FDA Scraps Pregnancy Labeling Classification System in Favor of New Standard

Regulatory NewsRegulatory News | 03 December 2014 |  By 

The labeling on many prescription drug products approved after 2001 will need to be reconfigured to include clearer information about whether a drug is safe to use during pregnancy, the US Food and Drug Administration (FDA) announced today.


Prescription drug labeling has been subject to standardization measures in the US since 1979, when measures to introduce labeling uniformity were first passed. Those measures were substantially updated in 2006 under FDA's Requirements on Content and Format of Labeling for Human Prescription Drug and Biological Products, better known as the Physician Labeling Rule (PLR).

The PLR is intended to make information on prescription drugs easier to read. For example, labels now include a "highlights" section containing bulleted information, a table of contents, bolded warnings and other useful information. However, the rule only applies to products approved under a New Drug Application (NDA), Biologics Licensing Application (BLA) or efficacy supplement (ES) approved between 2001 and 30 June 2006, as well as all products thereafter.

Sponsors of older drugs may update the drug's labeling, but are not required to do so.

The PLR also contained requirements for how sponsors should label their products with information intended for pregnant women. Pregnancy information was split among several sections. The sections "Pregnancy", "Labor and Delivery", and "Nursing Mothers" contained pregnancy-specific information, while other sections ("Information for Patients", "Drug Interactions," etc) could also contain information relevant to pregnant women on a more general level.

New Standards

Now, after more than a decade of development, FDA has released a new regulation, Content and Format of Labeling for Human Prescription Drug and Biological Products; Requirements for Pregnancy and Lactation Labeling, set to make major changes to the way in which drug products are labeled with information about how a drug may be used during pregnancy.

The so-called Pregnancy and Lactation Labeling Rule (PLLR) "provides a framework for clearly communicating information on the benefits and risks of using a drug during pregnancy and lactation to help facilitate prescribing decisions," FDA explained in an accompanying guidance document, Pregnancy, Lactation, and Reproductive Potential: Labeling for Human Prescription Drug and Biological Products —Content and Format.

Under FDA's PLLR, sponsors of drugs will now be required to label their products with three sections:

  • Pregnancy
  • Lactation
  • Females and Males of Reproductive Potential

The "pregnancy" section is actually an amalgamation of the former "pregnancy" and "labor and delivery" sections, FDA said. The "lactation" section, meanwhile, is set to replace the "nursing mothers" section.

The third, new section—females and males of reproductive potential—will provide information "on pregnancy testing, contraception and infertility," FDA explained in its guidance. The inclusion of men in the pregnancy section follows FDA's realization that some drugs can cause fetal risk through men (e.g. Thalomid) at the time of contraception, or might cause infertility.

Other Changes

In another major change, FDA said it is doing away with its "pregnancy categories" (A, B, C, D and X), which had been used by some consumers to assess the potential of a drug to harm a fetus. Regulators said they determined the categories "were often confusing and did not accurately or consistently communicate differences in degrees of fetal risk." Reliance on the categories "could result in poorly informed clinical decision making," FDA added.

Instead, companies will need to include a "risk summary" of potential risks, such as structural abnormalities, embryo/fetal/infant mortality, functional impairments or growth problems potentially caused by a drug.

Labels will also be required to include information about "scientifically acceptable pregnancy exposure registries." The intent, FDA said, is to let healthcare providers know to what extent a product has been tested in pregnant women, and also to encourage women to participate in those registries.

FDA said it expects changes to labeling for existing drug products to take "several years" to complete. Drug companies will be required to submit proposed labeling changes to FDA as a prior approval supplement (PAS), which requires FDA approval. Companies will have between three and five years to finalize their labeling, according to the rule. New applications will need to conform to the rule as of 30 June 2015.


FDA Final Rule

FDA Guidance (FR)

FDA Press Statement


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