Summary
The selection of the optimal normal flow filter is highly process dependent because of the varied performance requirements
demanded by each process step. When considering the three main applications of normal flow filters, one should consider filters
with the following characteristics:
- Media sterilization: Filters incorporating high capacity/high flow membrane formats minimize filtration system sizes while
meeting full validation and integrity test requirements.
- Buffer filtration: Sterilizing-grade and bioburden reduction filters providing high permeability and wide chemical compatibility.
- Product stream filtration: Bioburden reduction filters reduce or eliminate bioburden and particulates immediately before chromatography
columns and UF/DF operations. Sterilizing-grade filters provide the highest level of assurance before product hold steps and
during bulk drug substance formulation and final vial filling. The quick guide to selection of normal flow filters (inset)
provides additional details.
Regardless of the application, proper selection of normal flow filters leads to increased process efficiency from early phase
product development through to full-scale biopharmaceutical production.
Acknowledgments
The authors would like to thank our colleagues Jozsef Vasi, Daniel Calnan, Helena Skoglar, Alisa Liten, Olivier Boizet, and
Kristian Nilsson for their valuable contributions to this work.
Jonathan Royce is a senior application scientist and Jeffrey Carter, PhD, is director of filtration R&D, both at GE Healthcare,
14 Walkup Drive, Westborough, MA, Jonathan.Royce@ge.com
Jakob Liderfelt is a scientist at GE Healthcare, Björkgatan 30, 751 84 Uppsala, Sweden.
References
1. US Department of Health and Human Services, Food and Drug Administration, Guidance for Industry Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice U.S. Department of Health and Human Services, Food and Drug Administration, September 2004.
2. ASTM Standard F838 - 05, "Standard Test Method for Determining Bacterial Retention of Membrane Filters Utilized for Liquid
Filtration," ASTM International, West Conshohocken, PA,
http://www.astm.org/.
*Bioburden reduction filters are not defined by an industry standard. The term "bioburden reduction" is a designation used
to describe a class of filters which provide a high level of microorganism retention (i.e., LRV4-6), but do not yield a sterile
effluent under the high bacterial load called for in the ASTM F838-05 test method. Manufacturer claims on bioburden reduction
filters vary from "typical" retention data to full validation of a minimum LRV. In practice, most bioburden reduction filters
are of a 0.45 or 0.2 urn rating and may yield a sterile fluid in common usage, where bacterial loads are much lower than those
used in the ASTM challenge. Nevertheless, process-specific claims of fluid sterilization through the use of a bioburden reduction
filter are generally not appropriate.
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