A lifecycle approach to bioassay validation

Tim Schofield , CMC Statistics and Regulatory Science, Germantown, MD 20876, USA
(timothylschofield@gmail.com)

Recent global and national guidelines have advocated for the implementation of a lifecycle approach to analytical method development and management.  The principles and practices cited in these directives have come to be called analytical quality by design (AQbD).  A USP suite of bioassay chapters, USP <1032> on design and development, <1033> on validation, and <1034> on analysis were written with this in mind. 

These accompany recently published ICH Q2(R2) Validation of Analytical Procedures and ICH Q14 Analytical Procedure Development, as well as USP <1220> Analytical Procedure Lifecycle and ongoing reviews of a revision of USP <1225> Validation of Compendial Methods and a new chapter, USP <1221> Ongoing Procedure Performance Verification. 

In many ways the lifecycle approach is a formalization of historical practices in method development and lifecycle management.  However, more emphasis has been given to “fitness for use” through the introduction of the analytical target profile (ATP), while the overall process is characterized as a continuum from method inception through retirement.  The uses of statistical concepts such as confidence and prediction intervals, and formal study design have been included to address business and patient risks.  Similar to the introduction of QbD for manufacturing process development, it has been acknowledged that the implementation of AQbD is likely to be a hybrid of traditional and enhanced approaches until industry and regulators have gotten more familiar with this paradigm.

This talk will give a high-level overview of the concepts behind a lifecycle approach to bioassay validation, and the potential advantages of considering these.  Most notably the method control strategy will be described as a sensible tool to efficiently ensure method validity over time.  While emphasizing the application of AQbD to bioassay, its potential power as an accelerator in development of any analytical method will be illustrated.

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Short Biography of Presenting Author

Tim Schofield was a scientific and regulatory professional in the pharmaceutical and biologicals industries. Prior to retiring Tim worked at:

• Merck Research Laboratories heading the Nonclinical Statistics department,
• GSK as a Director in US Regulatory Affairs, and later as a Senior Advisor in Global Vaccines Technical R&D,
• Arlenda Inc. as US Managing Director and Head of Nonclinical Statistics,
• MedImmune as a Senior Fellow heading the Regulatory Sciences department in Analytical Biotechnology, and
• Owner and Consultant at CMC Sciences, LLC.

An early adopter of quality by design, Tim worked together with industry scientists and engineers, as well as global regulators to help develop principles and guidelines focused on managing risk during product and analytical development and lifecycle management, while ensuring patient safety, efficacy, and product supply.

Tim received a Bachelor of Science degree in Mathematics in 1973 from Lafayette College, and a Master of Arts degree in Statistics and Operations Research in 1976 from the Wharton School of the University of Pennsylvania. He was a member of the USP Statistics Expert Committee from 2010 to 2025 where he led efforts in the development of chapters on design and development, validation, and analysis of bioassays, and a revision of a chapter on analytical data interpretation and treatment. He has also participated in industry initiatives related to Quality by Design, analytical method development and validation, comparability, stability, and specifications.