Standardized pyrogen testing of medical products with the bacterial endotoxin test (BET) as a substitute for rabbit Pyrogen testing (RPT): A scoping review

• Published in: Toxicology in vitro 2021-08, Vol.74, p.105160-105160, Article 105160
• Main Authors: Spoladore, Janaína, Gimenes, Izabela, Bachinski, Róber, Negherbon, Jesse P., Hartung, Thomas, Granjeiro, José Mauro, Alves, Gutemberg Gomes
• Format: Article
• Language: English
• Subjects: Alternative methods; Bacterial endotoxin test; Contamination; Endotoxins; In vitro methods and tests; Medical equipment; Medical products, pyrogens, rabbit Pyrogen test; Nanoparticles; Pyrogen; Pyrogens; Qualitative analysis; Scoping review
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2021.105160

The Bacterial Endotoxin Test (BET) is a method for exclusion of endotoxin-related pyrogen contamination in pharmaceutical products, as an alternative to the Rabbit Pyrogen Test (RPT). However, BET does not detect a broad range of biologically relevant pyrogens, and interferences can limit its practical use for different medical products. This work aimed to scope the evidence in the scientific literature for case-by-case validity assessments of BET in different uses for medical products. A search strategy was conducted in PubMed, Scopus, and Web of Science in April 2020, according to the PRISMA-ScR statement. Twenty-two references were included, evaluating medical products for endotoxin contamination through both BET and RPT according to standardized protocols. A critical appraisal was performed through ToxRTool, followed by data extraction and qualitative synthesis of outcomes and methodological issues. Four classes of products assessed by BET were identified, including nanoparticles, drugs, blood and biological products. A considerable variation was observed on the BET methods used. Collectively, the evidence indicates different factors influencing the outcome of BET, including the chemical nature of samples that may cause interference depending on the selected method. While some applications to medical products appear adequate, others, such as nanoparticles, may require the use of different in vitro pyrogen testing methods, reinforcing the need for case-by-case validation for each BET method and type of medical product. •The Bacterial Endotoxin Test (BET) assesses pyrogen contamination in medical products.•Case-by-case validity assessments of BET for health products were revised.•Comparisons of BET and RPT were found for 4 different classes of health products.•The outcomes of BET are affected by a considerable variation on the test method.