The surge in the number of biologics in the drug-development pipeline, over 900 according to the latest report from the Pharmaceutical Research and Manufacturers of America, introduces pressure on manufacturers to handle increasing numbers of small-volume products (1). In fill-finish operations, this means manufacturers must have the ability to quickly and efficiently switch their fill line from product to product without compromising product quality or sterility. Manufacturers are beginning to take advantage of the benefits afforded by single-use technologies to address these needs.
Fill-finish is the last step in the manufacturing operation, after which the product is passed to the patient. As such, product quality and the possibility of contamination are of special concern when a manufacturer is considering whether to implement single-use technologies. The fill occurs downstream of the last filtration step, so there is a heightened sensitivity to sterility risks and the introduction of particulates. As with all disposable applications, product/material interactions and extractables and leachables are also concerns.In some cases, manufacturers may be reluctant to switch to a disposable line from a well-validated stainless-steel fill line, where process engineers have extensive experience in cleaning and validating the system and are confident in their quality control operation. Kent Payne, vice-president and general manager of Development Services at Catalent Pharma Solutions indicated that in general, a big obstacle to adopting single-use technologies in other parts of the manufacturing process has been a reluctance to change. "The biggest challenge we faced in successfully applying single use systems elsewhere was first changing mindset to be open to new approaches from what we were used to," he says. For single-use systems, validation of sterility and integrity is done by the supplier of the components, rather than the manufacturer. Handing these important quality checks over to another party requires a leap of faith that some may not be comfortable making.
On the other hand, single-use technologies offer advantages over stainless systems in control of contamination. In the PharmTech survey, a majority of respondents listed reduced risk of contamination as an advantage to single-use systems (2). A single-use filling line can be configured to have fewer connection points than a fixed-pipe line, thus reducing the risk of microbial contamination. Moreover, since the line is only used for a single product, there is no risk of carryover contamination. Althea Technologies uses disposable technologies in all of its fill operations. According to Chris Duffy, vice-president of operations, "Preventing cross-contamination is an issue that Althea takes very seriously. To ensure that there is no carryover from project to project, Althea has stringent changeover procedures and operates its fill facility with disposable technology in virtually 100% of our fill operations, from small-scale Phase I clinical supplies to commercial manufacturing."