On July 8, 2016, the U.S. Food and Drug Administration released draft guidance amending the process for manufacturers to update labeling of generic drugs in situations where the reference drug labeling has been withdrawn for reasons other than safety or effectiveness.
The FDA generally requires a generic drug to have the same labeling as the reference drug at the time of approval. Moreover, all marketing application holders have an ongoing obligation to ensure that their product labeling is accurate, and not false or misleading. In particular, when new information becomes available that causes the labeling to be inaccurate or misleading, the application holder must update its labeling.
Where the reference drug is still on the market, the reference drug manufacturer frequently proposes changes to the labeling, and generic drug manufacturers are expected to update their labeling accordingly to reflect any approved relevant changes. While this process is fairly clear cut, the FDA admits there is confusion about what generic drug application holders must do to update labeling when the reference drug is off the market (for reasons other than safety or effectiveness). This draft guidance seeks to clarify that process.
Notably, generic drugs that rely on reference drug labeling may continue to market their products even after the reference drug is withdrawn. There is risk, however, that new scientific understanding of the drug may evolve based on data from published literature and postmarketing data that would not be reflected in the withdrawn reference product’s labeling. This could in turn cause the generic drug’s labeling reliant on the reference drug to include outdated information that is false and/or misleading, putting the generic manufacturer at risk of violating the FD&C Act.
The new draft guidance makes clear that a generic drug labeling can – and must – continue to be updated even where its reference product has been withdrawn. Importantly, holders of generic drug applications are responsible for reviewing postmarketing data and published literature as appropriate to satisfy applicable reporting requirements. Additionally, labeling updates maybe also come about if the FDA is aware of data relevant to the generic drug from other sources.
The FDA provided examples of when the generic drug labeling may need to be updated after the reference product is withdrawn, such as: revising the “adverse reactions” section to include a new adverse reaction based on postmarketing experience, revising the “overdosage” section to include overdose management strategies consistent with the current Poison Control recommendations, or updating the indication statement in the “indications and usage” section to reflect current disease terminology. These are just a sample of the situations which might arise in which a generic drug manufacturer may need to update its labeling.
In order to update a labeling under the new draft guidance, generic drug manufacturers must submit a “prior approval supplement” (PAS). If the FDA determines the change is appropriate and approves the PAS, then the FDA may request other application holders relying on the same withdrawn reference drug to make the same update. The FDA hopes to achieve uniform labeling across generic drugs as a result of this process. In addition, the FDA may request a “changes being effected” (CBE-0) supplement from generic drug manufacturers if the FDA becomes aware of changes needed to be made to the labeling.
The draft guidance is open for commentary for a 60-day period. Although the draft guidance offers recommendations, and does not establish legally enforceable responsibilities, drug manufacturers must always be vigilant in monitoring postmarketing data and published literature and ensuring that their labeling always conforms to the current information. Manufacturers should consult experienced counsel to guarantee these responsibilities are satisfied.