BioPharm June eBook: Single-Use Systems

Issue link:

Contents of this Issue


Page 14 of 46

14 BioPharm International eBook June 2018 well. I would estimate 60–70% of our projects use 100% disposable tech- nology from start to finish (bulk for- mulation through filling). There are many components on the bulk manu- facturing, upstream side that are not single-use, but on the fill/finish end of things, almost everything we use involves single-use components. Bell (MilliporeSigma): Fifteen years ago, simple single-use assemblies con- taining tubing, bags, and filters were being used in the industry for low- risk applications like media and buf- fer storage and intermediate filtration. As new components, such as sterile connectors, single-use pumps, single- use sensors, and innovative filtration technologies were launched, assem- blies have become more advanced and are being used for more critical applications, such as final fill. The extent to which single-use is employed for final fill operations varies; in some cases, formulation through to final filling is performed with single-use, in other cases a hybrid approach is taken where some systems are stainless-steel and others are single-use. In a fully sin- gle-use system, formulation can be performed in a single-use mix sys- tem and then transferred using ster- ile connectors and tubing to sterile filtration capsules, and, ultimately, the single-use filling assembly, which includes the filling needles. The increased complexity of biomanufac- turing, a consequence of the increas- ing number of clinical runs and smaller batch sizes, sometimes con- taining highly potent ingredients, makes single-use systems an attrac- tive alternative to traditional stain- less-steel, particularly for the final filling operations. Single-use offers lower upfront investment, increased flexibility and productivity, and reduced con- tamination risk. These benefits have resulted in a significant number of single-use systems being adopted for both new and existing fill lines over the past five years. It is very common for drug manufacturers to retrofit their existing fill line to support sin- gle-use processing. Filling machine manufacturers understand the ben- efits of single-use technologies and collaborate closely with single-use suppliers to design single-use assem- blies that fit with the filling machine, and deliver the performance to assure filling accuracy, product qual- ity, and patient safety. Feussner (Vetter): As a service pro- vider for injectable drug products, we operate in both the fill/finish process of drugs for the clinic as well as for the commercial stage. With that in mind, we see several distinct areas within the manufacturing workflow of drug products where single-use technology can be seen as a promis- ing pathway. Consider that a number of process steps in biopharmaceutical manufacturing are increasingly mov- ing toward single-use technology in order to enhance operational flexibil- ity and to reduce capital investments in equipment. We hold strongly the one guideline that has broad con- sensus in its application to single-use technology—the fact that it is espe- cially suitable when drug substances come into direct contact with equip- ment. This includes API and excipi- ent weighing, material preparation, compounding and filtration, as well as the core area being the actual fill- ing process itself. SYSTEM INNOVATIONS BioPharm: What are newer/recent innovations in components, equip- ment, or technology that support the implementation of single-use sys- tems in fill/finish? Bell (MilliporeSigma): As the use of single-use systems has expanded to more critical applications, suppli- ers have been challenged to develop new technologies that have suf- ficient robustness, flexibility, and the appropriate chemical compat- ibility for use in biomanufacturing. Suppliers are expected to provide comprehensive information on the system components including bags, tubing, and connectors as well as details on materials of construction and well-characterized extractables and leachables (E&L) profiles. This information is used by drug manu- facturers to conduct risk assessments, develop testing protocols, and gen- erate documentation packages for regulatory filings to support single- use implementation. A few of the more recent innova- tions in components and technolo- gies are highlighted below. Barrier filters: These filters have both a hydrophobic and hydro- philic membrane, which simplifies pre-use post-sterilization integrity testing (PUPSIT) of final sterile fil- tration systems, by enabling liquid to evacuate during filter flushing and air to vent during filter blow- down, while maintaining sterility of the filtration system. Sterile connectors: Sterile con- nectors enable modular processing, which means assemblies can be bro- ken down into smaller, more man- ageable pieces, and then connected at point of use without the need for a biosafety cabinet or laminar flow hood. This helps reduce the number of total part numbers required, while also allowing drug manufacturers the flexibility to process multiple products with varying batch sizes. Single-use rapid transfer ports: These ports, which are easily inte- grated into single-use assemblies, allow the sterile transfer of materials or liquid into and out of isolators. Single-use pumps: There are now single-use rolling diaphragm and pis- ton pumps on the market, which allow drug manufacturers to easily retrofit their existing stainless-steel filling lines with single-use compo- nents, to allow filling flexibility. Single-Use Systems Fill/Finish

Articles in this issue

Links on this page

Archives of this issue

view archives of BioPharm - BioPharm June eBook: Single-Use Systems