Building Quality

Mary Jo Wojtusik of Waters explains the benefits of using a Quality by Design approach.

“Developing quality methods the first time allows for problem-free validation, transfer and operation”
-Mary Jo Wojtusik

What are the benefits of a Quality by Design (QbD) approach for chromatographic method development?

Mary Jo Wojtusik. Quality by Design is all about building quality into a product or process by focusing on gaining scientific understanding and knowledge during the development process, and having a goal of reducing variation and consistently producing a quality product. Liquid chromatography is the preferred analytical technology for final product testing and release and is also used throughout the entire drug development process. Using a QbD approach for chromatographic method development builds robustness into a method during the development phase that can be carried forward through manufacturing, eliminating the costs and delays associated with having to redevelop and revalidate unreliable methods.

How does using a QbD approach lead to quality or fit-for-purpose methods?

MW. QbD, as I mentioned, focuses on gaining scientific understanding. Guidance documents from both the US Food and Drug Administration (FDA) and International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) state that the information and knowledge gained during the development process should provide sufficient scientific understanding to support establishment of the design space, specifications and controls. Design space, as defined in the guidance documents, is the multidimensional combination and interaction of input variables and process parameters that have been demonstrated to provide assurance of quality. It is very reasonable and easy to think of a chromatographic separation as a process with various inputs and parameters such as type of column, mobile phase composition and pH, flow rate and temperature, with all of these inputs and parameters interacting simultaneously to effect a separation of the sample constituents. The process of developing a valid design space investigates all of the chromatographic interactions that participate in achieving the desired method and includes an evaluation of robustness. Achieving the desired optimal method performance and ensuring that the method is robust so that it will continue to perform for the life of the product is the definition of a quality method.

What is the role of regulatory authorities in extending the application of QbD principles to chromatographic method development?

MW. The regulatory authorities recognize that robustness is a key attribute of any analytical method. The ICH guidance document, ICH Q2B Validation of Analytical Procedures: Methodology (November 1996) states "the evaluation of robustness should be considered during the development phase...." The challenge for chromatographic methods is that there has been no good way to do this. Robustness is evaluated during the validation phase where we are essentially testing it in to the method rather than building it in. So, the intention of the regulatory guidance document is to recommend an approach that builds robustness into a chromatographic method while the method is being developed.

What do you see as the future of complementary analytical technologies?

MW. The focus in the industry is on shortening drug development times while reducing operating costs. I see the path forward as being driven by the integration of technologies that streamline and automate the chromatographic method development workflow and incorporate Quality by Design principles to achieve the necessary productivity improvements and cost reduction. At Waters, we have been working with one of our software partners, S-Matrix Corporation, a developer of advanced software that automates R&D experimental work according to QbD principles and methods, to bring together the superior chromatographic performance of the Waters ACQUITY UPLC system and our industry-leading chromatography data software, Empower 2, with S‑Matrix Fusion Method Development software to provide an integrated and automated, Quality by Design method development solution that dramatically reduces the amount of time that it takes to development a method and uses an approach that ensures that a robust, fit-for-purpose method is developed. Developing quality methods the first time allows for problem-free validation, transfer and operation, thereby eliminating the time and cost associated with having to redevelop and revalidate chromatographic methods.

Mary Jo Wojtusik joined Waters Corporation in 2007 and has more than 15 years of experience in bringing innovative analytical and process-scale products and solutions to the pharmaceutical and biotech industry. As Business Manager for Pharmaceutical Development at Waters, Mary Jo works closely with customers and industry experts developing solutions that meet their scientific and critical business needs.