I've written several editorials and articles for BioPharm and PTE in the past, and I am also a member of the editorial advisory boards for both of these publications. For those who are not familiar with me, I've been in the biopharmaceutical industry for more than 31 years and have worked in filtration process development and validation with many pharmaceutical and biotech companies since before the biotech revolution. As an active member of the Parenteral Drug Association (PDA), the International Society for Pharmaceutical Engineering (ISPE), the American Society for Mechanical Engineering–BioProcess Equipment Committee (ASME–BPE) and the Bio-Process Systems Alliance (BPSA), I've been a contributor or reviewer on numerous industry guides and standards, and have conducted training for regulatory agencies in the Western hemisphere, Europe, and Asia. In my present role as chairman of the board and the Technology Committee of the BPSA, I have had the opportunity to interact with suppliers and users of single-use technologies worldwide and look forward to sharing that perspective here.
Over the past 10 years or so, we've seen singleuse technologies explode from production-scale filter capsules, tubing, and simple biocontainers to encompass sterile connectors, membrane-chromatography adsorbers, bioreactors, mixers, and integrated platform systems with increasing levels of sensors and automated controls. Many articles have been published, and singleuse conferences have become regular events, with topics evolving from fundamental technologies to user evaluations, and on to process and facility integration.The main issues today include implementation, quality, security of supply, regulatory expectations, system design, integrity/installation testing, QbD, PAT, quality agreements, standardization, disposal and environmental issues, and economic justification. As this column progresses, let me know what singleuse issues and topics you would like to see further explored. This month, I will touch on some recent developments in standardization and quality agreements, and provide an update about some of the latest BPSA initiatives in this area.
Standardization of singleuse components has become a frequent topic in articles, on chat boards, and at conferences. Interest has been expressed in standardizing the materials for films and tubing, as well as the dimensions of sterile connectors, hose barb, and sanitary flange fittings. When considering standardization of singleuse components, it is important to bear in mind that although some aspects of singleuse components can be standardized (e.g., approaches to sterilization, characterization of extractables, particle and endotoxin testing, tubing ID, hose barb, and flange dimensions), it is unlikely that any materials or design features will become a commodity subject to standardization because of the proprietary nature of many singleuse components. Other than ASME–BPE and ASTM International, none of the primary industry professional or trade associations (PDA, ISPE, and BPSA) or regulatory bodies issue formal standards. Pharmaceutical standards bodies, such as the US or European Pharmacopoiea or the International Organization for Standardization, tend to focus on the final drug product and packaging. These can be extrapolated or adapted to singleuse equipment, but the industry organizations themselves primarily issue best practice recommendations and technical guides rather than formal or obligatory standards.
One of the key roles of BPSA, in addition to producing its own best-practice guides, is to stimulate other organizations to also develop guides or standards that facilitate implementation of singleuse equipment. For example, BPSA recently submitted a letter to ASME, encouraging a review of the ASME–BPE standard for sanitary flange fittings with regard to using polymeric material instead of traditional metal alloys. The current ASME–BPE standard for sanitary flanges was developed with stainless steel in mind and specifies dimensions and tolerances that are costly to achieve in a variety of polymers. A modified standard addressing the properties of polymer-based flange connectors that maintains critical fitment requirements, while accommodating the unique properties of molded polymers, could reduce cost of ownership and ensure that all parts can work with singleuse and stainless steel systems. For flange-connector manufacturers, tooling and production costs also could be reduced if more liberal tolerances were allowed.
Many singleuse systems integrators now offer standardized singleuse assembly configurations for common functions, or subassemblies that can be custom assembled aseptically with sterile connectors by the user. Such rationalization can help reduce complexity and cost, but further standardization of designs or materials among suppliers is practically difficult and would be a barrier to further product development. Singleuse technology may have moved out of its infancy, but standardization to create commodities needs to be considered very carefully. Establishing standards for equivalency of designs or materials would stifle innovation and conflict with market demands for improved designs and materials.