CLINICAL RESEARCH COMPLIANCE Michael A. Swit, Esq. Vice President, Life Sciences PharmaCongress Washington, D.C. Thursday, November 8, 2007

2 ANCIENT CHINESE CURSE May You Live in Interesting Times …

3 THESE ARE INTERESTING REGULATORY TIMES September 30, 2004 – the beginning of the current era of drug regulation –Vioxx –SSRI’s and suicidal ideation Since then: –Tysabri –Avandia New Lynchpin of Regulatory Process – Drug Safety

4 INTERESTING REGULATORY TIMES … FDA Leadership –Top -- In disarray McClellan left to go to CMS; Crawford interim Commissioner Summer 2005 – Crawford confirmed by Senate Sept – Crawford abruptly resigns 2006 – Andrew von Eschenbach becomes acting December 2006 – von Eschenbach confirmed Sept – General Counsel resigns –Deputies & Associates – many leave at end of 2006

5 The Perfect Storm? The Current FDA Regulatory Equation -- (Drug Safety Lynchpin) + (Leadership Vacuums) = an approval process mired in uncertainty, fear and decision paralysis PLUS A Democratic Congress PLUS September 30, 2007 – Deadline Day –PDUFA Reauthorization Sunsets –Pediatric Exclusivity and Pediatric “Rule” Sunsets EQUALS Congress in driver’s seat to drive change?? –But, still have 2 more years of Bush

6 KEY FDA CONCERNS SHOULD INFORM YOU Informed Consent Handling –Timing issues (enrollment before IC) –Wrong forms (e.g., different study) –Total absence of informed consent –Person doing consent not trained on process –L.A.R. handling –Translations –Exculpatory language

7 KEY FDA CONCERNS … Absence of an IND (Johns Hopkins) AE Handling –Not reported to IRB –Not reported to FDA Protocol deviations –Dosage –Timing of events

8 FDA Audits at the Sponsor To measure compliance with GCP, FDA audits sponsors’ SOPs for –informed consent –protocol preparation –adverse experience reporting –data entry and compilation –recordkeeping –site monitoring CRO’s – ride herd on them

9 FDA -- Site Inspection Concerns Site Qualification -- how (e.g., telephone, memo, etc.) the monitor explained to investigator status of the test article, nature of the protocol, and the obligations of a clinical investigator Delegation of Authority -- Whether authority for the conduct of the various aspects of the study was delegated properly so that the investigator retained control and knowledge of the study

10 FDA -- Site Inspection Concerns If and why the investigator discontinued the study before completion If laboratory tests are performed in the investigator’s own facility, whether that facility is equipped/staffed to perform each test specified (example: CLIA high complexity certification) Protocol and all IRB approvals and modifications are up to date

11 Protocol Changes Changes to protocol must be: –documented by an approved amendment (and may need FDA pre-clearance under IND rules) –dated –maintained with the protocol –approved by the IRB and reported to the sponsor before implementation, except where necessary to eliminate apparent immediate hazard to human subjects

12 Other Key Concerns Clinical Sites – –source document handling –Completeness of Patient Records –Signature logs –Test article accountability –Record retention IRB Matters – –continuing review –Expedited review Data integrity – Fraud – –AIP –Investigator disqualification

13 Downstream Damage – Collateral Consequences NDA denial FDA administrative or legal actions (seizure, injunction, criminal prosecution) Products liability exposure Shareholder litigation Etc., etc., etc.

14 Final Sermon: Please Teach Vigorous Corporate Risk Avoidance P = Procedures T = Training V = Validated C = Compliance Culture from the Top R = Records A = Audit

15 Call, , fax or write: Michael A. Swit, Esq. Vice President, Life Sciences THE WEINBERG GROUP INC. 336 North Coast Hwy. 101 Suite C Encinitas, CA Phone Fax Cell D.C. Office Questions?

16 About your speaker… Michael A. Swit, Esq., is Vice President, Life Sciences at THE WEINBERG GROUP, where he develops and ensures the execution of a broad array of regulatory and other services to drug and biologics clients seeking to market products in the United States. His expertise includes FDA and CMS development strategies, compliance and enforcement initiatives, recalls and crisis management, submissions and related traditional FDA regulatory activities, labeling and advertising, and clinical research efforts. Mr. Swit has been addressing critical FDA legal and regulatory issues since His multi-faceted experience includes serving for three and a half years as corporate vice president, general counsel and secretary of Par Pharmaceutical, a prominent, publicly-traded, generic drug company and, thus, he brings an industry and commercial perspective to his work with FDA-regulated companies. Mr. Swit then served for over four years as CEO of FDANews.com, a premier publisher of FDA regulatory newsletters and other specialty information products for the FDA-regulated community. His private FDA regulatory law practice has included service as Special Counsel in the FDA Law Practice Group in the San Diego office of Heller Ehrman White & McAuliffe and with the Food & Drug Law practice at McKenna & Cuneo, both in the firm’s Washington office and later in San Diego. He first practiced FDA regulatory law with the D.C. office of Burditt & Radzius. Mr. Swit has taught and written on a wide variety of subjects relating to FDA law, regulation and related commercial activities, including, since 1989, co-directing a three-day intensive course on the generic drug approval process and editing a guide to the generic drug approval process, Getting Your Generic Drug Approved. A former member of the Food & Drug Law Journal Editorial Board, he also has been a prominent speaker at numerous conferences sponsored by such organizations as RAPS, FDLI, and DIA. A magna cum laude graduate of Bowdoin College, he received his law degree from Emory University Law School and is a member of the California, D.C. and Virginia bars.

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