Auditing for Compliance It is important to periodically do self-inspections to assure that your policies, practices, procedures, etc. meet the minimum cGMP requirements. 1

Internal Audit Program Trained auditors Know the regulations and requirements Report what they see Team that will manage follow up/corrective action 2

FDA’s Inspection Authority Section 704 of FD&C Act FDA trains auditors to seek more than the law allows so know your rights May enter and inspect physical premises, raw materials, equipment, procedures, etc. during reasonable times, limits and manner. Inspection does not extend to financial data, sales data, pricing data, personal data For OTC drug, food and cosmetic companies FDA can only inspect shipping records, labels and labeling. The Act does not authorize the inspector to look at your formulas, batch and production records, complaint files and other documents Can examine and copy records of regulated products you have received May take samples of raw materials, work-in-process and finished product 3

The Six-System Inspection Model Quality System Packaging & L a b e l i n g S y s t e m Production Facilities & Equipment Laboratory Controls System M a t e r i a l s Quality System Production System Facilities and Equipment System Laboratory Control System Materials System Packaging and Labeling System Procedure Audit Based on the 21st Century Initiative, the approach for inspections has changed, but is still based on the audit against 21 CFR 210 and 211. 4

FDA Inspection Process 482 Notice of Inspection EIR Establishment Inspection Report 483 Notice of Observations & product sample FDA Local Field Office Supervisor Discussed in Exit Interview Company cc’d No action required in response to 483 & EIR Action required 483, EIR and samples sent to Company response to 483 WARNING LETTER issued District Office Compliance Officer District Director 136

You can have it your way, Mr. Veckman . . . Overzealous Environmental Protection Agency (EPA) agent Walter Peck thinks the Ghostbusters are frauds, and he has the Ghostbusters put in jail. Peck is forced to believe the Ghostbusters when New York City is put under siege by an ancient Sumerian God named Gozer the Gozerian, who is channeled through the apartment building that Dana and Louis live in, and the mayor has no choice but to let the Ghostbusters out of jail to face Gozer. 6 6

in a non-argumentative way ! Surviving an FDA Audit Arguing with an inspector is like wrestling with a pig in mud. After a while you realize that the pig actually enjoys it! Defend your position in a non-argumentative way ! . 7

Four Major Factors of the Quality System Model Management Responsibilities Resources Manufacturing Operations Evaluation Activities 8

Warrantless Inspections are the Norm The Supreme Court held that warrants are not required for inspections of those industries that are “pervasively regulated” by the government. The FDA maintains that all the industries it regulates meet that exception and the courts generally agree. The Act makes refusal to permit an inspection a “prohibited act” subject to potential criminal penalties. FDA generally tries to avoid this and will obtain a warrant if necessary. 9

How to fail an FDA inspection The cGMPs are the minimum guidelines - Adherence to a guideline does not guarantee GMP compliance. Co-operation between the FDA and industry is the goal. 10

Suggested Company Policies Have a written and well-vetted SOP prior to inspection Delegate appropriately trained person(s) or team Do not leave FDA inspector unescorted Instruct employees not to engage in casual conversation with FDA inspector Do not volunteer information or show areas not specifically requested to see Attempt to record all that happens Take and keep identical samples Do not sign anything. If the inspector asks for something in writing from you ask for a formal written request Always be absolutely honest in responding to legitimate questions to establish credibility and a good relationship Assign an FDA audit the highest priority 11

Possible outcomes of FDA audit Continuous improvement of your QA/QC systems Some type of regulatory action Warning letter or “483” Seizure of products Injunction against shipping products Criminal penalties against corporation or individuals Freedom of information act 12

Top cGMP 483 Letters Validation Microbial Contamination Process Methods Cleaning Microbial Contamination Water Raw Materials Preventive & Corrective Action OOS - Out Of Specification Failure Investigation Adherence to SOPs Stability Testing Batch/Process Control Lot Number Assignment Water Systems Validation Maintenance Adequate Testing Change Control 13

FDA Enforcement Actions When does the FDA take action? DOMESTIC - When the FDA shows a domestic product in interstate commerce is adulterated or misbranded IMPORTS – When the FDA shows that a product appears to be adulterated or misbranded What does the FDA do? Warning letters Targeted establishment inspections & sampling programs Seizure Detention (imports) Injunction Criminal prosecution ‘Voluntary” recalls (21 CFR 7.45-7.59) Other 14

FDA audits of cosmetic firms The FDA can inspect: Qualifications & training of personnel involved in making the product Manufacturing & filling equipment Finished & unfinished materials Storage containers & labeling materials Distribution, vehicles & warehouses QC Lab & procedures Cleaning & sanitation procedures Samples of raw materials, in-process material, packaging, finished product The FDA can not inspect: Research data Financial data Sales & marketing data Manufacturing records Source: Draft of CTFA’s Quality Assurance Guidelines 2007 146

FDA Audit Quick Guide Company obligated to provide Access to processing, filling and assembly areas Access to storage areas for raw materials, packaging and finished goods Access to QC laboratories Reasonable samples of raw materials, packaging components, and finished goods Reasonable documenting receipt in interstate commerce of goods Not required but may be made available at the discretion of the company Production & processing procedures and records Photographs (FDA may dispute this) Access to qualitative or quantitative formulae Product test data Copies of specific batch production records Personnel records Complaint files Sales & financial data Source: Draft of CTFA’s Quality Assurance Guidelines 2007 16

Proper Documentation Enables us to prove our products are: Safe Pure Effective Whether made in a pilot plant or a full manufacturing plant F D A 17 17

In the Eyes of the FDA Rule #1 If it isn’t written down, it didn’t happen. Rule #2 If it isn’t written down properly, you’re not sure exactly what happened. Rule #3 If the records aren’t correct, neither is the product. F D A “Inadequate documentation” “Failure to follow SOP” “Insufficient detail” “Documentation incomplete” 18 18

Summary and Conclusions GMP Documentation is one critical aspect of our business. All documentation required by GMP regulations must be issued, managed, and controlled by a document management system. QA have a major role to play in managing GMP documentation. Inspections and audits regularly identify issues with documentation system. 19

Summary and Conclusions (con’t) Document management system needs to be clear and logical Use a top down approach (QA must take the lead!) Use flow chart and other tools to define documentation needs Includes all types of documentation (including electronic) Ensure a robust document cycle from drafting to archiving Review and evaluate the performance of documentation system. 20

US References FDA Cosmetics Home Page http://www.fda.gov/Cosmetics/default.htm FDA Authority over Cosmetics http://www.fda.gov/Cosmetics/GuidanceComplianceRegulatoryInformation/ucm074162.htm#.T153_22Dae0.email Inspection of Cosmetics - An Overview http://www.fda.gov/Cosmetics/GuidanceComplianceRegulatoryInformation/ComplianceEnforcement/ucm136455.htm#.T154oEtOubE.email Cosmetic GMP Guidelines/Inspection Checklist http://www.fda.gov/Cosmetics/GuidanceComplianceRegulatoryInformation/GoodManufacturingPracticeGMPGuidelinesInspectionChecklist/default.htm#.T153Jdp9HQM.email FDA Cosmetics Handbook http://www.mlmlaw.com/library/guides/fda/Coshdbok.htm 50+ FDA Acronyms http://app.en25.com/e/f2.aspx?elqFormName=clickThruTracking-1330025649346&elqSiteID=1106&e=popk12156@yahoo.com&BlindSource=text-email&elq=6e0f55925f5041ada01974c80f559c5f&elqCampaignId=97

US Society of Cosmetic Chemists Continuing Education Program cGMPs for Cosmetics and OTC Drugs February 15, 2012 Joseph Albanese, 3V USA Technical Marketing Manager – Personal Care Susan Freije, Colgate-Palmolive Global Quality Systems

EU References Council of Europe - Guidelines for good manufacturing practice of cosmetic products (GMPC) http://book.coe.int/EN/ficheouvrage.php?PAGEID=36&=EN&produit_aliasid=1835 GMP for Producers of Cosmetic Ingredients http://www.touchbriefings.com/pdf/846/scholtyssek_WEB.pdf European Compliance Academy - Directory of GMP Guidelines http://www.gmp-compliance.org/eca_sitesearch_search_cosmetic.html

ASEAN References ASEAN GMPs for Cosmetics http://www.aseansec.org/apris2/file_pdf/Project%20Materials/ASEAN%20Guidelines%20for%20Cosmetic%20GMP.pdf ASEAN Cosmetic Documents http://elib.fda.moph.go.th/fulltext2/word/14697/1.pdf ASEAN Cosmetic GMP Training Modules http://www.aseansec.org/18514.htm Singapore Health Regulations http://www.hsa.gov.sg/publish/hsaportal/en/health_products_regulation/GMP/gmp_gdp_standard.html

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