BioPharm June eBook: Single-Use Systems

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Page 17 of 46 June 2018 BioPharm International eBook 17 dedicated equipment. We also save money by incurring less preparation time by avoiding cleaning validation work associated with qualifying multi- use equipment and regular mainte- nance and upkeep of the equipment. Finally, space. Classified GMP manu- facturing space is at a premium, and using disposable, single-use materials allows us to store the items in the ware- house along with our other released components. This eliminates the need for storage of bulk tanks, pumps, and other processing equipment. In our experience, there have not been any show stoppers. There are the expected compatibility issues and leachable/extractable concerns, but many of those are present with many of the product contact surfaces, what- ever equipment train you choose. We have had an occasional pin hole in a bulk manufacturing bag, but often times we find these are the result of handling and storage issues, and not manufacturing defects of the items themselves. Careful handling and pre-use testing of these items is critical. It is our recommendation to select the highest-grade bag available from the various vendors. It is worth the extra money because a leak in the bulk formulation bag can result in product loss. Our main challenge in using dis- posable technologies is typically the customization of the components to meet the specific product require- ments. The size of the bulk batch, the processing steps and filtration requirements, and fill volume and final presentation all play a role in the materials we select. We often design a custom setup for that prod- uct's specific needs. This results in design time with the manufacturers and lead times and minimum order quantities, which are challenging at times when it comes to meeting product timelines. Bell (MilliporeSigma): The speed and flexibility of deployment, cou- pled with a reduction in capital costs, are the key drivers pushing industry adoption of single-use. Furthermore, the advantages of pre-sterilization and reduced risk of cross-contamina- tion have made these systems the pre- ferred choice for final fill applications. With traditional stainless-steel equipment, drug manufacturers are required to clean and sterilize in between each process batch. This can add significant prep and set up time to the filling operation and add costs associated with utilities and cleaning solutions. Additionally, the cleaning and sterilization cycles need to be validated to demonstrate there is no risk of contamination, either from the environment or from the previ- ous process batch. Single-use systems come pre-assembled and pre-steril- ized and are thrown away after use, which significantly reduces risk and batch turn-around time, increasing productivity. There are many benefits that sin- gle-use technologies can provide for the final filling of biologics; however, there are also challenges that should be considered. Perhaps the biggest challenge is the lack of clear guid- ance from health authorities and regulatory bodies on expectations with implementation of single-use systems. This has resulted in drug manufacturers relying heavily on single-use suppliers to help define the data and documentation that is appropriate to support implementa- tion of single-use technologies. MilliporeSigma monitors trends in the industry, such as pre-use post- sterilization, pre-use filter integrity testing, point-of-use leak testing for single-use systems, and E&L testing, so that we can advise users through their implementation and regulatory filings. The expertise, products, and services we offer help drug manufac- turers develop, formulate, manufac- ture, and test their products, to ensure product quality and patient safety. Unlike traditional stainless-steel systems, single-use systems are most commonly comprised of polymeric materials, which are not as well- known and characterized for biophar- maceutical processing. Depending on the conditions, these materials can produce E&L, which may interact with, alter, or affect a biopharmaceu- tical process and the resulting drug product. Specific properties of the biologic such as pH and concentra- tion, as well as parameters such as temperature and duration of the pro- cess, can impact the extent and quan- tity of leachables that may end up in the drug product formulation. For this reason, a different approach is needed to qualify single-use systems as suitable for use. Drug manufactur- ers must understand how every poly- mer in the single-use systems interact with their drug product. In addition, w ith single-use, many of the critical control strate- gies—such cleanliness, integrity, and sterility—are shifted from the drug manufacturer to the single-use sup- plier. Drug manufacturers must prove that adequate processes are used and qualified to maintain cleanliness, integrity, and sterility of single-use systems to prevent product contami- nation and ensure patient safety. From an implementation perspec- tive, it is critical to have a strong part- nership and collaboration between the drug manufacturer, single-use supplier, and filling machine vendor. If it is a new filling line, fit testing should be performed throughout the manufacture of the filing machine. This will ensure a more robust design for the single-use system, but also provide operators with the oppor- tunity to learn how to handle sin- gle-use systems and start developing their procedures. Moving from a tra- ditional stainless-steel process to a single-use process is a big change, and in-depth operator training and experience is required. BP Single-Use Systems Fill/Finish

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