Q&A with the FDA: Implementing the Pregnancy and Lactation Labeling Rule

On June 30, pharmaceutical and biological manufacturers will begin implementing the Food and Drug Administration’s revised rules for pregnancy and lactation drug labeling. The Pregnancy and Lactation Labeling Rule (PLLR) amends the Physician Labeling Rule (PLR, issued in 2006) and new labels aimed at providing clearer and more accurate information on drug risks will gradually roll out over the next 5 years.

The new rule – several years in the making – replaces pregnancy categories A, B, C, D, and X with short, integrated summaries that provide physicians with more information for discussing with patients the risks and benefits of a medication. The summaries will be brief and easy to read, and will contain evidence-based information that specifically addresses drug risks for women during pregnancy and lactation, as well as for men and women of reproductive potential. Under the PLLR, the pregnancy subsection of the risk summary will include for the first time information for any drug that has a pregnancy exposure registry.

Dr. John Whyte, director of Professional Affairs and Stakeholder Engagment (PASE) at the FDA Center for Drug Evaluation and Research, answers questions about the new rule from Ob.Gyn. News journalists and our Drugs, Pregnancy & Lactation columnists.

Question: Instead of the traditional letter categories, prescribers will now have to read the pregnancy and lactation subsections of the labeling. What can the agency do to ensure prescribers are reading all of the new contextual information in the drug label?

Answer: The agency has initiated outreach efforts to help prescribers become familiar with the new information in labeling. The most important information is now under a new heading called Risk Summary. This narrative summary replaces the pregnancy letter categories with a summary of information that is known about a product. The new labeling rule explains, based on available information, the potential benefits and risks for the mother, the fetus, and the breastfeeding child. The decision to replace the pregnancy letter categories with the summary paragraph was reached after extensive consultation with experts and stakeholders who were concerned that the traditional letter categories were overly simplistic.

Q: PLLR praises the value of pregnancy exposure registries and mandates that if a registry exists for an approved product, then the label must include the registry’s website address. There is no requirement, however, that industry actually fund these registries. Why did the agency stop short of requiring companies to provide ongoing support for pregnancy exposure registries?

A: FDA has the authority to require the establishment of pregnancy registries when there is a safety concern that would benefit from the collection of data in a postapproval study, or when a particular product will be used by a large number of females of reproductive age. However, FDA does not have the authority to require companies to fund existing pregnancy exposure registries.

Q: How does the FDA plan to review all of the summary statements of available data regarding reproductive safety considering the breadth of drugs in various therapeutic areas that will need to be reviewed?

A: All labeling changes, including the changes required by the PLLR, must be submitted to the FDA for review and approval. Changes to the Pregnancy and Lactation subsections of labeling have been integrated into standard labeling review processes. In addition, the Division of Pediatric and Maternal Health, in the Office of New Drugs, works with the primary review divisions to help coordinate PLLR review processes.

Q: Are the manufacturers of generic drugs expected to “piggyback” the label for a branded molecule with respect to the pregnancy label?

A: Generic drug products (Abbreviated New Drug Applications) are required by regulation to have the “same” labeling as the reference drug listed. When the labeling is revised for the referenced drug, generic drug manufacturers also are required to update their labeling.

Q: In the new system, how will labeling stay up to date when important new data are published on a drug sometimes two to three times a year?

A: When new information becomes available that causes the labeling to be inaccurate, false, or misleading, drug manufacturers are required by regulation to update labeling.

Q: The rule is phased in over time. Drugs already on the market are given more time to switch to the new system. How long will physicians need to deal simultaneously with the old and the new formats?

A: There have been two labeling formats in use for some time as products approved prior to 2001 are not required to conform to either PLLR or PLR. The agency encourages manufacturers to voluntarily convert labeling of older products into PLR format. However, products approved prior to 2001 will be required to remove the pregnancy letter category by June 30, 2018, (3 years after the implementation of the PLLR).

Q: Does the FDA have any plans to address labeling for over-the-counter products in terms of their impact on pregnancy, lactation, and reproductive potential?

A: The PLLR does not apply to over-the-counter products. However, the agency is continually reviewing the safety of products used over the counter, including impacts on pregnancy, lactation, and reproductive potential.

Q: How does the FDA plan to assess over time the usefulness of the new labeling for prescribers and patients and make revisions?

A: The draft guidance was issued concurrently with PLLR. Based on the comments received from the public on the draft, as well as learning from the initial revisions of labeling, the guidance will be revised as needed. Guidance statements issued by FDA are regularly reviewed and revised as needed.

Dr. Whyte, a board-certified internist, is the director of Professional Affairs and Stakeholder Engagement at the FDA. Do you have other questions about the PLLR? Send them to [email protected].

On June 30, pharmaceutical and biological manufacturers will begin implementing the Food and Drug Administration’s revised rules for pregnancy and lactation drug labeling. The Pregnancy and Lactation Labeling Rule (PLLR) amends the Physician Labeling Rule (PLR, issued in 2006) and new labels aimed at providing clearer and more accurate information on drug risks will gradually roll out over the next 5 years.

The new rule – several years in the making – replaces pregnancy categories A, B, C, D, and X with short, integrated summaries that provide physicians with more information for discussing with patients the risks and benefits of a medication. The summaries will be brief and easy to read, and will contain evidence-based information that specifically addresses drug risks for women during pregnancy and lactation, as well as for men and women of reproductive potential. Under the PLLR, the pregnancy subsection of the risk summary will include for the first time information for any drug that has a pregnancy exposure registry.

Dr. John Whyte, director of Professional Affairs and Stakeholder Engagment (PASE) at the FDA Center for Drug Evaluation and Research, answers questions about the new rule from Ob.Gyn. News journalists and our Drugs, Pregnancy & Lactation columnists.

Question: Instead of the traditional letter categories, prescribers will now have to read the pregnancy and lactation subsections of the labeling. What can the agency do to ensure prescribers are reading all of the new contextual information in the drug label?

Answer: The agency has initiated outreach efforts to help prescribers become familiar with the new information in labeling. The most important information is now under a new heading called Risk Summary. This narrative summary replaces the pregnancy letter categories with a summary of information that is known about a product. The new labeling rule explains, based on available information, the potential benefits and risks for the mother, the fetus, and the breastfeeding child. The decision to replace the pregnancy letter categories with the summary paragraph was reached after extensive consultation with experts and stakeholders who were concerned that the traditional letter categories were overly simplistic.

Q: PLLR praises the value of pregnancy exposure registries and mandates that if a registry exists for an approved product, then the label must include the registry’s website address. There is no requirement, however, that industry actually fund these registries. Why did the agency stop short of requiring companies to provide ongoing support for pregnancy exposure registries?

A: FDA has the authority to require the establishment of pregnancy registries when there is a safety concern that would benefit from the collection of data in a postapproval study, or when a particular product will be used by a large number of females of reproductive age. However, FDA does not have the authority to require companies to fund existing pregnancy exposure registries.

Q: How does the FDA plan to review all of the summary statements of available data regarding reproductive safety considering the breadth of drugs in various therapeutic areas that will need to be reviewed?

A: All labeling changes, including the changes required by the PLLR, must be submitted to the FDA for review and approval. Changes to the Pregnancy and Lactation subsections of labeling have been integrated into standard labeling review processes. In addition, the Division of Pediatric and Maternal Health, in the Office of New Drugs, works with the primary review divisions to help coordinate PLLR review processes.

Q: Are the manufacturers of generic drugs expected to “piggyback” the label for a branded molecule with respect to the pregnancy label?

A: Generic drug products (Abbreviated New Drug Applications) are required by regulation to have the “same” labeling as the reference drug listed. When the labeling is revised for the referenced drug, generic drug manufacturers also are required to update their labeling.

Q: In the new system, how will labeling stay up to date when important new data are published on a drug sometimes two to three times a year?

A: When new information becomes available that causes the labeling to be inaccurate, false, or misleading, drug manufacturers are required by regulation to update labeling.

Q: The rule is phased in over time. Drugs already on the market are given more time to switch to the new system. How long will physicians need to deal simultaneously with the old and the new formats?

A: There have been two labeling formats in use for some time as products approved prior to 2001 are not required to conform to either PLLR or PLR. The agency encourages manufacturers to voluntarily convert labeling of older products into PLR format. However, products approved prior to 2001 will be required to remove the pregnancy letter category by June 30, 2018, (3 years after the implementation of the PLLR).

Q: Does the FDA have any plans to address labeling for over-the-counter products in terms of their impact on pregnancy, lactation, and reproductive potential?

A: The PLLR does not apply to over-the-counter products. However, the agency is continually reviewing the safety of products used over the counter, including impacts on pregnancy, lactation, and reproductive potential.

Q: How does the FDA plan to assess over time the usefulness of the new labeling for prescribers and patients and make revisions?

A: The draft guidance was issued concurrently with PLLR. Based on the comments received from the public on the draft, as well as learning from the initial revisions of labeling, the guidance will be revised as needed. Guidance statements issued by FDA are regularly reviewed and revised as needed.

Dr. Whyte, a board-certified internist, is the director of Professional Affairs and Stakeholder Engagement at the FDA. Do you have other questions about the PLLR? Send them to [email protected].

On June 30, pharmaceutical and biological manufacturers will begin implementing the Food and Drug Administration’s revised rules for pregnancy and lactation drug labeling. The Pregnancy and Lactation Labeling Rule (PLLR) amends the Physician Labeling Rule (PLR, issued in 2006) and new labels aimed at providing clearer and more accurate information on drug risks will gradually roll out over the next 5 years.

The new rule – several years in the making – replaces pregnancy categories A, B, C, D, and X with short, integrated summaries that provide physicians with more information for discussing with patients the risks and benefits of a medication. The summaries will be brief and easy to read, and will contain evidence-based information that specifically addresses drug risks for women during pregnancy and lactation, as well as for men and women of reproductive potential. Under the PLLR, the pregnancy subsection of the risk summary will include for the first time information for any drug that has a pregnancy exposure registry.

Dr. John Whyte, director of Professional Affairs and Stakeholder Engagment (PASE) at the FDA Center for Drug Evaluation and Research, answers questions about the new rule from Ob.Gyn. News journalists and our Drugs, Pregnancy & Lactation columnists.

Question: Instead of the traditional letter categories, prescribers will now have to read the pregnancy and lactation subsections of the labeling. What can the agency do to ensure prescribers are reading all of the new contextual information in the drug label?

Answer: The agency has initiated outreach efforts to help prescribers become familiar with the new information in labeling. The most important information is now under a new heading called Risk Summary. This narrative summary replaces the pregnancy letter categories with a summary of information that is known about a product. The new labeling rule explains, based on available information, the potential benefits and risks for the mother, the fetus, and the breastfeeding child. The decision to replace the pregnancy letter categories with the summary paragraph was reached after extensive consultation with experts and stakeholders who were concerned that the traditional letter categories were overly simplistic.

Q: PLLR praises the value of pregnancy exposure registries and mandates that if a registry exists for an approved product, then the label must include the registry’s website address. There is no requirement, however, that industry actually fund these registries. Why did the agency stop short of requiring companies to provide ongoing support for pregnancy exposure registries?

A: FDA has the authority to require the establishment of pregnancy registries when there is a safety concern that would benefit from the collection of data in a postapproval study, or when a particular product will be used by a large number of females of reproductive age. However, FDA does not have the authority to require companies to fund existing pregnancy exposure registries.

Q: How does the FDA plan to review all of the summary statements of available data regarding reproductive safety considering the breadth of drugs in various therapeutic areas that will need to be reviewed?

A: All labeling changes, including the changes required by the PLLR, must be submitted to the FDA for review and approval. Changes to the Pregnancy and Lactation subsections of labeling have been integrated into standard labeling review processes. In addition, the Division of Pediatric and Maternal Health, in the Office of New Drugs, works with the primary review divisions to help coordinate PLLR review processes.

Q: Are the manufacturers of generic drugs expected to “piggyback” the label for a branded molecule with respect to the pregnancy label?

A: Generic drug products (Abbreviated New Drug Applications) are required by regulation to have the “same” labeling as the reference drug listed. When the labeling is revised for the referenced drug, generic drug manufacturers also are required to update their labeling.

Q: In the new system, how will labeling stay up to date when important new data are published on a drug sometimes two to three times a year?

A: When new information becomes available that causes the labeling to be inaccurate, false, or misleading, drug manufacturers are required by regulation to update labeling.

Q: The rule is phased in over time. Drugs already on the market are given more time to switch to the new system. How long will physicians need to deal simultaneously with the old and the new formats?

A: There have been two labeling formats in use for some time as products approved prior to 2001 are not required to conform to either PLLR or PLR. The agency encourages manufacturers to voluntarily convert labeling of older products into PLR format. However, products approved prior to 2001 will be required to remove the pregnancy letter category by June 30, 2018, (3 years after the implementation of the PLLR).

Q: Does the FDA have any plans to address labeling for over-the-counter products in terms of their impact on pregnancy, lactation, and reproductive potential?

A: The PLLR does not apply to over-the-counter products. However, the agency is continually reviewing the safety of products used over the counter, including impacts on pregnancy, lactation, and reproductive potential.

Q: How does the FDA plan to assess over time the usefulness of the new labeling for prescribers and patients and make revisions?

A: The draft guidance was issued concurrently with PLLR. Based on the comments received from the public on the draft, as well as learning from the initial revisions of labeling, the guidance will be revised as needed. Guidance statements issued by FDA are regularly reviewed and revised as needed.

Dr. Whyte, a board-certified internist, is the director of Professional Affairs and Stakeholder Engagement at the FDA. Do you have other questions about the PLLR? Send them to [email protected].