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Collaboration between users and suppliers to increase understanding, clearly define user requirements, and mitigate risk is facilitating acceptance by industry and regulators.
The advantages of single use systems (SUS), including lower capital cost and increased flexibility, are well understood. Some disadvantages, however, have grown larger than life due to a lack of understanding and a low level of comfort with something new, says Chris Smalley, director of engineering in the Sterile & Validation Center of Excellence, Global Technical Operations at Merck. "Stainless steel and glass don't have to prove themselves, but single-use plastic is the 'new kid on the block'." Issues that are seen as obstacles include extractables and leachables, container integrity (i.e., leaks), and waste disposal. Various industry groups have been working to increase understanding of how to get past these obstacles and to develop standards to drive acceptance of SUS. For example, an updated version of the American Society of Mechanical Engineers (ASME) Bioprocessing Equipment Standard includes a section on shelf life and storage of SUS (1). The Bio-Process Systems Alliance (BPSA) published an update to its Single-Use Manufacturing Component Quality Test Matrices Guide in November 2015 (2). In addition, the International Society for Pharmaceutical Engineering (ISPE) is authoring a Good Practice Guide, with a draft planned for 2016.
The industry has been talking about standardization since 2009, and, although all the issues have not yet been resolved, knowledge has been developed and significant progress has been made, says Smalley. Collaboration between users and suppliers has been one of the keys to this progress, as users have more fully delineated their requirements and communicated with suppliers about how to meet these needs.
Clear user-requirement specifications are needed to mitigate the risk of technology selection and qualification, and a partnership between users and suppliers is needed to minimize risks throughout the lifecycle and to have better change control, said Sabrina Restrepo, associate director of component engineering in the Sterile & Validation Center of Excellence, Global Technical Operations at Merck, in a presentation at the ISPE annual meeting (3). "If you have a design space and clearly understand risk, you can better deal with changes because you can see how they might affect the process," she explained.
"Users should implement SUS with the same validation procedures they would use with a stainless steel system," added Smalley in a presentation (4). "First, define the user requirements, and identify specifications, such as processing temperature. Have a knowledge repository and a system for handling documentation." One small difference in SUS documentation is that some items in a data-set about the part might come from the supplier of the plastic tubing, for example, and other information might come from the supplier of the plastic material used to make the tubing. Users should also note that the same component may have different requirements depending on where in the process it is used, and any inventoried part should be identified as to where it is approved for use. For example, a bag used in buffer storage may have less stringent requirements for particulates, extractables, and leachables than the same bag used in fill/finish.
Understanding the risk of extractables, which depend on the component material, and leachables, which depend on the actual use of the SUS in the pharmaceutical process, is crucial and requires collaboration between users and suppliers, explained Malik Belattar, deputy director of the nonprofit organization, the Single-Use Technology Assessment Program (SUTAP), based in Switzerland (5). SUTAP was founded in December 2014 for the purpose of facilitating single-use standards development.
Users and suppliers are now cooperating on both the individual company level and the industry level. The BioPhorum Operations Group (BPOG), which is primarily an end-user group, and the BPSA, which is primarily a supplier group, are now doing some projects together. For example, in two ongoing BPOG-BPSA collaboration efforts regarding supplier change notifications and user requirements, data from surveys taken by participants have been leveraged to better understand the opportunities. These efforts should drive increased use of SUS by creating a more robust understanding of its capabilities. "Presenting a unified message to regulators will help to show that industry has gained understanding of SUS and will alleviate some of the fear of the newness of SUS," suggests Restrepo. The high level strategy was published last October (6), and authors are encouraging readers to provide feedback via e-mail.