Single-use technology requires a good relationship between customer and supplier

More and more pharmaceutical and bio companies are using CMOs*. The complexity of the 'new' proteins increases the need for CMOs to offer customers the greatest possible flexibility. Because there are various choices that need to be made:

Fed-Batch or perfusion?
There are two main processes for growing and harvesting the cell product: fed-batch and perfusion. In a fed-batch process, production cells are inoculated in a bioreactor where they will grow until they reach a certain level. The cells are grown under conditions of controlled temperature, pH and dissolved gases and fed until they eventually start to die. Such processes usually run between twelve and eighteen days in the bioreactor. Once the cells have finished producing the desired protein, they are removed. The protein is purified from the culture medium in which the cells were growing.

In perfusion, operators continually remove the recombinant protein and the waste products and add fresh glucose, amino acids and vitamins. This is done in a way which retains the cells in the bioreactor so that they continue growing and the product can produce for a longer period. The protein of interest can continuously be extracted and purified from the perfusate. Bioreactor processes take much longer than fed-batch processes, usually 30 to 60 days.

The recommended bioreactor approach will vary, depending on the sensitivity of the protein.

Stainless steel or single use?
Another decision is whether to use a single-use bioreactor or a traditional stainless steel tank for cell growth.

Stainless steel is still the best known, a tank with hard pipes installed in the facility with a certain capacity, as requested by the customer. Whichever size you choose, that is what you have, so you are less flexible. If you are going to develop more than 2,000 litres, you need stainless steel because disposable bags become too cumbersome, which eliminates the option for single use. The biopharmaceutical industry has steel tanks with options of 5,000 litres, 10,000 litres, 20,000 litres and 25,000 litres.

If a company is provided with a specific stainless steel installation but suddenly needs an option which is not available in-house, the project can easily be outsourced to a CMO which can offer that option. If less than 2,000 litres are going to be produced, Single-Use technologies are an interesting option, both for use in-house and in a CMO.

The relationship between user and single-use supplier
In a survey carried out by Pharma IQ (2015), more than 100 users were asked about their relationship with their single-use supplier. Although many expressed their satisfaction with their suppliers (89 percent said that they used more than one), 27 percent said that they weren't satisfied (no details were given). Of the most important factors identified when choosing a single-use supplier, 64 percent of the respondents said that the relationship with the supplier is the most important.

The implementation of single-use technology requires a much stronger relationship with the supplier of a company than when a company uses stainless steel, because it goes further than a single exchange. This goes beyond the relationship with your CMO, because you want the supplier to understand where the need lies. As Kimball Hall said in her presentation of BioProcess International 2015: "For single-use equipment, your supplier's supply chain is an extension of your own equipment. You need to think differently about its robustness and have deeper insight into where you can experience problems."

By highlighting your wishes as a customer, the supplier can contribute solutions.

It requires a lot of give and take. By highlighting your wishes as a customer, the supplier can contribute solutions, but also help with the testing. Invite your producer during a test phase to see what challenges there are and arrive at the most optimal arrangement. Knowing that the supplier can do more than just manufacture a standard item not only makes the cooperation closer but also much more enjoyable.

The preparation - deciding which single-use assembly is most suited to the application in this specific process - is also much more intensive than when ordering a stainless steel tank. There are very many more customised options for single-use applications, so it's very important to be clear about exactly what you need. Make the drawing together, involve the supplier and the users on your side wherever possible to produce the ideal solution.

Standardisation within single use
"When you use single use to create flexibility in an existing clinical environment, custom work is exactly what you want," says Tony White, director of the BioPharm Operations Group (BPOG). "But when you want to use a new technology for commercial activities, you want 'plug&play', connectivity, rapidly available validation packages and the comfort that redelivery will always be excellent. This is where standardisation is the key." He says that the lack of standardisation stops some companies from implementing single use unless they have a very strong vision of where they want to go operationally and are prepared to work hand in hand with the supplier(s). Do you see possibilities to standardise, but you aren't sure whether single use is suitable? Contact me and we're sure to find a good solution.

* a CMO (Contract Manufacturing Organisation) is a company that serves other companies in the pharmaceutical industry on a contract basis to provide comprehensive services from drug development to manufacturing.