Medicines and Pregnancy Labeling and Beyond

1. Medicines and PregnancyLabeling 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

2. 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

3. Goals for This Talk • Progress on label model • Discuss ongoing activities related to “data” • Partnerships and leveraging • Considerations beyond fetal outcomes

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

5. 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

6. 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

7. Committee’s 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

8. 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

9. 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

10. 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

11. Pregnancy Labeling:Scope of FDA Activities • Label model development • Improving data • Expanding • Other aspects of risk management

12. 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

13. 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

14. 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

15. 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

16. 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

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

18. Lactation (continued) • FDA Activities • FDA Pediatrics Team - integrating concerns • Assess state of art/science • Combined meeting: Pregnancy Labeling and Pediatrics Advisory Committees

19. 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

20. 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

21. 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

22. The End