fda regulatory considerations for the biomedical companies michael a. swit, esq. vice president,...

FDA Regulatory Considerations for the

Biomedical Companies

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

LARTA

NIH-CAP COMMERCIALIZATION WORKSHOP

Marina Del Rey, CaliforniaOctober 17, 2007

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ANCIENT CHINESE CURSE

May You Live in Interesting Times …

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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

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INTERESTING REGULATORY TIMES …

• FDA Leadership– Top -- In disarray

• 2004 -- McClellan left to go to CMS; Crawford interim Commissioner

• Summer 2005 – Crawford confirmed by Senate• Sept. 2005 – Crawford abruptly resigns• 2006 – Andrew von Eschenbach becomes acting• December 2006 – von Eschenbach confirmed• Sept. 2007 – General Counsel resigns

– Deputies & Associates – many leave at end of 2006

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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

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The Result – FDAAA• FDAAA -- Food and Drug

Administration Amendments Act of 2007 -- H.R. 3580 (422 pages)

• Negotiated compromise – passed House on September 20 and Senate on September 21

• Signed by President on Thurs., September 27, 2007

• Public Law 110-85

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Key Provisions for Drug Industry

• PDUFA Reauthorization• Prescription Drug Advertising Review Fees• DTC Advertising Penalties• Drug Safety Provisions• Clinical Trials Registry & Results Data Base• Critical Path Initiative – Reagan-Udall

Foundation• Pediatric Exclusivity and Pediatric “Rule”

Reauthorization• Citizen Petitions – limits FDA authority to delay

approvals• Biosimilars – NOT COVERED by FDAAA

FDA's Three Key Development Roles:

•"Gatekeeper" to the marketplace -- the new drug approval process

•"Cop on the beat" or "Enforcer" -- ensuring quality compliance via inspection and enforcement actions (e.g. criminal charges)

•"Sentinel" of Safety Concerns - during development and post-approval 8

What Data – Quantity & Quality – Will FDA

Require?•Will vary -- FDA has extensive discretion here

•Key task -- try to get clarity as soon as possible in the process -- Ways to do so:– Pre-IND or Pre-IDE meeting -- encouraged

by FDA prior to start of human clinicals– End of Phase 2 Meeting - also encouraged

-- here's where you want to "lock" them in9


Require?•FDAMA § 119(a) --

– FDA must meet with you on design of studies; and

– Any agreement on study design must be written and can't be changed later w/o your consent unless a new safety or effectiveness issue arises later

– “Special Protocol Assessments” – FDA process for implementing – aka “SPA” (see Slide 7)

•FDAMA § 115(a) -- data from one adequate and well-controlled study and confirmatory evidence can be used to show substantial evidence of effectiveness

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Require? …•"Pure" proof of clinical effectiveness may not be needed -- e.g., under “Fast Track,” may be able to use:– Surrogate endpoints– Clinical endpoints– Phase IV study will be needed

usually11

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The SPA – Panacea or Pablum?

• Good news – you theoretically have FDA locked in

• Bad news – FDA is locked in to your plan and, if problems arise in clinicals, are you boxing your firm in to a lack of flexibility?

The FDA Review -- Priority and Speed

•"Fast Track" -- FDAMA § 112– treats a "serious or life threatening

condition"– shows "potential to address unmet

medical needs for such condition"– If so, FDA must "facilitate the

development and expedite and review" of the drug

– Request at time of or after IND filingSee 1998 Guidance on Fast Track

http://www.fda.gov/cder/guidance/2112fnl.pdf

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The FDA Review – Key Issues Impacting Speed &

Criteria• Vioxx Backlash –

– FDA – • Now Very Risk adverse• Slower• Leadership fragmented – Crawford

resignation– “New” or “Renewed” “Regulators”

• Congress – as now seen via FDAAA• Products Liability Lawyers• U.S. Attorneys• States Attorney General• “Qui Tam” relators

Tips to avoid problems & speed review

•Make sure R&D and Sales & Marketing are talking early on -- ensure the indication being studied is one you want to sell

•Understand, that an approval is not enough – you need to get Medicare &/or private payer reimbursement– Start the reimbursement qualification

process early– Design clinical protocols to address payer

expectations• Private & Government• Example -- study your drug in Medicare-age

patients

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Tips to avoid problems & speed review…

•Make sure you are ready to go to “D” from “R” – – Internally – people and systems– Formulation has been rigorously reviewed so as

to optimize your chances when going into humans

•Study and file electronically, if possible•Respond to FDA deficiency letters during review promptly, fully, and honestly– Know how the system works – if you don’t

agree with a reviewer’s decision, work up the chain of command

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•If outsourcing, audit aggressively your "vendors:”– CROs, clinical investigators, contract

manufacturers, API makers– IRBs – they have been shut down in past– Joint venture partners – e.g., Cialis® – Lilly

manufacturing plant problems – delayed about one year

– Remember – even when you outsource, you are still ultimately responsible for what happens and you still need to have systems and people in place to ensure your vendors are working correctly

•Don't bury your head to problems -- investigate and disclose promptly

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• Don’t fall madly in love with your technology – understand that you have to prove safety and effectiveness – “I just know it works” is not the standard

• The process is very complex – this is a mere overview – build the right team to tackle– But, be careful with involving lobbyists,

Congressmen/women, etc., at any stage

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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 760.454.2979Cell 760.815.4762

[email protected]

Questions?

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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 1984. 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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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

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fda regulatory considerations for the biomedical companies michael a. swit, esq. vice president,...

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