(45b) Challenges in Pharmaceutical Development and Manufacturing

The pharmaceutical industry is facing significant challenges to maintain high quality and competitiveness. In the U.S. the FDA has lead the drive towards more science based practices and regulations. This is captured in the concepts of Quality by Design (QbD). Quality by design in product development and its use in scale up and manufacturing is really no more than the application of accepted scientific and engineering principles to design for function. The gaps in our knowledge and ability in implementing QbD concepts in a comprehensive manner fall largely into three categories: 1) Materials Science gaps, 2) Process Modeling gaps, and 3) Information management and informatics. These concepts are captured in measure by the ICH CTD and guidelines in the form of the development rationale for review and in the design space for flexible control limits.

The ?business case? for such activities is in some ways more complicated than the scientific case. Comparing the potential gains in efficiency, the decrease in OOS investigations, and the lower hurdle for incorporating new technology against the start-up resources required and the sustainable benefit is challenging, yet there are some data to help in the analysis. The analysis for generic and OTC products in emerging markets such as China may be more favorable towards modernization due to the reduced margins, but the start up resources must still be assessed.

Concepts in combining the scientific, business, and regulatory aspects of modernization will be discussed and examples will hopefully help provide some insight into the challenges.