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8 Pharmaceutical Technology ® Quality and Regulatory Sourcebook eBook March 2024 PharmTech.com Manufacturing Convention (USP), ISO, ASTM International, and the American Society of Mechanical Engineers (ASME) (with its Bioprocessing Equipment group). BPSA guides cover irradiation and sterilization val- idation, determination of E&L, and disposal of SUS. BPSA has published quality assurance templates that look at quality requirements and product specifica- tions. ASTM is working on a standard for the deter- mination and characterization of extractables from single-use materials with considerable input from BioPhorum and BPSA. ASME, ASTM, and BioPhorum are looking at leachables. USP and ASTM are address- ing sub-visible particles from single-use components. ASTM, ASME, and BPSA are working on system integ- rity testing issues. Patient safety concerns The next major concern is patient safety from E&L that might migrate from the product contact parts of the single-use components used in disposable sys- tems into the drug product. Regulatory scrutiny of patient safety assessment from process equipment related leachables (PERLs) is stringent when using single-use components for f inal formulation and filling processes. Matching the risk that PERLs could adversely af- fect the quality of the drug product to the required level of testing and assessment is achieved by an ini- tial risk assessment followed by a risk assessment. T he i n it ia l r isk a ssessment est abl ishes whet her component testing is required. Once t he need to perform a testing is established, a risk assessment is performed to establish what testing must be per- formed. The testing proceeds as per section 4.1 of USP <665> (18) and the BioPhorum E&L protocol (19). BioPhorum published two key guidance documents to help control potential risks associated with leach- able impurities released by single-use components: Best Practices Guide for Evaluating Leachables Risk from Polymeric SUS Used in Biopharmaceutical Manufactur- ing and Standardized Extractables Testing Protocol for SUS in Biomanufacturing (19). The results of the extractables profiling are then interpreted in the context of suitability for use and patient safet y assessment via the toxicological as- sessment. PERLs will be f ur ther evaluated for pa- tient safety by the toxicity assessment. If the results are proven safe to the patient, the documents are then ready for regulatory submission, and one can use the single-use components in the manufacture of drug products. USP chapters <665> (18) and <1665> (20), when com- bined with International Council for Harmonisation principles Q8 Pharmaceutical Development and Qual- ity by Design and Q9 Quality Risk Management, early in the component selection and drug development stages, will ensure and confirm that the single-use manufacturing systems selected are suitable for their intended purpose. Summary The biopharma industr y has matured as a globa l community with an increased focus on monoclonal antibodies, recombinant proteins, biosimilars, and vaccines. SUTs have become an integral element in most of the bioprocessing steps, including upstream processi ng, ha r vest i ng, bu f fer storage, pu r i f ica- tion, mi xing, f iltration, formulation, and f ill/f in- ish. While some of the steps are completely in SUT mode, many of them are yet in a hybrid mode, used with conventional stainless-steel equipment. The manufacturers adopting SU Ts have various g uid- ance documents that can be used from the start of setting up a business case, to a changeover to SUT, to being compliant in regulatory submissions related to E&L, patient safety, and disposal of the used plas- tics in a sustainable manner. Single use is a promis- ing technology, and the adoption of this technology is evolving rapidly, leading to the eventual evolution of the next stages: modular bioprocessing and con- tinuous bioprocessing. References 1. Rathore, A. S.; Agarwal, H.; Sharma, A. K.; Pathak, M .; Mut hu k u m a r, S. Cont i nuou s P r o ce s s i n g For P r oduc t ion O f Bioph a r m ace ut ic a l s. P re p. Biochem. Biotechnol. 2015, 45 (8), 836–849. DOI: 10.1080/10826068.2014.985834. 2. Klutz, S.; Magnus, J.; Lobedann, M.; et al. Devel- oping the Biofacility of the Future Based on Con- tinuous Processing and SU T. J. Biotechnol. 2015, 213,120–130. DOI: 10.1016/j.jbiotec.2015.06.388 3. Langer, E. S.; Rader, R. A. Biopharmaceutical Man- ufacturing is Shifting to SUS. Are the Dinosaurs, the Large Stainless Steel Facilities, Becoming Ex- tinct? Am. Pharm. Rev. online, Oct. 23, 2018. 4. Lim, J.; Cox, S.; Leveen, L.; Monge, M.; Sinclairm A. The Environmental Impact of Disposable Technol- ogies. BioPharm Int. supplement 2008, 7. 5. Single Use Support. Pioneering Biopharma. www. susupport.com (accessed Jan. 21, 2024). The main challenge is the security of the single-use component supply chain.