Validation of Test Result Equivalence for Alternative BET assays, Including Recombinant Methods

Both the FDA’s 2012 Guidance for Industry and USP <1223> specifically use the term “equivalence” as a requirement for validating an alternative test. Traditional methods, such as the Limulus amebocyte lysate (LAL) assay, are widely accepted and have a proven record of assuring parenteral drug and device safety, but they have limitations, including reagent variability and sustainability concerns. As a result, new methods using a number of innovative platforms, including recombinant technology such as Recombinant Factor C and Recombinant Cascade Reagents (rFC and rCR), have emerged. The concept of test result equivalence bridges the gap between old and new technologies, offering cost-effective, environmentally friendly, and reproducible means of endotoxin detection, advancing the industry’s ability to ensure continued product quality and patient safety.  This webinar will explore the concepts of equivalence, comparability, and the statistical methods used to evaluate them.

Presented by Karen Zink McCullough, Owner, Principal Consultant at MMI Associates

Karen Zink McCullough is the principal consultant at MMI Associates, a firm focusing on GMP and microbiology in the drug, biologics, cell therapy, and medical device industries, with a speciality 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 the editor of the book “The Bacterial Endotoxins Test: A Practical Guide.” She is a well-respected international speaker on GMP and 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 a 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.

John Duguid, Executive Director, Research & Development at Vericel Corporation

John Duguid is the Executive Director of Research and Development at Vericel, where he is the CMC technical lead for commercial-stage autologous cell therapy products. Previously a Principal Scientist at Genzyme, Mr Duguid was responsible for developing and implementing rapid microbiological methods and had also managed QC operations. Prior to Genzyme, he worked as an analytical chemist at Abbott Laboratories and Arthur D. Little. Mr. Duguid received his BS in Chemistry from the University of Michigan

Steven Walfish, Principal Consultant at Statistical Outsourcing Services

Mr. Walfish is the Principal Consultant at Statistical Outsourcing Services, a consulting company that provides statistical analysis and training to the FDA regulated industries. Mr. Walfish has held roles at United States Pharmacopeia (USP) as Principal Statistician at Becton Dickinson in Franklin Lakes, NJ, responsible for supporting continuous improvement efforts and process development for worldwide operations. Mr. Walfish brings over 30 years of industrial expertise in the development and application of statistical methods for solving complex business issues. Steven has experience applying statistical methods to analytical method verification, validation, and stability analysis. Mr. Walfish holds a Bachelor of Arts in Statistics from the University of Buffalo, a Masters of Science in Statistics from Rutgers University, and an Executive MBA from Boston University.

Allen L. Burgenson, Global Subject Matter Expert, Testing Solutions at Lonza

Allen L. Burgenson has over 35 years of experience in industries regulated by the FDA, including foods, drugs, biologics, medical devices, and cosmetics. He has worked in R&D, QC, QA, regulatory affairs, and now marketing as an SME for endotoxin detection. Allen is involved in several scientific organizations, including the immediate past chair of the Horseshoe Crab Advisory Panel for the Atlantic States Marine Fisheries Commission (ASMFC) and the immediate past president of the Capital Area Chapter of the Parenteral Drug Association (PDA). He was Chair of the 2004 PDA Annual Meeting.  He is a co-author of three PDA technical reports, including, TR-50 and 51 regarding mycoplasma detection and filtration and TR-82 regarding Low Endotoxin Recovery (LER). Allen also contributed to USP Informational Chapter <1228.5> on Endotoxin Indicators. Allen has a BA in Microbiology from Rutgers University and an MS in Biotechnology Management from the University of Maryland

Alan Hoffmeister, Senior Global Technology and Market Development Manager at Charles River

Alan Hoffmeister is the Senior Global Technology and Market Development Manager for Charles River, Microbial Solutions Division, specialising in the Bacterial Endotoxins Test. Alan’s experience with the Bacterial Endotoxins Test (BET) dates to 1988, since when he has been actively involved in all aspects of the assay. Alan has directed workshops and training courses and lectured internationally on a variety of BET topics including, amongst others, LAL Methodologies, Product Validations, Interference Matrices, Data Integrity and BET Regulatory Affairs. He has also contributed to the development of BET protocols, technical guides and fact sheets internally as well as for clients and industry organisations.

Sponsored by Lonza and Charles River Laboratories

About Lonza

Lonza is the preferred global partner for the pharmaceutical, biotech, and nutrition markets. We focus on enabling treatments that prevent illness and support healthier lifestyles. We optimize scientific innovation and manufacturing technology to enable our customers to serve their patients and consumers. Our comprehensive range of testing solutions supports your efforts in pyrogen and endotoxin testing of raw materials, in-process samples, and manufactured products.

No matter where you are in your process, Lonza’s testing products optimized with our world-class software and hardware solutions and supported by our experts will help streamline your workflows and meet regulatory requirements for injectable drugs and implantable medical devices, including for new modalities used in modern vaccines and biologics. We can help answer your questions about endotoxin testing, whether you use qualitative gel clot, quantitative turbidimetric, or quantitative chromogenic LAL-based assays, or want sustainable recombinant factor C endotoxin testing or sustainable pyrogen testing.

Our BioScience Division provides a large portfolio of testing solutions to support the pharmaceutical and medical device industries, including classical LAL assays (Pyrogent® gel clot, Pyrogent-5000® kinetic turbidimetric, and KineticQCL® kinetic chromogenic assays) and sustainable recombinant Factor C (PyroGene®) assays for endotoxin detection.  We provide monocyte activation assays to detect pyrogenic substances as a sustainable alternative to the Rabbit Pyrogen Test.  We also supply the industry-leading MODA software for laboratory data that eliminates paper from the process, as well as the PyroTec^TM PRO Automated Endotoxin Testing solution, which is the industry leader in automated endotoxin detection.

About Charles River Laboratories

For 30 years, Charles River has been dedicated to the development of precise, robust micro-QC solutions that help bring your products to market safely and efficiently. Our mission is to provide industry-leading scientific and technological advances that not only meet ever-changing regulatory guidelines but set a new standard in the way you perform testing. We’ve purposely built our portfolio to bring you progressive products and services that deliver accurate, relevant, and measurable data to fuel confident decisions on product quality for release. Our unique combination of Endosafe® endotoxin testing, Celsis® rapid microbial detection, and Accugenix® microbial identification and strain typing keeps your manufacturing operations running efficiently and smoothly, lowers your cost to manufacture, and protects your reputation.