FDA Guidance Breakdown: Revising ANDA Labeling Following Revision of the RLD Labeling
The guidance is intended to assist applicants and holders of an ANDA in updating their labeling following revisions to the approved labeling of an RLD.
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Late last week, the FDA finalized its guidance for ANDA sponsors on updating their product labeling after changes have been made to the reference listed drug (RLD) label.
(The FDA requires ANDA holders to regularly update their labeling in response to changes in the RLD's labeling. This process is not just a best practice but a regulatory requirement to maintain the drug's approval status. Failure to update labeling can lead to compliance issues, including potential withdrawal of the drug's approval.)
The most recent draft version of the guidance was published in 2022, along with several other guidances as part of the FDA’s Drug Competition Action Plan (DCAP). It replaces an April 2000 guidance, and some of the major changes from the previous guidance include how sponsors can obtain information on changes to the RLD labeling and how to submit their ANDA labeling changes for FDA approval.
“The final guidance provides clear expectations for when updates to labeling are required, the process for updating labeling, and the types of submissions for labeling updates.”
Here’s a quick breakdown of the key policy details:
Introduction and background
The guidance assists ANDA holders in updating their labeling after revisions to the approved labeling of an RLD. It outlines the expectations for when labeling updates are required, the updating process, and the types of submissions needed for these updates.
FDA reiterates that ANDAs are applications for drugs that are duplicates of previously approved drugs, relying on the FDA's finding of safety and efficacy for the RLD. Generic drugs must generally have the same labeling as the RLD, with some exceptions due to manufacturer differences or other factors. ANDA holders have an ongoing obligation to ensure their product labeling is accurate and not misleading.
Obtaining information on changes to RLD labeling
ANDA holders are advised to regularly monitor the Drugs@FDA website for recent approvals and updates on RLD labeling. The FDA also offers LISTSERVs for email updates about new approvals and labeling changes.
Approved RLD labeling can also be obtained from the FDA’s Division of Freedom of Information through written requests.
Submitting revised labeling
Labeling changes must be submitted electronically via the FDA's Electronic Submissions Gateway.
Required documents include:
Form FDA 356h
A cover letter
Patent and exclusivity statements
The revised labeling
A detailed comparison of the proposed ANDA labeling with the RLD's approved labeling
Types of submission
For unapproved ANDAs, labeling changes are submitted as amendments following specific FDA procedures. Tentatively approved ANDAs should submit labeling changes as amendments to the application, adhering to guidelines for timely submission. Approved ANDAs must submit labeling updates to conform to RLD updates using the appropriate reporting category, as per section 314.70.
When submitting labeling updates, ANDA holders must consider all labeling aspects, ensuring that updates are consistent throughout the labeling document.
Here are a few things ANDA holders may want to consider in light of this guidance:
Set up a system to actively monitor for RLD labeling changes. Establish a routine process for monitoring updates to the labeling of Reference Listed Drugs (RLDs). This can involve regularly checking the FDA’s Drugs@FDA website and subscribing to relevant FDA LISTSERVs for timely notifications.
Develop an SOP to promptly and efficiently update labeling in response to RLD changes. This includes reviewing and revising the labeling, preparing the necessary documentation, and submitting it to the FDA. We recommend developing an SOP for responding to RLD labeling changes. This SOP should outline the steps for internal review, revision of labeling, and preparation for submission.