1. 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

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

3. 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

4. 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

5. 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

6. 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

7. 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

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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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 )
Other 14

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. US References FDA Cosmetics Home Page
FDA Authority over Cosmetics
Inspection of Cosmetics - An Overview
Cosmetic GMP Guidelines/Inspection Checklist
FDA Cosmetics Handbook
50+ FDA Acronyms

22. 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

23. EU References
Council of Europe - Guidelines for good manufacturing practice of cosmetic products (GMPC)
GMP for Producers of Cosmetic Ingredients
European Compliance Academy - Directory of GMP Guidelines

24. ASEAN References ASEAN GMPs for Cosmetics
ASEAN Cosmetic Documents
ASEAN Cosmetic GMP Training Modules
Singapore Health Regulations

25. Thank You