FDA finalizes guidance on assessing bioequivalence of topical drugs
The US Food and Drug Administration (FDA) has finalized guidance for manufacturers on using physicochemical and structural (Q3) characterization studies to establish bioequivalence in abbreviated new drug applications (ANDAs) for topical medications.The guidance pertains to ANDAs for liquid or semisolid products applied to the skin, including integumentary and mucosal membranes.
This guidance is nearly the same as the draft version issued on 21 October 2022; FDA stated that only editorial changes were made for clarity. (RELATED: FDA releases new draft guidances on topical generic drugs, Regulatory Focus 25 October 2022)
The guidance outlines the concepts of sameness, similarity, and difference in the Q3 of topical products. It also details specific product characterization studies that can be used to demonstrate these qualities between test topical products and reference products.
“When comparing the Q3 attributes of two topical products (e.g., to support a demonstration of BE), we generally advise that applicants conduct a comparative Q3 characterization of their proposed generic product against the reference standard, which ordinarily is the reference listed drug (RLD),” FDA wrote.
The guidance provides general recommendations of the studies manufacturers should conduct to develop a detailed profile of relevant Q3 attributes.
According to the guidance, sponsors should describe the look, feel, and smell of the proposed product. These observations should address the color, clarity, opaqueness, texture, and odor. Sponsors should also assess the structural organization of the product’s matter by evaluating particle-size distribution, crystal habit, and the size distribution of emulsion globules.
Additionally, sponsors are expected to examine the polymorphic forms of the active ingredient, including in situ characterization within the drug product. The guidance states that “an absence of evidence for the existence of polymorphs does not constitute evidence that polymorphs do not exist.”
Lastly, sponsors should analyze rheological behavior using a rheometer to monitor the flow behavior of liquid and semisolid dosage forms.
These Q3 characterizations should be submitted in the ANDA within the pharmaceutical development section of the electronic Common Technical Document, section 3.2.P.2.
The guidance does not address specific reference standards for topical products or list the specific tests and comparative product characterizations for each type of product.
FDA advises applicants to consult this guidance alongside any relevant product-specific guidances (PSGs) when designing and conducting Q3 studies.
The guidance was created as part of the FDA’s Drug Competition Action Plan, which aims to promote competition in the prescription drug market. FDA noted that because of the complex delivery methods and intricate formulations associated with these products, topical products are classified as complex.
Final guidance
