Traditional process validation addressed only basic aspects of quality assurance; that is, the quality of only the validation batches was assured and the quality of subsequent batches was inferred. In the evolving paradigm, the quality of a product must be built in rather than confirmed through downstream testing. Today, a holistic approach to product development and commercialization has to be proposed using a lifecycle management approach wherein
are inextricably linked. The application of science, innovation, contemporary manufacturing practices, and continuous improvement are strongly endorsed.
Pharmaceutical companies have to initiate a complete development program which incorporates Quality by Design (QbD). Identification of all potential quality attributes as well as raw material and process parameters which may impact safety/efficacy and quality sets the foundation for a development program that will deliver a high-quality pharmaceutical product. This will provide not only patient benefit but also sustain the organization lower rework rates and production costs, and higher efficiency and product yields.
Development success and efficiency can be enhanced with the application of risk management concepts. Risk management concepts are applied in order to better understand and to demonstrate the efficiency and explicit knowledge which develop as a result.
Concepts related to Process Understanding which means, according to ASTM E2475, understanding of the "why" and "how" things work is critical to long-term success of any product. Application of this knowledge to future compounds or activities is part of a larger context referred to as Knowledge Management.
Multivariate approaches to experimental design is another key issue. There are huge benefits of such methods, and there are advantages and limitations of several well-known statistical methods. Pharmaceutical development departments have to define how to use and apply existing theory in combination with empirical methods in order to rapidly develop and optimize synthetic routes, formulations and processes.
Modern concepts of process validation or better yet continuous verification assure that all batches produced are fit for purpose. This includes the requirements of continuous verification and the tools such as multivariate experimental design and process monitoring to achieve the desired state for product quality.
Finally, Continuous Improvement has to be introduced by demonstrating the need for continuous process monitoring & evaluation which can, in combination with prior knowledge and understanding, lead to identification of product variation due to either common or special cause variation and also a refinement in the knowledge and understanding of the product and process.
Jean-Marie Geoffroy, PhD
Takeda Global Research & Development, USA
(Speaker at the University of Heidelberg QbD/PAT Conference 2010)