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20 BioPharm International eBook June 2018 www.biopharminternational.com Single-Use Systems Qualification biophar maceutical manufact ur- ing since its start. With decades of historical data, stainless-steel has proven not to be add it ive, subt rac t ive, or reac t ive to bio - ph a r m ac e ut ic a l pr o c e s s e s a nd the resulting drug products. The m a i n q u a l i f i c a t i o n a c t i v it i e s related to stainless-steel systems a re for c le a n i ng , s a n it i z at ion, and/or sterilization. Drug manu- fac t u rers must prove t hat t hey have developed cycles that ade- quately clean and ster ilize sys- tems to prevent contamination and ensure patient safety. Si ng le -use systems a re most com mon ly compr ised of poly- meric materials which aren't as well known and characterized for biopharmaceutical processing. The plastics used to construct single- use systems can produce extract- ables and leachables (E&L) under cer tain conditions, which may interact, alter, or impact a bio- pharmaceutical process and the resulting drug product. The con- centration, pH, temperature, and duration of the process can all impact the extent and quantity of leachables that may end up in the drug product formulation. For this reason, a much different qualifica- tion approach is needed for single- use systems. Drug manufacturers must understand how every dif- ferent polymer used in single-use systems interacts with every step in their process. Q u a l i f i c a t i o n o f s i n g l e - u s e systems is t y pica lly per for med using a combination of supplier- provided information and user- led testing, performed at either a contract lab or at a lab within the drug manufacturer's network. Extractables testing is required to understand the worst-case load of extractables from the single-use system. Theoretical calculations are then performed, considering t he spec if ic biopha r maceut ica l manufacturing process to assess, which process steps add leach- ables to the process, and which ones can clear or remove them. The goal is to determine the quan- tity that end up in the final drug product. Through a risk assess- ment, it is then determined if pro- cess-specific leachables testing is required. As with stainless-steel systems, sterility is paramount in single- use systems as well. The method of sterilization for stainless-steel and single-use is different, but the requirement to ensure steril- ity is the same. Drug manufactur- ers must prove adequate processes are used and qualified to steril- i ze single -use systems, to pre - vent contamination, and ensure patient safety. The major difference between stainless-steel and single- use is that sterilization qualifica- tion is performed by the supplier and not the drug manufacturer. T he r e for e, si n g le - u s e s y s te m s require a more thorough review and analysis to confirm exactly how the drug product interacts and how that impacts product quality and patient safety. These qualification challenges can be addressed by using high- purity polymeric materials with well-characterized chemical com- patibility and extractables profiles, as well as having a strong part- nership and collaboration between drug manufacturer and single-use supplier. Hower and Lu (SGS): In all produc- tion lines where stainless-steel has been used, the leaching problem is at a lower risk compared to pro- cesses where single-use technology has been used. Due to the poly- meric nature of single-use systems, the major challenge associated with qualification is the neces- sity to understand the interaction between the drug product and the single-use system components. Unlike stainless-steel components, there is a potential for migration of unwanted substances from the si ngle -use system components i nto t he pha r maceut ica l prod- uct. As most single-uses systems are made of plastics, those plastic additives may leach out into the drug products as E&Ls, which may pose safety risks to patients. The leachable compounds may also change the efficacy of the drug products due to interaction with drug product, especially biolog- ics. It is required by the regulatory bodies that a risk assessment be performed on all components used in the manufacturing of pharma- ceuticals. Based on the results of this risk assessment, the necessity of performing E&L testing can be deduced. Pora (Pall Biotech): With so many options on the market, the diffi- culty of qualification is often how to choose the best products and components; the combinations really are endless. This can be a challenge because, from the end user standpoint, each new compo- nent must be qualified, and as a supplier, the challenge is finding the best ways to offer more robust and f ully validated systems. By controlling the number of compo- nents, it is possible to keep things more streamlined and avoid creat- ing too many extra layers in supply chain complexity assembly pro- cesses. And by reducing complex- ity, there is less need for additional validation, yet the end user can still get the fit for purpose systems they need. STEPS FOR QUALIFYING SINGLE-USE SYSTEMS BioPharm: Can you briefly summa- rize the process for qualifying sin- gle-use systems; what are key steps?