April 2008 presentation to Swedish-American Chamber of Commerce Entrepreneurial Days on FDA issues for product development, including focus on: Planning, approval process, barriers to entry

1. Michael A. Swit, Esq.
Vice President

2. FDA Regulatory Considerations for
Life Sciences Companies
Swedish-AmericanChamberof Commerce
E-Days
LifeSciencesProgram
April9,2008
SanDiego,California

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Standard Disclaimers
 Views expressed here are solely my own and do not
necessarily reflect those of my firm or any of our clients.
 These slides support an oral briefing and may not be relied
upon solely on their own to support any conclusion of law
or fact.

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Establish FDA Strategy Early!!
 Some considerations follow . . .

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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


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Regulatory Status – Drug, Device or
Biologic? …
 Drug:
 described in USP or
 intended (via labeling)
 to affect the body of man or other animals
 to be used in the diagnosis, cure, mitigation, treatment
or prevention of disease in man or other animals

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Regulatory Status – Drug, Device or
Biologic? …
 Device: defined as involving: "instrument, apparatus, implement,
machine, contrivance, implant, in vitro reagent, or "similar or related
article including any component, part or accessory."
 in USP/NF or
 intended to be used in diagnosis … cure, mitigation,
treatment or prevention of disease or other conditions
 intended to affect the body of man

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Regulatory Status – Drug, Device or
Biologic? …
 Device definition can capture products that resemble drugs if they do
not achieve their result via being metabolized in the body or via
chemical action within or on the body -- regulated by FDA Center for
Devices & Radiological Health (CDRH)
 Examples of "drug-like" devices:
 Ultrasound contrast media
 Contact lens solutions
 Oral rinse used as barrier to plaque formation

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Regulatory Status – Drug, Device or
Biologic? …
 Devices …
 Risk of device determines how regulated
 Class I – simplest – “General Controls”
 Class II – more risky – “Special Controls”
 Class III – most risky – Premarket Approval required
 Problem – totally new technology is automatically placed in
Class III
 Can petition to take out of Class III if you don’t think the new
technology is “risky”

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Regulatory Status – Drug, Device or
Biologic? …
 Biologics --
 Generally, if derived from human or animal tissue
 Not, technically, approved under Federal Food, Drug & Cosmetic
Act; but under Public Health Service Act
 Therapeutic biologics -- were regulated by FDA Center for
Biologics (CBER) using approval standards similar to CDER
 therapeutic biotech products now at CDER
 vaccines – remain behind
 NOTE: "true" biotech products usually are biologics

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Regulatory Status – Drug, Device or
Biologic? …
 Is it a “drug,” “device” or “biologic” … or both --
"Combination" or "hybrid" products --
 are regulated per their "primary mode of action" (“PMOA”)
 but this may be difficult to discern -- get clarification very
early as will impact FDA Center you deal with
 can request in writing -- under FDAMA § 416, FDA can't
later change its mind w/o your consent or public health
reasons exist
 FDA -- final rule on “PMOA” – Sept. 2005

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Type of Submission Required for
FDA Approval or Clearance
 Drugs:
 Full New Drug Application (NDA)
 505(b)(2) NDA or "Paper NDA“ – can be avenue for
“innovative” products based on already-approved ingredients
 Abbreviated New Drug Application
 The OTC Drug route --
 Rx/OTC Switch
 OTC Review monograph change
 NDA – direct to OTC -- very rare – Abreva® (Avanir/SKB)

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Type of Submission Required for FDA
Approval or Clearance
 Devices:
 Premarket Approval Application (PMA) – Class III
devices
 clinical studies will be needed – efficacy and safety
 detailed safety data
 Premarket Notification under § 510k – Class II
(most) and some Class I devices
 Standard – “substantial equivalence” to a lawfully
marketed product – thus, technically, you are not
proofing either safety or effectiveness.
 clinical studies MAY be needed (or wanted)

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Type of Submission Required for FDA
Approval or Clearance
 Biologics
 Biologic License Application (BLA) – covers both
 Product
 Facility
 Generic versions not possible – may change …
 Omnitrope approved in EU & U.S.
 Legislation pending in U.S.
 Still likely to be approached on a case-by-case basis

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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 in

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What Data – Quantity & Quality – Will FDA
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
 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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What Data – Quantity & Quality – Will FDA
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 usually
 But – under strict scrutiny from Congress – many safety
issues linked to “fast” approvals

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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 filing
 See 1998 Guidance on Fast Track
 http://www.fda.gov/cder/guidance/2112fnl.pdf

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The FDA Review -- Priority and Speed
 General NDA classification system
 1 -- New molecular entity
 2 -- New Salt of Previously Approved Drug (not a new molecular entity)
 3 -- New Formulation of Previously Approved Drug (not a new salt OR a
new molecular entity)
 4 -- New Combination of Two or More Drugs
 5 -- Already Marketed Drug Product - Duplication (i.e., new manufacturer)

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The FDA Review -- Priority and Speed
 General NDA classification system …
 6 -- New Indication (claim) for Already Marketed Drug (includes switch in
marketing status from prescription to OTC)
 7 -- Already Marketed Drug Product - No Previously Approved NDA
(e.g., Unithroid)
 NDA Review Priority:
 S - Standard -- drugs similar to currently available drugs
 P - Priority -- significant advances over existing treatments.

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The FDA Review -- Priority and Speed
 Vioxx Backlash –
 FDA –
 Now Very Risk adverse
 Slower
 Leadership fragmented – Crawford resignation
 “New” or “Renewed” “Regulators”
 Congress
 Products Liability Lawyers
 U.S. Attorneys
 States Attorney General
 “Qui Tam” relators

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FDA-Enforced Barriers to Entry
 Orphan Drug Exclusivity -- 7 years for orphan drug for orphan
indication
 can't “remake the wheel” – blocks brand & generics
 Does not block non-orphan indications
 Waxman-Hatch Exclusivity – blocks generics
 5 years -- New Chemical Entities
 3 years -- New uses, dosage forms, etc. of previously-approved products
 New indications – less useful to prevent generic competition

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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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Tips to avoid problems & speed review…
 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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Tips to avoid problems & speed review…
 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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The Approval Gate
 Hopefully, will open for you!!
 But the odds are long, the cost is high, and the time is
lengthy
 Good luck!!

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Call, e-mail, fax or write:
Michael A. Swit, Esq.
Vice President
The Weinberg Group Inc.
336 North Coast Hwy. 101
Suite C
Encinitas, CA 92024
Phone 760.633.3343
Fax 760.454.2979
Cell 760.815.4762
michael.swit@weinberggroup.com
www.weinberggroup.com
Questions?

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About your speaker…
Michael A. Swit, Esq., is a Vice President at The Weinberg Group, Inc., a premier international scientific and regulatory
consulting firm, where he develops and ensures the execution of a broad array of regulatory and other services to clients, both
directly and through outside counsel. His expertise includes product development strategies, compliance and enforcement
initiatives, recalls and crisis management, submissions and related traditional FDA regulatory activities, labeling and
advertising, and clinical research efforts for drug, biologic, device, IVD, and other life sciences companies, as well as those in
the food and dietary supplement industries.
Mr. Swit has been addressing critical FDA legal and regulatory issues since 1984. His vast and 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 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. He received his A.B. degree, magna cum laude, with high honors in history, from Bowdoin College
and his law degree from Emory University; he belongs to the California, Virginia and District of Columbia bars.

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