Controlling variability to increase accuracy in the BET Assay

05th June 2013 | | Karen McCullough, Principal consultant at MMI Associates and Alan Baines, Head of Strategic Projects for Lonza Pharma, Bioscience Solutions |WATCH FOR FREE


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Karen Zink McCullough is the principal consultant at MMI Associates, a firm focusing on GMP and Microbiology in the drug, biologics, and medical device industries, with a specialty in the Bacterial Endotoxins Test (BET). Ms. McCullough was the first to publish on the use of the BET as a replacement for the rabbit pyrogen test for small volume parenterals. She has published over 50 articles and book chapters, and is a well respected international speaker on GMP and the BET. Ms. McCullough is chairperson of the LAL Users’ Group, is a United States Representative to Working Group 2, TC 209 for the revision of ISO 14698, and is an elected member of the United States Pharmacopeia Expert Committee on Microbiological General Chapters. She holds a Bachelor’s degree in Bacteriology from Rutgers University, and a Master’s degree in Molecular Biology from the University of Oregon.

Follow-up presentation by Alan Baines, Head of Strategic Projects for Lonza Pharma, Bioscience Solutions

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The vast majority of endotoxin test results generated in the QC laboratory are negative, in that they show endotoxin concentration values that are ‘undetectable’ or below the Endotoxin Release Limit (ERL). However, when positive results are observed, it is the manufacturer’s responsibility to determine if the result is attributable to laboratory error(s), or will be adjudged to be Out-Of-Specification (OOS) and result in batch failure. Similarly, Out-Of-Trend (OOT) results, such as those that could be caused by failure to control variability in the BET assay, also require investigation. Conducting an OOS or OOT investigation can be extremely time-consuming, and expensive, with root causes sometimes difficult to identify. The use of a focused and logical approach coupled with the use of data trending tools, can considerably facilitate such investigations, reducing costly manufacturing delays such as increased hold times for suspect batches, or production stoppages and leading to the introduction of more effective Corrective And Preventative Actions (CAPAs).

Alan Baines is an Honours graduate in Pharmacology from Leeds University, England. He has been involved in endotoxin testing since the introduction of the LAL test to the UK pharmaceutical industry in 1976. Since that time he has been routinely involved with the design and development of endotoxin assays, instrumentation and software and has assisted many companies world-wide with adoption, implementation and achieving regulatory compliance for the Bacterial Endotoxins Test. Alan has lectured at numerous international meetings, seminars and workshops and is a contributory author to several books including the chapter ‘Routine testing’ in the recent PDA publication “The Bacterial Endotoxins Test, A Practical Guide”. Alan is also largely responsible for the development and maintenance of the Lonza portfolio of BET training modules including topics such as BET methodologies, product characterisation and validation, reaction kinetics, data analysis, conducting OOS and OOT investigations involving the BET assay.