Issue link: https://www.e-digitaleditions.com/i/1517802
PharmTech.com Quality and Regulatory Sourcebook eBook March 2024 Pharmaceutical Technology ® 7 Manufacturing by 68.8% of respondents. Material incompatibility with process f luids and reluctance to becoming "ven- dor-dependent" (i.e., single-source issues) were tied for fifth place with 56.7% of respondents citing both as a downside to SUTS. The main challenge is the security of the single-use component supply chain. Suppliers of single-use components are as critical to ensuring that dr ug products reach patients in both a reliable manner and with on-time delivery and consistent quality. A second challenge is the time, cost, and regulator y approvals needed when changing over from tradi- tional stainless-steel systems to the construction ma- terial for SUS. The third challenge is the regulatory requirement and validation or qualification costs needed while establishing alternate vendors during the changeover. The fourth challenge is the realiza- tion that SUTs might not always be the most effective or economical solution for the manufacture of low- cost formulations such as ophthalmic products and traditional large-volume parenteral injectables. In those cases, a hybrid approach using a combination of disposable and traditional stainless steel becomes more viable option. Industry guidance There are guidance documents available to work around overcoming these challenges. PDA's Technical Report Number 66, Application of Single Use Systems in Pharmaceu- tical Manufacturing, describes a risk-based decision-mak- ing process for determining if implementation of SUTs is appropriate for a given process (7). ISPE's Good Practice Guide: Single-Use Technology (8) provides a roadmap for efficient implementation of SUT with minimum dis- ruptions to existing operations. The guidance docu- ment is structured with two major sections. The first section describes process f low for arriving at the de- sign of assemblies/systems. The activities described in this section include the selection of components with the design of assemblies and systems, the qual- ity requirements for SUT equipment, assessment of supplier quality, defining the criteria for audits, and developing the user requirements specifications. The second section deals with implementation and use of SUTs, the regulations typically applicable with pro- cesses using SUTs, training programs and when to apply them during the implementation process, and the criteria that lead to a robust and reliable supply chain. The guide also includes specific chapters and appendices that contain tools to suppor t the t wo main sections, including the evaluations of extract- ables, criteria to evaluate and apply in a risk assess- ment, and the overall implementation schedule and detailed schedules for specific activities. Another concern is the waste disposal and sustain- ability related to single-use components. Compared to global plastic waste in total, the consumption of SUTs in the biopharma industry is negligibly small (0.03 x 10 6 t); never theless, the high consumption of plastic material per unit of product and during research and process development is becoming a major concern among more and more scientists and biopharma market stakeholders (9). There has been increased use of SUTs in recent years, and concerns have been expressed on the environmental aspects of single use. A detailed study has been conducted to address this concern (10). The study revealed that the environmental aspect of end-of-life due to use of plas- tic is quite small, and the highest contribution to en- vironmental pollution is from the energy required for electricity generation for the manufacturing plant. The achievement of a solution to solve environ- mental issues and improve sustainabilit y among all production steps might be possible by instilling a sense of ownership among workers across indus- t r y a nd beyond to encourage a feel i ng of ta k i ng responsibility for sustainability (11). International Sta nda rds Orga n izat ion (ISO) established a sta n- dard for life cycle assessment (LCA) that provides general principles for the methodology and content of an LCA. ISO 14040 contains the principles and framework for an LCA, while ISO 14044 considers the requirements and guidelines for carrying out an LCA study (12–15). ISPE's End-Of-Life Management for Single-Use Products in Bioproduction Part 1 (16) and Part 2 (17) discuss the details of the current dis- posal practices for SU Ts, successf ul best practices for end-of-life management, and opportunities to improve single-use waste in the future. There are two regulatory requirements impacting components used in SUS from a biological safety and patient safety perspective, material biocompatibility and E&L. Biological reactivity and safety are required to be performed in compliance as per United States Pharmacopeia (USP) <88>, Biological Reactivity Tests for Class VI Plastics. Biocompatibility testing require- ments fall within USP <87>, USP <88>, and ISO 10993, depending on the application. The following organizations are actively involved in developing workable standards related to the use of disposable technologies, Bioprocess Systems Al- liance (BPSA), BioPhorum, PDA, US Pharmacopeial The advantages of SUT drive its adoption in biopharma manufacturing.