FDA PROPOSED DISCLOSURE RULE

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FDA PROPOSED DISCLOSURE RULE
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An Example of Complexity Gene Therapy Products
Ex Vivo Transduced CD34 Cells Expressing
GammaC-R for X-SCID
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Gene Therapy and Xenotransplantation Products
Come From Nature...

• Natura enim non imperatur, nisi parendo Nature
  cannot be ordered about, except by obeying her
• Novum Organum (1620), Sir Francis Bacon
• in nature there are no rewards or punishments
  there are consequences.
• Some Reasons Why (1881), Robert Ingersoll
• For every intended consequence, there are a
  hundred mostly unknown unintended consequences
  that we must address...
• FDA reviewers lament

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Consequences From Biologics

• Jenner, 1796
• Prevention of smallpox, but spread of syphilis
• St. Louis, 1901
• Diphtheria antitoxin, children died with tetanus
• Salk, 1950s
• First successful killed vaccine, large scale
  manufacturing failure

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Consequences From Biologics

• RSV Vaccine, 1960s
• Killed vaccine, vaccinated died
• U Penn, 1999
• 18 year old patient dies in experimental gene
  therapy trial
• Rotavirus Vaccine, 2000
• Prevention of infantile diarrhea, but causes
  intussuception

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Proposed Rule on Public Disclosure

• Availability for Public Disclosure and Submission
  to FDA for Public Disclosure of Certain Data and
  Information Related to Human Gene Therapy or
  Xenotransplantation
• Published for comment 1/18/01 (66 FR 4688-4706
  docket number 00N-0989)

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SCOPE and PURPORSE

• Gene Therapy and Xenotransplantation
• Unique areas of clinical research with potential
  for unique public health risks and modification
  of the human genome
• Complexity of products
• Provide consistent amount of information for
  public discussion and public access
• Enhance patient awareness and consumer protection
• Ensure accurate up to date informed consent
• Allow FDA to fully participate in public
  discussions

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WHAT IS NOT DISCLOSABLE

• Patient information
• Trade secret information (must be productive
  process, not idea)
• Limited amount of commercial confidential
  information, based on experience with RAC, DHHS
  Xeno Group and Xeno Subcommittee

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WHAT IS DISCLOSABLE, 601.52

• (1) Product and patient safety data and related
  information.
• (2) The name and address of the sponsor.
• (3) The clinical indications to be studied.
• (4) A protocol for each planned study...
• (5) Written informed consent form(s) as provided
  in 50.27 of this chapter.

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WHAT IS DISCLOSABLE, 601.52

• (6) Identification of the biological product(s)
• (7) IND safety reports, as provided in 312.32...
• (8) Information submitted in the annual report...
• (9) The regulatory status of the IND, such as on
  hold, in effect, inactive, or withdrawn...
• (10) Other relevant data and information that the
  Director, CBER, determines are necessary for the
  appropriate consideration of the public health
  and scientific issues, including relevant ethical
  issues, raised by human gene therapy or
  xenotransplantation.

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HOW WILL THIS INFORMATION BE DISCLOSED? 601.53

• Official and redacted version of each submission
  to an IND
• Redacted document to not contain patient
  information trade secrets, and certain limited
  confidential commercial information
• FDA Public Docket for each IND
• Redacted documents to specific docket through
  life of IND

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lessons from the past enable the
futureWhat can be imagined, will be done
with hope humility compassion