"Continuous Process Verification as a Replacement for Standard Revalidation in the Manufacturing Process"

 

Pharmaceutical companies should periodically revalidate their processes in accordance with Good Manufacturing Practice. These activities verify that the process achieves the intended results, meets quality requirements and is safe for the patient. 

To cover the above requirement, companies still carry out (or have carried out) periodic revalidation. During such revalidation, the entire process, e.g. the manufacturing technology of a medicine, is revalidated, usually to its full extent. Such revalidation takes place at a frequency defined and justified by the manufacturer.

In recent years, this approach has begun to change. Standardized revalidation is being replaced by Continuous Process Verification.

What is Continuous Process Verification?

This is an alternative to traditional process validation based on the Quality by Design concept, an approach that emphasizing understanding the product, the process, and the process control.

We already know what Continuous Process Verification is, so let's return for a moment to the basics of validation itself....

Process validation encompasses a series of activities that take place throughout the product and process life cycle:

 

 

Stage 1 - Process design - at this stage a commercial manufacturing process is defined based on the knowledge gained from the development and scale-up work.

Stage 2 - Qualification / Process Validation - at this stage the process design is assessed to determine whether the process is capable of reproducible commercial production.

Stage 3 - Continuous Process Verification - during routine production, continuous assurance is obtained that the process remains under control.

Now let's focus on Stage 3. Its purpose is to ensure that the process remains in a state of continuous control ('validated' status) during standard commercial production. Adherence to the requirements of the Current Good Manufacturing Practices (CGMP) and, in particular, the collection and evaluation of process information and data allow the detection of unwanted process variation and the analysis of process disturbances.

Assessing process performance identifies problems and determines whether action needs to be taken to correct, anticipate and prevent problems so that the process remains under control.

The data collected is statistically trended and reviewed by trained staff.

This data can suggest ways to improve and/or optimize the process by changing relevant process and product aspects, such as operational parameters (ranges and set-points), process control, properties of components and materials used in the process. If changes are required, a description, justification for the change, and an implementation plan are documented and approved accordingly. Depending on how the proposed change may affect product quality, additional process design and qualification activities may be justified.

In that case, what is better Periodic Revalidation or Continuous Process Verification?

In my opinion, it is the second one. Why?

Periodic revalidation must be planned in advance, and it would be good to carry it out on a minimum of three production runs to ensure process repeatability. By doing so, we expose the company to additional costs, and occupy the production line. We place a burden on the quality control laboratory by ordering additional validation analyses. And what is most important, it may turn out that the product which we have to validate is not very popular on the market and by producing 3 series we will burden our warehouse with unnecessary goods which will linger for unknown lengths of time.

Now let's find out what we achieve if we apply Continuous Process Verification?

We will not burden production. We will not generate an artificial demand for a product. We do not burden the laboratory with additional analyses, which are often very time-consuming. The only person who will be burdened is the employee-validator who has to statistically process the collected data and draw the appropriate conclusions. The only cost we generate is the cost of human labor. In addition, we do not perform such a verification every 7 years or every 5 years. The parameters for evaluation are collected continuously, so the process is under control all the time. We are able to quickly detect abnormalities and implement appropriate corrective measures to ensure the highest quality of manufactured products.

 

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