Sterility And Closed Systems: A Challenge Under Any Circumstances
Biologic drug development demands sterility for success and safety. Biologics also are notoriously expensive to make. The further they progress in the manufacturing process, the higher their value climbs, and by the time they reach downstream processes like chromatography, the financial consequences of a batch lost to contamination can tally in the millions of dollars.
Traditional methods of sterility assurance involving clean rooms and laminar flow hoods placed great time and cost burdens on companies. SUT systems have largely replaced or at least augmented these processes over the past couple decades, but the development of SUT components also is continually evolving as the industry identifies the challenges and shortcomings that available products and practices pose. For example, tube welding – one of the most common methods for securing closed, sterile SUT flowpaths – still presents the potential for leaks, spills, and contamination by leachables, and can be very demanding in terms of time and the costs of equipment, components, and maintenance. When SUT systems fail and leaks or spills occur, companies do not just lose millions in product. They lose time and momentum as they analyze their procedures, materials, vendors, and the chemicals they are using. If the chemicals cannot be changed, then the company must make changes elsewhere, which can create unforeseen delays.
Sterile connectors are among the great advances in SUT. CPC’s AseptiQuik connector portfolio was developed to address the inconsistencies in size, functionality, compatibility, quality, and sustainability of commercially available connectors. Among other novel designs intended to address the problems of tube welding and unreliable SUT components, CPC developed the AseptiQuik line of genderless connectors to assure fast, easy, secure connections and quick assembly.
These polycarbonate connectors have enjoyed great success on the market, having largely withstood many of the most common chemicals used in downstream processing. They form fast, sterile connections in a way that ensures the interior of the flowpath is never exposed to the exterior environment. However, a client recently approached CPC about a project that demanded the use of at least eight fermentation or purification chemicals that would test or exceed the limits of what our connectors could tolerate. Other commercially available connectors, made of polyethersulfone (PESU) – a material more chemically resistant than polycarbonate but not as mechanically strong – still were not sufficient for the project’s demands. As the AQG line had become an integral part of their SUT system, they feared the loss of familiarity and a reliable supply chain.
What was required was a plastic material that, like polycarbonate, was strong enough to hold up against handling, processing, and shipping, but also chemically inert so that it could handle the corrosive substances that would flow through it. The material also had to meet regulatory standards for plastic purity.