In this feature with Manufacturing Chemist, John McDermott, Vice President of Scientific Consulting, addresses challenges within the industry and discusses how our Translational Pharmaceutics® platform can offer numerous benefits.
Conventional approaches to develop and optimize formulations are suboptimal and require extensive pharmaceutical development activities to be undertaken prior to clinical evaluation and performance validation.
At the root of this challenge is a vertically integrated structure with ‘make’ functions separated from ‘test’ functions.
Formulation development under the current industry structure typically comprises the identification of formulation prototypes, which are then screened in preclinical species to select candidates for clinical assessment. Manufacturing processes for these candidates must then be scaled-up to generate the product to support extensive stability studies that drive regulatory submissions, with the remaining material packed, labelled and shipped to a clinical site for evaluation. This process can take 12–18 months to complete and requires significant investment before the product is known to meet the drug delivery need.
Translational Pharmaceutics® has enabled a reconfiguration of conventional formulation development and optimization processes, addressing gaps in observed human performance, by proceeding directly to clinic without conducting poorly predictive preclinical pharmacokinetic investigations. This data-driven, streamlined formulation development approach — termed RapidFACT — allows drug products to be screened iteratively in human subjects, dramatically increasing the accuracy of formulation evaluation and selection.
Significant benefits can be derived from adopting the Translational Pharmaceutics® approach of horizontal GMP manufacturing and clinical testing integration. Efficiency in early development shortens timelines, reduces costs and improves flexibility by being able to manufacture drug products in real-time, allowing the development team to evaluate and optimize new formulations in the clinic.
Reductions in development time are enabled, with the formulation team able to capitalize on clinical data emerging from as early as 4 months into the program. An additional key benefit is greatly reduced API consumption, as only the drug products needed to support the immediate dosing period are manufactured (compared with the need for extensive stability studies to allow formulations to be assessed clinically, which require larger batches).
To date, more than 100 programs have been completed across a wide range of applications. Solubility enhancement has been studied using all of the major techniques, including salt form and particle size changes, solubilization strategies, lipidic formulations and spray-dried amorphous formulations. Modified release programs have been conducted to optimize sustained release, delayed release and gastroretentive technologies, as both tablet and multiparticulate systems. In addition, non-oral drug delivery has been studied, including inhaled, transdermal and ocular drug products.
Combined, the benefits of a Translational Pharmaceutics approach is allowing industry to reconfigure development programs and improve R&D efficiency and productivity.
To read the full article, visit the Manufacturing Chemist site here.