PubChem. Accessed October 24, 2026. pubchem.ncbi.nlm.nih.gov/compound/445154 Primary source
  8. PubChem Compound Summary, Capsaicin (CID 1548943): C18H27NO3, MW 305.4 g/mol, XLogP3 3.6 (computed); melting point 65 °C (HSDB) as listed in PubChem. Accessed October 24, 2026. pubchem.ncbi.nlm.nih.gov/compound/1548943 Primary source
  9. PubChem Compound Summary, Epigallocatechin gallate (CID 65064): C22H18O11, MW 458.4 g/mol, XLogP3 1.2 (computed); melting point 140–142 °C (HMDB) as listed in PubChem. Accessed October 24, 2026. pubchem.ncbi.nlm.nih.gov/compound/65064 Primary source
  10. PubChem Compound Summary, Ursolic acid (CID 64945): C30H48O3, MW 456.7 g/mol, XLogP3 7.3 (computed); melting point 284 °C (HSDB) as listed in PubChem. Accessed October 24, 2026. pubchem.ncbi.nlm.nih.gov/compound/64945 Primary source
  11. PubChem Compound Summary, Beta-carotene (CID 5280489): C40H56, MW 536.9 g/mol, XLogP3 13.5 (computed); melting point 183 °C (HSDB) as listed in PubChem. Accessed October 24, 2026. pubchem.ncbi.nlm.nih.gov/compound/5280489 Primary source
  12. Kim SH, Ji YS, Lee ES, Hong ST. Ostwald ripening stability of curcumin-loaded MCT nanoemulsion: influence of various emulsifiers. Prev Nutr Food Sci. 2016;21(3):289–295 (Tables 1–2; open access, CC BY-NC). doi.org/10.3746/pnf.2016.21.3.289 Peer-reviewed
  13. Qian C, Decker EA, Xiao H, McClements DJ. Nanoemulsion delivery systems: influence of carrier oil on β-carotene bioaccessibility. Food Chem. 2012;135(3):1440–1447 (abstract). doi.org/10.1016/j.foodchem.2012.06.047 Peer-reviewed
  14. Mueller SC, Uehleke B, Woehling H, Petzsch M, Majcher-Peszynska J, Hehl EM, et al. Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin. Clin Pharmacol Ther. 2004;75(6):546–557 (abstract). doi.org/10.1016/j.clpt.2004.01.014 Peer-reviewed

Large Botanical Model: scaling, compute and adaptation

  1. Hoffmann J, Borgeaud S, Mensch A, et al. Training compute-optimal large language models. arXiv:2203.15556; 2022 (Eq. 2, 4, 10; Tables 1–3). arxiv.org/abs/2203.15556 Peer-reviewed
  2. Besiroglu T, Erdil E, Barnett M, You J. Chinchilla scaling: a replication attempt. arXiv:2404.10102; 2024 (Table 1). arxiv.org/abs/2404.10102 Peer-reviewed
  3. Kaplan J, McCandlish S, Henighan T, et al. Scaling laws for neural language models. arXiv:2001.08361; 2020 (Section 2.1). arxiv.org/abs/2001.08361 Peer-reviewed
  4. Muennighoff N, Rush AM, Barak B, et al. Scaling data-constrained language models. arXiv:2305.16264; 2023. arxiv.org/abs/2305.16264 Peer-reviewed
  5. Grattafiori A, Dubey A, Jauhri A, Pandey A, et al. The Llama 3 herd of models. arXiv:2407.21783; 2024 (Sections 1, 3.2, 3.3; Table 4). arxiv.org/abs/2407.21783 Peer-reviewed
  6. Meta. Llama 3.1 model card (training GPU-hours, license). github.com/meta-llama/llama-models. Accessed October 22, 2026. github.com/meta-llama/llama-models/blob/main/models/llama3_1 Primary source
  7. Team OLMo, Walsh P, Soldaini L, Groeneveld D, et al. 2 OLMo 2 Furious. arXiv:2501.00656; 2024. arxiv.org/abs/2501.00656 Peer-reviewed
  8. Allen Institute for AI. OLMo-2-1124-7B model card and config.json (Apache 2.0; 4 trillion tokens; 32 layers, hidden size 4,096, MLP size 11,008). Accessed October 22, 2026. huggingface.co/allenai/OLMo-2-1124-7B Primary source
  9. Hu EJ, Shen Y, Wallis P, et al. LoRA: low-rank adaptation of large language models. arXiv:2106.09685; 2021. arxiv.org/abs/2106.09685 Peer-reviewed
  10. Dettmers T, Pagnoni A, Holtzman A, Zettlemoyer L. QLoRA: efficient finetuning of quantized LLMs. arXiv:2305.14314; 2023. arxiv.org/abs/2305.14314 Peer-reviewed
  11. Rajbhandari S, Rasley J, Ruwase O, He Y. ZeRO: memory optimizations toward training trillion parameter models. arXiv:1910.02054; 2019 (Section 3.1). arxiv.org/abs/1910.02054 Peer-reviewed
  12. NVIDIA. H100 Tensor Core GPU, specifications (BFLOAT16 Tensor Core 1,979 teraFLOPS with sparsity, H100 SXM). Accessed October 22, 2026. nvidia.com/en-us/data-center/h100/ Primary source
  13. NVIDIA. A100 Tensor Core GPU, specifications (BFLOAT16 Tensor Core 312 TFLOPS dense, 624 with sparsity). Accessed October 22, 2026. nvidia.com/en-us/data-center/a100/ Primary source
  14. NVIDIA. L40S GPU, specifications (BFLOAT16 Tensor Core 362.05 TFLOPS dense, 733 with sparsity). Accessed October 22, 2026. nvidia.com/en-us/data-center/l40s/ Primary source
  15. Andersch M, Palmer G, Krashinsky R, et al. NVIDIA Hopper architecture in-depth. NVIDIA Technical Blog, March 22, 2022 (Table 3; with-sparsity values labeled effective TFLOPS). developer.nvidia.com/blog/nvidia-hopper-architecture-in-dept Primary source

Large Botanical Model: representations, retrieval and evaluation

  1. Schwaller P, Gaudin T, Lányi D, Bekas C, Laino T. "Found in Translation": predicting outcomes of complex organic chemistry reactions using neural sequence-to-sequence models. Chem Sci. 2018;9(28):6091–6098. doi.org/10.1039/c8sc02339e Peer-reviewed
  2. Schwaller P, Laino T, Gaudin T, et al. Molecular Transformer: a model for uncertainty-calibrated chemical reaction prediction. ACS Cent Sci. 2019;5(9):1572–1583. doi.org/10.1021/acscentsci.9b00576 Peer-reviewed
  3. Schwaller P. MolecularTransformer repository, README, smi_tokenizer. Accessed October 22, 2026. github.com/pschwllr/MolecularTransformer Primary source
  4. Ross J, Belgodere B, Chenthamarakshan V, Padhi I, Mroueh Y, Das P. Large-scale chemical language representations capture molecular structure and properties. Nat Mach Intell. 2022;4(12):1256–1264. doi.org/10.1038/s42256-022-00580-7 Peer-reviewed
  5. Chithrananda S, Grand G, Ramsundar B. ChemBERTa: large-scale self-supervised pretraining for molecular property prediction. arXiv:2010.09885; 2020. arxiv.org/abs/2010.09885 Peer-reviewed
  6. Bushuiev R, Bushuiev A, Samusevich R, Brungs C, et al. Self-supervised learning of molecular representations from millions of tandem mass spectra using DreaMS. Nat Biotechnol. 2026;44(4):630–640 (published online May 23, 2025). doi.org/10.1038/s41587-025-02663-3 Peer-reviewed
  7. GeMS dataset card (roman-bushuiev/GeMS), Hugging Face; declared license MIT. Accessed October 22, 2026. huggingface.co/datasets/roman-bushuiev/GeMS Primary source
  8. Yang Z, Song J, Yang M, Yao L, et al. Cross-modal retrieval between 13C NMR spectra and structures for compound identification using deep contrastive learning. Anal Chem. 2021;93(50):16947–16955. doi.org/10.1021/acs.analchem.1c04307 Peer-reviewed
  9. van den Oord A, Li Y, Vinyals O. Representation learning with contrastive predictive coding. arXiv:1807.03748; 2018. arxiv.org/abs/1807.03748 Peer-reviewed
  10. Radford A, Kim JW, Hallacy C, et al. Learning transferable visual models from natural language supervision. arXiv:2103.00020; 2021. arxiv.org/abs/2103.00020 Peer-reviewed
  11. Lewis P, Perez E, Piktus A, et al. Retrieval-augmented generation for knowledge-intensive NLP tasks. arXiv:2005.11401; 2020. arxiv.org/abs/2005.11401 Peer-reviewed
  12. Gao T, Yen H, Yu J, Chen D. Enabling large language models to generate text with citations (ALCE). arXiv:2305.14627; 2023. arxiv.org/abs/2305.14627 Peer-reviewed
  13. Guo C, Pleiss G, Sun Y, Weinberger KQ. On calibration of modern neural networks. arXiv:1706.04599; 2017. arxiv.org/abs/1706.04599 Peer-reviewed

Large Botanical Model: public data sources and terms

  1. USDA Agricultural Research Service. Dr. Duke's Phytochemical and Ethnobotanical Databases, data.gov catalog entry (License: Creative Commons CCZero). Accessed October 22, 2026. catalog.data.gov/dataset/dr-dukes-phytochemical-and-ethnobot Primary source
  2. IMPPAT: Indian Medicinal Plants, Phytochemistry And Therapeutics, home page (version 3.0 counts). Accessed October 22, 2026. cb.imsc.res.in/imppat/ Primary source
  3. MassBank record format documentation (LICENSE field, mandatory; allowed licenses). Accessed October 22, 2026. github.com/MassBank/MassBank-web/blob/main/Documentation/Mas Primary source
  4. National Library of Medicine. Terms and conditions for NLM data. Accessed October 22, 2026. nlm.nih.gov/databases/download/terms_and_conditions.html Primary source
  5. National Library of Medicine. Web policies, copyright section. Accessed October 22, 2026. nlm.nih.gov/web_policies.html Primary source
  6. PubMed Central. PMC Open Access Subset (license terms; permitted automated retrieval services). Accessed October 22, 2026. pmc.ncbi.nlm.nih.gov/tools/openftlist/ Primary source
  7. 17 U.S.C. §105, Subject matter of copyright: United States Government works. law.cornell.edu/uscode/text/17/105 Regulation or statute

Multi-objective screening (v14, checked Oct 24, 2026)

  1. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46(1-3):3–26 (reprint of 1997;23:3–25). doi.org/10.1016/S0169-409X(00)00129-0 Peer-reviewed
  2. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002;45(12):2615–2623. doi.org/10.1021/jm020017n Peer-reviewed

Cases: primary reports

  1. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med. 2000;343(25):1833–1838. doi.org/10.1056/NEJM200012213432502 Peer-reviewed
  2. FDA. Final rule declaring dietary supplements containing ephedrine alkaloids adulterated because they present an unreasonable risk. 69 FR 6788 (Feb. 11, 2004); Docket 1995N-0304; effective Apr. 12, 2004. federalregister.gov/documents/2004/02/11/04-2912/final-rule- Regulation or statute
  3. Nutraceutical Corp. v. Von Eschenbach, 459 F.3d 1033 (10th Cir. Aug. 17, 2006), No. 05-4151. law.resource.org/pub/us/case/reporter/F3/459/459.F3d.1033.05 Regulation or statute
  4. FDA. DMAA in Products Marketed as Dietary Supplements. Content current as of Feb. 22, 2023. fda.gov/food/dietary-supplement-ingredient-directory/dmaa-pr Primary source
  5. Hawaii Department of Health; CDC. Notes from the field: acute hepatitis and liver failure following the use of a dietary supplement intended for weight loss or muscle building — May–October 2013. MMWR Morb Mortal Wkly Rep. 2013;62(40):817. cdc.gov/mmwr/preview/mmwrhtml/mm6240a1.htm Primary source
  6. U.S. Department of Justice, Office of Public Affairs. Five individuals and two companies plead guilty to felony charges in multimillion dollar scheme (Mar. 13, 2019). justice.gov/opa/pr/five-individuals-and-two-companies-plead- Primary source
  7. Wu DT, Deng Y, Chen LX, Zhao J, Bzhelyansky A, Li SP. Evaluation on quality consistency of Ganoderma lucidum dietary supplements collected in the United States. Sci Rep. 2017;7:7792 (summarizes the 2015 New York attorney general action). doi.org/10.1038/s41598-017-06336-3 Peer-reviewed
  8. Ivanova NV, Kuzmina ML, Braukmann TWA, Borisenko AV, Zakharov EV. Authentication of herbal supplements using next-generation sequencing. PLoS One. 2016;11(5):e0156426. doi.org/10.1371/journal.pone.0156426 Peer-reviewed
  9. FDA. Action Levels for Lead in Processed Food Intended for Babies and Young Children; Guidance for Industry; Availability. 90 FR 1135 (Jan. 7, 2025); Docket FDA-2022-D-0278 (final guidance). federalregister.gov/documents/2025/01/07/2024-31534/action-l Agency guidance
  10. FDA. Tianeptine Products Linked to Serious Harm, Overdoses, Death. Consumer update; content current as of May 9, 2025. fda.gov/consumers/consumer-updates/tianeptine-products-linke Primary source
  11. HHS. FDA 7-OH scheduling recommendation. Press release, July 29, 2025. hhs.gov/press-room/fda-7-oh-scheduling-recommendation.html Primary source
  12. FDA. Import Alert 54-15: Detention without physical examination of dietary supplements and bulk dietary ingredients that are or contain Mitragyna speciosa or kratom (version published Aug. 17, 2026). accessdata.fda.gov/cms_ia/importalert_1137.html Regulation or statute
  13. FDA. Import Alert 54-10: Detention without physical examination of bulk/finished dietary supplement products containing aristolochic acid (version published Dec. 10, 2020). accessdata.fda.gov/cms_ia/importalert_141.html Regulation or statute

Dose, evidence and claims

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  2. Barry MJ, Meleth S, Lee JY, et al. Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial. JAMA. 2011;306(12):1344–1351. doi.org/10.1001/jama.2011.1364 Peer-reviewed
  3. Turner RB, Bauer R, Woelkart K, Hulsey TC, Gangemi JD. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl J Med. 2005;353(4):341–348. doi.org/10.1056/NEJMoa044441 Peer-reviewed
  4. Newton KM, Reed SD, LaCroix AZ, et al. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006;145(12):869–879. doi.org/10.7326/0003-4819-145-12-200612190-00003 Peer-reviewed

Solvent classes (v14)

  1. U.S. Food and Drug Administration. Q3C — Tables and List. Guidance for Industry, Revision 3. June 2017. Accessed October 24, 2026. fda.gov/media/71737/download Agency guidance

COSMO-RS and COSMO-SAC (v14 review)

  1. Eckert F, Klamt A. Fast solvent screening via quantum chemistry: COSMO-RS approach. AIChE J. 2002;48(2):369–385. doi.org/10.1002/aic.690480220 Peer-reviewed
  2. Dassault Systèmes BIOVIA. BIOVIA COSMOtherm datasheet (DS-9888-0724; ©2024). Accessed October 24, 2026. 3ds.com/assets/invest/2025-04/biovia-cosmotherm-ds.pdf Primary source

Life-cycle assessment: standards and published studies

  1. ISO 14040:2006. Environmental management — Life cycle assessment — Principles and framework. Edition 2; Amd 1:2020; last reviewed and confirmed 2022. iso.org/standard/37456.html Regulation or statute
  2. ISO 14044:2006. Environmental management — Life cycle assessment — Requirements and guidelines. Edition 1; Amd 1:2017 and Amd 2:2020; last reviewed and confirmed 2022. iso.org/standard/38498.html Regulation or statute
  3. European Commission, Knowledge4Policy glossary. Functional unit (definition quoted from EN ISO 14040:2006). knowledge4policy.ec.europa.eu/glossary-item/functional-unit_ Primary source
  4. Bruna L, Marty C, Draye M, Cravotto G, Chatel G. Subcritical or supercritical? A comparative life cycle assessment of bioactive compound extraction from apple pomace. Cleaner Environmental Systems. 2025;18:100311. doi.org/10.1016/j.cesys.2025.100311 Peer-reviewed
  5. Gaalich I, Lee D, Aymonier C, Sonnemann G, Olchowka J, Philippot G, Loubet P. Environmental impacts of supercritical fluids processes: A critical review of life cycle assessment studies. Environmental Impact Assessment Review. 2026;116:108106. doi.org/10.1016/j.eiar.2025.108106 Peer-reviewed

Solvent selection and residual solvents

  1. Prat D, Wells A, Hayler J, Sneddon H, McElroy CR, Abou-Shehada S, Dunn PJ. CHEM21 selection guide of classical- and less classical-solvents. Green Chemistry. 2016;18(1):288–296. doi.org/10.1039/C5GC01008J Peer-reviewed
  2. Heeley J, Boobier S, Hirst JD. Solvent flashcards: a visualisation tool for sustainable chemistry. Journal of Cheminformatics. 2024;16:60. Dataset CHEM21_full.csv (AI4Green/solvent_flashcards, GNU AGPL v3). doi.org/10.1186/s13321-024-00854-9 Peer-reviewed

Ecotoxicity: test guidelines, classification and U.S. rules

  1. OECD. Test No. 201: Freshwater Alga and Cyanobacteria, Growth Inhibition Test. OECD Guidelines for the Testing of Chemicals, Section 2. oecd.org/en/publications/2011/07/test-no-201-freshwater-alga Primary source
  2. OECD. Test No. 202: Daphnia sp. Acute Immobilisation Test (2004). oecd.org/en/publications/test-no-202-daphnia-sp-acute-immobi Primary source
  3. OECD. Test No. 203: Fish, Acute Toxicity Test. oecd.org/en/publications/test-no-203-fish-acute-toxicity-tes Primary source
  4. United Nations. Globally Harmonized System of Classification and Labelling of Chemicals (GHS), tenth revised edition. ST/SG/AC.10/30/Rev.10. New York and Geneva, 2023. Chapter 4.1, Table 4.1.1; Annex 3 (H410–H412). ls-fts.unog.ch/sites/default/files/2024-04/GHS%20Rev10e.pdf Regulation or statute
  5. eCFR. 40 CFR 158.630 (terrestrial and aquatic nontarget organisms data requirements table) and 158.660 (nontarget plant protection), current to October 21, 2026. ecfr.gov/current/title-40/chapter-I/subchapter-E/part-158 Regulation or statute
  6. OSHA. 29 CFR 1910.1200 Appendix D, Safety Data Sheets (Sections 12–15 non-mandatory). osha.gov/laws-regs/regulations/standardnumber/1910/1910.1200 Regulation or statute

Wild harvest, conservation and trade

  1. Jenkins M, Timoshyna A, Cornthwaite M. Wild at Home: Exploring the global harvest, trade and use of wild plant ingredients. Cambridge (UK): TRAFFIC; 2018. traffic.org/site/assets/files/7339/wild-at-home.pdf Third-party estimate
  2. IUCN. Wild at home: threats and opportunities from the trade in wild plants. News release, June 28, 2018. iucn.org/news/species/201806/wild-home-threats-and-opportuni Third-party estimate
  3. U.S. Fish and Wildlife Service. Information for Ginseng Diggers, Dealers, and Exporters (accessed October 24, 2026). fws.gov/international-affairs/permits/ginseng Primary source
  4. Federal Register, April 26, 1999 (Vol. 64, No. 79; FR Doc. 99-10342). CITES: listing of goldenseal (Hydrastis canadensis) in Appendix II and its implementation by the United States. govinfo.gov/content/pkg/FR-1999-04-26/html/99-10342.htm Regulation or statute
  5. United Nations. UN Comtrade public API (preview), reporter United States (842), flow imports, HS 1211, 1211.20 and 0910.30, annual 2015–2024, partner World and all partners; CIF primary value and net weight. Retrieved October 24, 2026. comtradeapi.un.org/public/v1/preview/C/A/HS?reporterCode=842 Primary source

Thermodynamic stability (v14)

  1. Prausnitz JM, Lichtenthaler RN, Gomes de Azevedo E. Molecular Thermodynamics of Fluid-Phase Equilibria. 3rd ed. Upper Saddle River, NJ: Prentice-Hall; 1999. ISBN 0-13-977745-8. web.tecnico.ulisboa.pt/egazevedo/MTFPE.htm Peer-reviewed

Regulations (eCFR, current to Oct 22, 2026; checked Oct 24, 2026)

  1. 21 CFR Part 117, Subpart F, Requirements Applying to Records That Must Be Established and Maintained (§§ 117.301–117.335). ecfr.gov/current/title-21/chapter-I/subchapter-B/part-117/su Regulation or statute
  2. 21 CFR Part 1, Subpart S, Additional Traceability Records for Certain Foods (§§ 1.1300–1.1465; 87 FR 71077, Nov. 21, 2022). ecfr.gov/current/title-21/chapter-I/subchapter-A/part-1/subp Regulation or statute

Laws and Federal Register documents

  1. FDA Food Safety Modernization Act, Pub. L. 111-353, 124 Stat. 3885 (Jan. 4, 2011), § 204, Enhancing tracking and tracing of food and recordkeeping. govinfo.gov/link/plaw/111/public/353 Primary source
  2. FDA. Requirements for Additional Traceability Records for Certain Foods; final rule. 87 FR 70910 (Nov. 21, 2022). federalregister.gov/documents/2022/11/21/2022-24417/requirem Regulation or statute
  3. FDA. Requirements for Additional Traceability Records for Certain Foods: Compliance Date Extension; proposed rule. 90 FR 38084 (Aug. 7, 2025). federalregister.gov/documents/2025/08/07/2025-14967/requirem Regulation or statute
  4. Continuing Appropriations, Agriculture, Legislative Branch, Military Construction and Veterans Affairs, and Extensions Act, 2026, Pub. L. 119-37 (Nov. 12, 2025), § 780. govinfo.gov/content/pkg/PLAW-119publ37/html/PLAW-119publ37.h Primary source
  5. FDA. Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements; final rule. 72 FR 34752 (Jun. 25, 2007). govinfo.gov/content/pkg/FR-2007-06-25/pdf/07-3039.pdf Regulation or statute
  6. FDA. Current Good Manufacturing Practice, Hazard Analysis, and Risk-Based Preventive Controls for Human Food; final rule. 80 FR 55908 (Sep. 17, 2015). federalregister.gov/documents/2015/09/17/2015-21920/current- Regulation or statute

FDA guidance and pages

  1. FDA. Guidance for Industry. Part 11, Electronic Records; Electronic Signatures — Scope and Application. August 2003. fda.gov/media/75414/download Agency guidance
  2. FDA. Data Integrity and Compliance With Drug CGMP: Questions and Answers. Guidance for Industry. December 2018. fda.gov/media/119267/download Agency guidance
  3. FDA. Food Traceability List (web page, content current as of Jul. 24, 2026). fda.gov/food/food-safety-modernization-act-fsma/food-traceab Primary source
  4. FDA. FSMA Final Rule on Requirements for Additional Traceability Records for Certain Foods (web page, content current as of Oct. 8, 2026). fda.gov/food/food-safety-modernization-act-fsma/fsma-final-r Primary source

Standards and international guidance

  1. PIC/S. PI 041-1. Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments. Entry into force July 1, 2021; sections 7.4–7.5. picscheme.org/docview/4234 Agency guidance
  2. ISO/IEC 17025:2017, General requirements for the competence of testing and calibration laboratories, clauses 7.4 and 7.11, as quoted in PJLA (Perry Johnson Laboratory Accreditation) training slides, Aug. 14, 2024. pjlabs.com/downloads/webinar_slides/8.14.2024_74-711.pdf Primary source
  3. NIST Office of Weights and Measures. ISO/IEC 17025:2017 clause 7.8 crosswalk, Reporting results. February 2018. nist.gov/document/7-8-17025-crosswalk-reporting-results-2018 Primary source

Hashing, time-stamping and ledgers

  1. Haber S, Stornetta WS. How to time-stamp a digital document. Journal of Cryptology. 1991;3(2):99–111. doi.org/10.1007/BF00196791 Peer-reviewed
  2. NIST. FIPS PUB 180-4. Secure Hash Standard (SHS). August 2015. doi.org/10.6028/NIST.FIPS.180-4 Primary source
  3. Dang Q. NIST SP 800-107 Rev. 1. Recommendation for Applications Using Approved Hash Algorithms. August 2012; Table 1. doi.org/10.6028/NIST.SP.800-107r1 Primary source
  4. Yaga D, Mell P, Roby N, Scarfone K. NISTIR 8202. Blockchain Technology Overview. October 2018; sections 7.1 and 7.3. doi.org/10.6028/NIST.IR.8202 Primary source
  5. Adams C, Cain P, Pinkas D, Zuccherato R. RFC 3161. Internet X.509 Public Key Infrastructure Time-Stamp Protocol (TSP). August 2001. rfc-editor.org/rfc/rfc3161 Primary source

How EUTECNIQ differs: peer scale

  1. Peer financials (Eurofins, SGS, Intertek, Bureau Veritas, Givaudan, dsm-firmenich, IFF, Glanbia, Symrise, Kerry, Balchem, Lonza, Siegfried, Natural Alternatives International): latest annual results documents as listed in the data table, compiled and verified for /insights/market-data/ (October 2026). Primary source

U.S. regulations and FDA data

  1. eCFR versioner API, structure of 21 CFR Part 111 as of 2026-10-22 (section counts by subpart), retrieved October 24, 2026. ecfr.gov/api/versioner/v1/structure/2026-10-22/title-21.json Primary source

Management-system, food-safety and laboratory standards

  1. ISO 9001:2026, Quality management systems: Requirements. Edition 6, published September 16, 2026; replaces ISO 9001:2015 (withdrawn September 16, 2026). ISO catalogue pages checked October 24, 2026. iso.org/standard/9001 Primary source
  2. ANSI blog. ISO 9001:2026, Quality Management Systems Requirements (the revision maintains the 2015 version's core framework and process approach). blog.ansi.org/ansi/iso-9001-2026-qms-revision-updates/ Primary source
  3. ISO 22000:2018, Food safety management systems: Requirements for any organization in the food chain. Edition 2; confirmed 2023; to be revised (ISO/DIS 22000 under development). Integrates HACCP principles; same high-level structure as ISO 9001; certification is not a requirement. iso.org/standard/65464.html Primary source
  4. ISO. Certification (ISO does not perform certification; certification and accreditation defined). iso.org/certification.html Primary source
  5. ILAC. ILAC MRA and signatories (testing and calibration laboratories accredited to ISO/IEC 17025). ilac.org/ilac-mra-and-signatories/ Primary source
  6. FSSC 22000. Scheme page (Version 6 published March 2023, mandatory since April 1, 2024; based on ISO 22000, sector PRPs such as ISO/TS 22002-1, and FSSC requirements; GFSI-recognized). fssc.com/schemes/fssc-22000/ Primary source
  7. UKAS. Technical bulletin: FSSC 22000 v7 transition (v7 published May 7, 2026; all audits to v7 from May 1, 2027; transition window to April 30, 2028). August 27, 2026. ukas.com/resources/technical-bulletins/fssc-22000-v7-transit Primary source
  8. SQFI. Food Safety Code: Dietary Supplement Manufacturing, Edition 10 (FSC 31; Module 2 SQF System Elements; 2.1.2.1 management review; 2.4.3 food safety plan under Codex; 2.5.4.1 internal audits). sqfi.com/the-sqf-code/choose-your-code/library-of-codes/diet Primary source
  9. SGS. SQF Edition 10 released (March 25, 2026; audits anticipated from January 1, 2027). sgs.com/en-au/news/2026/03/sqf-edition-10-released Primary source
  10. GFSI. Recognised certification programme owners (benchmarking version 2020 list includes FSSC 22000 and SQF; ISO 22000 alone is not listed). Checked October 24, 2026. mygfsi.com/how-to-implement/recognition/certification-progra Primary source

Six Sigma and statistical quality methods

  1. ISO 13053-1:2011, Quantitative methods in process improvement: Six Sigma, Part 1: DMAIC methodology; ISO 13053-2:2011, Part 2: Tools and techniques. Both confirmed 2022. iso.org/standard/52901.html Primary source
  2. ISO 7870-2:2023, Control charts, Part 2: Shewhart control charts (edition 2, March 2023). iso.org/standard/78859.html Primary source
  3. ASQ. What is a SIPOC diagram? (suppliers, inputs, process, outputs, customers). asq.org/quality-resources/sipoc Primary source
  4. Montgomery DC. Introduction to Statistical Quality Control. 8th ed. Hoboken, NJ: Wiley; 2019. Peer-reviewed
  5. NIST/SEMATECH e-Handbook of Statistical Methods, section 6.3.2: What are variables control charts? (WECO rules, trend rules, false alarms every 371 versus about 91.75 points). itl.nist.gov/div898/handbook/pmc/section3/pmc32.htm Primary source
  6. NIST/SEMATECH e-Handbook of Statistical Methods, section 6.3.2.1: Shewhart X-bar and R and S control charts (average run length about 371 for p = 0.0027). itl.nist.gov/div898/handbook/pmc/section3/pmc321.htm Primary source
  7. Champ CW, Woodall WH. Exact results for Shewhart control charts with supplementary runs rules. Technometrics. 1987;29(4):393–399. doi.org/10.1080/00401706.1987.10488266 Peer-reviewed
  8. Houf RE, Berman DB. Statistical analysis of power module thermal test equipment performance. IEEE Trans Compon Hybrids Manuf Technol. 1988;11(4):516–520. doi.org/10.1109/33.16692 Peer-reviewed
  9. SAS Institute. SAS/STAT 14.1 User's Guide, The VARCOMP Procedure, Example 121.2: Using the GRR Method (Houf and Burman 1988 data; ANOVA, variance components, PTR(18,58,6) = 0.20145, SNR 7.31767). support.sas.com/documentation/cdl/en/statug/68162/HTML/defau Primary source
  10. Burdick RK, Borror CM, Montgomery DC. A review of methods for measurement systems capability analysis. J Qual Technol. 2003;35(4):342–354. doi.org/10.1080/00224065.2003.11980232 Peer-reviewed
  11. Minitab. Is my measurement system acceptable? (AIAG MSA Reference Manual, 4th ed., 2010: %GRR below 10% acceptable, 10–30% acceptable depending on the application, above 30% not acceptable; ndc of 5 or more). support.minitab.com/en-us/minitab/help-and-how-to/quality-an Primary source
  12. Minitab. Methods and formulas for crossed gage R&R: number of distinct categories = (standard deviation for parts / standard deviation for gage) × 1.41, truncated. support.minitab.com/en-us/minitab/help-and-how-to/quality-an Primary source
  13. Minitab. Specify the default settings for gage R&R studies (alpha to remove interaction term, default 0.05; study variation multiplier, default 6). support.minitab.com/en-us/minitab/help-and-how-to/minitab-en Primary source
  14. NIST/SEMATECH e-Handbook of Statistical Methods, section 5.6.1: Eddy current probe sensitivity case study (2^3 full factorial; data, coefficients and residual standard deviations in 5.6.1.1, 5.6.1.5 and 5.6.1.6). itl.nist.gov/div898/handbook/pri/section6/pri61.htm Primary source

CFR atlas: data, regulations and rulemaking documents

  1. Office of the Federal Register. eCFR API, versioner v1 (structure, full and versions endpoints), titles 7, 16, 19, 21, 29, 31, 40 and 50, up to date as of October 22, 2026. Retrieved October 24, 2026. ecfr.gov/reader-aids/ecfr-developer-resources/rest-api-inter Primary source
  2. National Archives, Office of the Federal Register. About the e-CFR (the e-CFR is an unofficial editorial compilation). archives.gov/federal-register/cfr/about-ecfr Primary source
  3. 21 CFR Part 1, General enforcement regulations (Subparts D, E, H, I, J, L, O, R, S). eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-A/part-1 Regulation or statute
  4. 21 CFR 10.115, Good guidance practices. eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-A/part-10/sub Regulation or statute
  5. 21 CFR Part 1308, Schedules of controlled substances (DEA). eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-21/chapter-II/part-1308 Regulation or statute
  6. 7 CFR Part 205, National Organic Program. eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-7/subtitle-B/chapter-I/subchapter-M/p Regulation or statute
  7. 7 CFR Part 357, Control of illegally taken plants. eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-7/subtitle-B/chapter-III/part-357 Regulation or statute
  8. 40 CFR Part 152, Pesticide registration and classification procedures. eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-40/chapter-I/subchapter-E/part-152 Regulation or statute
  9. 40 CFR Part 180, Tolerances and exemptions for pesticide chemical residues in food. eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-40/chapter-I/subchapter-E/part-180 Regulation or statute
  10. 16 CFR Part 260, Guides for the use of environmental marketing claims. eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-16/chapter-I/subchapter-B/part-260 Regulation or statute
  11. 19 CFR Part 149, Importer security filing. eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-19/chapter-I/part-149 Regulation or statute
  12. 29 CFR 1910.1200, Hazard communication. eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-29/subtitle-B/chapter-XVII/part-1910/ Regulation or statute
  13. 31 CFR Part 560, Iranian Transactions and Sanctions Regulations. eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-31/subtitle-B/chapter-V/part-560 Regulation or statute
  14. Electronic Records; Electronic Signatures. Final rule. 62 FR 13430, March 20, 1997. federalregister.gov/documents/1997/03/20/97-6833/electronic- Regulation or statute
  15. Premarket Notification for a New Dietary Ingredient. Final rule. 62 FR 49886, September 23, 1997. federalregister.gov/documents/1997/09/23/97-24737/premarket- Regulation or statute
  16. Regulations on Statements Made for Dietary Supplements Concerning the Effect of the Product on the Structure or Function of the Body. Final rule. 65 FR 1000, January 6, 2000. federalregister.gov/documents/2000/01/06/00-53/regulations-o Regulation or statute
  17. National Organic Program. Final rule. 65 FR 80548, December 21, 2000. federalregister.gov/documents/2000/12/21/00-32257/national-o Regulation or statute
  18. Registration of Food Facilities Under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002. Interim final rule. 68 FR 58894, October 10, 2003. federalregister.gov/documents/2003/10/10/03-25849/registrati Regulation or statute
  19. Prior Notice of Imported Food Under the Public Health Security and Bioterrorism Preparedness and Response Act of 2002. Interim final rule. 68 FR 58974, October 10, 2003. federalregister.gov/documents/2003/10/10/03-25877/prior-noti Regulation or statute
  20. Hazard Communication. Final rule. 77 FR 17574, March 26, 2012. federalregister.gov/documents/2012/03/26/2012-4826/hazard-co Regulation or statute
  21. Food Labeling: Revision of the Nutrition and Supplement Facts Labels. Final rule. 81 FR 33742, May 27, 2016. federalregister.gov/documents/2016/05/27/2016-11867/food-lab Regulation or statute
  22. Substances Generally Recognized as Safe. Final rule. 81 FR 54960, August 17, 2016. federalregister.gov/documents/2016/08/17/2016-19164/substanc Regulation or statute
  23. National Organic Program (NOP); Strengthening Organic Enforcement. Final rule. 88 FR 3548, January 19, 2023. federalregister.gov/documents/2023/01/19/2023-00702/national Regulation or statute
  24. Guides Concerning the Use of Endorsements and Testimonials in Advertising. 88 FR 48092, July 26, 2023. federalregister.gov/documents/2023/07/26/2023-14795/guides-c Regulation or statute
  25. Hazard Communication Standard. Final rule. 89 FR 44144, May 20, 2024. federalregister.gov/documents/2024/05/20/2024-08568/hazard-c Regulation or statute
  26. Trade Regulation Rule on the Use of Consumer Reviews and Testimonials. Final rule. 89 FR 68034, August 22, 2024. federalregister.gov/documents/2024/08/22/2024-18519/trade-re Regulation or statute
  27. USDA APHIS. Implementation of Revised Lacey Act Provisions (notice). 89 FR 47122, May 31, 2024: the declaration requirement has been enforced in phases since April 1, 2009; Phase VII, beginning December 1, 2024, adds HTS 1211201090 wild ginseng roots, 1211500000 ephedra, 1211600000 bark of Prunus africana, 1302140100 ephedra saps and extracts, and certain essential oils. govinfo.gov/content/pkg/FR-2024-05-31/pdf/2024-11901.pdf Regulation or statute
  28. USDA APHIS. Lacey Act: Implementation Schedule ("Since 2009, APHIS has been phasing in the Lacey Act declaration requirement"; table of HTS chapters and headings that require a declaration). Last modified January 13, 2026; read October 24, 2026. aphis.usda.gov/plant-imports/lacey-act/implementation-schedu Primary source

Registry data and large botanical trials (added October 24, 2026)

  1. ClinicalTrials.gov API v2 (U.S. National Library of Medicine). Interventional studies with intervention type Dietary Supplement, with results, and all interventional studies, counted by start year 2000–2025. Retrieved October 24, 2026. clinicaltrials.gov/data-api/api Primary source
  2. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial. JAMA. 2002;287(14):1807–1814. doi.org/10.1001/jama.287.14.1807 Peer-reviewed
  1. U.S. FDA, Human Foods Program. Response to citizen petition on β-nicotinamide mononucleotide (NMN), docket FDA-2023-P-0872 (document FDA-2023-P-0872-2754), September 2025. downloads.regulations.gov/FDA-2023-P-0872-2754/attachment_1. Primary source
  1. California Health and Safety Code § 25249.6 (Required warning before exposure) and § 25249.11(b) (2025 code). Justia. law.justia.com/codes/california/code-hsc/division-20/chapter Regulation or statute
  2. New York General Business Law § 391-oo, Sale of over-the-counter diet pills and dietary supplements for weight loss or muscle building (revision April 26, 2024). nysenate.gov/legislation/laws/GBS/391-OO Regulation or statute

Data behind the v14 figures

  1. U.S. FDA. openFDA drug enforcement reports (recalls) API; search product_description:"dietary supplement"; data last updated October 14, 2026; retrieved October 24, 2026. open.fda.gov/apis/drug/enforcement/ Primary source
  2. 21 CFR 7.3(m), recall classification (Class I, II, III). eCFR, up to date as of October 22, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-A/part-7/subp Regulation or statute

Quality standards: regulations and FDA data (USP, ICH and COA page)

  1. 21 CFR 117.410, General requirements applicable to a supply-chain program. eCFR, current as of October 21, 2026. ecfr.gov/current/title-21/chapter-I/subchapter-B/part-117/su Regulation or statute

Quality standards: USP chapters and ICH guidelines

  1. United States Pharmacopeia. General Chapter ⟨2021⟩ Microbial Enumeration Tests—Nutritional and Dietary Supplements. USP–NF. doi.org/10.31003/USPNF_M99965_01_01 Primary source
  2. United States Pharmacopeia. General Chapter ⟨2023⟩ Microbiological Attributes of Nonsterile Nutritional and Dietary Supplements. USP–NF. doi.usp.org/USPNF/USPNF_M99967_01_01.html Primary source
  3. United States Pharmacopeia. General Chapters ⟨2750⟩ Manufacturing Practices for Dietary Supplements and ⟨2740⟩ Manufacturing Practices for Dietary Ingredients. USP–NF. doi.usp.org/USPNF/USPNF_M99987_02_01.html Primary source
  4. United States Pharmacopeia. General Chapter ⟨2251⟩ Screening for Undeclared Drugs and Drug Analogues (USP course page). usp.org/node/484421 Primary source
  5. United States Pharmacopeia. ⟨232⟩ Elemental Impurities—Limits and ⟨233⟩ Elemental Impurities—Procedures: revision history and notices (including the omission of ⟨231⟩ Heavy Metals). usp.org/node/13296 Primary source
  6. ICH Q1 Expert Working Group. Work Plan, July 10, 2026 (Step 2 April 2025; Step 3 sign-off and Assembly review for Step 4 targeted December 2026). database.ich.org/sites/default/files/ICH53_Q1_EWG_WorkPlan_2 Primary source
  7. ICH Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances (Step 4, October 6, 1999); scope excludes herbal products. database.ich.org/sites/default/files/Q6A%20Guideline.pdf Agency guidance
  8. ICH Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (Step 4, November 10, 2000). database.ich.org/sites/default/files/Q7%20Guideline.pdf Agency guidance
  9. ICH Q8(R2) Pharmaceutical Development (August 2009); Q10 Pharmaceutical Quality System (June 4, 2008); Q11 (May 1, 2012); Q12 (November 20, 2019). database.ich.org/sites/default/files/Q8_R2_Guideline.pdf Agency guidance
  10. U.S. FDA. Q9(R1) Quality Risk Management, final guidance (docket FDA-2022-D-0705). fda.gov/regulatory-information/search-fda-guidance-documents Agency guidance

Quality standards: certificates of analysis, adulteration and sampling

  1. WHO. WHO guidelines for sampling of pharmaceutical products and related materials. WHO Technical Report Series No. 929 (2005), Annex 4. who.int/publications/m/item/annex-4-trs-929 Primary source
  2. Govindaraghavan S. Pharmacopeial HPLC identification methods are not sufficient to detect adulterations in commercial bilberry (Vaccinium myrtillus) extracts. Fitoterapia. 2014;99:124–138. doi.org/10.1016/j.fitote.2014.09.007 Peer-reviewed
  3. ILAC. ILAC-G8:09/2019, Guidelines on Decision Rules and Statements of Conformity (sections 1, 4 and 5.2; Table 1). ilac.org/latest_ilac_news/revised-ilac-g8-published/ Primary source
  4. JCGM 106:2012. Evaluation of measurement data: The role of measurement uncertainty in conformity assessment. Joint Committee for Guides in Metrology (BIPM). doi.org/10.59161/JCGM106-2012 Primary source

Data behind the v14 figures (rulemaking activity, recalls)

  1. U.S. FDA. openFDA food enforcement reports (recalls) API; search product_description:"dietary supplement"; data last updated October 14, 2026; retrieved October 24, 2026. open.fda.gov/apis/food/enforcement/ Primary source

Screening, validation and confidence

  1. Hollender J, Schymanski EL, Ahrens L, et al. NORMAN guidance on suspect and non-target screening in environmental monitoring. Environ Sci Eur. 2023;35:75. doi.org/10.1186/s12302-023-00779-4 Peer-reviewed
  2. Schymanski EL, Jeon J, Gulde R, Fenner K, Ruff M, Singer HP, Hollender J. Identifying small molecules via high resolution mass spectrometry: communicating confidence. Environ Sci Technol. 2014;48(4):2097–2098. doi.org/10.1021/es5002105 Peer-reviewed

Mass accuracy and molecular formulas

  1. Kind T, Fiehn O. Metabolomic database annotations via query of elemental compositions: mass accuracy is insufficient even at less than 1 ppm. BMC Bioinformatics. 2006;7:234. doi.org/10.1186/1471-2105-7-234 Peer-reviewed
  2. Kind T, Fiehn O. Seven Golden Rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry. BMC Bioinformatics. 2007;8:105 (Table 1, element limits; Table 2, element ratios). doi.org/10.1186/1471-2105-8-105 Peer-reviewed
  3. National Institute of Standards and Technology. Atomic Weights and Isotopic Compositions for All Elements (relative atomic masses of 1H, 12C, 14N, 16O, 31P, 32S). Accessed October 24, 2026. physics.nist.gov/cgi-bin/Compositions/stand_alone.pl?ele=&as Primary source
  4. NIST. CODATA value: electron mass in u, 5.485 799 090 441 × 10⁻⁴ u. Accessed October 24, 2026. physics.nist.gov/cgi-bin/cuu/Value?meu Primary source

Data processing and molecular networking

  1. Watrous J, Roach P, Alexandrov T, et al. Mass spectral molecular networking of living microbial colonies. Proc Natl Acad Sci USA. 2012;109(26):E1743–E1752. doi.org/10.1073/pnas.1203689109 Peer-reviewed
  2. Nothias LF, Petras D, Schmid R, et al. Feature-based molecular networking in the GNPS analysis environment. Nat Methods. 2020;17(9):905–908. doi.org/10.1038/s41592-020-0933-6 Peer-reviewed
  3. GNPS documentation. Molecular networking: parameter walkthrough (defaults: min pairs cosine 0.7; minimum matched fragment ions 6; node TopK 10; maximum connected component size 100; ±17 Da precursor filter; top 6 peaks in ±50 Da window; 0.02 Da recommended for high-resolution data). Accessed October 24, 2026. ccms-ucsd.github.io/GNPSDocumentation/networking/ Primary source
  4. GNPS documentation. GNPS spectral libraries (LEAFBOT, Library Enabling Annotation of Botanical Natural Products; Cech and Kellogg) and batch-upload license note: reference spectra contributed directly to GNPS carry a CC0 license by default. Accessed October 24, 2026. github.com/CCMS-UCSD/GNPSDocumentation/blob/master/docs/gnps Primary source
  5. GNPS spectral library LEAFBOT, MGF export (802 spectra). Downloaded October 24, 2026. external.gnps2.org/gnpslibrary/LEAFBOT.mgf Primary source
  6. Schmid R, Heuckeroth S, Korf A, et al. Integrative analysis of multimodal mass spectrometry data in MZmine 3. Nat Biotechnol. 2023;41(4):447–449. doi.org/10.1038/s41587-023-01690-2 Peer-reviewed
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Databases, classification and dereplication

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Building blocks, scaffolds and chemical space

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