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

Internal Audit Program

• Trained auditors• Know the regulations and requirements• Report what they see• Team that will manage follow up/corrective

action

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3

FDA’s Inspection AuthoritySection 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

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The Six-System Inspection Model

1. Quality System

2. Production System

3. Facilities and Equipment System

4. Laboratory Control System

5. Materials System

6. Packaging and Labeling System

FDA Inspection Process482

Notice of Inspection

EIREstablishment

Inspection Report

483Notice of Observations

& product sample

FDA Local Field Office

Supervisor

Discussed in Exit InterviewCompany cc’d

No action required in response to 483 &

EIR

Action required 483, EIR and samples sent

to

Company response

to 483

WARNING LETTERissued

FDA District Office

Compliance Officer

FDA District Director

136

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You can have it your way, Mr. Veckman . . .

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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 !

.

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Four Major Factors of the Quality System Model

• Management Responsibilities

• Resources

• Manufacturing Operations

• Evaluation Activities

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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.

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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.

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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

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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

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Top cGMP 483 Letters

• Validation– 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

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FDA Enforcement ActionsWhen 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

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

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Proper Documentation Enables us to prove our

products are:– Safe– Pure– Effective

Whether made in a pilot plant or a full manufacturing plant

FFDDAA

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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.

FFDDAA

“Inadequate documentation”

“Failure to follow SOP”“Insufficient detail”

“Documentation incomplete”

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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.

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Summary and Conclusions (con’t)• Document management system needs to be clear and

logicalUse 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.

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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 DrugsFebruary 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