Single-use Technologies in Fill–Finish Operations - Pharmaceutical Technology

Latest Issue

Latest Issue
PharmTech Europe

Single-use Technologies in Fill–Finish Operations
Single-use components in the fill–finish line provides increased flexibility to multiproduct manufacturers.

Pharmaceutical Technology
Volume 35, Issue 10, pp. 58-60

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.

Single-use technologies are now widely-accepted tools in drug manufacturing, particularly manufacturing of biologics. A recent biomanufacturing survey in Pharmaceutical Technology indicated that 66% of respondents use at least some disposable components in their manufacturing operations, and an additional 9% of respondents indicated that they use all disposables (2). Disposable upstream-processing tools, such as bioreactors and media storage containers have made a natural transition from bench-top to large-scale cell culture, and have evolved in size and complexity to fit the special needs of manufacturing-scale operations. Disposable downstream-processing tools have also been adapted to meet the demands of large-scale bioprocessing. At the very end of the biomanufacturing line is the fill-finish operation, where single-use technologies are just beginning to make inroads.

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."


blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
| Weekly

FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
View Results
Eric Langerr Outsourcing Outlook Eric LangerTargeting Different Off-Shore Destinations
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAsymmetric Synthesis Continues to Advance
Jill Wechsler Regulatory Watch Jill Wechsler Data Integrity Key to GMP Compliance
Sean Milmo European Regulatory WatchSean MilmoExtending the Scope of Pharmacovigilance Comes at a Price
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Ebola Outbreak Raises Ethical Issues
Better Comms Means a Fitter Future for Pharma, Part 2: Realizing the Benefits of Unified Communications
Better Comms Means a Fitter Future for Pharma, Part 1: Challenges and Changes
Source: Pharmaceutical Technology,
Click here