Process Validation

Several standards on Process Validation have been published. According to the FDA Guidance, process validation includes a series of activities taking place over the lifecycle of the product and process. The three-stage life cycle links product and process development to qualification and Continued Process Verification in order to control variability and maintain the process in a state of control until product discontinuation.

The concept of process validation is evolving. Effective validation may represent a significant decrease of costs. A validation not performed in an efficient manner may represent a loss of productivity or waste. For companies it is a challenge to quantify validation in terms of hours for each activity and find the best option to ensure quality. So, what will be the state-of-the-art approach to validation in the future?

From the FDA Guidance on Process Validation the product and process will be designed at stage 1. The Quality Target Product Profile (QTPP) may be the first document. Telstar recommends identifying the whole spectrum of quality attributes based on QTPP. At this early stage the Critical Quality Attributes (CQAs) should be assessed by a rigorous analysis, because all of them may impact on safety and efficacy. At stage 1 it will be also defined how to control material (CMAs). The whole stage is driven by science and risk management.

Once Telstar has obtained the list of quality attributes, each of the identified CQAs will be linked by risk assessment to one or more critical process parameters (CPPs). Possible operational ranges and set points will also be obtained through manufacturing process development during stage 1. This data may be represented by an Ishikawa diagram, which will be the input for further validation stages, provided that the process has been characterized, the control strategy and operative limits have been established and there is sufficient knowledge to face the next stage.

C&Q (see section A5.1) may be integrated into the FDA Process Validation at stage 2, as a sub-stage 2a), where FDA Guidance requires controlling variability. Variability depends on “critical aspects”, a concept introduced by ISPE Guidelines. The critical aspects are identified and documented by risk assessment, being the risk control strategy to be implemented which is subject to qualification.

C&Q activities may precede PPQ Process Validation at sub-stage 2b), where the established control strategy (at a higher degree than in routine production) is verified and assessed if the process is capable of reproducible commercial manufacturing, ensuring that the system is fit for intended use.

During stage 3 “Continued Process Verification”, the process is monitored and the process capability and impact on variability is verified. Telstar will adapt the risk-based control strategy according to variability.