At the TOTAL 2004 exhibition in Birmingham, UK, earlier this week, Miriam Monge of French company Stedim presented a virtual model of a manufacturing unit that uses all available single-use technologies - from filters to bags and piping - with the obvious exception of the bioreactors. At present, these are still made of stainless steel, although Stedim has a collaboration in place to make even these core components from disposable plastic.
Traditionally, manufacturers of biopharmaceuticals used a wide range of stainless steel components, all of which had to be cleaned, sterilised and validated between each batch run. It has recently become possible to replace all the key elements of the unit process with disposable materials that can reduce the cost of manufacturing and shorten the time it takes to bring drugs to market.
Monge presented a concept facility to the conference that is designed to make the maximum use of disposable technologies, as well as implement some other design advances such as the segregation of Solutions - where media and buffers are made up - from Process.
The concept has not yet been fully put into practice, although Stedim's customers have adapted various elements to suit their own projects. But the model has been used to estimate the overall cost of the concept lab compared to a traditional stainless steel facility.
Stedim has found that the concept lab costs around €22.6 million to set up, a 41 per cent reduction on the €38.5 million capital investment for a stainless steel unit. The cost of process equipment was cut to €4.1m from €7.1m, while other savings accrued from process installation (€4.5m versus €8.9m) and building costs (€5.7m versus € 7.3m), the latter mainly from the absence of fixed piping and fewer electrical sources.
Monge told In-Pharmatechnologist.com that this saving could increase to 50 or 60 per cent once disposable bioreactors can be added to the model. This could be possible by the end of the year, as Stedim's collaboration with Applikon on the design of single-use reactors should yield it first product by then, she noted.
Meanwhile, there are a number of other elements that can reduce the ongoing costs associated with running the concept facility. For example, there is no need to purchase autoclaves for sterilisation, and clean-in-place (CIP) is pretty much done away with. The only washing needed is for the bag containers, she noted, while the utility also reduces the requirements for pure water, clean steam and water for injection (WFI).
Solutions are held in sterile single-use disposable systems, and automated vehicles are used for transport around the facility, reducing the number of people - and therefore contaminants - going into the process area.
"The concept facility…enables better regulatory compliance by enhancing product security through a totally closed single-use system," said Monge, noting that US Food and Drug Administration (FDA) warning letters often cite cleaning as an area of infringement.
Also, once a new plant is constructed, validation can take as much as 30 months. This can be trimmed down by 6-9 months using disposable components, said Monge.
She noted that companies such as GlaxoSmithKline, Protherics and Wyeth contributed their expertise in developing the concept facility, while Stedim, Pall, Integrated Biosystems and IDC manufacture the single-use items used in the project.