“To BE or not to BE” – Bio-equivalence strategies for topical formulations

Establishing bio-equivalence (BE) for topical dermatological drug products has been up for discussion for many years between pharmaceutical development community and the regulatory agency.  Despite great advances in addressing the issues related to topical bioequivalence, many challenges remain and the lack of harmonized guidance documents tend to exacerbate the challenge.

The FDA’s Guidance for Industry document entitled “Topical Dermatological Drug Product NDAs and ANDAs —In Vivo Bioavailability, Bioequivalence, In Vitro Release, and Associated Studies” suggests that establishing bio-equivalence through the various in-vivo methods might be waived if the inactive ingredients in the product are qualitatively identical and quantitatively similar.

Unique challenges confront companies attempting to show bioequivalence of topically delivered drugs.  One way to reduce the amount of work involved in proving bioequivalence to existing drug products is to plan a drug development strategy that involves quantitative and qualitative equivalence to active and inactive components of drug formulation. This equivalence is, in part, verified by using a number of analytical techniques. The critical attributes include particle size distribution and polymorphic form of the active pharmaceutical ingredient (API).

The Morphologi G3-ID from Malvern Instruments is used throughout the generic pharmaceutical development community to perform equivalence testing such as this, as described in this application note exploring the requirements for the analysis of topical formulations .

In addition to the standard chemistry, manufacturing, and control (CMC) tests, the active bulk drug substance for NDA or ANDA should be studied and controlled via appropriate specifications for polymorphic form, particle size distribution, and other attributes important to the quality target profile of the resulting drug product. The Morphologi G3-ID can be applied not only in the case of a CMC strategy, but also more and more in monitoring and controlling above mentioned important quality attributes.

In April, the next blog in this series will take a look at dry powder inhalation formulations.

Download the app note: “Component specific particle characterisation of the active components in a pharmaceutical topical formulations.”

Read the first part of this series: Viva la “sameness” – generic drugs and ensuring equivalence