REGULATORY UPDATE
Recent Regulatory Issues Concerning Bacterial Endotoxin Testing
Michael E. Dawson, Ph.D., RAC
Director of Regulatory Affairs Associates of Cape Cod, Inc.
This article is developed from articles published in the LAL Update, the Associates of Cape Cod newsletter
Introduction Within the last two years, there have been developments in two areas of regulatory significance to endotoxin testing. The first concerns changes to the Bacterial Endotoxins Test (BET) chapter in the United States Pharmacopeia (USP). The second is the release by the US Food and Drug Administration (FDA) of a guidance document on pyrogen and endotoxins testing in June of 2012.
Chapter <85> Bacterial Endotoxins, United States Pharmacopeia
The Second Supplement to United States Pharmacopoeia (USP) 35 included a few changes to chapter <85>, Bacterial Endotoxins Test (BET). The changes became effective on December 1, 2012, and were incorporated into the BET chapter in USP 36 [1], which became effective on May 1, 2013. These changes are described and discussed in turn below.
The first three changes described were made in the interests of harmonization with the European and Japanese Pharmacopeia endotoxin test chapters. These changes were announced on the USP website in late 2011 (see
http://www.usp.org/usp-nf/harmonization/stage-6/bacterial-endotoxins-test.)
Changes and Comments 1. Specification that the Default Endotoxin Test is the Gel-Clot Limit Test
In the introductory paragraphs to the BET chapter, the instruction that in the event of doubt or dispute, the final decision is made based upon “the gel-clot technique” was changed to specify “the gel-clot limit test”, unless otherwise indicated.
This is a rather minor change and has little effect because the only other gel-clot technique in the BET chapter is the Quantitative Test, which includes all the elements of the limit test plus additional standard endotoxin concentrations and dilutions of the specimen.
The limit test is simpler to
perform. If the specification is to be met, the specimen must test negative, so there is no merit in testing dilutions of the specimen.
2. Elimination of Reference to Testing of Extracts
In the REAGENTS AND TEST SOLUTIONS section, under the sub-heading Sample Solutions, references to testing medical device extracts have been removed and specific mention of testing extracts has
Dr. Michael Dawson is responsible for world-
wide compliance of ACC’s products. He has broad experience in the manufacture and application of endotoxin testing reagents, instrumentation
and of software. Dr. Dawson speaks frequently on endotoxin-related issues. He has authored many publications, served on expert panels and edits the ACC newsletter, LAL Update.
Disclaimer
The information in this article is given for the purposes of education and to stimulate discussion. It is not intended to be, and it should not be used as, a substitute for regulations or regulatory guidance. It should be read in conjunction with the original documents being discussed. Decisions and actions should be based on the relevant regulations, guidance documents and pharmacopeial chapters, not on this article. Use the current revision of the source documents.
10 American Pharmaceutical Review | Endotoxin Supplement 2013
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