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
1. Quality System
2. Production System
3. Facilities and
Equipment System
4. Laboratory Control
System
5. Materials System
6. Packaging and
Labeling System
4
FDA Inspection Process
482
Notice of Inspection
483
Notice of Observations
& product sample
EIR
Establishment
Inspection Report
Discussed in
Exit Interview
Company cc’d
Company
response
to 483
FDA
Local Field Office
Supervisor
No action required
in response to 483 &
EIR
FDA
District Office
Compliance Officer
Action required
483, EIR and samples sent
to
FDA
District Director
WARNING LETTER
issued
136
You can have it your way,
Mr. Veckman . . .
6
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
– 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?
What does the FDA do?
• Warning letters
• DOMESTIC - When the FDA • Targeted establishment
shows a domestic product in
inspections & sampling
interstate commerce is
programs
adulterated or misbranded
• Seizure
• Detention (imports)
• IMPORTS – When the FDA
shows that a product appears • Injunction
• Criminal prosecution
to be adulterated or
misbranded
• ‘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
F
D
A
Enables us to prove our
products are:
– Safe
– Pure
– Effective
Whether made in a pilot
plant or a full
manufacturing plant
17
In the Eyes of the FDA
Rule #1 If it isn’t written down,
it didn’t happen.
F
D
A
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.
“Documentation incomplete”
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/ucm07
4162.htm#.T153_22Dae0.email
Inspection of Cosmetics - An Overview
– http://www.fda.gov/Cosmetics/GuidanceComplianceRegulatoryInformation/Compl
ianceEnforcement/ucm136455.htm#.T154oEtOubE.email
Cosmetic GMP Guidelines/Inspection Checklist
– http://www.fda.gov/Cosmetics/GuidanceComplianceRegulatoryInformation/Good
ManufacturingPracticeGMPGuidelinesInspectionChecklist/default.htm#.T153Jdp9
HQM.email
FDA Cosmetics Handbook
– http://www.mlmlaw.com/library/guides/fda/Coshdbok.htm
50+ FDA Acronyms
– http://app.en25.com/e/f2.aspx?elqFormName=clickThruTracking1330025649346&elqSiteID=1106&e=popk12156@yahoo.com&BlindSource=textemail&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.gmpcompliance.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