2023-06-15

With a diversified portfolio and a changing market, flexibility is a great tool to manage risk.

Treatments are becoming more and more specifically targeted. This means that the potential patients for a new drug are often fewer. This new trend has a significant impact on the strategy followed by pharmaceutical companies. The revenue generated by sales of a drug may not be sufficient to justify a dedicated production facility.

Faced with this situation, the industry is moving towards the most economically viable solution: multiproduct facilities. And although it is common to relate this type of plant to CMOs (Contract Manufacturing Organisations), there are also pharmaceutical companies that choose to build multiproduct facilities.

Some of the elements that contribute to uncertainty when considering to build or not to build a new plant are:

• Variations in demand for a product.
• Emergence of competing drugs.
• Changes to increase process efficiency.
• Prioritisation between products in the same portfolio.

Cross-contamination                             

It is almost inevitable to think of multiproduct plants and not have a red light turning on in an engineer's head saying: Risk of cross-contamination. Therein lies the main challenge of this type of facility.

Having different processes in the same non-segregated space carries the risk that one product X will end up contaminating another product Y. This implies a risk to patient safety and drug quality.

These risks can be mitigated by implementing a good cross-contamination control strategy. This should take into account:

• In-plant processes.
• The potency and toxicology of the different products.
• Actions to ensure that risk levels do not compromise the efficacy and safety of the product.

Both the EMA and the FDA have documents with guidelines and recommendations to limit the risks of cross-contamination.

• EMA: ICH Q8, Q9, Q10
• FDA: 21 CFR 600.11
• ISPE: Risk-Based Manufacture of Pharma Products

In addition, the cleaning strategy and cleaning validation becomes even more critical. Quantifiable limits must be set on the amount of contaminants that can be ‘accepted’ after a clean-up in order to continue with the next production batch.

There are limits to the multiproduct concept

Being able to use multiproduct plants is a resource that the biopharmaceutical industry must take advantage of. But there is a limit to what can and cannot be done. This limit is imposed by the state of the art in pharmaceutical equipment containment technology (as well as other factors that provide flexibility). Of course, as this technology advances, more combinations will become possible.

When starting a project, it is important to be clear about the products to be manufactured, their toxicological characteristics and the processes. Using these elements and a good feasibility study, we can conclude whether or not:

• An idea is feasible or not (on a multiproduct facility basis).
• It makes ‘economic sense’. Gaining flexibility often means compromising efficiency. A good balance must be made between these two features, in order to conclude whether a project makes sense or not.
• Limiting project uncertainty.

Containment starts with design

Avoiding cross-contamination starts at the plant design stage. Good design minimises the risk of cross-contamination, increases flexibility, facilitates plant operation and reduces production costs.

A good level of definition in the early stages of the project means that the design will bring great advantages to the multi-product plant. Experience, knowledge of cGMP and expertise in pharmaceutical processes / bioprocesses are key. That is why Klinea, as an engineering company specialised in the biopharmaceutical sector, is a reliable partner for the design of multi-product plants.