FDA Regulatory Considerations for the Biomedical Start-Up

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FDA Regulatory Considerations for the Biomedical
Start-Up
LARTA CAP Program Newport Beach, CA October 7,
2005
Michael A. Swit, Esq.Vice President, Life
Sciences
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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
  dont 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

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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 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

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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
• Does not block non-orphan indications
• Waxman-Hatch Exclusivity
• 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 RD 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 dont agree
  with a reviewers 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

• Dont 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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Questions?
Call, e-mail, fax or write Michael A. Swit,
Esq. Vice President, Life Sciences THE WEINBERG
GROUP INC. 336 North Coast Hwy. 101 Suite
C Encinitas, CA 92024 Phone [phone] Fax
760.633.3501 Cell 760.815.4762 D.C. Office
202.730.4123 michael.swit_at_weinberggroup.com www.we
inberggroup.com
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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 clients, both
directly and through outside counsel. 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 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 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 firms 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.
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