Safety labeling: FDA proposes updated guidance on postmarket changes

The US Food and Drug Administration (FDA) published a draft guidance detailing what safety information drug and biologic companies should include in their labeling if they detect serious safety issues after their product has been approved. The guidance would update a 2013 guidance on the same topic to include new authorities granted to the agency under a 2018 law.

In 2018, Congress passed the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act (SUPPORT Act), which gave FDA additional authorities to require manufacturers to inform users about postmarket safety information. The updated draft guidance outlines what safety labeling changes (SLC) manufacturers should include with certain products based on postmarket data per the SUPPORT Act.

The guidance applies to prescription drugs with approved new drug applications (NDA) and abbreviated new drug applications (ANDA)s. It also applies to biological products with approved biologics license applications (BLAs).

“Updates in this draft guidance include the addition of information related to Congress’ 2018 changes to the definition of adverse drug experience regarding reduced effectiveness such as the clarification that the Agency can require changes to labeling to include information about a serious risk that results from reduced effectiveness,” said FDA. “Additional changes were made reflecting current SLC processes and procedures adding a description of how FDA reviews and acts on SLCs when new safety information applies to multiple application holders, and clarifying when FDA may disclose SLC notification and order letters.”

FDA noted that the guidance applies to approved drugs, generics, and biologics, even if they are not being marketed. However, it would not apply to products whose approvals have been revoked.

“Thus, even if an application holder is not actively marketing the drug(s) approved under its NDA, ANDA, or BLA, it is required to make the applicable SLCs under section 505(o)(4) unless and until approval of the application is effectively withdrawn in a Federal Register notice or the U.S. biologics license to manufacture the product has been revoked,” the agency clarified.

FDA said that it will require companies to add SLC based on new post-market serious or unexpected serious risk information. The agency has a broad interpretation of what it considers new safety information and said it can be based on clinical trials, adverse event reports, post-approval studies, peer-reviewed biomedical literature, postmarket risk identification data and analysis systems, and other scientific data that it deemed appropriate.

FDA also noted that the new safety information could trigger the Risk Evaluation and Mitigation Strategy (REMS) process and require the company to make changes to its REMS documents and materials.

“Once FDA has determined that there is new safety information that should be included in labeling, FDA sends an SLC notification letter to the application holder(s),” said FDA. “A holder of an approved NDA, BLA, or ANDA (if the RLD is not currently marketed) will be notified of the requirement to make the SLC, unless approval of the application has been formally withdrawn in a Federal Register notice or the U.S. biologics license to manufacture the product is revoked.

“If the new safety information applies to more than one application holder, FDA intends to send a letter on the same day to each holder of an approved NDA, BLA, and/or ANDA (if the RLD is not currently marketed),” the agency added.

The guidance includes additional details on the process that FDA will follow if it decides the company needs an SLC based on the new safety information, how it expects the company to respond, and what the following review process will look like. It also addresses the dispute resolution system for companies that argue they should not be required to issue an SLC, and what enforcement steps the agency plans to take if they don't comply.

Stakeholders can comment on the draft guidance on www.regulations.gov under docket no. FDA-2011-D-0164 through 18 November.

Draft guidance

Safety labeling: FDA proposes updated guidance on postmarket changes

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