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Disposables simplify the flow of people and materials through a facility, decreasing both its footprint and amount of equipment needed, as well as minimizing upfront capital costs.
At home, the bioprocess engineer recycles his or her plastic bags, bottles and other bits with the rest of us. At work it's a different story, as plastic — and disposable plastic, at that — starts to replace stainless steel in the biopharmaceuticals business. A manufacturing facility today might use disposable filters, membranes, dispensers, connectors and fittings, sensors, storage bags, and bioreactors. Single-use plasticware (made from composite polymers) is being applied in the preparation, sterilization and storage of cell culture media. It is also used in buffer preparation, filtration and sterilization, chromatography and, of course, the production process itself. Big Pharma is also affected by the throwaway revolution, as plastic plays an increasingly important role in fill-and-finish.
Manufacturers are turning towards disposables because they allow more flexibility than stainless steel; with plastic kit, the production set-up can be constructed afresh for each campaign, which can be especially valuable for multiproduct facilities. For instance, at the newly-opened UK National Biomanufacturing Centre (NBC) the need for flexibility drove an early decision to rely on disposables wherever possible, and many of the big players such as Amgen and Genentech are now replacing stainless steel with plastic.
Disposables simplify the flow of people and materials through a facility, decreasing both its footprint and amount of equipment needed, as well as minimizing upfront capital costs. Switching to plastic can also help drive down manufacturing costs. The transfer of sterile fluids through various process steps has traditionally been done through an array of stainless steel pipes, valves, manifolds and vessels, all of which must be cleaned and sterilized — operations that must be validated before the system is re-used. "It is just so much easier to throw everything in the bin at the end of the day," explains Dr Richard Dennett, technology transfer manager at Eden Biodesign, which runs the NBC.
Research shows that the cost of disposables compares favourably with stainless steel. For instance, Andrew Sinclair, managing director of consultancy BioPharm Services, and Miriam Monge, marketing director of Stedim, a leading disposables supplier, conducted a comparison study of single-use disposable bag technology versus fixed stainless steel vessels in the manufacture of a monoclonal antibody using a 2000 L fermentation vessel (typical of the kind of process that is widespread in the industry). Their model found savings of nearly 10% in cost of goods from using disposables, which applied whether the facility was a new build or a retro-fit. The decreased requirement for cleaning was the major factor in these cost reductions.
But before a manufacturer goes disposable, some tough questions need addressing. First, the supplier must provide reassurance on extractables and leachables as part of their validation package. The former refers to substances that appear when a disposable component is tested by solvents and conditions that are generally harsher than those of the process where it is to be used. The latter are substances that might end up in the final product because of its interaction with the disposable. Both have the potential to cause problems with the regulatory authorities, a prospect that might persuade some to stick with the tried-and-tested stainless steel.
And is there not something contrary about generating mountains of plastic waste in times when we are all being urged to recycle and consume less? Sinclair and Monge acknowledge this concern. In any case, in purely financial terms, waste management accounts for only a fraction of the production cost and waste water treatment is more expensive than disposables incineration.
Work is also needed in standardization, validation, supply chain issues and integrating systems. The Bio-Process Systems Alliance (BPSA [www.bpsalliance.org]) is part of the Society of the Plastics Industry and wants to promote confidence in the use of disposables throughout the biotech industry. BPSA brings together the key suppliers including Stedim, SAFC Biosciences, Pall Life Sciences, HyClone and Millipore with a mission to educate, and develop standards and guidelines for disposables that should ease their more widespread acceptance. The International Society of Pharmaceutical Engineers is also doing work in this area.
Meanwhile, suppliers are moving increasingly towards integrated solutions that make the adoption of disposables so much easier. For example, Invitrogen and Wave Biotech have just agreed to supply media-filled bioreactors. However, disposables are not yet the industry standard in biopharmaceuticals. Both Dennett and Sinclair say it is unlikely the conversion to single-use will ever be universal — the main issue being one of scale. Some large-scale production processes will always require stainless steel vessels. But for small batches (which could become more common with the advent of personalized medicine) and certain products — such as gene therapies and vaccines — production in disposables is highly appropriate. There is also a need for suppliers to keep developing new products; currently there is little available for microbial production of biopharmaceuticals, for example.
A change in technological culture is always difficult for companies to deal with. Where high-value products, such as monoclonal antibodies, are concerned, new methods may be even harder to accept. With disposables, however, manufacturers have travelled some way up the learning curve during the last 5 years. Large companies will already be moving towards disposables in-house, while academics or small biotechs tend to be fairly open-minded and may have already used plastics in the research setting. Biotech is nothing if not innovative and may not need much more persuading to adopt the throwaway approach.