Cost-effective process development of complex cream ensures consistent quality and on-time delivery of clinical trial material

MedPharm was asked to provide multiple 25 kg batches of a complex cream for an important Phase 2 atopic dermatitis clinical trial by a large global pharmaceutical company. Failure to supply or delay would have had major financial consequences for the project. Due to the nature of the request, the client valued MedPharm’s detailed understanding of the multi-stage manufacturing process.

Our experts used their understanding of the formulation and their many years of experience in scaling-up complex semi-solid products to identify the ‘Critical Process Parameters’ (CPP) as homogenization speed and time, and cooling rates at different stages. They laid out a suitable factorial design of 12 runs using 1kg lab reactors which model the large scale. The key ‘Critical Quality Attribute’ was identified to be the rheology profile of the final product. This work showed that the rheology could be particularly sensitive to the homogenization time and speed and appropriate parameters were set. An initial run at the larger scale confirmed that the process and parameters selected gave a product which met all specifications.

Subsequently, over 15 clinical batches were manufactured with reproducible quality using the optimized manufacturing process. Given the sensitivities to key parameters observed this almost certainly would not have happened without the process evaluation work. Additional large batch production would have wasted significant amounts of a high-value API and impacted the completion of the trial.