Special report: Operations support

Validating cleaning methods used
for production equipment

Werner Swoboda Cleaning Validation, Vienna, Austria

As part of the international regulatory framework in which Octapharma operates, the Cleaning Validation department contributes to patient safety by validating the cleaning methods of all equipment in production.

I am proud to be part of the cleaning validation department which my colleague and I built from the ground up. I was the first member of the team, which was established as part of attaining the US Food and Drug Administration (FDA) licence. It’s my “baby”. As part of the international regulatory framework in which Octapharma operates, our department contributes to patient safety by validating the cleaning methods used for production equipment.

Performing a Micro Bicinchoninic Acid (BCA) test in the Operations Support laboratory.

We ensure that the cleaning methods applied reduce the risk of cross-contamination between production batches in line with the regulations. Our role is to demonstrate that the cleaning methods effectively reduce product residue from the equipment surfaces, e.g. from vessels, chromatography columns, filter presses and filling machines.

Two cleaning methods are applied: automatic cleaning (cleaning in place – CIP – for vessels, pipes, filling and washing machines for production equipment, etc.) and manual cleaning (for small parts used in the production process).

Due to the substantial extension plans currently realised in Vienna, my main activity is the cleaning validation of new equipment. For example, the new pilot plant will have 24 new vessels (from 100 litres capacity up to 1,100 litres), two new washing machines and one new filter press. We must validate the cleaning methods of all of this equipment. I attend planning meetings and thus am able to evaluate any potential issues in terms of cleaning validation activities from the very beginning.

When new equipment is purchased, Octapharma performs factory acceptance tests (FATs) at the vendor’s site to check the quality. For example, in the case of a new vessel, the FAT includes a spray pattern test during which the vessel’s inner surface is investigated for spray shades. After installation of the tank at Octapharma, installation qualification and operation qualification tests are performed and the spray pattern test is repeated.

We ensure that the cleaning methods applied reduce the risk of cross-contamination between production batches in line with the regulations.

Validation of the cleaning process of production tanks using spray patterns and UV light.

Prior to release to routine production, three surrogate runs are performed: the vessel is soiled with a surrogate solution and, after a drying period (i.e. dirty hold time), the CIP cycle is started. If a vessel is big enough, we climb into it and take swab samples from the inner surfaces to check for any product residue after each completed cleaning cycle.

Safety regulations prohibit entering vessels without colleagues in attendance (staff safety is our priority when anyone climbs into a vessel). Therefore, my colleagues and I perform the cleaning validation of such equipment together. The person climbing into the vessel wears a helmet and harness with a security belt. This is necessary because a large vessel is three or four metres high and can be slippery.

In the next validation step, the cleaned vessel has to be kept for a defined period in the status “cleaned” (i.e. clean hold time). After the period has passed, contact samples are drawn from the inside of the vessel. The samples are sent to our colleagues in the microbiological laboratory to analyse for microbiological growth.

Due to the complexity of the cleaning validation process, the validation of equipment can take up to 30 days.

After this qualification, the vessel is ready to be used in routine production. Nonetheless, additional cleaning validation runs are performed after use of the vessel with each product by taking swab samples again, since each product matrix has individual characteristics that might potentially affect cleaning. For each cleaning validation acceptance criteria, such as visually clean and no detectable product residues, are defined upfront. In case a cleaning validation is not successful the root cause for failure is investigated. After implementation of corrective and preventive measures, the procedure for cleaning validation is repeated.

There is no education offered by any type of school to train you in cleaning validation. The only chance to acquire knowledge is to learn by doing it. The longer you stay in this job, the more you will see, learn and enhance your experience. This all helps to solve cleaning validation issues if equipment, for example, does not get thoroughly cleaned by the applied cleaning procedures.

I enjoy my job in the cleaning validation department because I am in contact with different departments – production, engineering, QC etc. – as well as with my colleagues at other Octapharma production sites, with whom I share knowledge and find solutions. My work is varied and interesting, I really never have the same work every day. Every day is different to the day before.

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