Several gaps in current regulatory guidelines that govern the analytical method life cycle for the testing of biopharmaceuticals are identified. Strategic guidance on how to monitor and control the life cycle of an analytical test method is provided. Analytical method transfer, analytical method component equivalency, and analytical method comparability protocols are discussed in light of risk-based strategies for validation extensions. The use of an analytical method maintenance program is illustrated in relation to the predictable risk to patients and firm.
ANALYTICAL METHOD MAINTENANCE (AMM)
There are several points to consider when running an AMM programme. Usually, assay control results that are within established limits (e.g., ±3 s.d.), will yield valid assay results for the test sample(s). Whenever possible, the assay control should yield a similar assay response when compared with the test sample. Monitoring the assay control will then indicate when unexpected assay result drifts or spreads may have occurred. Whenever the assay control results are close or over their established limits, there is a high probability that test sample results are also going in the same direction. This is something that should not be ignored because it causes predictable, although not exactly measurable, errors in test results (cases 1B and 2B).1
Furthermore, controlling and fixing process problems could save more batches from rejection. These steps would also be very much in line with the recently published principles for quality and process analytical technology leading to faster licence approvals and reduced inspections.2–6
From the robustness studies performed during analytical method development (AMD) and the intermediate precision results during AMV, the identity of the method component that may be responsible for changing test results when replaced is clarified.