When Should Revalidation be Performed?

The pharmaceutical industry is in constant change. The continuous improvement of technology related to processes and computer systems creates a domino effect with regulatory requirements. The current trend of merger and acquisition among pharmaceutical companies is also a driving force of change. Manufacturers involved in mergers need to incorporate the acquisition as an efficient part of their existing system. Even without major changes, there is still a need to ensure that the validated system is maintained. All these are possible reasons to establish the need for revalidation.

Change control system

After the initial qualification and validation activities, the validation team must identify processes, systems and equipment in the plant that are subject to validation. All these must be covered by a change control system that will enable formal reporting and recording of changes.  The records will be used to identify if the change will impact the validated status and the requirements for revalidation.

A change control standard operating procedure (SOP) must be prepared. This should identify which changes do and do not require revalidation. The following is a list of items that may be included in the change control system. The inclusions however are not limited to this list.

• Procedures that are required to be validated such as operation, cleaning and sterilization
• Process equipment and plant
• Facilities
• Utilities
• Production process
• Commodities (i.e. primary packaging components, filters, sterile clothing, disinfectants, cleaning agents)
• Raw materials
• Computer systems
• Test methods and specifications

The change control system SOP must allow all proposed changes to be subject to review and approval of Quality Assurance, Research and Development, Production and Engineering. The reviewers will identify whether the changes must undergo revalidation and to what extent the revalidation activities should be.

Revalidation must be done periodically as part of maintenance of the processes, systems, facilities, equipment and methods. However, changes in the aforementioned items will also require revalidation upon approval based on any of the following:

• Change control system
• Annual product review
• Plant certification system
• Internal audit

The process of validation is tedious and requires valuable resources. The decision to perform revalidation must therefore be carefully strategized and properly embedded into the Validation Master Plan.