preparing and handling an inspection

Preparing for and Handling an FDA Inspection at Your Facility

Dawn Tavalsky Sanofi Pasteur, Inc.

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Objectives

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FDA’s Authority to Inspect

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FDA’s Authority to Inspect

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Inspection Process for Clinicals

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GMP Inspection Process

Types of GMP Inspection

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Types of GMP Inspection

Objective of the inspection !  Routine inspection !  Concise inspection !  Follow-up inspection !  Special inspection !  Quality systems review

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Types of GMP Inspection

Routine Inspection !  Full inspection of all components of GMP !  Newly established manufacturer !  Renewal of a license !  Changes:

new product or product lines modifications to manufacturing methods key personnel, premises or equipment

!  History of non-compliance with GMP !  Not inspected in the last 3-5 years

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Types of GMP Inspection

Concise Inspection !  Consistent record of compliance with GMP !  Focus on limited number of GMP requirements  selected as indicators

!  Identify significant changes !  Indicate attitude towards GMP !  Non-compliance  should trigger comprehensive inspection

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Types of GMP Inspection

Follow-up Inspection

!  Reassessment or re-inspection

!  Monitor result of corrective actions

!  6 weeks to 6 months after initial inspection  nature of defects  work undertaken

!  Specific GMP requirements  not observed

– not adequately implemented

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Types of GMP Inspection

Special Inspection

!  Spot check focusing on  one product, a group of related products  specific operations, e.g. mixing, labelling

!  Complaints or recalls

!  Adverse drug reactions

!  Marketing approval or export certificate

!   Information or investigation  specific information  advice on regulatory requirements

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Types of GMP Inspection

Quality Systems Review !  Assess the quality assurance (QA) system !  Description of the QA system (e.g. manual) !  Policy and standards to be observed !  Management structure

 implementation !  Procedures

 quality standards set for products  correctly defined manufacturing processes  records kept  QC and QA functions are performed

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Types of GMP Inspection

Frequency of Inspections

!  Depends on type of inspection !   Inspectorate resources (e.g. workload, number of inspectors) !  New facilities - before licensed !  All companies - regular schedule

 ideally annual !  Large companies

 several visits over a period, e.g. 5 years  validity of manufacturing license or GMP certificate

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Types of GMP Inspection

Duration of Inspections

!  Depends on type of inspection

!   Inspectorate resources (e.g. workload, number of inspectors)

!  Size of the company

!  Purpose of the visit

!  Days to weeks

!  Number of inspectors  including specialist support

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Types of GMP Inspection

Announced and unannounced inspections !  Depends on type of inspection !  Announced

 comprehensive inspection !  Unannounced

 routine inspection (depending on country policy)  concise inspection  follow-up inspection  special inspection

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Centers and Offices

! Office of the Commissioner Organization ! Center for Biologics Evaluation and Research Organization ! Center for Devices and Radiological Health Organization. ! Center for Drug Evaluation and Research Organization ! Center for Food Safety and Applied Nutrition Organization. ! Center for Tobacco Products Organization ! Center for Veterinary Medicine Organization ! National Center for Toxicological Research Organization ! Office of Regulatory Affairs Organization.

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Office of Regulatory Affairs (ORA) http://www.fda.gov/ora/

Headquarters:

Rockville, MD

Regional Office: Philadelphia, PA

District Office:

Detroit, MI

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FDA Field Investigators

!  Conduct inspections to enforce the Food, Drug and Cosmetic Act

!  Train themselves in “evidence

collection” !  “If it’s not documented, it didn’t happen.”

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1.  Select Site

2.  Contact Site

3.  Schedule Site

4. Arrive (482)

5. Review Records

6. Interview Staff

7. Present Findings

8. Depart (483) 9. Write Report (EIR)

10. Classify Inspection

FDA Office Site Location

FDA Inspection Process

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Overview of FDA Enforcement Actions

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FDA Forms

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Selection Criteria

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Preparing for the Audit

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!  While there are several types of audits with several different types of focus’: !  Annual Flu Vaccine !  Bi-annual audit !  Pre Approval Inspection (PAI) !  For Cause Audit !  Etc

!  We will now discuss preparing for a PAI inspection – however many of the points apply to any type of FDA audit.

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INSPECTION DOs

ü DO PLAN FOR INSPECTION ü DO PROVIDE REVELANT DOCUMENTATION ü DO ANSWER QUESTIONS TO SPECIFIC ACTIVITY ü DO ESCORT THE INSPECTOR ü DO TAKE NOTES ü DO COPY DOCUMENTS REMOVED ü DO STAMP THE REMOVE DOCUMENTS ü DO COOPERATE WITH THE FDA ü BE POLITE BUT FIRM WITH YOUR RIGHTS

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REFUSE FDA ACCESS

Ø FINANCIAL DATA Ø SALES VALUES Ø PRICING Ø PERSONNEL DATA Ø MANAGEMENT REVIEWS Ø INTERNAL AUDITS Ø SUPPLIER AUDITS

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INSPECTION DON’Ts

ü DON’T OVER SPEAK OR SAY IT’S IMPOSSIBLE ü DON’T ALLOW RECORDINGS ü DON’T SIGN AFFIDAVITS ü DON’T ALLOW ACCESS TO FILES ü DON’T GUESS AT AN ANSWER ü DON’T ANSWER “WHAT IF ?” ü DON’T ENGAGE IN ARGUMENT

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