Five Critical Endotoxin Testing Concerns

As pharmaceutical manufacturing processes continue to become more streamlined and therapy delivery continues to evolve, so has endotoxin control. Five topics in particular have dominated recent discussions around endotoxin control: low endotoxin recovery,non-LAL detection methods, modulating impurities, data integrity and depyrogenation.

These five topics are integral to the future of endotoxin testing, and the industry recognizes the need to discuss the role they will play in this future.

In a continued effort to keep the community updated, PDA will host the 2018 PDA Endotoxins Workshop, with specific sessions focused on each of these five areas. This meeting follows up on last year’s successful endotoxin workshop. Below is an overview of how the workshop will address these topics:

1. Low Endotoxin Recovery (LER)

PDA’s LER task force plans to publish a technical report in September. The task force, composed of subject matter experts from academia, U.S. FDA, biopharmaceutical industry, and reagent-supplier/testing companies, will address critical LER concerns such as:

1. The root cause of LER
2. Standardization of the experimental protocols for spike/hold recovery studies
3. Potential safety impact of LER and mitigation strategies

Key technical report authors will speak on each of these topics, giving the audience the unique opportunity to get firsthand information on LER.

2. Non-LAL Endotoxin Detection Methods

For years, compendial endotoxin testing has been dominated by the Limulus Amoebocyte Lysate (LAL) assay. But interest in non-LAL endotoxin detection methods is growing. Non-LAL methods, such as the Monocyte Activation Test (MAT) and Recombinant Factor C Testing (rFC), have been shown to overcome some of the limitations presented by LAL testing. At this session, key experts from academia and industry will look at method development and applications for these solutions.

3. Endotoxins and Other Microbial Immune-Modulating Impurities

Endotoxins and other microbial impurities can cause varying levels of immune responses when introduced to the blood system. Therefore, the rapidly growing area of innate and adaptive immunity needs to be explored. This session will explain innate immune response-modulating impurities and discuss strategies for control.

4. Data Integrity

Recent years have seen a strong focus from regulators on data integrity topics. This session will allow attendees to discuss data integrity strategies for manual (gel clot), kinetic and automated endotoxin LAL testing with experts from industry.

5. Depyrogenation

In previous years, sterility and depyrogenation have often been combined as a single topic. USP, however, has recently created a dichotomy between the two, expanding understanding about the use of depyrogenation in manufacturing processes. In this session, compendial representatives will discuss the USP chapters <1228> Depyrogenation, <1228.1> Dry Heat Depyrogenation, <1228.3> Depyrogenation by Filtration and<1228.5> Endotoxin Indicators.

Anyone interested in delving more deeply into these five topics is encouraged to attend the 2018 PDA Endotoxins Workshop.