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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

Poster Guy

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Jail time for Many

Business Week March 5 1990

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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A Profound Impact

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of statistics August 1991

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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Thank you for attending!