Meeting the challenge of bringing new complex generic drugs to market requires access to appropriate physicochemical characterization methods to enable rapid deformulation of the reference listed drug product (RLD) and assess whether Q3 equivalence has been achieved as part of in vitro bioequivalence testing. In this webinar, Malvern Instruments' scientific team will introduce a toolset of physicochemical analysis techniques which are increasingly being applied to complex generic formulation development. Specific case studies describing approaches to deformulation and Q3 in vitro bioequivalence testing for topical drug products and orally inhaled and nasal drug products (OINDPs) will be presented.

One of the most significant challenges facing heath care providers is that of maintaining access to drug products based around complex formulations at a price which is sustainable. The overall market for generic products is growing rapidly, with the industry delivering billions of dollars of cost reductions, and supplying over 80% of patient prescriptions in the US. However, this growth has mainly been driven by the development of traditional immediate-release oral solid dose generics. In contrast, there remains a significant number of off-patent complex product drugs for which there are few or no generic versions. In response to this issue, regulators such as the US FDA are actively encouraging drug companies to take on the challenge of developing and launching complex generics by releasing product-specific guidance describing in vitro bioequivalence approaches which may be used in lieu of clinical studies. This guidance offers significant benefits to developers by illustrating routes to market for complex generic products which have reduced risk, costs and time required.

Traditional routes for establishing bioequivalence can be challenging for complex generic products, especially those designed for local action, such as topicals and nasal sprays. Clinical studies for obtaining in vivo pharmacokinetic (PK) and pharmacodynamic (PD) data are expensive and time-consuming – the latter being the greatest barrier to generics developers. In addition, systemic exposure, as measured as part of a PK study, may not provide a good basis for assessing bioequivalence for locally-acting drug products, as it is the in situ (non-systemic) drug concentration at the site of action which determines bioavailability. To address these challenges, recent US FDA guidance for complex generics has outlined the requirements for assessing Q3 equivalence - that is, the equivalence of physicochemical properties between the reference listed drug product and the test product – as a route to determining bioequivalence in vitro. Regulators and leading companies engaged in the research and development of complex generics are therefore seeking to both apply existing physicochemical measurement technologies and also invest in new techniques in order to aid deformulation and rapidly establish Q3 bioequivalence within complex generic drug product development programs.

Malvern Instruments' toolset of analytical techniques includes methods for measuring many of the physicochemical properties referenced by the US FDA, including critical quality attributes such as drug particle size and shape, formulation rheological profile and spray droplet size distributions. These technologies are widely applied as part of deformulation and in vitro bioequivalence testing, as the studies presented in this webinar will show.