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 MethodologiesKey Challenges
September 10, 2013
Ben Firschein, J.D., LL.M.
Director, Government Affairs and Policy
United States Pharmacopeial Convention (USP)
Topics
– Key Points
– FDA/FSMA: Implications
– USP: How Standards Can Help
•
•
•
•
USP Standards
Verification
Spectral Libraries
Food Fraud Database
– Conclusion
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
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is obsolete
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
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)
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
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
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
Background on USP…and How Standards
Can Help
• Set public quality standards for prescription and over-thecounter 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
USP’s Standards
1.
The United States Pharmacopeia-
2.
National Formulary (USP–NF)
3.
Food Chemicals Codex (FCC)
4.
USP Dietary Supplements
Compendium (DSC)
5.
USP Medicines Compendium (MC)
6.
USP on Compounding
7.
Herbal Medicines Compendium
(HMC)

Other Resources
–
–
–
–
Pharmacopeial Forum (PF)
FCC Forum (FCCF)
USP Dictionary
Chromatographic Columns
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
Role of USP Quality Standards in Law
 First
USP standards 1820; role in Federal law added
1906 (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
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
How Do Compendial Standards Help?
Compendial
Standards
 Set
standards for
identity, strength, quality
and purity
 Help
ensure the right
dosage
 Help
prevent
economically-motivated
adulteration
Strength
Identity
Is
the ingredient
what it purports to be
Is
enough of the
ingredient present
Quality/Purity

Are levels of impurities,
particularly toxic
impurities, appropriately
controlled
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
111.75(h) (1)
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 111.75(c))
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
18
Key Elements of the Verification Programs
1. Product
appropriate for
inclusion in
program
2. Audit of
manufacturing sites
for GMP compliance
6. Continuous
surveillance:
Surveillance audits
Internal audit report,
Annual product report
Product testing
Phase II
3. Review of
chemistry,
manufacturing and
controls
product
documentation
5. Review of
conformance with
mark usage
guidelines
4. Laboratory testing
of product samples
Mark
Approval
Phase I
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
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