Traditional bio-pharma practices are being ever-more challenged. With the growth of advanced therapy medicinal products (ATMPs), many manufacturers are now seeking to understand whether these kinds of technologies can be combined with more traditional bio-pharma production in the same building.
ATMPs often require significant segregation from other processes. However, by following a few relatively simple steps, a framework can be developed to understand this challenge and what's required.
The first step is to identify the business need - to make sure you know what you want to achieve and at what kind of scale. Then there is the most important step of all — data gathering. This will encompass a detailed review of the relevant regulatory requirements, any operational constraints that may exist, and some guiding principles based on legacy practices and benchmark data.
Then you will need to conduct risk assessments. These are critical for both employee and end-user safety. In doing so it’s best to construct matrices for both the risk profile of each process and for the features your new or updated facility will require. Hand-in-glove with that will be a segregation strategy to ensure that each modality has the correct level of segregation.
It’s important to note that this concept of mixing modalities may include processes that run from very low risk (such as the use of characterised CHO cells, or therapeutic proteins) to high risk (such as those that include human-donated cells and viruses). Very high-risk processes, for example penicillin, are not part of this discussion and are deemed unsuitable for facilities with mixed modalities.
High-risk modalities, for example CAR-T manufacturing which involves potentially biohazardous cells from patients, may require entirely dedicated material handling, work stations and waste management. These may be difficult to incorporate unless you are starting with a clean sheet for your facility design.
In developing your risk matrix, two elements are crucial; Your own organisation’s appetite for risk, and a clear understanding of the underlying science of any modality you are seeking to incorporate. It is important to include any variations of the existing knowledge as and when it becomes available.
When developing your facility features by risk group matrix it is important to capture any operational constraints that may exist. For example, an ‘agnostic’ facility into which multiple modalities can easily be installed may present very different challenges to an existing operation with fallow space for a new modality. The level of segregation will depend on the level of primary and secondary containment, whether multi-modal on a concurrent or campaign basis, and the level of toxicity or potential for viral contamination.
Needless to say, once your risk assessment and matrix is complete, risk assessments on the scenarios under consideration being considered should be completed to verify the required facility features. That broader risk assessment and the individual risk assessments for all the modalities under consideration should include robust failure assessments and plans for coping with those failures.
For more on the mixing of modalities and the best practices involved, be sure to read ‘Multiple Modalities In Manufacturing’ by Tom Bannon and Alfred Penfold, published in Pharmaceutical Engineering, the official magazine of ISPE.
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