FDA's Endotoxin Training Overview

FDA's Endotoxin course will provide an overview of the FDA posted on their web site on Tuesday, July 12, 2011 a notice that they had withdrawn the 1987 Guideline on Validation of the Limulus Amebocyte Lysate Test as an End Product Endotoxin Test for Human Parenteral Drugs, Biological Products and Medical Devices. They advised that the 1987 Guideline is considered obsolete and does not reflect the Agency's current thinking on the topic. In lieu of this document, the FDA advised that they would be issuing a Guidance for Industry on Pyrogen and Endotoxins Testing: Questions and Answers during the November/ December 2011 timeframe. After much delay, this NEW Guidance was released in June 2012. The EP also revised their guidance document 5.1.10 Guidelines for Using the Test for Bacterial Endotoxins (Oct 2014).

The FDA referenced, however, three documents that they believe have more than offset the previous FDA Guidance that was withdrawn. They advise that these documents be referenced for the fundamental principles of the gel clot, photometric and kinetic test methods. This NEW, revised Guidance supplements the above three documents and addresses those issues that may be subject to misinterpretation, not covered in compendial procedures or in the previously available Guidance document. The EP General Chapter 5.1.10 has undergone several revisions to include

1) endotoxin limits for specific substances or product,

2) the use of 2.6.30 Monocyte Activation Test as an alternative to rabbit pyrogen,

3) limiting the Rabbit Pyrogen test, and

4) the use of Recombinant Factor C.

Low Endotoxin Recovery has recently dominated endotoxin discussions since this was observed within a monoclonal antibody formulation in 2013. The USP Microbiology Expert Committee has remained interested in this subject and in 2016 provided their opinion after extensive peer and regulatory reviews. This subject, along with the various Endotoxin Test Guidances will be presented during this interactive, live training webinar.

The objective of this live training webinar is to explore the NEW/REVISED Guidances for Industry on Pyrogen and Endotoxins Testing which addresses those issues that may be subject to misinterpretation, and are not covered in compendial procedures or in the currently available Guidance documents and how they impact testing within the typical Quality Control laboratory. Examples of FDA Warning Letters which illustrate problems associated with endotoxin will also be provided. It will also discuss the issue of LER and the conclusions reached by the USP Microbiological Expert Committee.

This live training webinar includes the following for each registered attendee:

  • A copy of the presentation slides
  • A certificate of training for attendee records

Webinar Takeaway

  • Definitions
  • Examine the Background of the 1987 Guidance for Industry document,
  • Review current testing requirements,
  • Overview of the NEW Guidance for Industry for LAL,
  • Examine the Bases for the Bacterial Endotoxin Tests,
  • Learn of the documents supporting the proposed, new FDA Guidance,
  • Learn which specific Chapter is yet to be harmonized,
  • Learn of the typical issues confronting the end user of LAL testing,
  • Exploring Low Endotoxin Recovery (LER) and its regulatory outcome
  • Warning Letter examples,
  • Live Questions & Discussion

Learning Objective

  • Provide a review of the current testing requirements.
  • Understanding what happened to the old 87/91 LAL Guidance for Industry document.
  • Learn what has replaced it and why.
  • Learn of common issue misunderstandings and misinterpretations.
  • Determine who comprised the Agency Guidance team involved within this new proposed Guidance.
  • Learn of the documents supporting this new Guidance.
  • Learn about sampling, storage, handling and pooling.
  • How does one transition from one bacterial endotoxin test to another
  • Understand the RPT (Rabbit Pyrogen Test).
  • Learn about the Monocyte Activation Test (MAT).
  • Determine when the Rabbit Pyrogen Test is appropriate to use in lieu of the LAL.
  • Understand the issues surrounding the Low Endotoxin Recovery (LER) and its regulatory outcome
  • Understand the FDA's expectation for screening of therapeutic products.

Who Will Benefit from this FDA New Course Online

The following individuals or disciplines will benefit from attending this Webinar:

  • Quality Assurance personnel
  • Quality Control personnel
  • Research & Development
  • Regulatory Affairs Professionals
  • Validation
  • Auditing Professionals

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Barry A. Friedman

Barry A. Friedman (30+ year exp.)

Ph.D. at The Ohio State University

Sarasota, Florida

Barry A. Friedman, Ph.D., is a Senior Consultant in the Biotechnology, Regulatory Compliance and Aseptic Processing arena. From 2000 to 2007, Dr. Friedman was associated with Cambrex Bio Science Baltimore, a contract manufacturer of GMP bulk biopharmaceuticals located in Baltimore, MD. In that capacity as the Director, Quality Control, he managed a multi-shift Department of thirty one individuals involved in Client management, the receipt and testing of raw materials, environmental monitoring and microbiology, analytical chemistry and QC compliance for the production of Phase 1, 2, 3 and commercial products manufactured from bacteria, yeast and mammalian cells. In this capacity Dr Friedman enjoyed many client and regulatory interactions.