managing sponsor/investigator relationships 5 th national conference on managing legal risks in...

Managing Sponsor/Investigator

Relationships5th National Conference on Managing Legal Risks in

Structuring and Conducting Clinical Trials

American Conference Institute

Boston

September 27, 2006

Michael A. Swit, Esq.Vice President, Life Sciences

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Understand the Objectives of Each Party

Sponsor Objectives– Continued study of test article– Meet enrollment objectives– Obtain valid usable data

Investigator Objectives– Access to new therapies for

patients– Prestige -- e.g., journal publications– Supplement income

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Understand the Responsibilities of Each Party

Sponsor Responsibilities– Develop Protocol and

Investigational Plan– Select Qualified Investigators– Provide investigator with

Investigator Brochure (Update as necessary)

– Maintain Effective IND

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Sponsor Responsibilities (cont.):

− Monitor Investigations to assure compliance with protocol, investigational plan, and FDA requirements

− Data Review for safety and efficacy− Notify FDA and Investigators about

significant new adverse effects or risks

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Sponsor Responsibilities (cont.) – Maintain required records – Study Drug control documentation – Investigator financial interest – File required reports with FDA:

-Annual Report -IND Safety Reports

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Sponsor Responsibilities (cont.)− A sponsor who discovers investigator

noncompliance with the signed agreement (form FDA -1572), the investigational plan, or any applicable FDA regulation shall promptly secure compliance or discontinue shipment of the investigational new drug to the investigator and end that investigator’s participation in the study. The sponsor shall notify FDA when an investigator is no longer participating in the study.

21 C.F.R. 312.56.

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Investigator Responsibilities

Complete Financial Disclosure Information and update as necessary

Complete and sign Form 1572 Comply with Commitments

• Conduct study in accord with protocol, • Only make changes to protocol after

notifying sponsor, and with IRB approval, except when necessary to protect safety, rights, or welfare of subjects

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Investigator Responsibilities (cont.)• Comply with Commitments (cont.):

– Comply with all FDA requirements– Personally conduct or supervise the

investigation—Comply with informed consent and IRB

requirements—Report adverse experiences to sponsor and IRB—Read and understand investigator brochure—Assure that those assisting in study are

informed about their obligations to meet these commitments

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Investigator Responsibilities (cont.)

Comply with Commitments (cont.)—Comply with informed consent and IRB

requirements—Report adverse experiences to sponsor and

IRB—Read and understand investigator brochure—Assure that those assisting in study are

informed about their obligations to meet these commitments

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• Control Investigational New Drug • Prepare Records

− Prepare adequate and accurate case histories

− Case report forms and supporting data− Informed consent− Medical records

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Investigator Responsibilities (cont.)Reports• Progress Reports (at least annually)• Safety Reports

• Prompt report to sponsor of any effect that may reasonably be regarded as caused by, or probably caused by the study drug. Report alarming adverse effect immediately.

• Final Report• At end of study, provide sponsor with a report

discussing the investigator’s participation in the study.

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• Maintain all records for a period of 2 years following the date a marketing application is approved, or if no application is filed or approved, 2 years after the investigation is discontinued and FDA is notified (21 CFR 312.62(c)

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Other Investigator Responsibilities

• HIPAA Compliance

• Reimbursement Compliance

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Trouble in Paradise: What can happen when things go wrong

FDA Inspection Authority

– Inspection of clinical research records & reports at reasonable times. 21 C.F.R. 312.68 - Investigator

21 CFR 312.58 - Sponsor

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FDA Enforcement Measures• Public Notice (Policy Response)

– Notice of Violation– FDA Warning Letters

• Investigator Disqualification– 21 C.F.R. 312.70– Repeated or deliberate failure to comply

with applicable FDA regulations, or submission of false statements to FDA or sponsor in any required report

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FDA Enforcement Measures (cont.)

• Debarment– Generic Drug Enforcement Act of 1992

(Debarment Act); 21 U.S.C. § 355a– Bars a person from providing any

services to companies with approved or pending NDAs or ANDAs

– Historically applied to employees of pharmaceutical company

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FDA Enforcement Measures (cont.)

Application Integrity Policy– FDA Compliance Policy Guide

7150.09 (July 1, 1999)– FDA will conduct investigations

to identify all instances of fraud or wrongful acts

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Criminal Prosecution Federal Food, Drug, and Cosmetic

Act Violation Federal Violations (felony)

False Statements

Wire Fraud

Mail Fraud

Conspiracy


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Congressional Investigations• Constitutional Authority: McGrain v. Daugherty, 273

U.S. 135 (1927) Congress may conduct investigations to further its legislative function pursuant to Article 1 of the United States Constitution

• Rules of EngagementTitle II of the United States CodeStanding Rules of the Senate, Rule XXVI, Committee ProcedureRules of the House, Rules X and XI

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Senate Committee on Finance (Recent Activity)• Investigation of sponsor funding

of research• Investigation of sale by clinical

researchers of drug-study secret• Investigation of human subject

protections at clinical research site

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Measures to Increase Compliant Collaboration/Decrease Liability

1.Assure Detailed and Complete– Clinical Trial Agreement -- use to

regulate the relationship• Key issue – financial disclosure re conflicts

– Protocol – both initial and amendments – ensure amendments are communicated effectively and, if needed, with training

– Investigator’s Brochure

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2. Require Investigator Training** GCP** Product – especially important for

devices

3. Require Standard Operating Procedures

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4. Conduct Investigator Due Diligence:– Check FDA databases for disqualified and

debarred investigators– Check FDA’s NIDPOE database– Check FDA Warning Letter database– Check HHS Office of Research Integrity’s

database for Research Misconduct Cases– Check/PHS Actions/Debarment Actions database– FOIA FDA inspection documents on investigators– Check State Licensing Board to verify current

Medical License– Google!!!

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5.Employ an Effective Monitoring Program– Pre-Study Visit– Study Initiation Visit– Periodic Visits– Closeout Visit– Monitor your Monitors– Monitor your CRO if you have one– Follow up on deficient monitoring

visits

The End

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About the speaker …Michael A. Swit, Esq., who is Vice President, Life Sciences at THE WEINBERG GROUP INC., has extensive experience in all aspects of FDA regulation with a particular emphasis on drugs and medical device regulation. In addition to his private legal and consulting experience, Mr. Swit also served for three and a half years as vice president and general counsel of Pharmaceutical Resources, Inc. (PRI) a prominent generic drug company and, thus, brings an industry and commercial perspective to his representation of FDA-regulated companies. While at PRI from 1990 to late 1993, Mr. Swit spearheaded the company’s defense of multiple grand jury investigations, other federal and state proceedings, and securities litigation stemming from the acts of prior management. Mr. Swit then served from 1994 to 1998 as CEO of Washington Business Information, Inc. (WBII) a premier publisher of FDA regulatory newsletters and other specialty information products for the FDA publishing company. Before joining THE WEINBERG GROUP, he served in the FDA Regulatory Law Practices at both Heller Ehrman and McKenna & Cuneo, first in that firm’s D.C. office and then in its San Diego office. He first practiced FDA regulatory law with the D.C. office of Burditt & Radzius from 1984 to 1988. Mr. Swit has taught and written on a wide variety of subjects relating to FDA law including, since 1989, co-directing a three-day intensive course on the generic drug approval process, serving on the Editorial Board of the Food & Drug Law Journal, and editing a guide to the generic drug approval process, Getting Your Generic Drug Approved, published by WBII. Mr. Swit holds an A.B., magna cum laude, with high honors in history, in 1979, from Bowdoin College, and earned his law degree from Emory University in 1982. He is a member of the California, Virginia and District of Columbia bars.

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Call, e-mail, fax or write:

Michael A. Swit, Esq.Vice President, Life SciencesTHE WEINBERG GROUP INC.

336 North Coast Hwy. 101Suite C

Encinitas, CA 92024Phone 760.633.3343

Fax 760.633.3501Cell 760.815.4762

D.C. Office [email protected]

www.weinberggroup.com

Questions?

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For more than twenty years, leading companies have depended on THE WEINBERG GROUP

when their products are at risk. Our technical, scientific and regulatory experts deliver the

crucial results that get products to market and keep them there.

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managing sponsor/investigator relationships 5 th national conference on managing legal risks in...

Documents

party sponsor responsibilities

party sponsor objectives

investigator noncompliance

investigator brochure

irb requirements

effective ind slide

investigational plan

fda requirements data