Dispatches from AAPS
Extractables & leachables the biggest barrier to SU adoption, says WuXi
Contract biomanufacturer WuXi Apptech opened the first biologics facility in China that complies with European and US GMP standards in 2012. The 16.5 acre site has a total capacity of 5,500L and, according to Director of downstream process development Jason Li, is fully equipped with disposable technology systems.
Li was speaking at the AAPS annual meeting this week in San Diego, where he discussed the how single-use operations in biomanufacturing will account for almost $3bn of the total biomanufacturing market by 2016, up from $0.65bn in 2011.
Yet while the advantages of such technology have been well documented – low upfront costs, flexibility, expediting process development, lower skill set needed, and reduction in cross-contamination risks – Li said there were still a number of factors limiting uptake (which is less than 1% of the total market), with the number one problem being extractables & leachables (E&L).
“With polymers used in disposable systems there are many chemicals involved,” he said, adding he had experienced a couple of clients using CHO cells to produce monoclonal antibodies choose to use different systems due to the potential leachable effect of a certain single-use bioreactor.
Antioxidants, antiozonants, plasticisers, process aids, antistatic agents, UV stabilisers, curing agents, filters, and modifiers can all react with biomaterials reducing yields and titres and, most seriously, potentially contaminating drugs. One such example is bis(2,4,-ditert-butylphenyl) phosphate (btDtBPP) – a leachable compound discovered to be detrimental to cell growth by Amgen last year.
The second major problem with disposable technology, Li said, is scalability with 2,000L being pretty much the top end in bioreactor bag size for now. However, this issue will be overcome by materials being developed made up of nano-composite fibres which will strengthen the polymer to cope with greater volumes.
Other issues with single-use include standardisation of systems, the dependability to vendors, and the supply chain and waste management, Li added, but “if we can overcome extractables & leachables we will eventually be able to scale up to many thousands of litres.”
