ingredients & sourcing: supplier qualification & the … · ingredients & sourcing:...
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Ingredients & Sourcing: Supplier Qualification & the Need for Industry Guidance
Andrew Shao, PhDVice President, Global Product Science & SafetyHerbalife InternationalMay 12, 2011
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Supplement Challenges
“…The area of most concern for FDA is in the pharmaceutical spiking of dietary supplements…because we’re talking about very serious risk and injuries that can happen to people..”, Joshua Sharfstein MD, former Deputy Commissioner, FDA, testimony to the Special Senate Committee on Aging May 25, 2010
“(These) products that are marketed as dietary supplements and that contain hidden or deceptively labeled ingredients are often promoted for weight loss, sexual enhancement, and body building. These products not only pose risks to consumers but undermine confidence in legitimately marketed dietary supplements in these and other categories”
Margaret A. Hamburg, M.D., Commissioner of FDA Joint FDA-trade association letter to DS manufacturersDecember 15, 2010
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U.S
. Bo
rder
FOREIGN DOMESTICRaw
MaterialFinished Product
Contract Manufacturer(s)(bottler, labeler, ingredient manufacturer,
encapsulator)
Large Distributors
Niche/CommunityDistributors
Own LabelDistributors
Consumer
Importer
Tainted Supplement Pathway to Market
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FDA Enforcement
• Warning letters• Hundreds of product recalls and consumer alerts• Import Alerts, detentions, and refusals• Some seizures, injunctions and prosecutions• Despite agency efforts, remains a public health (and industry) concern
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Examples of Economically Motivated Adulteration
Dietary supplement/ingredient AdulterantAcerola cherry extracts Synthetic vitamin CBees wax Paraffin wax after yellow coloration
BilberryRed dye; mulberry; black bean skin; grape skin; amaranth; elderberry; black current
Black cohosh (Actae racemosa L.) White cohosh, yellow cohosh, blue cohoshChondroitin Dermatan sulfate; carrageenan; organic sulfatesCoenzyme Q10 RiboflavinFeverfew MelatoninFish oil Corn or other vegetable oilsGinkgo Biloba Rutin; Quercetin; KaempferolGoldenseal Bloodroot; Coptis; XanthorrhizaGrape extracts Blue dyeGrape Skin Extract Red dye Pomegranate extract Concentrated ellagic acid from other sources (eg. Nutgall)Pygeum extract Beta-sitosterolRice, milk proteins MelamineSaffron TurmericSaw Palmetto extract Palm oilSchizandra chinensis extract Schizandra sphenantheraSkullcap GermanderSlippery elm bark Rice flourSoy germ isoflavones Spiked with synthetic genesteinStephania AristolochiaTribulus terrestris Wild yam or fenugreek which both contain the chemical protodioscin
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21 CFR Part 111, Subpart E §111.75
• A firm may rely upon a certificate of analysis (CofA) from its supplier of a component, provided that certain criteria are met which include the following:
– The firm first qualifies the supplier by establishing the reliability of the supplier’s CofA through confirmation of the results of the supplier’s tests or examinations;
– maintains documentation of how it qualified the supplier;– periodically reconfirms the supplier’s CofA; – quality control personnel review and approve the documentation setting
forth the basis for qualification (and requalification) of any supplier.
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Far Apart: Part 110 vs. Part 111
Food cGMPs
Dietary supplement cGMPs
Dietary Supplement Manufacturers
Ingredient suppliers
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Ingredient Qualification:Testing Alone may be Inadequate
• Cannot test for that which you don’t know about
• Requires specifications (e.g. limits on contaminants and adulterants)
• Requires scientifically valid methods
• Both can be difficult or even impossible for all known or suspected adulterants (what about unknown?)
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FDA Food Safety Modernization Act of 2011
Title One – Prevention:• Inspection of records• Registration of facilities• Hazard analysis• Performance standards• Produce safety• Intentional adulteration• Re-inspection fees• NDI agreementTitle Two – Response:• Risk-based inspection • Accreditation of Labs• Traceback and record keeping• Mandatory recall authority
Title Three – Import Safety:• Foreign supplier verification• Voluntary qualified importer• Inspection of foreign facilities• 3rd party accreditation • FDA foreign officesTitle Four – Misc. Provisions: • Funding for food safety • Jurisdiction
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• “I want to assure you that respect for the food industry’s foundational role in food safety, recognition of the complexity of the global food supply, and the idea of supply chain management will inform all we do in implementing our new food safety law, and that includes its import provisions”
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FSMA – Supplier Qualification-Related
• SEC. 106. PROTECTION AGAINST INTENTIONAL ADULTERATION.– Not later than 18 months after the date of enactment of the FDA Food
Safety Modernization Act, the Secretary, in coordination with the Secretary of Homeland Security and in consultation with the Secretary of Agriculture, shall promulgate regulations to protect against the intentional adulteration of food subject to this Act
– (1) specify how a person shall assess whether the person is required to implement mitigation strategies or measures intended to protect against the intentional adulteration of food; and(2) specify appropriate science-based mitigation strategies or measures to prepare and protect the food supply chain at specific vulnerable points, as appropriate.
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FSMA – Supplier Qualification Related
• TITLE III--IMPROVING THE SAFETY OF IMPORTED FOOD SEC. 301. FOREIGN SUPPLIER VERIFICATION PROGRAM.
– Verification requirement.--Except as provided under subsections (e) and (f), each importer shall perform risk-based foreign supplier verification activities for the purpose of verifying that the food imported by the importer or agent of an importer is--"(A) produced in compliance with the requirements of section 418 or section 419, as appropriate; and"(B) is not adulterated under section 402 or misbranded under section 403(w).
– "(1) In general.--Not later than 1 year after the date of enactment of the FDA Food Safety Modernization Act, the Secretary shall promulgate regulations to provide for the content of the foreign supplier verification program established under subsection (a).
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FDA On Supplier Qualification
“A strong program of qualifying your suppliers, testing incoming ingredients, and verifying the contents of finished products – all of which are required by the CGMP regulations – can help minimize those risks.” Margaret A. Hamburg, M.D., Commissioner of FDA, Joint FDA-trade association letter to DS manufacturers, December 15, 2010
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FDA Warning Letters“You failed to qualify suppliers of components…by
establishing the reliability of the suppliers' certificate of analyses through confirmation of the results of their tests or exams, prior to their use.” Warning letter to Kabco Pharmaceuticals, Inc. 11/10/10
http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm234131.htm
““…we understand that you do not qualify any of the suppliers of such components used in your products…You are required to qualify a supplier that tests or examines components that are not dietary ingredients and maintain documentation of how you qualified the supplier.”
Warning letter to Soluble Products Co., LP 3/25/11http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm249424.htm
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Supply Chain Challenges
• Global supply chain increasingly complex– Economically motivated adulteration (EMA) – testing alone may
not be adequate• Food safety legislation requirements
– Traceability, Supplier verification• GMP requirements
– For DS, supplier qualification required for CofA reliance (but no guidance)
• “We anticipate that Industry will be creative in qualifying the global supply chain” CFSAN, FDA officials at numerous conferences and trade shows
– For drugs, FDA revising the GMP regulation→DS industry guidance needed
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Joint SIDI™ Working Group
Voluntary Supplier Qualification Guideline
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• Voluntary Component Supplier Qualification Guideline
– Standardized Information on Dietary Ingredients (SIDI™) protocol
– CofA Guideline
www.crnusa.org/SIDI
Objective• Establish voluntary guidelines following risk-based principles
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Voluntary Supplier Qualification Guideline – 12 Sections
1. Introduction 7. CofA Verification Recommendations
2. General Guidance 8. Requalification Considerations
3. Supplier Risk Management Principles
9. Disqualification
4. Pre-assessment Criteria 10.Supplier Management Recommendations
5. Supplier Capability/Audit Assessment
11.Best Business Practice Considerations
6. CofA Recommendations 12.Appendices
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Section StatusSection Description Status
1. Introduction Supply Chain Historical Background Purpose, Scope, Principles Adopted Risk Management – ICH Q9 Quality Risk Management Compliance with US GMP’s Layout
Draft of Section Complete, incorporated into Master Document
2. General Guidance
Supplier/Manufacturer Communication- Dietary Supplement Manufacturer’s Expectations- Component Supplier’s ExpectationsMaterial Intended UseCross-functional Decision MakingDocumentation and Recordkeeping
Draft Section To Be Completed
3. Supplier Risk Management Principles
Risk Assessment- Risk Identification - Risk Analysis, Risk EvaluationRisk Control - Risk Reduction, Risk Mitigation, Risk AcceptanceSupplier Qualification – Risk Factors
Draft of Section Complete, incorporated into Master Document
4. Pre-assessment Criteria
Pre-Qualification Documentation - Excipient Information Protocol (EIP), Standardized Information on Dietary Ingredients Protocol (SIDI)Supplier Questionnaire Self Audit AssessmentRaw material Pre-Qualification – Physical, Chemical, Microbiological, Organoleptic Requirements
Draft Section to be Completed
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Section StatusSection Description Status
5. Supplier Capability/Audit Assessment
Supplier Quality Management System ReviewAuditing Technique Recommendations - Direct GMP Audit, 3rd Party Audit, 3rd Party Certification
Draft of Section Completed, incorporated into Master Document
6. CofA Recommendations
SIDI WG COA GuidelineEstablishing Specifications – strength, purity, composition, limits on contaminantsProposition 65 Considerations
Draft Section to be Completed
7. CofA Verification Recommendations
Testing VerificationPhase 1 Testing (Pre-commercial/Product development)Phase 2 Testing (Commercial)Component Risk ConsiderationsPeriodic Re-verification
Draft of Section CompleteDraft Section has been incorporated into Master Document
8. Requalification Considerations
Certificate of Analysis ReconfirmationGMP AuditChange Control/Notification
Draft of Section Partially Complete
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Section StatusSection Description Status
9. Disqualification Disqualification CriteriaSupplier PerformanceRisk Mitigation
Draft of Section Completed, incorporated into Master Document
10. Supplier Management Recommendations
Supply Agreements / Quality AgreementsDocumentation and RecordkeepingChange ManagementContinuous ImprovementClaims Substantiation
Draft Section to be Completed
11. Best Business Practice Considerations
Business Continuity and CapabilitySarbanes Oxley/Corporate Accountability/Financial StabilityEnvironmental StewardshipLabor and SafetyCrisis ManagementRecall CapabilityLiability Coverage
Draft Section to be Completed
12. Appendices Low, Moderate, High Risk Component & Supplier ExamplesSpecial Considerations - Economically Motivated Adulteration
Draft of Section Completed, incorporated into Master Document
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Risk-Based Supplier Qualification
EMA
HIGH
MEDIUM
LOW
Special Cause Testing
Testing, Auditing, On-site CAPA
More Frequent C of A Monitoring
Routine C of A Verification
Supplier/Component Risk Pyramid
Resource Allocation
High
Low
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Voluntary Supplier Qualification Guideline
• Intended for industry to use to help develop internal program and SOPs
• Intended for FDA to use as basis for future guidance/rulemaking, if needed
• Completion of initial draft expected by 2012
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Proactive Precedent from Other Industries
http://www.rx-360.org/Default.aspx
http://www.gma-safe.org
www.ipecamericas.org
http://www.mygfsi.com/
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Global Emphasis• IADSA Global Guide to Good Manufacturing Practice for
Supplements
• Tool for industry and governments worldwide
• Covers quality management, premises and equipment, personnel and training, product and process development, manufacture, storage, transport and distribution.
• Provides recommendations on re-working of materials, documentation, self-inspections, sub-contracting operations, laboratory testing, complaints procedures, product recall and emergency procedures.
• Compilation of input from the ASEAN region, Europe, Japan and US
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ABC-AHP Botanical Economic Adulterants White Paper
• An extensive, peer-reviewed report of EMAs in various botanical raw materials:
– Bulk herb material– Botanical Extracts– Essential oils– Etc.
• References & links to validated analytical methods, compendial standards, etc. providing test methods for EMA detection.
• To be released in batches (8 or 10 or 12) building on the initial electronic version which will become the central material for a proposed database and webpage on ABC's site
Courtesy Mark Blumenthal, ABC Executive Director
