Presentation to Strategies for Success in Virtual Drug Development Conference on April 15, 2013, in San Diego, focusing on: • General Considerations • Why Quality & Regulatory Matter • What Problems to Look For • How to Find Problems • Special Considerations

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Regulatory & Quality Considerations
in Virtual Drug Development
April 15, 2013
Michael A. Swit, Esq.

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Standard Disclaimers
• Views expressed here are solely mine and do not
reflect those of my firm or any of its clients.
• This presentation supports an oral briefing and
should not be relied upon solely on its own to
support any conclusion of law or fact.
• This presentation, and the materials included
herewith, are provided for general educational
purposes and should not be construed as legal
advice.
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What We Will Cover
• General Considerations
• Why Quality & Regulatory Matter
• What Problems to Look For
• How to Find Problems
• Special Considerations
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Why Regulatory & Quality Matter
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Why Regulatory & Quality Matter
• A “new drug” or biologic must be approved or subject to
an effective IND to be shipped
• A drug or biologic (D/B) made in a facility that does not
comply with the D/B Good Manufacturing Practices
(GMP) in 21 CFR Part 211 -- is adulterated under
§501(a) of the Federal Food, Drug, and Cosmetic Act
(“the Act”) – even if the drug is perfectly good
• Shipping an unapproved D/B (or one not under an IND)
or an adulterated D/B or causing the adulteration of a
D/B is a “prohibited act” under Section 301 of the Act
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Why Regulatory & Quality Matter …
• Key consequences of committing a “prohibited act”
under §301:
– Criminal Prosecution
– Injunctions (and consent decrees)
– Seizure
– Civil Penalties
– Debarment (in some cases)
– Disqualification from federal health programs (in some cases)
– FDA inspections/warning letters
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Why Regulatory & Quality Matter …
• It’s Just Good Business – maximizes your chance to
have successful development
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What Problems to Look For
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Manufacturing
• How will the product be supplied or manufactured?
– Can they make it
– Are there any particularly sensitive systems involved that
deserve special attention such as:
 Aseptic processing
 Bioreactors
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Good Clinical Practice (GCP) Compliance
• GCP Violations – can undermine reliability of data –
FDA can throw it out
• Key issues in virtual clinical developments
– Pick the right CRO – monitoring study is key
– Principal Investigators
 Qualify carefully – a KOL who does not know GCP is a receipe
for
 Verify – to extent possible – the P.I. actually can recruit
– IRBs – also must be qualified – “Coast-ing” is not what you
want
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Regulatory
• Filings – who will handle?
– If under an IND, there must be a specific assignment of duties
to a CRO or they are deemed retained by the sponsor
– If buying partially done virtual research, you will need to make
sure that the IND dossier has been properly maintained before
you take it over
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How to Probe
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History of Compliance
• Does the vendor have a history of issues with FDA
relating to quality?
– Inspections – 483s
– Warning Letters
– Official action -- consent decrees, injunctions, seizures, criminal
prosecutions
• Assess company responses
– Did they hear FDA’s “D.R.U.M.?”
 Direct, Related, Universal, Monitoring and Management
– Any continued duties?
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FDA Inspectional History
• When did FDA last inspect?
• How many inspections over five years?
– For cause (e.g., recalls, complaints, AEs)
– Routine
• What is relationship with FDA District Office?
• If 483s, are responses great, good or “oh no”
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Audits
• Does firm have an internal audit procedure?
– Ensure it was followed
– Review reports
• Has the firm had audits commissioned outside
experts to audit its operations?
• Has the firm been the subject of a third-party
audit (e.g., a partner or customer)?
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Diligence Techniques
• Review FDA “correspondence”
– 483’s
 Company responses
– Warning letters
 Company responses
• Assure yourself that problems have been corrected
– If necessary, audit the facility to confirm (at least selected key
issues)
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Diligence Techniques …
• Verify if any litigation exists that raises quality
concerns (e.g., personal injury suits alleging injury or
illness from a defectively-made drug)
– Ask if any exist
– Review complaints/answers if any exist for allegations of
defective operational practices that might have escaped FDA’s
eyes
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Special Considerations

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Phase-Specific Concerns
• Phase III to Commercial
– Scale-up validated?
 FDA won’t approve product if commercial scale does not relate
to clinical study supply
– Formulation changes documented and validated?
– Contract labs – did they meet GLP?
 Example: MDS Montreal – out of compliance; 100s of studies
compromised that needed audits
– Contract manufacturers – GMP compliant?
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Imported Products or Components
• FDA powers to stop questionable imports is much
greater
– Action can occur without physical examination
– Example -- bulk APIs going through the New York District
Office several years ago were all being detained pending proof
they were not counterfeit, adulterated or misbranded --
without physical examination.
• FDA scrutiny – much higher now than five years ago
due to Heparin and other “scandals”
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Specific Problems…A few unique ones….
• Back-up Manufacturing Plant
– When needed: whenever manufacturing is contracted out
for IND or approved
– Example: Lilly – 7/18/02 public announcement on 2nd
Quarter results and plant problems not being cured until
2003
– What clause says: lets non-mfg. party seek a backup
contractor under appropriate circumstances (e.g., Lilly had
GMP problems holding up NDA approvals)
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Specific Problems…A few unique
ones….
• Who Owns the Data?
– When needed: whenever studies of any sort are farmed out
– Example: Client has major study done at University;
contract is ambiguous on who controls the data, although
clear client can use in FDA product approval filing
– What clause says: makes clear who owns both raw data and
results and the right to authorize publications and references
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Specific Problems…A few unique
ones….
• Copies of Data Generated by Contract Labs
– When needed: whenever testing is contracted out for
IND or approved products
– Example: Oread
– What clause says: obligates the contract lab to maintain
raw data, reports, etc. and provide a copy in event of
insolvency; also could require creation of an extra archival
copy of data.
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Who You Need on Your Team
• People that really understand drug development
– Regulatory
– Quality
– Clinical effectiveness issues – design and execution
– Preclinical safety issues
– CMC
– Legal – so the contracts are right!
• If you don’t have them internally, need to hire great
consultants
– CROs vs. non-CRO consultants – pro’s and con’s
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Questions?
• Call, e-mail or fax:
Michael A. Swit, Esq.
Special Counsel, FDA Law Practice
Duane Morris LLP
San Diego, California
direct: 619-744-2215
fax: 619-923-6248
maswit@duanemorris.com
• Follow me on:
– LinkedIn: http://www.linkedin.com/in/michaelswit
– Twitter: https://twitter.com/FDACounsel
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About Your Speaker
Michael A. Swit, Esq., is a Special Counsel in the San Diego office of the international law
firm, Duane Morris, LLP, where he focuses his practice on solving FDA legal challenges
faced by highly-regulated pharmaceutical, medical device and food companies. Before joining
Duane Morris in March 2012, Swit served for seven years as a vice president at The Weinberg
Group Inc., a preeminent scientific and regulatory consulting firm in the Life Sciences. His
expertise includes product development, compliance and enforcement, recalls and crisis
management, submissions and related traditional FDA regulatory activities, labeling and
advertising, and clinical research efforts for all types of life sciences companies, with a
particular emphasis on drugs, biologics and therapeutic biotech products. Mr. Swit has been
addressing vital FDA legal and regulatory issues since 1984, both in private practice with
McKenna & Cuneo and Heller Ehrman, and as vice president, general counsel and secretary of
Par Pharmaceutical, a top public generic and specialty drug firm. He also was, from 1994 to
1998, CEO of FDANews.com, a premier publisher of regulatory newsletters and other specialty
information products for FDA-regulated firms. He has taught and written on many topics
relating to FDA regulation and associated commercial activities and is a past member of the
Food & Drug Law Journal Editorial Board. He earned his A.B., magna cum laude, with high
honors in history, at Bowdoin College, and his law degree at Emory University.
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