Current Edition

What is the Right Validation Model? Practical Considerations and Applications

It is now widely accepted that validation in the life sciences industry follows a lifecycle model.1,2 What is not always clear is the specific model – or models – to follow and how to navigate through those models in the real world; in other words, the specific deliverables that make up that model, and how those deliverables change during the various interactions along the validation journey. Drawing on my experience in the field of validation, I propose organisations follow a dynamic validation model that can support the efficient and optimal operation of their Commissioning, Qualification, and Validation (CQV) program.

Other related terms such as building commissioning (Cx), C&Q, Q&V, and process validation suggest additional or sub-models within the larger proposed CQV operational model. However, my experience has found that they are often loosely defined and even used interchangeably. The use, advantages, and drawbacks of these models and their applicability to each of the five elements subjected to validation – facilities, utilities, systems, equipment, and processes, need to be understood in order to determine the right validation model in any given situation. The wider proposed CQV Operational Lifecycle Model is best understood within the context of regulatory expectations and best industry practices.

The following analysis explores well[1]known validation models and how they fit into a CQV program and observed best practices to support and enhance these models.

Validation Models

The most common validation models in the biopharmaceutical industry are:

The V-model3

• The W-model4

• Risk-based models for C&Q:

• ASTM-E2500 (2007)5

• ISPE’s Science & Risk-based C&Q Model (2019)6

• FDA’s Process Validation Model (2011)1

The V-Model

Since its appearance in 1994 as a model for system (software) development lifecycle (SDLC)3 [3] and its subsequent adaptation for equipment qualification in 2001,7 the V-model continues to be a constant reference in validation literature and across many CQV programs. One side of the V sets the specifications while the other side refers to the testing conducted against those specifications to formally qualify the equipment or system. The bottom of the V is where the equipment or system is built.

Implicitly embedded in this model is the commissioning testing, which has traditionally been conducted in the form of Factory Acceptance Tests (FAT) and Site Acceptance Tests (SAT).3 Depending on the system and the involvement from the vendor, these standard tests may be supplemented, or even replaced, by additional on-site testing. These tests, which are from my own experience and industry best practices, include Installation Commissioning (IC) or Installation Verification (IV), followed by Operational Commissioning (OC) or Operational Verification (OV).

The largest criticism toward this model has been its lack of reference for science and risk-based elements.5,6 Specifically, the V-model is silent about product and process understanding, which constitutes the science that would feed into – and otherwise enhance – the specification side of the V. The options to potentially simplify the testing side of the V in the form of Risk Assessments are also not shown in this model. In other words, the links with ICH Q98 and ICH Q89 are not illustrated. Nonetheless, for a representation of the fundamental CQV requirements, it is my experience that the V-model remains valid.