Regulatory guidance documents are written by committees, resulting in statements that are both exact and generic. Meeting regulatory requirements involves not only interpreting these documents correctly but also addressing their omissions. This article provides practical guidance on issues that are not thoroughly covered by current guidance documents regarding validation of analytical methods for biopharmaceuticals.
We can generate evidence for the validity of analytical data in the formal method-validation program where all critical parameters are extensively tested under a detailed protocol that includes scientifically justified and logical step-by-step experimental approaches. All planned data sets must fall within pre-established protocol acceptance criteria limits. These criteria should be derived from and justified in relation to historical data and product specifications. Once evidence for all critical elements is provided, the validated method will become the official, licensed procedure for that particular product and process step, and it will then support production and product release. The relationship between "valid" or "suitable and validated" is often overlooked, but there is a high price when "validated" test systems are simply inappropriate.Incentives to replace existing licensed test procedures may come from regulatory agencies, or they could be motivated by potential cost savings, ease of use (automation), and the opportunity to generate more accurate and reliable results.
The International Conference on Harmonization (ICH)'s Q2(R1),1 should be used for basic guidance. However, following just these guidelines will not necessarily produce a "valid" method and may not provide sufficient evidence that this method is suitable for product release. The intent of USP 30 <1225> is to provide guidance only on validation requirements for test methods for inclusion into USP with the expectation that validated USP methods still require verification from users.6–7 The US Food and Drug Administration (FDA) and European Medicines Agency (EMEA) provide guidance on some of the scientific issues that are not covered by Q2(R1).
Process Map. A process map showing the recommended steps for the selection, development, validation, and potential transfer of analytical methods, illustrating all proposed functional responsibilities was developed. Frequently, larger companies have separate functional units for method development, validation, and testing. The process flow in Figure 1 describes an ideal sequence of steps for better analytical method validation (AMV).