FDA drafts guidance, orders on minor changes to OTC drugs and packaging

The Food and Drug Administration (FDA) has released draft guidance and a proposed administrative order regarding the documentation required for minor dosage form changes in over-the-counter (OTC) monograph drugs that are highly soluble and highly permeable. Additionally, the FDA has issued a second administrative order mandating that certain OTC monograph drugs be packaged in single-dose or unit-dose containers.

The initial administrative order and guidance focus on transitioning from a tablet or capsule to alternative forms such as chewable tablets, orally disintegrating tablets, or films. This order permits these changes without the need for companies to submit an OTC monograph request. The aim is to simplify the process for companies to develop new dosage forms for their products, reducing the wait time for FDA monograph orders.

The issuance of the guidance and administrative orders fulfills a mandate from the OTC Monograph Drug User Fee Program (OMUFA). This program was established in March 2020 as part of the Coronavirus Aid, Relief, and Economic Security Act (CARES Act) with the goal of modernizing the regulation of over-the-counter (OTC) monograph products. The CARES Act introduced a new Section 505G to the Federal Food, Drug, and Cosmetic Act, which allows for changes to OTC drugs to be made through administrative orders instead of the traditional notice-and-comment rulemaking process.

The guidance specifies that the changed product must have the same active ingredient, the same strength, the same labeled ingredients and the same route of administration as the reference product.

In addition, the guidance states that companies must conduct solubility, permeability, in vitro dissolution studies, and packaging studies to support these changes.

In terms of product-specific quality considerations, the guidance states that “all three of the dosage forms that could be marketed subject to [administrative order] C001, if finalized, can be vulnerable to changes in quality due to exposure to high humidity and other external factors. The container closure system of a drug must meet the requirement that container closure systems provide adequate protection against such factors. For OTC monograph drugs with a minor change in dosage form, the results of testing conducted to comply with 21 CFR 211.166 must confirm the stability of the drug product in its marketed container closure system over the shelf life of the drug product.”

The guidance states that companies should be aware that critical quality attributes for chewable tablets include hardness, disintegration, and dissolution. Additional considerations include tablet size and taste, which can affect a consumer's ability or willingness to chew the chewable tablet. FDA recommends that companies consult its August 2018 guidance on “Attribute Considerations for Chewable Tablets” for more information.

FDA also issued a proposed order that would require OTC monograph drugs in an orally disintegrating tablet (ODT) or film dosage form be packaged in single-unit or unit-dose containers to be considered generally recognized as safe and effective and not misbranded.

The guideline specifies that administrative order B001, addresses potential safety and efficacy concerns. “The palatability and rapid dissolution of ODTs and films make them more attractive to and can pose greater risks of accidental ingestion by young children. Moreover, ODTs can break apart when handled or stored in high humidity, which could result in underdosing from a multiple-unit container. Films packaged in multiple-unit containers have the potential to stick together, making it easy for a consumer to inadvertently dose more than one film at the same time. “

The deadline for submitting public comment on the two administrative orders and the guidance is 4 October.

Draft guidance, Administrative order for minor changes, Administrative order for packaging

FDA drafts guidance, orders on minor changes to OTC drugs and packaging

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