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Data Integrity The Early Days
©2017 Lachman Consultant Services, Inc. All rights reserved.
Robert W. Pollock Senior Advisor, Outside Director to the Board
Lachman Consultant Services, Inc.
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Waxman-Hatch Act 1984
Accelerate Approval of Generic Drugs
Reduce Costs of Health Care
Eliminate Redundant and Unnecessary Duplication of Clinical Trials
Promote Development of New Drugs Through Special Incentives
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Waxman- Hatch Implementation
60-Day Preparation Period
No Time for Adequate Training
Overwhelming Workload
Insufficient Resources
Inadequate Space
Unparalleled Pressure
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November 24, 1984
Trucks at Loading Docks
First 2 Months - 400 New ANDA’S for Post 62 drugs
Space Limitations Resulted in Decentralized Staff Locations
Congressional/Consumer/Industry Pressure
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Industry Lobbying
Waxman-Hatch “Gold Mine”
Agency Vulnerability
Brigade of Regulatory Affairs Reps
Full Court Pressure for Approval of Their Products
Company Management’s, Presidents’ & CEOs’ Follow-Up
Phone Calls
Personal Visits
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Why The Pressure?
First to Market Obtains Lion’s Share of Market
10 Billion Dollars in Untapped Products
Today 92 Billion Dollars of Products Coming Off Patent 2016 to 2020*
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* Source – Quintiles National Sales Presentation Sept 2016
Generics Delivered
Elimination of Initial Application Backlog
Unexpectedly Large Number of ANDA Approvals
Congress Was Pleased
Consumer Groups Claimed Victory
Agency Success Story
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What Went Wrong?
Greed, Money, Power
Unscrupulous Industry Personnel Found Weak Links in the System
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Complaints by Industry
Unfair Treatment
Un-level Playing Field
Without Proof, Agency Was Not Willing to Investigate
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Breaking The Case The Garbage Can Caper
Company Hired Private Investigator
Uncovered Evidence of Wrongful Acts on Behalf of FDA Employee
Resulted in Criminal Charges Involving Illegal Gratuities
Led to Wide Spread and Expanded Investigation into Fraudulent Activities in Generic Drug Industry
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FDA Wrongdoing Uncovered
Confidential Formulation Information Revealed
Manipulation of OGD’s Review Queue
Acceptance of Cash, Cars, Gifts, Illegal Gratuities
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“Bolar’s” Thioridazine
1982 - BE Lab’s letter to Bolar … not your product !!
1991 – FDA collects sample from Bolar’s retention sample
Dissolution studies reveals the overcoating
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FDA Wrongdoing Uncovered
Department of Justice Actions
22 Drug Company Criminal Convictions
70 Criminal Convictions of Individuals (Drug Company and FDA Officials) • CEOs
• VPs
• Bench chemists
• Regulatory staff
• FDA reviewers
• FDA senior staff
$50 Million in Fines
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Serious Violations and Obstruction (FD&C Act; Title 18 and other Federal Statutes)
Falsification of original records (entries and omissions)
Alteration of original records to confound investigations
Creation of records to confound investigations
Destruction of records re. matters under investigation
Fraudulent formulas and processes
Fraudulent bioequivalence samples
Substitution and switching of BE and retention samples The Dyazide debacle
Switching samples requested by FDA
Foot Dragging, Lies and Misrepresentations
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Falsified Manufacturing Records
Facilities and Equipment
• Development vs. Pilot vs. Commercial Scale
• Equipment Type and Size and Type
Batch Size
• Lab vs. Development vs. Pilot vs. Commercial
• Beaker batches of non-sterile “sterile” products
Ingredients
• Actual, substituted, added, amounts, grade/quality and suppliers
• Dispensing, utilization and accountability records
• Chronology … order; receipt; inspection; sampling; testing
• Supplier COA; QC test results
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Falsified Manufacturing Records Order of ingredient addition
Mixing/blending steps, equipment and
parameters
Compression/Encapsulation equipment,
parameters, dates, amounts, yields, in-
process sampling and results, etc.
Sterilization records … or lack thereof
Equipment utilization and cleaning records
(or lack thereof)
Sampling and accountability of retention,
release and stability testing
False reporting of investigations and results
… assuming deviations and non-
conformances were reported
Personnel Involved
Non-contemporaneous documentation
Off-the-Record Master Production and
Control Records
Off-Record Actual Executed Batch
Records
Off-the-Record List of Changes
Coating formulations, equipment,
process parameters and in-process
results.
Packaging dates, equipment, quantities,
yields, container-closures, and sampling
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All Lead to Policy, Regulatory, and Statutory Changes AIP Guidance Compliance Policy Guide 7150.09
Office of Compliance Bulletin No.1 (Sept 1992)
Office of Generic Drugs P&P Guide #34-92 (Rev. Oct 93)
Regulatory Changes Retention of bioequivalence samples for forensic testing
Statutory Generic Drug Enforcement Act 1992 (GDEA Act)
Congress’ Reaction to the FDA’S Remedial Action (AIP)
Congress Developed Its Own Statutory Remedy to Safeguard Against Fraudulent Actions
FD&C Act
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Relevance
Integrity
• Continue to remind all of the importance of integrity … data and practices
• Know the law and implementing policies and procedure
• Ethics is the foundation for Integrity regardless of what the law or implementing guidance may explicitly state
• Integrity is an integral part of a Company’s or Organizations culture
• Integrity starts from the top and is cultivated by management’s pronouncements, enabling resources and “walking the talk” every day.
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