Reformulation to Achieve Acceptable Stability Profile for NDA Submission
and Commercialization
Benefits of Case:
- Reformulation of unstable Phase III dose form
- Progress client to NDA submission with an acceptable dose form
Background and Challenge:
The Client had progressed into a clinical program with a sustained release combination drug formulation in which one of the drug substances exhibited an unacceptable long term stability profile, and the inert placebo layer consisted of a commercially unacceptable process. Alternate formulations had to be rapidly developed. Additionally, the new formulation could not infringe upon existing formulation patents covering a variety of methods to stabilize the drug in the solid dose form.
CoreRx™ Development Strategy:
- Tailor multidisciplinary team of formulation development, organic chemistry and manufacturing to identify possible approaches for formulation development,
- Review patent literature on the protected technologies used to stabilize the drug substance in the dosage form and determine which formulation approaches that permitted “freedom to operate”,
- Execute experiments to understand the degradation pathway and sustained release profile for the drug substance, and explore possible formulation and/or packaging approaches for stabilization,
- Identify a stable formula and manufacture batches to support an NDA filing.
The Objectives:
- Identify an approach for a stable formulation with scalability and freedom to operate
- Complete formulation work without disruption to the proposed NDA submission schedule
Value for the Client:
CoreRx™ staff identified a stable formulation that met the client’s needs for planned NDA submission and intellectual property requirements
Results from CoreRx™ Combined Experience and Expertise:
CoreRx™ quickly assembled a team with expertise in formulations, organic chemistry, patents, and manufacturing to perform a thorough analysis of technologies that could potentially solve the formula stability problem without infringing on existing patents. To quickly evaluate potential solutions to the stability problem, numerous experiments evaluating alternative formulation and packaging approaches were designed and performed. Once formulations were narrowed down, stability batches were made to identify the formula that would solve the stability problem and allow the development of the NDA to meet the client’s previously established schedule.
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