The FDA has finalized the Guidance for Industry titled Physicochemical and Structural (Q3) Characterization of Topical Drug Products Submitted in ANDAs (here). The final guidance is essentially the same as the draft of the same name issued on October 22, 2022 with the exception of minor editorial changes to increase clarity.
The use of classic bioequivalence testing for topical dosage forms has been a barrier to the development of generic topical products. In the past, the FDA had primarily relied on a combination of either pharmacokinetic studies and/or bioequivalence studies with clinical endpoints. For some products, the FDA would also use pharmacodynamic measures (such as blanching studies in the case of topical corticosteroids) to assess bioequivalence. These studies are time-consuming, expensive, and not as accurate as other methods.
However, as state-of-the-art analytical methodology and technology have advanced, the FDA recognized that qualitative (Q1) and quantitative (Q2) sameness could be used for some products to establish bioequivalence. In addition, the FDA has also come to rely on the concept of Q3 (or physicochemical and structural) sameness to add an extra level of assurance that the proposed generic product will behave the same as the reference listed drug.
The FDA says that “because Q3 characterization describes essential attributes of a drug product that may be critical to its performance, differences in Q3 attributes between a test product and the reference standard selected by FDA can indicate a risk that the differences may impact the respective bioavailability and/or bioequivalence of the two products.”
The guidance provides recommendations on the physicochemical and structural (collectively, “Q3”) characterizations that can be used to identify the dosage form of a proposed generic (test) topical product, and to describe properties of the drug product that may be critical to its performance to support a demonstration of bioequivalence.
The guidance recommends the use of a minimum of three test batches of the proposed generic product against three different lots of the reference listed drug product or the designated reference standard product to establish the bounds of Q3 sameness between the test and reference product.
It further provides general parameters for the establishment of Q3 sameness, similarity, and differences. The concepts outlined in the draft and now in this important final guidance have formed the basis for the issuance of Product-Specific Guidances (PSGs) that provide for the use of Q1, Q2, and Q3 comparative evaluations of a test and a reference product to establish their bioequivalence and, thus, has resulted, in many cases, in elimination of the conduct of unnecessary bioequivalence studies with clinical endpoints, which are a less sensitive method for the establishment of bioequivalence. The pre-publication notice announcing the availability of the guidance can be found here.
