REGULATORY UPDATE
European Pharmacopoeia and Japanese Pharmacopoeia) specify inclusion of a standard series with every photometric endotoxin test.
Conclusion
The issues addressed in the recent BET version and in the FDA’s Q&A guidance document do not fundamentally change the way endotoxin testing should be performed.
Most of the changes to the BET chapter made in the Second Supplement to USP 35 and incorporated into USP 36 are quite minor and are not likely to impact the majority of laboratories. An exception concerns drugs that are administered per square meter of body surface. In this case, the change slightly raises the endotoxin limit and consequently increases the maximum valid dilution (MVD). More important than this small difference was the previous halving of the endotoxin limits that resulted from the change in the value of K (for these products only) from 5 EU/kg to 2.5 EU/kg. This change had been made by USP in an interim revision announcement in 2011. If limits (and MVDs) have not been reduced from those determined using a value of K of 5 EU/Kg, they should be promptly recalculated using the current value of K (100 EU/m2 and submissions.
) and the changes applied to procedures
The Q&A document refers to the USP chapter <85>, Bacterial Endotoxins Test and to the standard, ANSI/AAMI, ST72 and makes it clear that the document is not intended to be all inclusive and that it only addresses a number of specific issues. As well as providing useful information on a number of subjects, the document contributes to a climate in which firms are expected to have justification for their testing activities (including sampling plans and validation of method change), as opposed to simply referring to
a guidance document. It emphasizes scientifically defensible decisions and process control. While a number of topics that were previously addressed in the withdrawn guidance documents are not included (most notably the use of archived standard curves), it is anticipated that scientifically defensible and appropriately controlled procedures will be expected in these areas, too.
References
1. <85> Bacterial Endotoxins Test (2012). United States Pharmacopeia 36, p. 90. United States Pharmacopeial Convention, Rockville, MD.
2.
Chapter <161>, Transfusion and Infusion Assemblies and Similar Medical Devices (2012). United States Pharmacopeia 36, p.131. United States Pharmacopeial Convention, Rockville, MD.
3. <85> Bacterial Endotoxins Test (2010). United States Pharmacopeia, Interim Revision Announcement. United States Pharmacopeial Convention, Rockville, MD.
http://www.usp. org/sites/default/files/usp_pdf/EN/USPNF/ accessed 9/26/2013
2011-02-2585BACTERIALENDOTOXINS.pdf 4.
United States Food and Drug Administration, “Guidance for Industry. Pyrogen and Endotoxins Testing: Questions and Answers,” June 2012.
http://www.fda.gov/Drugs/ GuidanceComplianceRegulatoryInformation/ Guidances/
ucm314718.htm. Accessed June 11, 2013.
5. ANSI/AAMI ST72:2011, “Bacterial endotoxins—Test methodologies, routine monitoring, and alternatives to batch testing.” Association for the Advancement of Medical Instrumentation, Arlington, VA.
6. Guilfoyle, D. E., J. F. Yager and S. L. Carito. 1989. The effect of refrigeration and mixing on detection of endotoxin in parenteral drugs using the limulus amebocyte lysate (LAL) test. J. Parenter. Sci. Technol. 43(4):183-187)
BEST QC Microbiology Training: A Review Elizabeth Thomas, Editor
Where: Chicago, IL When: September 11, 2013 What: Day 2 of BEST QC Microbiology Training – The Bacterial Endotoxins Test
EMD Millipore and Associates of Cape Cod offer microbiologists the opportunity for personalized training in their educational program: BEST QC Microbiology Training. The program is geared towards improving lab techniques and applications for in-process and product release quality control tests. Last month’s Chicago event was the fourth in a series of six sessions scheduled in 2013; the remaining two will be held in San Francisco and San Juan. The collaborative training spans three days: the first focuses on Bioburden, the second on Endotoxins, and the third on Sterility.
The endotoxin-focused segment provided familiarization with endotoxin detection, including step-by-step instructions for utilizing Associates of Cape Cod’s testing equipment. Troubleshooting techniques, method comparisons, and summaries of relative regulatory guidelines with a special focus on USP Chapter <85> Bacterial Endotoxins Test were also highlighted. The session was interactive, featuring videos, live demonstrations and hands-on trials by attendees, all of whom had at least rudimentary laboratory experience. Through the open forum environment, participants shared best practices and asked company representatives specific questions regarding the systems presented. The meeting was straight-forward and comprehensive, allowing attendees to grasp the basics of endotoxin testing.
14 American Pharmaceutical Review | Endotoxin Supplement 2013
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