The rules for the labeling of pregnancy related drugs in the United States have had three different eras. Before 1979 there was no formal regulated drug labeling requirements. From 1979 to 2015 pregnancy related drugs were labeled with ABCDX to signify the risks associated with a given drug. In 1994 these simplistic categories were put up for debate by the FDA. This public discussion resulted in the 2015 Pregnancy and Lactation Labeling Rule (PLLR) regulatory updates that forced all drugs to use an updated labeling system that is more detailed and informative of the risks of a drug and data available from any testing and trials.
PLLR History
Drug categories ABCDX established by FDA.
Pregnancy Drug Labeling initiative beings.
Part 15 hearing.
to
2003
Committe and focus groups to discuss new labeling requirements.
Draft label changes
Pregnancy Labeling Rule (PLR) created.
to
2013
Requests for public comment on PLR.
2015
New PLR drug labeling go into effect.
2018
All drug category labels must be removed.
All pregnancy drugs must use the new PLR format.
Pregnancy and Lactation Labeling Final Rule (PLLR)
The A, B, C, D and X risk categories used since 1979 are replaced with narrative sections and subsections to include:
Pregnancy (includes Labor and Delivery):
- Pregnancy Exposure Registry
- Clinical Considerations
- Risk Summary
- Data
Lactation (includes Nursing Mothers)
- Risk Summary
- Clinical Considerations
- Data
Females and Males of Reproductive Potential
- Contraception
- Pregnancy Testing
- Infertility
Pre 2015 PLLR Labels
Prior to the US FDA's Jun 30, 2015, ruling the following drug identifiers were used to inform people about the observed risks of using a specific type of drug during pregnancy. These drug categories labels were in common usage from 1979 until 2018,
Category A
Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
Category B
Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
Category C
Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Category D
There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Category X
Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.
References
- US FDA - 2105 Pregnancy and Lactation Labeling Final Rule (PLLR)
- US Department of Health - FDA Pregnancy Categories
- FDA Pregnancy Categories - drugs.com
- US DHHS 2008 - 21 CFR Part 201
- FDA newsletter from 2015 - Drugs in Pregnancy
- FDA presentation - An Evolution of Labeling Information
for Pregnant Women: PLLR History
and Background