Presentation to the Tech Coast Angels on key legal and regulatory considerations for biomedical (drug and device) start-up companies, given on March 7, 2003.

1. FDA Legal & Regulatory
Considerations for Biomedical
Startups
Tech Coast Angels
San Diego, California
March 7, 2003
FDACounsel.com

2. Michael A. Swit, Esq.
Michael A. Swit, Esq.
Law Offices of Michael A. Swit
539 Samuel Ct.
Encinitas, CA 92024
760-815-4762; fax: 760-454-2979
mswit@fdacounsel.com
FDACounsel.com

3. Establish FDA Strategy Early!!
 Some considerations follow . . .
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4. 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
FDACounsel.com

5. The Approval Gate …
 Preliminary Considerations --
Determining the Regulatory Status of
the product
 Is it a "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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6. The Approval Gate …
 Regulatory Status of the product -
con'd…
 Is it a "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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7. The Approval Gate …
 Regulatory Status of the product -
con'd…
 Is it a "drug", "device" or "biologic"?
 Thus -- 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
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8. The Approval Gate …
 Regulatory Status of the product -
con'd…
 Is it a "drug", "device" or "biologic"?
 Biologic --
 Generally, if derived from human or animal tissue;
 used to be regulated by FDA Center for Biologics (CBER) using
approval standards similar to CDER
 therapeutic biotech products going to CDER
 vaccines – remain behind
 NOTE: "true" biotech products usually are biologics
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9. The Approval Gate …
 Regulatory Status of the product -
con'd…
 Is it a "drug", "device" or "biologic"?
 OR BOTH??
 "Combination" or "hybrid" products --
 are regulated per their "primary mode of action" --
 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
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10. The Approval Gate …
 Regulatory Status of the product -
con'd…
 What type of submission is needed to get FDA
approval or clearance?
 Drugs:
 Full New Drug Application (NDA)
 505(b)(2) NDA or "Paper NDA"
 Abbreviated New Drug Application
 The OTC Drug route -- Abreva (Avanir/SKB)
 NDA
 OTC Review monograph change
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11. The Approval Gate …
 Regulatory Status of the product -
con'd…
 What type of submission is needed to get FDA
approval or clearance?
 Devices:
 Premarket Approval Application (PMA) --
clinical studies will be needed
 Premarket Notification under § 510k --
clinical studies MAY be needed (or wanted)
FDACounsel.com

12. The Approval Gate …
 Regulatory Status of the product -
con'd…
 What type of submission is needed to get FDA
approval or clearance?
 Biologics
 Biologic License Application (BLA)
 no generic versions now possible – may change …
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13. The Approval Gate …
 Regulatory Status of the product -
con'd…
 What quantity and quality of data will be
demanded by FDA to show safety &
effectiveness?
 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 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 inFDACounsel.com

14. The Approval Gate …
 Regulatory Status of the product -
con'd…
 What quantity and quality of data?
 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
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15. The Approval Gate …
 Regulatory Status of the product -
con'd…
 What quantity and quality of data?
 FDAMA § 115(a) -- data from must one
adequate and well-controlled study and
confirmatory evidence can be used to show
substantial evidence of effectiveness
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16. The Approval Gate …
 Regulatory Status of the product -
con'd…
 What quantity and quality of data?
 "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
FDACounsel.com

17. The Approval Gate …
 FDA -- Legal Barriers to entry
 Orphan Drug Exclusivity -- 7 years for drug for
orphan indication
 can't "remake the wheel"
 Waxman-Hatch Exclusivity
 5 years -- New Chemical Entities
 3 years -- New uses, dosage forms, etc. of previously-
approved products
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18. The Approval Gate …
 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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19. The Approval Gate …
 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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20. The Approval Gate …
 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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21. The Approval Gate …
 The FDA Review -- Pre-Approval
Inspections -- Expect one if NDA is:
 new chemical or molecular entities;
 for a narrow therapeutic range drug
 the first approval for the applicant; or
 are sponsored by a company with a history of CGMP
problems or that has not been inspected for a considerable
period.
 CDER's Compliance Program Guide 7346.832 @
 http://www.fda.gov/cder/handbook/insaccep.htm
FDACounsel.com

22. The Approval Gate …
A few tips to avoid problems in drug
development and speed FDA
review:
 If outsourcing, audit aggressively your "vendors":
 CROs
 Clinical investigators
 Contract manufacturers
 IRBs
 Duke
 University of Oklahoma
 Joint venture partners
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23. The Approval Gate …
 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
 If planning to get Medicare reimbursement, make
sure:
 start the reimbursement qualification process early
 study your drug in Medicare-age patients
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24. The Approval Gate …
 Tips to avoid problems & speed review…
 Study and File electronically
 Respond to FDA deficiency letters during review
promptly, fully, and honestly
 remember -- there are these folks called products liability
plaintiffs lawyers and Securities class actions folks waiting for
you to make a mistake
 Don't bury your head to problems -- investigate and
disclose promptly
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25. 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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