Current Status and Overview of the Rapid Microbiological Methods and Endotoxin Microbiology USP Chapters under Development

An Overview of Recent USP Bacterial Endotoxins Standards Development

Detection of bacterial endotoxins is a critical quality attribute of parenteral pharmaceuticals and medical devices.  Bacterial endotoxins are cell wall components of Gram-negative bacteria, ubiquitous in nature, difficult to destroy and can cause pyrogenic responses or worse.

We are at a generational change in bacterial endotoxins test method options.  Creating the infrastructure to enable broader use of recombinant reagents advances the science while maintaining the safety and quality of medicines.  Recombinant reagents are derived from established biotechnology principles which begin with the same mechanism of action as the natural protein derived from horseshoe crabs; the detection of bacterial endotoxins by the Factor C protein.  Recombinant reagents also afford improvements in quality, supply chain, and sustainability.

The USP Microbiology Endotoxin and Pyrogens Subcommittee developed a recombinant reagent bacterial endotoxins test chapter which is based on the underlying science, and data from the peer-reviewed literature, sponsor and supplier validations, and ring study trials.

The presentation will provide a general overview of the Subcommittee work, and detailed information regarding the recombinant bacterial endotoxins chapter, associated guidance, and the public health reference standard endotoxin.

Presented by Jay Bolden, Senior Director, Eli Lilly and Company Global Quality Laboratories

Mr. Jay Bolden is a Senior Director in the Eli Lilly and Company Global Quality Laboratories and a member of the United States Pharmacopoeia Microbiology Expert Committee. He is a bacterial endotoxins subject matter expert and leads a team with global QC oversight for developing, validating, transferring, and troubleshooting endotoxin, microbiology, QPCR and ELISA methodologies. Jay holds a B.S. in Biology and an Environmental Studies certificate from Indiana University. Jay has over 24 years of industry experience in development, process and laboratory microbiology, and microbiology laboratory leadership.  Jay has authored a book chapter and many peer-reviewed articles on endotoxin testing and recombinant reagents and is a highly sought-out speaker in industry pharmaceutical quality control forums.

Overview and Future Plans of the USP Rapid Microbiological Methods Subcommittee

The absence of adventitious agents is critical for the quality of pharmaceuticals, where contamination event can arise from a contaminated starting materials or during production (e.g., cell line, cell substrates, equipment, facilities and/or operators).

Rapid microbial methods offer alternatives to traditional compendial methods: reduced time for testing, reduced sample volume requirement, possible automation, increased sensitivity and accuracy. These technologies are most suitable for products with a short life, limited supply, and urgent needs and which may be infused into patients before the completion of the test.

The USP Microbiology RMM Subcommittee is drafting a series of official rapid microbial contamination tests based on the validation data from the peer-reviewed literature, submission from a sponsor, and, if necessary, collaborative proof of concept and validation studies.

The presentation will provide a general overview of the RMM chapters under writing as well the drafting and reviewing process within the USP microbiology expert committee. In addition, the general principles of the revised USP <72> and <73> chapters will be explained in detail.

Presented by Dr David Roesti, PhD. Microbiologist/Facilitator QA/QC at Novartis Pharma AG

Dr. David Roesti holds a PhD in microbial ecology from the University of Neuchâtel, Switzerland and has more than 25 years of experience in the field of microbiology. Currently he works at Novartis Pharma AG in Stein Switzerland in the Manufacturing Science & Technology department and is responsible to define the microbial control strategy at the site and is a global subject matter expert in microbiology for the Novartis group. Prior to this assignment, he led the Rapid Microbiological Methods team at Novartis Pharma AG and was the laboratory supervisor for the microbiological testing of non-sterile drug products at Novartis Pharma Stein AG. David Roesti is an elected member of the General Chapters Microbiology Expert Committee of the United States Pharmacopoeia 2022-2025 revision cycle and is a member of the advisory board of the European Compliance Academy Microbiology Group. Finally, David Roesti is main author or co-author of many different publications in either peer-reviewed journals or book chapters and has regularly held presentations in scientific congresses or expert groups.

Early Implementation of Recombinant Cascade Reagent PyroSmart NextGen® in Line With USP <86>

Veronika Wills, Manager, Technical Services at Associates of Cape Cod, Inc

Veronika Wills manages the Technical Services group at Associates of Cape Cod, Inc. She joined the team in 2007 and, thanks to her strong knowledge of biochemistry, microbiology, and immunology, brings an expertise that is vital to ACC customers when it comes to the technical support of testing complex samples, low endotoxin recovery matrixes, and troubleshooting of the Bacterial Endotoxins Test at all levels. Veronika speaks frequently at scientific conferences and seminars globally and is an established expert on endotoxin testing. Veronika holds a Master’s Degree in Biochemical Engineering from the Institute of Chemical Technology in Prague, Czech Republic.

A 3-Step Validation Blueprint for Recombinant Method Implementation

Nicola Reid, Associate Director of Endotoxin Products, Charles River

Nicola has over 20 years of experience with bacterial endotoxin testing and pharmaceutical microbiology. She has been involved in all aspects of the endotoxin assay, including the design and development of BET-specific instrumentation and software. Her work has led her to directing workshops and training courses, as well as lecturing internationally on a variety of BET-related topics including LAL methodologies, product validations, 21 CFR Part 11, and BET regulatory affairs.

Early detection of microbial contaminants in cell-based products using the Milliflex® Rapid System

Lamin Jallow, Microbiology Technology Specialist at Merck KGaA

Lamin Jallow is a Microbiology Technology Specialist for the life science business of Merck KGaA, Darmstadt, Germany, known as MilliporeSigma in North America. Lamin specializes in pharmaceutical microbiology applications with expertise in QC microbiology testing (sterility testing, bioburden testing, and pyrogen testing). He has a Master of Public Health and a B.S. in Microbiology and has over 18 years of industry experience. Before his current role, he was a Microbiology Applications Scientist, specializing in validation and method development, and a subject matter expert. He also worked as a QA auditor and quality engineer before joining the company

Implementation of BACT/ALERT® 3D in light of the USP <72> Chapter: Respiration-Based Microbiological Methods for the Detection of Contamination in Short-Life Products

Presented by Félix Montero-Julian, Scientific Director of Pharma Quality Control at bioMérieux

Félix is the Scientific Director of Pharma Quality Control at bioMérieux. Félix has over 25 years of experience in industrial and clinical diagnostics and previously served as the Chemunex R&D Director at bioMérieux. Félix graduated from the Autonomous Metropolitan University in Mexico as an Industrial Biochemistry Engineer and holds a Masters in Science and a PhD in Immunology from the Aix Marseille II University in France. Félix is a member of different scientific organizations (PDA, ISAC) and served as an expert in a panel for the development of compendial rapid sterility tests for the USP. Félix has been and continues to be extensively involved in the implementation and acceptance of rapid and alternative microbiological methods. He has authored more than 50 scientific publications in basic and applied immunology and microbiology and is an inventor of more than 6 patents on immune therapeutic approaches. He is a prominent speaker at congresses and conferences and a regular contributor to bioMérieux scientific whitepapers. Félix has extensive technical experience, including the development of in vitro diagnostic and research reagents and applications, cell and tissue culture systems, microbiology, alternative and rapid microbiological methods, sterility testing, mycoplasma detection, compendial methods, methods for blood bank testing, and the cell and gene therapy process.

Sponsored by Associates of Cape Cod, Inc, Charles River Laboratories and Merck KGaA and bioMérieux

About Associates of Cape Cod, Inc

YOUR ENDOTOXIN EXPERTS!

Specializing in chromogenic and turbidimetric reagent technologies, Associates of Cape Cod, Inc. (ACC) has been a global leader in endotoxin and (1→3)-ß-D-glucan detection products and services for more than 45 years. ACC pioneered the LAL testing methodology and was the first FDA-licensed company to manufacture LAL reagents. ACC has grown to be an internationally recognized leader in endotoxin detection. Our worldwide headquarters are located in East Falmouth, Massachusetts. With a dedication to quality, ACC is certified to I.S. EN ISO 13485:2016 and ISO 13485:2016. We are FDA-inspected and operate DEA-licensed and CLIA-certified laboratories. Our endotoxin detection reagents, instruments, and software are used within the pharmaceutical, medical device, biotechnology, compounding pharmacy, and dialysis industries for quality control, product release, and research. Our reagents are FDA-licensed and can be used for testing in compliance with USP, EP, and JP bacterial endotoxin test chapters, and our software is 21 CFR Part 11 compliant. ACC also operates a Contract Test Services (CTS) Laboratory, which has specialized in testing for endotoxin and glucan contamination for over 30 years. Our CTS laboratory is GMP-compliant, ISO-registered, and DEA-licensed and is capable of handling all controlled drug substances except those included in Schedule 1. All testing services can be performed according to FDA, USP, EP, and/or JP regulatory guidelines. In addition to routine testing, our CTS Laboratory will customize endotoxin testing, troubleshoot difficult samples, develop and/or transfer LAL test methods, design and produce custom depyrogenation controls for oven validation, and perform Low Endotoxin Recovery (LER) studies and protocols.

About Charles River Laboratories

For over 30 years, Charles River’s Microbial Solutions has led the way in optimizing microbiological quality control testing and minimizing contamination risks across industries. Our comprehensive portfolio includes Endosafe® endotoxin testing, Celsis® rapid microbial detection, and Accugenix® microbial identification and strain typing, all designed to enhance lab efficiency, support critical decision-making, and protect patients.

Our Endosafe® system offers rapid and traditional bacterial endotoxin testing with sustainable, animal-free recombinant reagents, allowing confident decisions on product safety. Celsis® accelerates product release, delivering sterility results in under seven days and bioburden results in less than two. Accugenix® provides unmatched accuracy in microbial identification services, leveraging the industry’s most extensive reference libraries.

Charles River is committed to advancing industrial microbiology, driving the adoption of modern technologies that enhance quality control, reduce costs, and ensure patient safety. Serving the pharmaceutical, consumer care, and cosmetics sectors, our solutions ensure smooth operations, lower manufacturing costs, and uphold your reputation in a competitive market.

About Merck KGaA, Darmstadt, Germany, known as MilliporeSigma in North America

Merck’s portfolio spans more than 300,000 products with 19,000 employees and 72 manufacturing sites worldwide. ​Our BioMonitoring division offers a complete range of high-quality QC safety solutions for industrial applications, while also providing intuitive products and services for lab efficiency and compliance, technical and regulatory expertise, and collaborative partnerships that can be trusted to support every stage of a workflow. ​Together, we are committed to ensuring that everything we do advances and supports safety to protect global health, today and tomorrow.

About bioMérieux

With more than 50 years of pioneering diagnostics, the people of bioMérieux understand the challenges you face when it comes to ensuring product quality and are proud to offer the most comprehensive portfolio of solutions for microbiology quality control of biopharmaceuticals and ATMPs.  Choosing the right microbiology diagnostic can boost efficiency with in-processes testing and automation simplifies the testing processes, reduces human error, and helps ensure data integrity. Rapid, simple, at-line testing of key parameters allows in-process tests to be performed closer to the production environment and provides certainty that your manufacturing process is secure.