Pregnancy Labeling Subcommittee Meeting

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Medicines and Pregnancy Labeling and Beyond

• Pregnancy Labeling Subcommittee Meeting
• March 28-29, 2000
• Sandra L. Kweder, MD
• Pregnancy Labeling Team
• Office of Drug Evaluation IV
• Center for Drug Evaluation Research

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Goals for Meeting

• Update on FDA activities related to pregnancy
  labeling
• Your feedback on guidance document on pregnancy
  registries
• Broader discussion of strategies
• Getting the most out of each effort
• Thinking beyond current models

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Goals for This Talk

• Progress on label model
• Discuss ongoing activities related to data
• Partnerships and leveraging
• Considerations beyond fetal outcomes

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Staffing

• Full Time for Pregnancy Labeling Activities
• Holli A. Hamilton, MD, MPH
• Dianne L. Kennedy, RPh

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Proposed Label Concept, 1999

• Goal Structure and organization adaptable to
  widely varying bodies of data and vastly
  different disease states
• Distinguish clinical considerations from risk
  information
• Different levels of information for different
  needs
• Narrative text, not letter categories

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Model Format

• Clinical Considerations
• Links risk assessment to practical application
• Summary Risk Assessment
• Incorporate human and animal data and clearly
  states relevant factors considered
• Discussion of Data
• Brief summary to convey body of science

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Committees Advice

• Model label is a good start
• Give clinical directives and advice sparingly
• Recognized the importance and challenge of
  consistency across labels
• There may be role for standard terminology,
  perhaps in risk assessment statements

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Progress Key Decision Points

• What requires regulation
• Elements more appropriate for guidance
• Implementation schedule
• How to make room for human data and experience
• How specific in clinical considerations

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Why Is This So Difficult?

• Complexity dictates need for clarity
• Uncertainty predominates in data
• Animal data are basis for risk assessments
• Human data are rare and often scattered
• Experts often disagree on interpretation
• Breadth of user needs is great
• Leave room for clinical judgement

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Why Does This Take So Long?

• Complex
• Paradigm shift from toxicity search
• Regulations are rarely simple or fast
• One of several labeling initiatives
• Essential that other systems be in place
• Data collection
• Data submission to FDA

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Pregnancy LabelingScope of FDA Activities

• Label model development
• Improving data
• Expanding
• Other aspects of risk management

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Improving Data

• Main focus remains fetal/infant outcomes
• Registries are principal tool
• Remain rare
• Reliance on product sponsors
• Where others conduct studies no link to label
• Confront controversy about value of normal
  outcomes when numbers are small

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FDA Improving Registry Data

• Guidance Document Establishing Pregnancy
  Registries
• New FDA regulation will require sponsors to
  address available data
• Facilitate inclusion in labels
• Expand discussion of registries
• CDC OTIS, March of Dimes - registry models
• International Society of Pharmacoepidemiology

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Thinking More Broadly

• Registries are important for collection of some
  types of data
• General pregnancy/fetal outcomes
• General margins of safety
• Other elements of safety and rational
  prescribing must be considered
• Pharmacokinetics and Pharmacodynamics
• Lactation

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Pharmacokinetics Pharmacodynamics

• Once treatment is decided, right dose is
  essential
• Few drug labels include PK or dose data
• Clinicians seek lowest effective dose
• Literature is limited
• Where it exists, it is not in labels (e.g.
  amoxicillin)
• Hormones of pregnancy warrant attention
• Physiologic changes
• Metabolism of drugs

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Pharmacokinetics Pharmacodynamics (Continued)

• FDA Activities
• New safety regulation labels
• NICHD Collaboration (Fall 2000 workshop)
• FDA sponsored conference, November 2000
• American Society of Clinical Pharmacology
  Therapeutics , 2001

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Lactation

• Product labels rarely informative
• Health benefits of breastfeeding
• Natural link from the pregnant or nursing mother
  to child
• Safety
• Pharmacokinetics
• Pharmacodynamics

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Lactation (continued)

• FDA Activities
• FDA Pediatrics Team - integrating concerns
• Assess state of art/science
• Combined meeting Pregnancy Labeling and
  Pediatrics Advisory Committees

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Dietary Supplements

• Hearing on 3/30/00
• Structure-function claims related to dietary
  supplements
• Distinct from disease or treatment claims
• How that relates to pregnancy and ensuring the
  safe use of such products

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Summary

• Steady progress in label model development
• Increasing emphasis on addressing data needs to
  enhance risk management
• Developing sound registries
• Thinking outside of usual models
• Finding ways to increase pk/pd data
• Lactation as link of mother to baby
• Collaboration is essential to progress

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Goals for Meeting

• Update FDA activities related to pregnancy
  labeling
• Joseph DeGeorge, PhD Preclinical
• Catherine Spong, MD NICHD
• Guidance document on pregnancy registries
• Evelyn Rodriguez, MD, MPH
• Broader discussion of strategies
• Getting the most out of each effort
• Thinking beyond current models

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The End