1. Role of Compendial Standards and Verification Programs to Safeguard the Global Supply Chain FDLI Conference on Safeguarding the Functional Food and Dietary Ingredient Supply Chain Panel on Meaningful Test Methodologies- Key Challenges September 10, 2013
Ben Firschein, J.D., LL.M.
Director, Government Affairs and Policy
United States Pharmacopeial Convention (USP)

2. Topics Key Points FDA/FSMA: Implications USP: How Standards Can Help
USP Standards
Verification
Spectral Libraries
Food Fraud Database
Conclusion

3. Key Points
Public (compendial) quality standards facilitate trade, help ensure product/ingredient identity, and advance global “safety net”
Help prevent adulteration/contamination
Help manufacturers source trusted ingredients and comply with FDA requirements
Verification programs based on compendial standards are a viable solution to many supply chain concerns for producers and purchasers

4. FDA: Global Challenges
Supply chain increasingly complex
FDA-regulated products originate from more than 150 countries
Growth in overseas products will continue
Distinction between domestic and imported products is obsolete

5. FDA: Global Strategy Places Greater Responsibility on Manufacturers/Others
Allocates resources based on risk
Leverages combined efforts of government, industry, and public-private partnerships (third parties)
Greater manufacturer accountability
Know your supplier
Testing of ingredients and finished product to establish safety and quality
Manage risk of incidents

6. FDA: Food Safety Modernization Act
Evaluation of hazards/risk-based controls (Sec. 103)
Performance standards (Sec. 104)
Identify food at highest risk of adulteration/mitigate (Sec. 106)
Foreign supplier verification (Sec. 301)
Voluntary qualified importer (Sec. 302)
Mandatory certification of imported food based on risk (Sec. 303)
Accreditation of third-party auditors (Sec. 307)

7. FDA: Food Safety Modernization Act
Proposed rules:
Foreign
Foreign Supplier Verification Program (certain exemptions for dietary supplements/components)
Accreditation of Third Party Auditors
Domestic
Preventive Controls: may include verification
Intentional adulteration- proposed rule forthcoming

8. FSMA: Legal Implications
1. Expansion of FDA authority/manufacturer requirements
Suspension of facility registration (informal hearing)
Recall (informal hearing)
Increased frequency of inspections (domestic and foreign facilities)
Denial of importation (failure to obtain requested certification or revocation of qualified importer status)
Recordkeeping and review (manufacturer)
2. More FDA warning letters and enforcement actions
3. “Proof of the pudding” will be in agency regulations, rules, and guidance to implement the Act

9. Background on USP…and How Standards Can Help
Scientific, independent, nonprofit organization
Established in 1820
Headquartered in Maryland, USA; Facilities in India, China, Brazil, Switzerland, Ethiopia, and Ghana
900+ employees
Mission: To improve global health through public standards and related programs that help ensure the quality, safety, and benefit of medicines and foods

10. Background on USP…and How Standards Can Help
Set public quality standards for prescription and over-the-counter medicines, excipients (inactive ingredients), dietary supplements, and food ingredients through volunteer experts
Works closely with U.S. FDA >100 years, developing and revising drug quality standards through expert volunteers; strict conflict of interest rules

11. USP’s Standards The United States Pharmacopeia-
National Formulary (USP–NF)
Food Chemicals Codex (FCC)
USP Dietary Supplements Compendium (DSC)
USP Medicines Compendium (MC)
USP on Compounding
Herbal Medicines Compendium (HMC)
Other Resources
Pharmacopeial Forum (PF)
FCC Forum (FCCF)
USP Dictionary
Chromatographic Columns

12. USP Reference Standards
More than 3,000 Reference standards that support FDA-enforceable monograph procedures
Rigorously tested by USP, industry, and government scientists
USP Reference Standards are highly characterized specimens of:
drug substances
excipients
impurities
degradation products
dietary supplements
compendial reagents
performance test tablets
USP expends ~60% of its resources, mostly in our world-wide laboratories, to bring official USP Reference Standards to the United States and to the world.
After intensive work in our laboratories to assess candidate material and determine content, resulting data were considered carefully by the Council of Experts’ Reference Standards Expert Committee.
We recently crossed a high water mark—2600 reference materials in commerce throughout the world. And many, many more are needed to undergird all the many public procedures needed to support test procedures for food and drugs moving in national and international commerce.

13. Role of USP Quality Standards in Law
First USP standards 1820; role in Federal law added (strength, quality, purity), 1938 (identity)
Federal Food, Drug, and Cosmetic Act (FDCA) adulteration & misbranding provisions apply to both Public Health Service Act biologics & FDCA drugs
Naming/Identity
A drug with a name recognized in USP–NF must comply with compendial identity or be deemed adulterated, misbranded, or both
Strength, Quality & Purity
Must also comply with compendial standards for strength, quality, and purity, unless labeled to show all respects in which the drug differs

14. Role of USP Quality Standards in Law
For dietary Supplements: misbranded if purports to be “USP” but does not meet compendial standard Food: FCC specifications for food ingredients incorporated by reference in over 200 FDA regulations

15. How Do Compendial Standards Help?
Identity
Strength
Quality/Purity
Set standards for identity, strength, quality and purity
Help ensure the right dosage
Help prevent economically-motivated adulteration
Is the ingredient what it purports to be
Is enough of the ingredient present
Are levels of impurities, particularly toxic impurities, appropriately controlled

16. How Do Compendial Standards Help?
The requirement to do testing is part of GMPs for dietary supplements
USP (and other) standards and Reference Materials can be used to perform the identity testing required under 21 CFR (h) (1)

17. How Do Compendial Standards Help?
Standards and reference materials can also be used for the testing on the finished batch of dietary supplements to ensure that they meet product specifications for:
Identity
Purity
Strength
Composition
Limits on those types of contamination that may adulterate or that may lead to adulteration of the finished batch of dietary supplement (21 CFR (c))

18. USP Verification Services
USP Dietary Supplement Verification
Launched 2002
Dietary Supplements
USP Dietary Ingredient Verification
Launched 2004
Dietary Ingredients
Traditional Chinese Medicine Ingredients
Ayurvedic Medicine Ingredients
USP Pharmaceutical Ingredient Verification
Launched 2006
Drug Substances
Excipients
Verification programs are based on compendial standards, manufacturer requirements, and GMPs

19. Key Elements of the Verification Programs
1. Product appropriate for inclusion in program
2. Audit of manufacturing sites for GMP compliance
3. Review of chemistry, manufacturing and controls
product documentation
4. Laboratory testing of product samples
5. Review of conformance with mark usage guidelines
6. Continuous surveillance:
Surveillance audits Internal audit report, Annual product report
Product testing
Phase II
Phase I
Mark
Approval

21. USP Food Fraud Database http://www.foodfraud.org/
Free resource
Collection of public reports on foods that have historically been reported adulterated and with what adulterant
Useful for assessing risk of fraud, counterfeiting, or economically motivated adulteration
Beyond listing ingredients subjected to food fraud, gives easy access to detection methods for adulterants as reported in peer-reviewed scientific journals, which can provide an excellent starting point for mitigation strategies

22. Conclusion
FDA is moving toward verification of food and certification of third party auditors
Appropriate standards and testing regimes can reduce risk of exposure/enforcement actions by FDA and other regulatory bodies
USP standards and USP verification programs can help