EXPANDED ACCESS

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EXPANDED ACCESS

• Karen Weiss, M.D.
• Center for Biologics Evaluation and Research

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History

• Access to unapproved therapies - unrecognized
  need
• Informal policies re compassionate use post
  1938 Act
• Formal procedures for access to promising
  therapies in life threatening/emergency situations

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Current Mechanisms

• Treatment Use of an IND
• 312.34
• Emergency Use of an IND
• 312.36
• Promotion and Charging for INDs
• 312.37
• Others
• parallel track, open protocols, extension
  protocols, single patient IND

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Listening to concerns

• Perception that FDA was inconsistent in
  application of the procedures
• inequitable access, decisions arbitrary
• Perception that broader access will confer health
  benefits
• Perception that available mechanisms favored
  certain diseases

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Caveats

• Expanded access should not interfere with drug
  development
• Data from access studies
• should be collected
• not be overly burdensome
• Need for protection of human subjects

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FDAMA Sec. 402 Basic Principles

• Formalized procedures
• Clear, simple
• Equitable, non-arbitrary application
• Opportunity should be available to anyone with
  life threatening or seriously debilitating
  illness for which no, effective, approved therapy
  available
• includes knowledge of availability

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Expanded Access - Provisions

• For individuals, small groups, and treatment use
• dx, tx, monitoring - serious or immediately life
  threatening disease or condition
• No comparable or satisfactory alternative

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Individual patient access

• Any person acting through a licensed MD may
  request
• Any manuf or distributor may provide, if
• MD determines no satisfactory alternative
• probable risk from the invest. drug is not
  greater than the probable risk from the disease
• Secretary determines sufficient evidence of S E
  to support use
• Secretary determines use will not interfere with
  clinical trials to support marketing

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Treatment IND applications

• Secretary shall permit a treatment protocol
  (expanded access protocol) if
• no satisfactory alternative
• investigational drug is under IND in a controlled
  trial or
• all trials completed
• pursuing marketing with due diligence

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402 - dissemination

• Secretary may inform medical profession, health
  associations about the availability of
  investigational products under expanded access
  protocols

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Issues for consideration

• Defining categories
• indications not being developed
• Evidentiary standards to support each type of
  access
• Procedures
• Safeguards
• IRB, informed consent

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(No Transcript)
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Pediatric Update

• 7th Annual DIA Biotechnology Workshop
• February 1-2, 1999Karen Weiss, M.D.

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Proposed Rule

• Regulations Requiring Manufacturers to Assess the
  Safety and Effectiveness of New Drugs and
  Biologic Products in Pediatric Patients
• 62 FR 43900, Aug. 15, 1997
• Response to 1994 rule
• voluntary efforts did not go far enough

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Voluntary efforts

• 1991 and 1996 comparison of drugs that have been
  approved for adults with potential usefulness for
  pediatrics
• 1991 - 50 vs 1996 - 37
• of 1991 approvals, 7 with post-mkt. commitments
  for pediatric studies, only 1 led to labeling
  change
• Impact of incentives?

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Final Rule

• 63 FR 66632 Dec 2, 1998
• Effective 6 mos from date of publication
• Manufacturers must submit required assessments 20
  months after effective date of the rule (unless
  waivers, deferrals)

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Highlights of final rule

• Presumption that manufacturers will assess drugs
  and biologics in pediatric patients
• new indication, new dosage form, new route, etc.
• New drugs/biologics will contain adequate
  labeling for pediatric use at time of approval or
  soon thereafter
• Can require studies on marketed products
• Not applicable - Orphan designation drugs

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Conditions to require studies

• Likely to be commonly used in pediatrics
• lt 50,000 overall, or lt 15,000/age group
• New drug or biologic which would provide a
  meaningful therapeutic benefit (MTB) to pediatric
  patients over existing therapies
• for some classes, need range of therapeutic
  options
• Marketed drug or biologic that provide MTB,
  absence of labeling could pose significant risk

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Types of studies

• Range is possible, appropriate
• from pK and safety up to RCT
• some or all pediatric age groups
• neonates - birth up to 28 days
• infants - 28 days up to 2 years
• children - 2 years up to 12 years
• adolescents - 12 years up to age 16
• Only for the indication claimed

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When to conduct studies

• Depends on seriousness of disease, prelimin. data
  in adults, availability of other therapies
• In general, earlier if more serious condition -
  e.g., after phase 1, for less serious, after
  phase 2 for me too drugs - perhaps not until
  after approval and post-mkt. experience in adult
• may need wording in label that other drugs are
  adequately labeled

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When to waive requirement?

• Waiver for some, all pediatric age groups
• not an advance, unlikely to be used, or
  ineffective
• studies impractical (too small, geograph.
  dispersed)
• inability to develop a pediatric formulation

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Deferral

• Where adult S or E data need to be collected
  before appropriate studies in pediatric patients
• Where product ready for approval in adults before
  pediatric studies completed

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Focus on pediatric development

• Early discussions with agency re need for,
  timing of, and type of pediatric data
• Inform of need NLT end of phase 2
• Sponsors include plans in EOP2 meeting
• If deferral, reach agreements re timing of
  pediatric data
• Update status of pediatric studies in annual
  reports status

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Carrots and sticks

• Incentives
• exclusivity
• waive user fees
• Penalties
• injunctive action - misbranding
• federal court to require submission, suffer
  contempt, fines, etc.
• agency will not withdraw approval

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Ongoing efforts

• Pediatric Exclusivity
• Pediatric PK guidance
• Guidance on clinical trials in Pediatrics
• Guidance on deferrals and waivers
• ICH E-11
• Pediatric advisory committee

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Pediatric exclusivity - FDAMA

• 6 months exclusivity or patent protection under
  Drug Price Competition and Patent Term
  Restoration Act and Orphan Drug Act
• Any eligible drug for which FDA has requested
  studies and manuf. complies
• granted even if studies inconclusive
• not applicable to most biologics, antibiotics
• Guidance Qualifying for Pediatric Exclusivity
  under 505A of FDC Act

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Pediatric advisory committee

• Subcommittee of existing AC
• Draw on pediatric expertise
• ethics, clinical pharmacology
• at least 1 industry rep
• Range of products, issues. e.g., trial design,
  when addtl options needed