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Jerold Martin was the senior vice president of global scientific affairs at Pall Life Sciences and the chairman of the Board and Technology Committee at Bio-Process Systems Alliance.
Regions around the world are starting to follow the US trend in disposables and are working to solve common challenges.
The use of single-use systems has become one of the biggest trends in biopharmaceutical manufacturing since the introduction of complex and sensitive biomolecules, such as monoclonal antibodies and recombinant protein biotherapeutics. In particular, single-use technologies have been widely adopted by global vaccine manufacturers as a means to eliminate cleaning and cleaning validation issues following the influenza vaccine shortage of 2005, which was attributed to contamination issues in a production facility located in the UK.
There has already been much discussion on single-use systems at US conferences and in US publications during the past 10–15 years, but interest is now expanding further across the globe to Europe and Asia. Despite this growth, there have only been a few dedicated conferences in these regions that focus on single-use systems, even though there has been significant implementation in European vaccine and biopharmaceutical manufacturing facilities. However, this trend may be changing. This year, I've been privileged to speak at and chair several international conferences focusing on single use. Such conferences provide an important opportunity for industry participants to share experience, concerns, and best practices.
On February 1–2, 2011, I visited Brussels (Belgium) to chair the International Quality and Productivity Center's (IQPC) Pharma–IQ Disposables Solutions for Biomanufacturing Conference, which was attended by nearly 100 European manufacturers and suppliers. The conference was Pharma–IQ's third Annual European Disposables meeting. The previous two annual conferences were held in London (UK), and the event is shaping up to be a key European conference for single-use activities. This year's meeting featured speakers from several European-based vaccine, biopharmaceutical and contract manufacturers, including Novartis, Vivalis, Genzyme, CMC Biologics, Cobra Biomanufacturing, Innogenics, Crucell, Eli Lilly, GlaxoSmithKline, Pfizer and Merck Serono, along with supplier presentations from Pall Life Sciences, Sartorius-Stedim Biotech, Novasep, JM Bioconnect, GE Healthcare, and ATMI Life Sciences.
National European regulatory authorities and the EMA have not made public statements about the acceptability or requirements for single-use technologies, but this has not deterred European drug sponsor and contract manufacturing facilities from implementing such systems for both clinical and production batches. Conference topics, for example, focused on everything from comparability of product quality and reduction of carbon footprints to implementation of single-use systems for buffer filling processes and preparation of regulatory submissions. The conference also featured several roundtable discussion sessions that facilitated the sharing of questions and experiences among participants.
Shortly after Pharma–IQ, I visited Tokyo in Japan (just before the earthquake and tsunami occurred) to give a presentation on single-use technologies and quality requirements at the International Society for Pharmaceutical Engineering (ISPE) Japan Sterile Products Processing Community of Practice meeting. Compared with Europe and the US, implementation of single-use systems in Japan has not been as extensive. However, Japanese pharmaceutical companies are very interested in new applications for single-use technologies. I also met with representatives from Japan's Ministry of Health, Labor and Welfare, who were eager to learn about best practices for implementing single-use systems in biopharmaceutical manufacturing.
At the end of February, I attended the ISPE Tampa Conference in Florida (USA), where I spoke at an aseptic processing seminar about sterilising filtration. One of the hot topics discussed related to European GMP Annex 1 recommendations, which call for integrity testing of sterilised filters prior to use and double filtration schemes to enhance sterilisation assurance. These recommendations can lead to complex systems and procedures, but are possible when using properly designed single-use systems (as opposed to stainless steel systems). One concern that the EMA cites, however, is a potential subtle change in membrane retention properties that might occur with exposure to moist heat (steam sterilisation), but this issue can potentially be resolved by filter plugging during the process.
With single-use filtration systems, sterilisation is most commonly performed with gamma irradiation, which does not introduce heat and has not been associated with changes to membrane filter porosity or bacterial retention property (so long as the filter materials are gamma compatible and validated for gamma irradiation stability). Single-use filtration systems are typically supplied presterilised, so that a poststerilisation integrity test is the only pre-use test a user can apply. Even without the hypothesised potential changes in membrane flow path and retention property caused by moist-heat sterilisation conditions, it can still be economically prudent to conduct a pre-use (poststerilisation) integrity test in many single-use filtration processes. This step ensures that the filter has not been damaged during shipment and handling. Such damage is not repairable by plugging and is a more valid reason to conduct pre-use integrity testing of the sterilised filter, especially where a drug product is sterile filtered through single (nonredundant) filtration schemes and filled into multiple final containers, or that cannot otherwise be refiltered in the event of post-use filter integrity failure. When designing single-use single or double filtration systems, it is important to consider how the filters will be initially wetted, how they will be tested and whether or how to displace the wetting liquid before product introduction. Approved system design should be discussed with the filter supplier, system-design engineer, and system integrator.
In March, I finished my single-use tour by chairing the second annual IBC Biomanufacturing and Single-Use Systems Asia Conference, which took place in Shanghai. Last year, the event was held in Seoul (South Korea). I was immediately struck by the progress in appreciation for the benefits of single-use manufacturing by many of the Chinese participants. Single-use manufacturing has been a difficult concept for many Chinese biopharmaceutical manufacturers to accept because they have historically focused on minimising the cost per batch, rather than the degree of cleaning and cleaning validation required in the West, or other beneficial aspects of single-use systems, such as reduced carbon footprint. At this meeting, participants heard case studies and considerations for single-use technologies from companies across Asia, including Simcere Pharmaceuticals, Shanghai Kanda Biotech, Wison and Autekbio, (all in China); Novartis and Green Cross (South Korea); Innobioventures (Malaysia); as well as Piramal Healthcare and Intas Biopharmaceuticals (India). In Asia, much of the biopharmceutical focus is on the development of biosimilars. Although the cost of single-use technologies versus cleanable and reusable stainless steel is still an issue for many process developers in Asia, disposable bioreactors and single-use tangential flow filtration are now being seen as potential ways to accelerate biosimilar development.
For those involved in or considering single-use processes, two upcoming US conferences may be of interest. The PDA Single-Use Workshop, taking place 22–23 June in Bethesda (MD), will include details about PDA's technical report on single-use technologies using quality-by-design principles. Workshop attendees will have the opportunity to preview and discuss the draft report during the workshop so that industry input can be incorporated into the final version, which will be published by PDA in Autumn 2011. More details are available at www.pda.org.
The Bio-Process Systems Alliance International Single-use Summit, which will be held on 27–30 July 27–30 in Washington, DC, is meant for biopharmaceutical business leaders and will focus on the impact of single-use manufacturing on the future of healthcare and biopharmaceuticals. The meeting will feature speakers from PricewaterhouseCoopers, Venable LLP, and FDA, as well as international single-use end-users and leading suppliers. More details are available at www.bpsalliance.org.