FDA withdraws Guideline on Validation of LAL Test

On 12 July, the FDA withdrew the Guideline on  "Validation of the Limulus Amebocyte Lysate Test as an End-Product Endotoxin Test for Human Parenteral Drugs, Biological Products, and Medical Devices" from 1987. 

In Questions and Answers on Current Good Manufacturing Practices, Good Guidance Practices, Level 2 Guidance - Laboratory Controls on the FDA website, the FDA answered: "Yes, the FDA withdrew the 1987 Guideline. The 1987 Guideline is considered obsolete and does not reflect the Agency’s current thinking on the topic."

To the question "Where can drug manufacturers find information regarding endotoxin testing? " the authority answered:
"The United States Pharmacopeia (USP) publishes endotoxin testing recommendations and acceptance criteria in General Chapter <85> Bacterial Endotoxins Test. USP <85> provides methods and calculation of limits for drugs. FDA may, as needed, provide additional guidance to clarify the Agency’s current thinking on use of LAL, recombinant LAL, and other endotoxin testing methods."

These as well as other Q&As are available on the FDA website.

Furthermore, the chapters

  • 2.6.14. Bacterial Endotoxins (2010) European Pharmacopoeia 7.0, p. 171 -175. and
  • 5.1.10. Guidelines for using the Test for Bacterial Endotoxins (2010), European Pharmacopoeia 7.0, p. 520 -523.

of the European Pharmacopoeia Commission, Strasbourg, France also provide useful information.

Other possibly useful statements on the withdrawal and the effects for drug manufacturers are published by Cape Cod and Charles River. They are no guidelines, but provide a summary.

Axel H. Schroeder
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)

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