Per FDA Guidance for Industry, Process Validation, process validation consists of 3 stages: Process Design, Process Qualification, and Continued Process Verification. The third stage is defined as “Ongoing assurance is gained during routine production that the process remains in a state of control.” Much like process validation, a continued (or continous) verfication is required to ensure that a company stays in compliance.
In general, regulatory compliance means conforming to a rule, such as a specification, policy, standard, or law.
https://en.wikipedia.org/wiki/Regulatory_compliance
The difficulty for the biotech industry is that there are many regulations that have to be followed spanning the entire lifecycle of a product. Take process validation. Just one overall area, but it involves many pieces as well as many departments within a company.
- Stage 1 – Process Design – is typically handled by Process Development groups. These may be further defined into early stage and late stage depending on the company. A new process relies on information gained from development of previous products, capabilities and strengths of a company, equipment that has already been implemented, and specific requirements based on the product’s quality. Traditionally, much of the information gained in Process Development was captured in lab notebooks, then Excel spreadsheets, and now e-notebooks and other digital transformations.
- Stage 2 – Process Qualification – involves many groups as this is typically part of the technology transfer from development to manufacturing. Everything that has been designed for this process – from raw materials to testing to process control – has to be transferred to the departments that will now produce this product, hopefully, for many years.
- Stage 3 – Continued Process Verification – is handled at the manufacturing site. While the number of groups involved may be reduced, the variety of information is not. Process Verification involves the process performance and operations as well as the product quality.
This is just the complexity of process validation. Now, imagine adding all the other aspects of the regulations: Quality Control assays, testing, and specifications; Equipment Qualification; Facility Qualification; Raw Material tracking, specifications, and testing; Risk Management; etc.
Ensuring compliance soon becomes a daunting task when one looks at all of the different parts involved.
- Are the manufacturing controls within the validation limits set? Within the license ranges?
- Can the equipment meet (and continue to meet) all the requirements of the processes?
- Do the specifications still align with the licenses?
Yes, change control is used to ensure that any changes to a process are evaluated for impact. However, with the number of systems and departments needed to manage the process lifecycle, it is likely that change control will not be enough to prevent errors from happening. Or a company stops making changes because the task of maintaining compliance is too daunting.