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Case Study: Achieving Product and Process Understanding by Execution of Design of Experiments...

 Case Study: Achieving Product and Process Understanding by Execution of Design of Experiments in a Quality by Design Approach in Developing a Generic Topical Product


Michael Fowler, Actavis Inc.

The US Food and Drug Administration (FDA) has repeatedly asked pharmaceutical companies to include components of Quality by Design (QbD) in ANDA product filings during the development phase of product lifecycles. This case study demonstrates how incorporating QbD, a “systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management”, can enhance product and process knowledge and enable sponsors to include statistical design of experiments (DoE) in process development. Specifically, this work describes how statistically designed experiments were utilized during development of a generic topical product. For generic pharmaceutical products, comprehensive or powerful DoE may not be feasible due to aggressive project timelines and lack of resources. However, using a risk and science based approach is feasible for many critical processes, enabling generic product development within the QbD paradigm. SAS JMP was used as a tool to implement QbD in process development. An Ishikawa diagram was created and used as a starting point to take into account potential risks that would impact product quality, safety, purity, and efficacy. Potential critical quality attributes and process parameters were explored by different methods, including: prior product and process knowledge, Quality Risk Management, and DoE. A container-filling process DoE was planned and executed for process optimization and design space generation. This approach not only optimized the container-filling process, but also simplified technology transfer and accelerated product scale-up, therefore decreasing overall development time.

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