Current Edition

Regulatory and Developmental Complexities Around Demonstrating Bioequivalence for a Topical Generic Product

Increasing Patient Access to HighQuality Topical Products

The topical dermatology market, although niche, was estimated to be valued at approximately $20.4 billion in 2020.1 In a study from 2010–2015, over half of the topical drug products experienced a price increase and the average price of topical generic drugs was 276% higher by the end of that period. This is being driven by the lack of competition among generic manufacturers, where approximately 80% of topical dermatological drug products have very few competitors or no approved generics at all. The lack of generic products can be attributed to the complexity of developing topical dermatological drug products, low market volumes, and/or the risk and expense of clinical endpoint bioequivalence (BE) studies.

Topical dermal formulation development is inherently challenging due to the distinct characteristics of dermal drug delivery, including the complex characteristics of the skin barrier (e.g., location, age, condition). Additionally, formulations are often applied to diseased skin that is likely perturbed or influenced by external factors (e.g., temperature, humidity, occlusion). Another distinct characteristic of topical formulation development is the complexity of the product. For example, the number of excipients required for a topically applied product can make development difficult. Each excipient used in a product can impact the formulation’s irritation and sensitisation, bioavailability, penetration, dose homogeneity, drug solubility and stability, and drug product physical and chemical stability (quality). In some cases, these properties can be markedly different between excipient suppliers, grade, and age making the development of exact generic copies of such formulations extremely difficult without commensurate excipient knowledge.

In efforts to make high-quality, affordable medicines available to the public, regulatory agencies have released guidance to create a modular framework for in vitro bioequivalence (BE) testing of topical products in lieu of clinical trials. The FDA released a draft guidance in 2016 on acyclovir cream which has served as a reference point for the other product-specific guidances (PSGs) that continue to be published by the FDA within 18 months of an NDA. The European Medicines Agency (EMA) released a similar general draft guideline on the quality and equivalence of topical products in 2018. These two guidances serve as the foundation for what has been a flurry of activity in the generic space for topical drug products. As generic companies would not have to undergo the same rigorous clinical studies that are required of the brand-name product, generic products can be developed, approved, and pushed to market more quickly. This can lower the cost of development by up to 85% when compared with the cost of developing the innovator product. Additionally, there is a significant decrease in the amount of time it takes for a generic product to be commercialised. These factors together can decrease the cost of the medicine when it reaches the market and helps to lower overall healthcare costs while delivering high-quality topical products to patients that meet current regulatory standards.