The U.S. Food and Drug Administration (FDA) recently released a draft guidance document with the goal of facilitating certain updates to abbreviated new drug application (ANDA) labels.[1] In particular, the draft guidance addresses updates to ANDA labels where the product’s reference listed drug (RLD) was withdrawn for reasons other than safety or effectiveness, providing insight on the responsibilities of ANDA holders to update their drug labels. It may also set expectations for future generic drug labeling requirements that would affect product liability for both brand and generic drug manufacturers.

Background

Federal law requires generic drug labels to conform to the labeling of the product’s RLD. Generally, the holder of the new drug application (NDA) for the RLD will propose any necessary changes to the drug label when new information becomes available. Once the FDA approves the changes, ANDA holders must update their labels with the corresponding modifications. But in cases where the RLD is withdrawn from the market, the NDA holder can no longer update the drug label. Until now, the process for ANDA holders to update their labels in such cases was unclear. This created the risk that a label would become outdated, inaccurate, false, or misleading.

FDA Draft Guidance

The draft guidance emphasizes that both NDA and ANDA holders have an ongoing obligation to ensure that their drug labels are accurate and up to date. In particular, when an RLD has been withdrawn, ANDA holders for products that are based on the withdrawn RLD should monitor published literature and post-marketing data to determine whether updates are necessary to maintain the accuracy of the drug label.

Specifically, the FDA notes that labeling changes may be necessary: (i) to “achieve consistency with the labeling of other products that have the same active ingredient or an active ingredient in the same pharmacologic or therapeutic class, or with the labeling of other products approved for the same indication”; (ii) to “correct outdated information related to a previously approved indication”; and/or (iii) to “achieve consistency with applicable regulations and current FDA labeling guidelines or other guidance . . . .”

When an ANDA holder determines that a labeling update is necessary, the FDA draft guidance states that it should submit a “prior approval supplement.” If the FDA approves the supplement, it may request that other ANDA holders relying on the same RLD make the same labeling updates. This will ensure consistency among generic drug products that rely on the same RLD. Additionally, the FDA may request a “changes being effected” supplement from ANDA holders if the FDA believes that labeling updates are necessary.

Implications for the FDA’s Proposed Labeling Rule

This draft guidance may foreshadow the FDA’s forthcoming decision with respect to the proposed labeling rule that is currently under review. The proposed rule would allow ANDA holders to update product labeling to reflect new safety information even if the updates differed from the RLD label and without obtaining prior FDA approval. This proposal has raised concerns across the industry, as well as among lawmakers. They worry that inconsistent labeling across generic drugs would result. However, the FDA’s position in this draft guidance, directing ANDA holders to submit a prior approval supplement before implementing labeling changes, may indicate that the FDA is reconsidering this aspect of its proposed labeling rule to require prior FDA approval before generic drug labeling changes can go into effect.

Regardless of whether generic drug manufacturers need to obtain prior FDA approval for label changes under the final rule, changes to the generic drug labeling requirements will have a wide impact on the industry. On the one hand, duties for generic drug manufacturers are likely to expand under the final rule. On the other hand, pressure on brand manufacturers to bear sole responsibility for labeling content is likely to diminish, providing relief in “innovator liability” jurisdictions. We will continue to monitor this field and provide updates on changes to the statutory and regulatory landscape governing generic drug labels.