FDA proposes downgrading drug color additive changes to CBE-30

The US Food and Drug Administration (FDA) has released draft guidance for pharmaceutical manufacturers wishing to replace a color in a drug product. These changes are now viewed as a moderate change and necessitate the filing of a changes being effected in 30 days supplement (CBE-30).

The new guidance, when finalized, will supersede questions 1 and 2 in the component and composition changes of an earlier guidance issued in February 1997 titled “SUPAC-IR Questions and Answers about SUPAC-IR Guidance.” SUPAC stands for Scale-Up and Post-Approval Changes. In the earlier guidance, changing colors was considered a major change that required the submission of a prior approval supplement (PAS).

The guidance applies to drug products marketed under a new drug application (NDA) or an abbreviated new drug application (ANDA), contract manufacturers, non-prescription drugs that are subject to a monograph, and compounded drug products under section 503B of the Federal Food, Drug, and Cosmetic Act.

FDA notes that while changes to the qualitative or quantitative formulation of the drug product, including inactive ingredients, are usually viewed as major changes, replacing a color additive with one that is listed in the color additive regulations is “unlikely to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product. Therefore, for a drug product marketed under an NDA or ANDA, replacing a color additive can generally be considered a moderate change that applicants can submit in a CBE-30.”

A CBE-30 must be submitted at least 30 days before distribution of the post change drug product.

To submit a CBE-30 for a color additive replacement, the change should not exceed 5% of the target unit dose weight. Additionally, incorporating diluents into the color mixture for specific populations, such as neonates, is classified as a major change. This type of modification requires a more comprehensive assessment beyond the CBE-30 process.

If a color additive is removed rather than replaced, it is considered a minor change that applicants must describe in an annual report.

FDA states that “when selecting a replacement color additive, manufacturers and applicants should review the color additive regulations. They must ensure that the color additive regulations list the proposed color for use in drugs and that the proposed level and use conform to the regulations.”

If a manufacturer or applicant intends to use a color additive not already listed in the FDA’s regulations for that specific purpose, they must submit a petition to the Human Foods Program.

Manufacturers and applicants making this change should also update their manufacturing records to reflect the new replacement color, its level, and the relevant regulations with which it complies.

The deadline for commenting is 29 July.

Draft guidance

FDA proposes downgrading drug color additive changes to CBE-30

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