Bacterial endotoxin test

USP (1995). Bacterial endotoxins test. United States Pharmacopeia. USP Convention, Rockville, Maryland, pp. 1696-1697. 

Injectables, Inhalation solutions a. Sterility test, b. CCI, AET. c. Bacterial endotoxin test Test all batches on stability with the exception of the first three batches for AE a. b. c. 0 only 0, 12, 24, 36 months 0 and expiry only... 

Endotoxin determination is performed according to the bacterial endotoxins test of the USP. Take a minimum of three condensate samples (sample volume 100 ml each) from each supply point. 

Product component bioburden. Endotoxin analysis involves testing twenty (20) pieces. Twenty (20) vials or stoppers are filled with or immersed in WEI, mixed and sonicated. Duplicate 0.1 mL aliquots are removed and tested for endotoxin per the USP <85> Bacterial Endotoxins Test. 

Bacterial Endotoxins Test (85)," "Biological Reactivity Tests, in vivo (88)," "Particulate Matter in Injections (788)," and "Purified Water," USP 23, The U.S. Pharmacopeial Convention, Rockville, Md., 1994. 

Failure to establish yields or acceptable levels of rejects for both in-process and finished product Failure to conduct stability studies Manufacturing equipment not identified and/or qualified Inadequate training of employees working in aseptic operations Inadequate process change procedures Validation protocols that lack acceptance criteria Incomplete investigations of laboratory failures Failure to follow United States Pharmacopeia (USP) procedures for the bacterial endotoxin test... 

Bacterial Endotoxins Test, United States Pharmacopoeia... 

The USP now recognizes two tests—the pyrogen test conducted with rabbits and the bacterial endotoxins test, also termed the limulus amebocyte lysate... 

LAL) test. Additionally the agency has approved the use of the bacterial endotoxins test for many drug and device products. 

Because, in the absence of bacterial growth in the product, the endotoxin level will not increase on storage during shelf life Bacterial Endotoxin Testing is not indicated in the stability protocol. If there is a continued need to... 

The General Tests, Processes, and Apparatus section contains 60 test methods, such as fluorometry and electrometric titration, dissolution and disintegration tests, content uniformity, and a bacterial endotoxin test. Qualitative tests, reagents and test solutions, and standard solutions are also included. The Infrared Reference Spectra of 124 chemical entities are included in an appendix and will be updated in subsequent editions. 

A harmonized text for <85> bacterial endotoxins test (BET) became effective in January of2001 It was a pro-... 

Bacterial endotoxins test. In USP 24-NF 19 The United States Pharmacopeial Convention, Inc. Rockville, MD, 2000 2875-2879, Supplement 2. 

Cooper, J.F. Bacterial endotoxins test. In Microbiology in Pharmaceutical Manufacturing Prince, R., Ed. Parenteral Drug Assoc., Bethesda, Davis Horwood International Publication, Ltd. Modalmeny, UK, 2001 537-567. 

Cooper, J.F. (2001) The bacterial endotoxins test past, present and future. Eur J Parenteral Sci, 6,89-93. 

Tests for pyrogens include a rabbit test, in which rabbits are administered with the radiopharmaceutical and their rectal temperatures are monitored. From the rise in temperature in the rabbits, pyrogenicity of a sample is determined. However, a simpler and quicker method is the so-called limsulus amebocyte lysate (LAL) test, also called the bacterial endotoxin test (BET). In this test, the lysate of amebocytes from the blood of the horseshoe crab (Limulus polyphemus) is mixed with the sample and incubated at 37° C. An opaque gel is formed within 15-60 min depending on the concentration of pyrogens. 

An example of calculating the limits for endotoxins A morphine containing injection solution with the strength of 100 mg/5 mL has been prepared. Because the product will be administered parenterally a bacterial endotoxins test has to be performed. Therefore the administration route has to be known is this intravenous or intrathecal or epidural. For endotoxins in intravenous administration the requirement is maximally 5 EU/kg body weight during 1 h. Based on a body weight of 70 kg this means 350 EU/h. Secondly the maximal dose (in volume of the product per hour) will determine the actual limit. This depends on the need of the patient as well. If he needs the full 5 mL, this makes the requirement for the product to be 350 EU/5 mL = 70 EU/mL. 

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