Biomaterial Database

Comparison of bacterial endotoxin testing methods in purified pharmaceutical water matrices. 2020

Marine Marius, and Frédéric Vacher, and Thierry Bonnevay

Analytical Sciences, Sanofi Pasteur, Marcy l'Etoile, 1541 Avenue Marcel Mérieux, 69280, France. Electronic address: marine.marius@sanofi.com.

Current bacterial endotoxin testing systems can be labor-intensive and time-consuming, involving several manual pipetting steps. In our quality control laboratory, annually, we test about 15,000 samples of different grades of purified water, WFI and water samples taken to validate cleaning procedures for endotoxins. We are currently using the Kinetic-QCL™ assay which is a pharmacopeia method that provides reliable results. We compared this assay with another Limulus amebocyte lysate (LAL)-based assay (Endosafe®-MCS) and an alternative endpoint fluorescent recombinant Factor C (rFC) assay (ENDOZYME II GO®). Both these assays have been developed to reduce analyst preparation time. Our objective was to assess if they could increase the throughput of our testing while maintaining low rates of invalid results. The results demonstrated that the two most appropriate methods for rapid endotoxin detection in water are our current assay, K-QCL, and the rFC-based assay, ENDOZYME II GO. This latter assay was found to be less sensitive to interference than our current assay, particularly in cleaning validation water samples. It also showed better performance, accuracy, repeatability and had a shorter time-to-results. ENDOZYME II GO assay allows quick testing of large numbers of samples with reliable results and is a good alternative for conventional LAL assays.

UI	MeSH Term	Description	Entries
D008033	Limulus Test	Sensitive method for detection of bacterial endotoxins and endotoxin-like substances that depends on the in vitro gelation of Limulus amebocyte lysate (LAL), prepared from the circulating blood (amebocytes) of the horseshoe crab, by the endotoxin or related compound. Used for detection of endotoxin in body fluids and parenteral pharmaceuticals.	Limulus Tests,Test, Limulus,Tests, Limulus
D004364	Pharmaceutical Preparations	Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.	Drug,Drugs,Pharmaceutical,Pharmaceutical Preparation,Pharmaceutical Product,Pharmaceutic Preparations,Pharmaceutical Products,Pharmaceuticals,Preparations, Pharmaceutical,Preparation, Pharmaceutical,Preparations, Pharmaceutic,Product, Pharmaceutical,Products, Pharmaceutical
D004731	Endotoxins	Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells.	Endotoxin
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001681	Biological Assay	A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc.	Bioassay,Assay, Biological,Assays, Biological,Biologic Assay,Biologic Assays,Assay, Biologic,Assays, Biologic,Bioassays,Biological Assays
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D014867	Water	A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	Hydrogen Oxide
D015203	Reproducibility of Results	The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.	Reliability and Validity,Reliability of Result,Reproducibility Of Result,Reproducibility of Finding,Validity of Result,Validity of Results,Face Validity,Reliability (Epidemiology),Reliability of Results,Reproducibility of Findings,Test-Retest Reliability,Validity (Epidemiology),Finding Reproducibilities,Finding Reproducibility,Of Result, Reproducibility,Of Results, Reproducibility,Reliabilities, Test-Retest,Reliability, Test-Retest,Result Reliabilities,Result Reliability,Result Validities,Result Validity,Result, Reproducibility Of,Results, Reproducibility Of,Test Retest Reliability,Validity and Reliability,Validity, Face
D019411	Clinical Laboratory Techniques	Techniques used to carry out clinical investigative procedures in the diagnosis and therapy of disease.	Clinical Laboratory Test,Clinical Laboratory Testing,Clinical Laboratory Diagnoses,Clinical Laboratory Testings,Clinical Laboratory Tests,Diagnoses and Laboratory Examinations,Diagnosis, Laboratory,Laboratory Diagnosis,Laboratory Examinations and Diagnoses,Laboratory Techniques, Clinical,Clinical Laboratory Technique,Diagnose, Clinical Laboratory,Laboratory Diagnoses,Laboratory Technique, Clinical,Laboratory Test, Clinical,Laboratory Testing, Clinical,Technique, Clinical Laboratory,Test, Clinical Laboratory,Testing, Clinical Laboratory