By Frank Leo, Cardinal Health, Inc., Patrick Poisson, Cardinal Health, Inc,, Colin S. Sinclair, Air Dispersions Ltd., and Alan Tallentire, Air Dispersions Ltd.
A collaborative study involving Cardinal Health, Inc. and Air Dispersions Ltd. has been carried out to further the understanding of the extrusion process and its impact upon the quality of Blow/Fill/Seal product. Controlled challenges to the extrusion system, comprising Low Density Polyethylene granulate contaminated with characterized levels of Bacillus atrophaeus (ATCC 9372) endospores and Escherichia coli 055:B5 bacterial endotoxin, have been conducted. Batches of spore contaminated polymer, at challenge levels varying from 103 to 106 spores g-1 polymer with derived D160 values ranging from 1.22 to 2.07 minutes’ and endotoxin contaminated polymer, at challenge levels varying from 102 to 104 EU g-1 polymer, were processed through a Blow/Fill/Seal machine employing Tryptone Soya Broth and Water for Injection as the fill mediums, respectively. Relationships have been established between the levels of challenge for each of spores and endotoxin and the extent of product contamination. The relationships allow for prediction of microbiological and pyrogenic quality based upon the microbiological and pyrogenic attributes of unprocessed polymeric granulate and for rationalized choices of polymeric granulate acceptance limits. It is stressed that the findings apply only to the particular Blow/Fill/Seal machine and to the specific conditions of machine operation.