The Third Planning Focus of VMPs: Validation Lifecycle Management

In addition to planning the systems inventory and the validation schedule, the VMP is a plan for validation lifecycle management. While the VMP assists with planning the design and execution phases of validation, post-validation activities are also included. A plan for managing the monitoring and control of validated systems and processes is just as essential as a plan for the design and execution phases.

Post-validation monitoring is frequently overlooked, but is an essential component of a VMP. Validation is never “done”. Validation is a quality system that is ongoing and requires maintenance, even after initial validation is complete. Therefore, the VMP must describe a plan for post-validation monitoring.

Continual monitoring of validated processes is required by regulatory agencies. FDA 820.75(b) for devices states that procedures for monitoring and controlling process parameters in validated processes must be established and maintained (1). Similar expectations are held of pharmaceutical and biotechnology manufacturers. Post-validation monitoring helps to confirm that the specified requirements of the process continue to be met. This, in turn, ensures that products continue to be safe and effective for patients.

Data gathered during validation is used for monitoring and controlling the validated state. The important output variables of the process were determined during process validation. Also, the critical quality attributes (CQA) and critical process parameters (CPP) should be known and documented. During post-validation, the output variables are monitored and the input variables are controlled.

There are several tools that can be used for post-validation monitoring. Some of these tools include:

• Statistical process control charts (SPC) used monitor and detect any process changes
• Control charts, which can be part of a capability study to demonstrate stability in the process over time
• Capability indexes that determine if the process is adequately centered with small variations
• CAPA, change control, or deviation and investigation reviews
• Trend analysis
• Alarm logs
• Revalidation
  

All of these tools can be used to monitor the process on a per-batch or per-year basis. Monitoring a process on a per-batch basis provides the lowest risk to the organization. Data is provided in real-time, which in turn, assures the highest level of quality assurance and the highest return on investment to the organization. Performing annual reviews of the data allows the big picture to be examined for trends or other indicators of process issues. Both methods can be employed when planning post-validation monitoring. Post-validation monitoring also provides benefits for other aspects of a process. These aspects include:

• Improving the quality and performance of a process, which can help a company save money
• Assisting with annual reports that may be required for some systems (e.g., Water-For-Injection system)

Post-validation monitoring can be used to not only monitor the process for continued high performance, but it can also be used to monitor business-related aspects of a process. Ultimately, post-validation monitoring can provide a real return on investment to the company beyond improved compliance.

Validation lifecycle management is an important part of any VMP. Post-validation monitoring is commonly overlooked, but is required by regulatory agencies. An adequate plan for post-validation monitoring must be outlined in the VMP. Managing the validation lifecycle via the VMP will assist with developing a process that continues to produce quality product that is safe and effective for the patient.

Any comments or questions regarding this blog are more than welcome. Thanks!

Best regards,

Megan K Gladfelter