Determination of pyrogen or endotoxin content may be measured by the Rabbit Pyrogen test as described in 21 CFR 610.13 or, if validated as an equivalent method, use of the Limulus Amebocyte Lysate (LAL) assay as described in the USP 23 Bacterial Endotoxins Test. Allowable endotoxin content for a number biological products can be found in the """"""""FDA Guideline On Validation Of The Limulus Amebocyte Lysate Test As An Endproduct Test For Human and Animal Parental Drugs, Biological Products, And Medical Devices""""""""; alternatively, product or manufacturer specific limits are established in conjunction with licensing. Chromogenic, Turbidimetric and gel clot methods fo the in-vitro LAL test are commercially; the gel clot method is considered definitive in the absence of enhancement or inhibition. In general, advantages of LAL methods over the Rabbit test include requiring less sample and the ability to perform repeat tests quickly and easily. This year, tow manufacturers have been able to provide sufficient data on individual products to replace the rabbit test with a LAL test method. Work is continuing to expand LAL testing to additional blood products and vaccines. Examination of possible cross contamination of glucans introduced during processing that react with the lysate also is continuing. We hope to continue research in this area in conjunction with other Center Offices.

National Institute of Health (NIH)
Center for Biologics and Evaluation - Product Quality Control (CBERPQC)
Intramural Research (Z01)
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