FDA offers guidance on minor label changes for OTC drugs

The US Food and Drug Administration (FDA) has clarified definitions and appropriate reporting of minor label changes for over-the-counter (OTC) drugs in draft guidance expected to reduce regulatory burden on both industry and FDA.

The draft guidance, issued 12 March, applies to nonprescription drug products approved through a new drug application (NDA) or abbreviated new drug application (ANDA). Per regulations, sponsors may make minor changes and distribute new packaging immediately to consumers, and then document updates in a summary in their next annual report, rather than applying for a label change.

“Minor changes include certain changes that have a minimal potential to have an adverse effect on the identity, strength, quality, purity or potency of a drug product as these factors may relate to the safety or effectiveness of the drug product,” FDA explained in the guidance document, titled Annual reportable labeling changes for new drug applications and abbreviated new drug applications for nonprescription drug products.

The draft guidance provides 18 detailed examples to help drugmakers understand whether their NDA and ANDA label changes are minor and do not require approval of a supplement by the agency.

“We anticipate that these recommendations may assist industry in understanding the circumstances in which it would be appropriate to document minor changes in the applicant’s next annual report rather than submitting a prior approval supplement or ‘changes being effected’ supplement, thereby reducing burden on industry and FDA,” the agency wrote in a Federal Register notice.

What are minor label changes?

Labeling changes are classified as minor, moderate, or major and the definitions vary depending on whether a product is prescribed under supervision by a healthcare professional or available over the counter. Nonprescription drugs are held to different standards than prescription drugs in that sponsors must ensure that consumers understand labeling and are able to take a product safely by themselves. Layout changes to labeling and packaging could affect comprehension and, consequently, safety in the OTC market.

Examples of minor label changes outlined in the draft guidance include a raft of editorial revisions, such as corrections of spelling and grammar, changes to manufacturing site information, and revisions to expiration dates and other details on coupons included in product packages.

“FDA generally does not expect that editorial and similar minor labeling changes to nonprescription drug labeling would affect consumers’ ability to appropriately self-select and use the nonprescription drug product without the supervision of a healthcare practitioner,” the agency wrote.

Other examples of minor changes are:

Removing a time-limited product label flag, e.g. a new count size or flavor, from a product’s principal display panel (PDP)
Adjusting the graphic design of the PDP in the FDA-approved labeling after removing a logo (or graphics) or a flag, without decreasing the font size of labeling elements
Modifying the graphical orientation of the carton PDP without changing readability
Adding a new package count without a change to the product’s approved container closure system and within its approved stability bracket
Revising bonus or free dosage units on approved bonus flag and revision of the declaration of net quantity of contents reflecting total package count

What to watch out for

The agency also clarified its stance on changes to the drug facts label (DFL). Moving the tamper-evidence statement from inside to outside the DF is considered to be a minor change but the “statement must remain prominently placed on the nonprescription drug product package,” according to FDA. Changing the color of the DFL is also a minor change.

But sponsors should be cautious about modifying the DFL.

“Generally, changes to the content of in the DFL of an approved nonprescription drug product are not considered minor changes and may not be documented in an annual report,” the agency wrote.

Also, multiple minor changes might be considered in combination to be more substantive, requiring more scrutiny.

“In certain cases involving implementation of multiple minor changes, the totality of the minor changes could affect consumers’ ability to understand the required labeling information and to appropriately self-select and use the nonprescription drug product,” FDA advised. “In such cases, applicants should submit a supplement rather than an annual report.”

In their annual reports, sponsors should be documenting all changes made within the last year or, alternatively, noting if no changes have been made. FDA reviews the annual reports and may decide to ask for an NDA or ANDA if there are multiple changes, “Especially changes to the PDP that cause the outer packaging to look new or different.”

“Upon review of the annual report, FDA may determine that a labeling change was inappropriate for documentation in an annual report, notify the applicant of the correct supplement category, and request the submission of such supplement,” the agency wrote.

FDA offers guidance on minor label changes for OTC drugs

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