M4 - Lesson 4 - Continued Process Verification

Continued Process Verification can take a number of forms, but at its core, it is a study plan with a list of
parameters and attributes that must be regularly controlled and observed during the lifecycle of the
GMP bioprocess. Review at regular intervals is critical to ensure that the changes are not having an
impact on present results.

The purpose is to provide ongoing assurance that the process remains in a state of control during
routine production or commercial production through quality procedures  and continuous improvement
initiatives which means that plan are not only to achieve compliance with regulatory authorities, but
also to prevent batch discards, mitigate process vulnerabilities, and find continuous improvement
possibilities. Various important considerations are also discussed, including which data may be included
in a Continued Process Verification plan, with what frequency should the attributes be monitored, and
what level of statistical sophistication is required.

The activities under this stage would include procedural data collection from every batch, data trending
and statistical analysis product review, equipment and facility maintenance calibration, management
review and production staff feedback and improvement initiative through process experience.

Adherence to the cGMP requirements, specifically, the collection and evaluation of information and data
about the performance of the process, will allow detection of undesired process variability. Evaluating
the performance of the process identifies problems and determines whether action must be taken to
correct, anticipate, and prevent problems so that the process remains in control.

A statistician or person with adequate training in statistical process control techniques develop the data
collection plan and statistical methods and procedures used in measuring and evaluating process
stability and process capability.

A manufacturer should use quantitative, statistical methods whenever appropriate and feasible. Scrutiny
of intra-batch as well as inter-batch variation is part of a comprehensive  continued process verification
program. Variation can also be detected by the timely assessment of defect complaints, out-of
specification findings, process deviation reports, process yield variations, batch records, incoming raw
material records, and adverse event reports. 

Data gathered during this stage might suggest ways to improve and/or optimize the process by altering
some aspect of the process or product, such as the operating conditions (ranges and set points), process
controls, component, or in-process material characteristics. A description of the planned change, a well-
justified rationale for the change, an implementation plan, and quality unit approval before
implementation must be documented