Ongoing/Continued Process Verification - The Perspective of an European GMP Inspector

With the introduction of a process validation life cycle, a new element came into play: ongoing/continued process verification. Although it has been known for at least 10 years, this stage still poses a challenge for the pharmaceutical industry. As part of an ECA course on this topic, Dr Franz Schönfeld, an European GMP inspector, presented his views on the matter. What does he expect?

He began his presentation with the statement: Your validation is only as good as your last batch.

Using an active ingredient synthesis as an example, he explained the entire process validation life cycle in the form of the PDAC cycle:

• Plan: Identification and control of potential causes of contamination 
•  Do: Validation of proven acceptable ranges' (traditional, hybrid or continuous)
• Check: Checking the results of the validation runs (report vs plan, deviations)
• Act: Accept or change the process (e.g. additional sampling)

It was very important to Dr Schönfeld that anomalies were also detected during the commercial phase. He gave the following examples:

• Changes in personnel (including management)
• Maintenance, repairs, changes to equipment
• Deviations in the manufacturing process
• Trends in analytical results
• Customer complaints
• Regulatory changes

And this is precisely why Dr Schönfeld sees ongoing/continued process verification as the ideal means of detecting these anomalies. The aim is also to further develop the process on the basis of the extensive data material.

Ongoing/Continued Process Verification replaces routine revalidation, at least in the non-sterile area. For him, an important aspect of Ongoing/Continued Process Verification is an approved plan that describes which process is being considered, the scope and frequency of verifications depending on process knowledge, performance and incremental changes over time in the life cycle.

He sees the use of statistics, which are already largely used for product quality review (PQR), as a further expectation of the authorities. However, PQR does not replace ongoing/continued process verification, as it is created relatively late and is also product- rather than process-related.

He recommends specifying in the validation master plan that a change control event should always also evaluate the control status of the process. Furthermore, in his opinion, the validation master plan should also specify the number of incremental changes that triggers consideration in the ongoing/continued process verification. He also recommends a rolling review to identify trends and evaluate the control status.

An ongoing/continued process verification report should show whether a process is in a controlled state or not and what additional measures (e.g. monitoring, sampling) may be necessary.

With regard to continued process verification in the US FDA Process Validation Guidance, he concluded: Different wording between EU and US but the same life cycle approach. Finally, Franz Schönfeld described three GMP deficiencies in process validation from his inspection practice.

ECA members can view the entire presentation in the members' area under Video Presentations.