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LAL Update® Newsletter
CURRENT ISSUE:
Withdrawal of FDA Guideline
VOL. 27, NO. 1 Download (350K PDF)
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Letter From The Editor
Dear LAL User:This issue of the LAL Update addresses a milestone event in the history of endotoxin testing. After almost 24 years of service, FDA has withdrawn the venerable 1987 "Guideline on Validation of the Limulus Amebocyte Lysate Test as an End-Product Endotoxin Test For Human and Animal Parenteral Drugs, Biological Products and Medical Devices". With it has gone the 1991 "Interim Guidance for Human and Veterinary Drug Products and Biologicals: Kinetic LAL Techniques." FDA determined that the guideline was obsolete and withdrew it along with the 1991 interim guidance that had been incorporated into the online version.
These had been important documents for those performing endotoxin testing, particularly in the late 20th century. That is before 2001, when the harmonized Bacterial Endotoxins Test (BET) chapters became official in the United States Pharmacopeia and the European and Japanese Pharmacopeia. Before the publication of the harmonized BET, the USP only addressed the gel-clot method, so the guidance documents were the primary source of regulatory information on testing by the chromogenic and turbidimetric methods.
We note that the action removes the only official document that mentioned archived or stored standard curves. Consequently, we suggest that any test using archived curves (whether in portable test systems or not) be validated as an alternative method to the procedure specified in the BET, unless already validated and/or approved.
The FDA had warned of the forthcoming demise of the guidances at a number of meetings over the last year and said that a new Question and Answer document on endotoxin testing would replace them. At the time of writing the Q and A document had not been released and there was no indication when that might be.
The article on the withdrawal looks at a number of issues that were addressed in the guidance documents and considers the impact of the removal. Where an issue is addressed in another document, that is pointed out.
If you have any questions regarding the withdrawal, or on any other matter related to endotoxin testing, please call our excellent Technical Service team or me.
With best wishes,
Michael Dawson, Ph.D.