FDA

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

Medicines and Pregnancy Labeling and Beyond

FDA

Goals for Meeting

Update on FDA activities related to pregnancy labeling

Your feedback on guidance document on pregnancy registries

Broader discussion of strategiesGetting the most out of each effortThinking beyond current models

FDA

Goals for This Talk

Progress on label modelDiscuss ongoing activities related to

“data”Partnerships and leveragingConsiderations beyond fetal outcomes

FDA

Staffing

Full Time for Pregnancy Labeling Activities

Holli A. Hamilton, MD, MPH

Dianne L. Kennedy, RPh

FDA

Proposed Label Concept, 1999

Goal: Structure and organization adaptable to widely varying bodies of data and vastly different disease statesDistinguish clinical considerations from risk

informationDifferent levels of information for different

needsNarrative text, not letter categories

FDA

Model Format

Clinical ConsiderationsLinks risk assessment to practical

application

Summary Risk AssessmentIncorporate human and animal data and

clearly states relevant factors considered

Discussion of DataBrief summary to convey body of science

FDA

Committee’s Advice

Model label is a good startGive clinical directives and advice sparingly Recognized the importance and challenge of

consistency across labelsThere may be role for standard terminology,

perhaps in risk assessment statements

FDA

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

FDA

Why Is This So Difficult?

Complexity dictates need for clarityUncertainty predominates in data

Animal data are basis for risk assessmentsHuman data are rare and often scatteredExperts often disagree on interpretation

Breadth of user needs is greatLeave room for clinical judgement

FDA

Why Does This Take So Long?Complex

Paradigm shift from toxicity search

Regulations are rarely simple or fastOne of several labeling initiativesEssential that other systems be in place

Data collectionData submission to FDA

FDA

Pregnancy Labeling:Scope of FDA Activities

Label model developmentImproving dataExpanding

Other aspects of risk management

FDA

Improving Data

Main focus remains fetal/infant outcomesRegistries are principal tool

Remain rareReliance on product sponsorsWhere others conduct studies no link to label

Confront controversy about value of normal outcomes when numbers are small

FDA

FDA: Improving Registry Data“Guidance Document: Establishing

Pregnancy Registries”

New FDA regulation will require sponsors to address available dataFacilitate inclusion in labels

Expand discussion of registriesCDC & OTIS, March of Dimes - registry modelsInternational Society of Pharmacoepidemiology

FDA

Thinking More Broadly

Registries are important for collection of some types of dataGeneral pregnancy/fetal outcomesGeneral margins of safety

Other elements of “safety” and rational prescribing must be consideredPharmacokinetics and PharmacodynamicsLactation

FDA

Pharmacokinetics & Pharmacodynamics

Once treatment is decided, right dose is essentialFew 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 changesMetabolism of drugs

FDA

Pharmacokinetics & Pharmacodynamics (Continued)

FDA ActivitiesNew safety regulation labelsNICHD Collaboration (Fall 2000 workshop)FDA sponsored conference, November 2000American Society of Clinical Pharmacology

& Therapeutics , 2001

FDA

LactationProduct labels rarely informative Health benefits of breastfeedingNatural link from the pregnant or nursing

mother to childSafetyPharmacokineticsPharmacodynamics

FDA

Lactation (continued)

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

Pediatrics Advisory Committees

FDA

Dietary Supplements

Hearing on 3/30/00Structure-function claims related to

dietary supplementsDistinct from disease or treatment claimsHow that relates to pregnancy and

ensuring the safe use of such products

FDA

SummarySteady progress in label model developmentIncreasing emphasis on addressing data

needs to enhance risk managementDeveloping sound registriesThinking outside of usual modelsFinding ways to increase pk/pd dataLactation as link of mother to baby

Collaboration is essential to progress

FDA

Goals for MeetingUpdate FDA activities related to pregnancy

labelingJoseph DeGeorge, PhD : PreclinicalCatherine Spong, MD: NICHD

Guidance document on pregnancy registriesEvelyn Rodriguez, MD, MPH

Broader discussion of strategiesGetting the most out of each effortThinking beyond current models

FDA