FDA Amendments Act FDAAA: New Regulatory Authorities

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FDA Amendments Act (FDAAA) New Regulatory
Authorities

• Paul J. Seligman, M.D., M.P.H.
• Associate Director, Safety Policy Communication
• U.S. Food and Drug Administration
• Royal Danish Embassy Conference
• Copenhagen November 4, 2008

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FDAAA Overview

• Title I Prescription Drug User Fee Amendments
• Title II Medical Device User Fee Amendments
• Title III Pediatric Medical Device Safety and
  Improvement Act
• Title IV Pediatric Research Equity Act
• Title V Best Pharmaceuticals for Children Act
• Title VI Reagan-Udall Foundation
• Title VII Conflicts of Interest
• Title VIII Clinical Trial Database
• Title IX Enhanced Authorities Regarding
  Postmarket Safety of Drugs
• Title X Food Safety
• Title XI Other Provisions

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FDA Amendments Act (FDAAA)

• Passed September 27, 2007
• Regulatory Authorities
• Postmarket studies
• Labeling
• Risk Evaluation and Mitigation Strategies (REMS)
• Large Databases
• Clinical Trials Database
• Reagan-Udall Foundation
• Public-private partnerships

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Post Market Studies and Surveillance

• Essential Elements
• Require postmarket studies at time of or after
  approval
• Timetable for completion
• Periodic reports
• Register in clinicaltrials.gov
• Enforcement provisions if sponsor fails to comply

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Post Market Studies and Surveillance

• Required studies must be based on new safety
  information
• Information derived from
• a clinical trial
• an adverse event report
• a postapproval study
• peer-reviewed biomedical literature
• postmarket risk identification and analysis
  system,
• a REMS assessment, or
• other scientific data deemed appropriate by the
  Secretary

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Post Market Studies and Surveillance

• Requirement must be based on scientific data and
  is limited to certain specific purposes
• To assess a known serious risk related to the use
  of the drug
• To assess signals of serious risk related to the
  use of the drug
• To identify an unexpected serious risk when
  available data indicates the potential for a
  serious risk
• Limited to Rx drugs and biologics

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Post Market Studies and Surveillance

• Before requiring a study, must find that
• adverse event reporting and
• active post market risk identification and
  analysis system (to be established under the Act)
  will not be sufficient to meet the purposes
  described previously
• Before requiring a clinical trial, must determine
  that a post approval study or studies
  (epidemiology) will not be sufficient

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Sponsor Requirements

• Submit a timetable for completion of the study or
  trial
• Periodic reports on the status of the study,
  including difficulties encountered
• For each required trial or trial otherwise
  undertaken by the sponsor
• Whether enrollment has begun
• Number of participants enrolled
• Expected completion date
• Difficulties completing
• Registration information in clinicaltrials.gov.

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Enforcement of Study Requirements

• May not introduce drug into interstate commerce
  if in violation of provision
• May be in violation if fails to comply with the
  timetable or violates any other requirement of
  the section, unless good cause shown
• FDA determines what is good cause

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Safety-Related Labeling Changes

• New authority to require labeling changes based
  on new safety information
• Strict timelines for negotiating changes
• Same enforcement mechanisms as for studies
• Applies to Rx drugs only to generic drugs if no
  innovator marketing

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Risk Evaluation and Mitigation Strategies (REMS)

• Applies to Rx applications only, drugs and
  biologics, certain special adaptations for
  generics
• Submission requirements pre-approval
• FDA may determine REMS is needed to ensure that
  the benefits of the drug outweigh the risks of
  the drug, inform the sponsor, and require sponsor
  to submit a REMS
• Certain factors must be considered
• Size of population likely to use drug
• Seriousness of disease
• Expected benefit of drug
• Expected duration of treatment
• Seriousness of known or potential adverse events
• Whether the drug is an NME

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REMS

• Submission requirements post-approval
• If no REMS in effect, FDA may determine REMS is
  needed and require sponsor to submit if the
  Secretary becomes aware of new safety information
  and determines that the benefits of the drug
  outweigh the risks of the drug
• If FDA requires REMS, sponsor must submit within
  120 days, or within such other reasonable time as
  FDA requires to protect the public health

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REMS - ELEMENTS

• Only required element is a timetable for
  submission of assessments of the REMS
• Required timetable
• Assess 18 months, 3 years, and 7 years after REMS
  approved
• FDA may specify other shorter or longer
  frequencies
• FDA can eliminate assessments after 3 years if
  determines serious risks of the drug have been
  adequately identified and assessed and are being
  adequately managed

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REMS Elements

• Medication Guides and PPI
• if it may help mitigate serious risk of the drug
• Communication plan
• if FDA determines plan may support implementation
  of an element of the REMS
• Plan may include
• letters to healthcare providers, disseminating
  info about the REMS to encourage implementation
• disseminating information through professional
  societies about any serious risks of the drug and
• any protocol to assure safe use

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REMS Enforcement

• Person may not introduce drug into interstate
  commerce if REMS required and person fails to
  comply with the requirements of strategy or
  requirements to submit assessments
• Public posting of REMS elements
• Civil monetary penalties specified

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Pharmacovigilance/Active Surveillance

• Applies to drugs and biologics
• Develop methods to obtain access to disparate
  data sources
• Develop validated methods for
• Risk identification
• Analysis
• Data system to include
• 25 million patients by 7/1/2010
• 100 million patients by 7/1/2012

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Pharmacovigilance/Active Surveillance

• Establish procedures for
• Using electronic health data (c/w HIPAA) to
• identify risks
• conduct analyses
• report AEs in a standardized form
• link both private and public sectors
• Contract with qualified entities to
• Analyze data
• Investigate priority drug safety questions
• Perform advanced research
• Timeframe
• GAO report privacy, confidentiality, security
  issues 18 months
• FDA Report to Congress how Agency has used this
  system for active surveillance 4 years

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Adverse Drug Reaction Reports

• Bi-weekly screening of ADR system
• Quarterly report of new safety information or
  potential signal of a serious risk
• Annual review entire backlog of postmarketing
  commitments
• which should be revised or eliminated
• assign start and completion dates, and
• report to Congress annually on determinations
• Report to Congress within 2 years of enactment
• procedures for addressing ongoing postmarket
  safety issues identified by OSE
• how OSE recommendations are handled by the agency

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Clinical Trials Database National Library of
Medicine

• Responsibility of NIH www.clinicaltrials.gov
• Public process for input on implementation
• Adds a results database
• Basic - 9/29/2008
• Expanded 9/29/2010
• Links to FDA documents
• Advisory committee summary documents
• Medical reviews
• Public health advisories
• Action packages
• Summaries of safety and effectiveness data

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Reagan-Udall Foundation

• Purpose - to advance FDA mission to
• modernize product development
• accelerate innovation
• enhance product safety (including post-market)
• Independent 501(c)(3) corporation
• Operates via grants, contracts, consortia,
  fellowships
• Privately funded
• Anticipated to fund important critical path and
  surveillance projects

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Summary and Questions

• Paul J. Seligman, M.D., M.P.H.
• Paul.Seligman_at_fda.hhs.gov
• 301-796-3513