Labeling Update for Generic OTC Drugs

FDA's guidance helps ANDA holders avoid multiple drug relabeling.

Erik Swain, Senior Editor

According to a new FDA guidance, manufacturers of generic over-the-counter (OTC) drugs don't have to change their labeling to FDA's new Drug Facts format until the manufacturer of their product's innovator drug—known as the reference listed drug (RLD)—does so.

The guidance, "Labeling OTC Human Drug Products—Updating Labeling in RLDs and ANDAs," clarifies some issues raised by generic OTC drug manufacturers after the agency came out with the Drug Facts regulation, 21 CFR 201.66. The new guidance was published October 18, 2002, and is effective as of that date. It can be viewed in its entirety at

Under section 505(j)(2) of the Federal Food, Drug, and Cosmetic Act, a drug product marketed under an abbreviated new drug application (ANDA) has to have the "same labeling" as its RLD. But generic OTC drug manufacturers worried that they would not be able to comply with the Drug Facts rule in time if they had to wait for the manufacturers of their respective RLDs to update their labels.

As a response, the new guidance gives generic OTC drug manufacturers —the ANDA holders—two options. They may choose to revise their product labeling before the relevant RLD holder has done its own revisions. In this case, ANDA holders must follow the agency's product-specific labeling examples included as part of the new guidance. Once the RLD holder's new labeling is approved by FDA, the ANDA holder must revise its labeling again. This is in accordance with the May 2000 guidance, "Revising ANDA Labeling Following Revision of the RLD Labeling."

If the ANDA holder does not want to make two revisions, then it can wait until FDA approves the revised labeling for the RLD and posts it on the Internet. Then the generic product must make the labeling switch in accordance with the May 2000 guidance. The agency says it is making this "enforcement discretion" because it wants to "relieve ANDA holders from the potential burden of having to re- label their products multiple times." It says it is justified in doing so because the labeling regulations do not require ANDA labeling to be "identical" to RLD labeling. The regulations also allow for differences "where the ANDA labeling revisions are made to comply with current FDA guidelines or other guidance."

The guidance includes 14 examples of product-specific Drug Facts labeling that cover approximately 60% of affected products. Other examples will be added to the guidance in the future.

If the ANDA holder wishes to change to the Drug Facts format before the RLD holder does, the agency recommends using its labeling examples, as it will automatically be considered in compliance that way. Other wording is permissible as long as it complies with the Drug Facts regulation.

But once the RLD holder has had its changes approved, then the ANDA holder must follow suit "at the very earliest time possible." If the ANDA holder anticipates a delay, it must contact FDA's Office of Generic Drugs.

RLD and ANDA holders need only report the changes in their annual report to the agency, provided that they use the agency's labeling examples, or change their labeling in accordance with 21 CFR 201.66 and 330.1(i) or (j). Those who wish to submit a preapproval supplement should do so as soon as possible.

Those whose changes go beyond the ones specified in 21 CFR 314.70, 314.97, 314.94, or 330.1(i) or (j) should also submit a preapproval supplement. The agency does not see the need for any manufacturer to submit a "Changes Being Effected" supplement in relation to this issue, but if a firm wishes to do so, it can.

ANDA holders who do not think they can comply by the end of the grace period should submit a deferral request in accordance with 21 CFR 201.66(e). The request should state the reason why it meets the criteria involved and the amount of additional time needed. There will be no across-the-board extensions for ANDA holders; they are expected to comply as soon as possible after their relevant RLD holder has.

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