This chapter reviews issues concerning facility design, sterility assurance, validation, and the operational performance of a b/f/s system developed for the manufacture of a sterile, liquid-packaged biopharmaceutical product. Specific concerns for filling a sensitive protein product include assessment of heat imparted to the product via plastic extrusion, extractables from plastic resin, and product stability. Bacterial challenge studies that test resin sterilization on b/f/s machines have been reported. The tests involved inoculation of resin feed pellets with Bacillus subtilis spores and performing media fills with tryptic soy broth. The choice of resin for the container is a primary concern, since it contacts the product. Polypropylene resin is commonly used for applications that require terminal sterilization due to its higher melt index and density that make it more suitable for steam sterilization conditions.