ICH V2 An FDA Update

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ICH V2An FDA Update

• Susan Lu
• Office of Drug Safety
• Center for Drug Evaluation and Research
• FDA
• January 21, 2003

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V2 Draft Version 3.0POST-APPROVAL SAFETY
MANAGEMENT DEFINITIONS AND STANDARDS FOR
EXPEDITED REPORTING AND GOOD CASE MANAGEMENT
PRACTICES
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Background

• Topic adopted February 2002 (Brussels)
• Meetings of Expert Working Group to date
• June 2002 London
• Sept 2002 Washington D.C.
• FDA representatives
• CDER - Susan Lu , Min Chen (back-up)
• CBER - Tim Cote

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Principles

• Expansion of ICH E2A to post-approval phase
• ?Consistency with E2A document in content
• Inclusion of relevant CIOMS-V recommendations
  where applicable

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Current Status

• Step 1- discussion and consensus building among
  EU, Japan, and U.S.
• Moving towards finalization of draft for Step 2

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Overview of FDA Goals and Comments

• Consistency with U.S. regulations
• -definitions
• Sound Good Reporting Practices
• Editorial
• Clarification and further discussion

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Overview of V2 draft document

• I. Introduction
• II. Definitions and Terminology Associated with
  Post-approval Drug Safety Experience
• III. Standards for Expedited Reporting
• IV. Good Case Management Practice

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I. Introduction

• To establish an internationally standardized
  procedure to improve the quality of post-approval
  safety information, to harmonize the way to
  gather information, and if necessary, to take
  action

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II. Definitions and terminology associated with
post-approval drug safety experience

• Basic terms - Adverse event (AE), Adverse Drug
  Reaction (ADR)
• Serious AE/ADR
• Expectedness and Listedness of ADR
• Other definitions
• Sources of Individual Case Reports

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Definition of Adverse Event

• An adverse event is an untoward medical
  occurrence in a patient administered a medicinal
  product and which does not necessarily have to
  have a causal relationship with this treatment

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Definition of adverse reaction

• A response to a drug which is noxious and
  unintended and which occurs at doses normally
  used in man for prophylaxis, diagnosis or therapy
  of disease or for modification of physiological
  function. (WHO technical report 498, 1972)
• All noxious and unintended responses to a
  medicinal product related to any dose should be
  considered adverse drug reactions. The phrase
  responses to medicinal products means that a
  causal relationship between a medicinal product
  and an adverse event is at least a reasonable
  possibility, i.e. the relationship cannot be
  ruled out. (ICH E2A)

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Definition of Expectedness of an Adverse Drug
Reaction

• An unexpected adverse reaction is one, the
  nature, severity, specificity or mechanism is not
  consistent with the term or description in the
  local product labeling. Class ADRs should not
  automatically be considered to be expected for
  the subject drugexpected only if the product is
  itself implicated.

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Sources of Individual Case reports

• Unsolicited sources- spontaneous reports,
  consumer reports, literature, internet, other non
  medical sources (lay press)
• Solicited sources- study reports, organized data
  collection systems
• Licensor-licensee interaction
• Regulatory authority sources

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III. Standards for Expedited Reporting

• A. What Should be Reported?
• B. Reporting Time Frames

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III. A. What Should be Reported?

• As a rule, cases of adverse drug reactions that
  are both serious and unexpected are subject to
  expedited reporting.

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III. B. Reporting Time Frames

• Time clock start point
• Minimum Criteria for Reporting

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IV.Good Case Management Practice

• Assessing Patient and Reporter Identifiability
• Role of Narratives
• Single Case evaluation
• Follow up information
• How to report