FDA Proposes New Requirements for Pregnancy and Lactation Labeling

May 29, 2008

On May 28, 2008, FDA announced the issuance of a proposed rule to amend the Agency’s regulations concerning the format and content of the “Pregnancy,” “Labor and Delivery,” and “Nursing Mothers” labeling subsections of the “Use in Specific Populations” labeling section for human prescription drug and biological products.  Although FDA substantially revised its labeling format and content regulations in January 2006 to provide, among other things, prescribing information highlights and a table of contents for the full prescribing information, the final regulations did not substantively revise the labeling subsections on pregnancy, labor and delivery, and nursing mothers, but rather moved these sections from the “Precautions” labeling section to the “Use in Specific Populations” labeling section.   (Additional information on FDA’s January 2006 final rule, which is also referred to as the “Physician Labeling Rule,” is available here.)

FDA’s proposal, which is “intended to create a consistent format for providing information about the effects of a drug on pregnancy and lactation,” would, if finalized: (1) require that prescription drug labeling include a summary of the risks of using a drug during pregnancy and lactation (as well as a discussion of the data supporting that summary); (2) require that prescription drug labeling include “relevant clinical information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy and/or lactation;” (3) eliminate the current A, B, C, D, and X pregnancy categories because they have been “criticized as being confusing and overly simplistic;” and (4) eliminate the “Labor and Delivery” labeling subsection, because such information is included in a new “Pregnancy” labeling subsection.

Under FDA’s proposed “Pregnancy” labeling subsection, prescription drug labeling would be required to contain pregnancy exposure registry information (if applicable), a general statement about the background risk of fetal developmental abnormalities, a fetal risk summary, clinical considerations, and a data component.  Under FDA’s proposed “Lactation” labeling subsection, prescription drug labeling would be required to contain information on the drug’s impact on milk production, what is known about the presence of the drug in human milk, the effects on the breast-fed child, a data component, and a “clinical considerations” component “to help health care providers make informed decisions about prescribing drugs for lactating women.”

FDA issued the proposed rule more than a decade after the Agency first discussed the practical utility, effects, and problems of the pregnancy categories at a Part 15 hearing in September 1997.  In the years after the hearing, FDA developed a model pregnancy labeling format, conducted focus group testing on the model, and in June 1999 presented a concept paper to the Pregnancy Labeling Subcommittee of the Reproductive Health Drugs Advisory Committee.  Based on the advisory committee’s recommendations, FDA further refined the model format and conducted additional focus group testing.  The advisory committee also recommended that FDA revise prescription drug labeling requirements for nursing mothers because of concern that “current labeling on lactation is not informative for a number of reasons, including lack of data and a tendency for clinicians to conclude, based on the current format of the labeling, that they should recommend to their patients that they choose between breast-feeding and taking a drug.”  Thereafter, FDA held an advisory committee meeting in September 2000 to discuss potential revisions. 

The new content requirements of the proposed rule would apply to all applications required to comply with FDA’s January 2006 Physician Labeling Rule, which went into effect on June 30, 2006.  This includes: (1) prescription drug products for which an application was approved by FDA between June 30, 2001, and June 30, 2006; (2) prescription drug products for which an application was pending on June 30, 2006; and (3) prescription drug products for which an application was or is submitted anytime on or after June 30, 2006.  Below is a copy of the table in FDA’s proposal describing the Agency’s implementation plan.

Table 1.–Implementation Plan

Applications Required To Conform to New Pregnancy/Lactation Content Requirements

Time by Which Labeling with New Pregnancy/Lactation Content Must Be Submitted to FDA for Approval

New or Pending Applications:

Applications submitted on or after the effective date of the pregnancy final rule

  Time of submission

Application pending on the effective date of the pregnancy final rule

4 years after the effective date of pregnancy final rule or at time of approval,

   whichever is later

Approved Applications Subject to the Physician Labeling Rule:

Applications approved any time from June 30, 2001, up to and including June 29, 2002, and from June 30, 2005, up to and including June 29, 2007

3 years after the effective date of pregnancy final rule

Applications approved any time from June 30, 2007, up to and including the effective date of the pregnancy final rule

4 years after the effective date of pregnancy final rule

Applications approved from June 30, 2002, up to and including June 29, 2005

5 years after the effective date of pregnancy final rule

By Kurt R. Karst    

Categories: Drug Development