[Accéder au contenu](https://www.sigmaaldrich.com#main-content) [](https://www.sigmaaldrich.com/FR/fr) Produits Panier0 FRFR Produits [Connexion / S'inscrire](https://www.sigmaaldrich.com/oidc-sign-in) [Recherche de commande](https://www.sigmaaldrich.com/FR/fr/order-lookup) [Commande rapide](https://www.sigmaaldrich.com/FR/fr/quick-order) Panier0 [Home](https://www.sigmaaldrich.com/FR/en)[Applications](https://www.sigmaaldrich.com/FR/en/applications)[Microbiological Testing](https://www.sigmaaldrich.com/FR/en/applications/microbiological-testing)Pyrogen Testing Methods # Pyrogen Testing Methods  Pyrogen testing determines the quantity of pyrogens in parenteral pharmaceutical or biopharmaceutical products and is regulated by several standards from organizations such as the Food and Drug Administration (FDA), United States Pharmacopeia (USP), or European Pharmacopeia (EP). The sterility of a product does not imply that it is free of pyrogens. Therefore, drugs that are purported to be sterile must also be tested for pyrogens to prevent febrile reactions in patients.  Pyrogen contamination can occur during production or the administration of pharmaceuticals, biotherapeutics, and medical devices, but the presence of pyrogens can also be an inherent characteristic of the product, such as adjuvants in vaccines or synthetic lipopeptides. [Request Information](https://www.sigmaaldrich.com/FR/en/campaigns/pyrogen-testing) * * * ## Related Products Slide 1 of 7 1 of 2 [ \ Millipore \ PYR0MATKIT \ Kit PyroMAT®](https://www.sigmaaldrich.com/FR/fr/product/mm/pyr0matkit) Aperçu rapide [ \ Millipore \ PYR0MATCELLS \ Cellules PyroMAT®](https://www.sigmaaldrich.com/FR/fr/product/mm/pyr0matcells) Aperçu rapide [ \ Millipore \ MATHKSA \ Système de contrôle NEP HKSA-PyroMAT® MAT](https://www.sigmaaldrich.com/FR/fr/product/mm/mathksa) Aperçu rapide [ \ Millipore \ MATFLAGELLIN \ NEP Control Flagellin- PyroMAT® System MAT](https://www.sigmaaldrich.com/FR/fr/product/mm/matflagellin) Aperçu rapide [ \ Millipore \ 1.44161 \ Reference Standard Endotoxin](https://www.sigmaaldrich.com/FR/fr/product/mm/144161) Aperçu rapide [ \ Millipore \ 1.44155 \ PyroDetect Cryoblood](https://www.sigmaaldrich.com/FR/fr/product/mm/144155) Aperçu rapide [ \ Millipore \ 1.44154 \ PyroDetect Kit](https://www.sigmaaldrich.com/FR/fr/product/mm/144154) Aperçu rapide * * * ## Featured Categories [](https://www.sigmaaldrich.com/FR/en/products/industrial-microbiology/pyrogen-testing) [Pyrogen Testing](https://www.sigmaaldrich.com/FR/en/products/industrial-microbiology/pyrogen-testing) Ensure safety: Pyrogen testing of pharmaceuticals with the Monocyte Activation Test (MAT) to detect endotoxin, non-endotoxin pyrogens. [Shop Products](https://www.sigmaaldrich.com/FR/en/products/industrial-microbiology/pyrogen-testing) [](https://www.sigmaaldrich.com/FR/en/products/industrial-microbiology/sterility-testing-consumables-media-and-filtration) [Sterility Testing Consumables, Media & Instruments](https://www.sigmaaldrich.com/FR/en/products/industrial-microbiology/sterility-testing-consumables-media-and-filtration) Laboratory instruments and consumables for sterility testing in microbiological quality control: Sterility test media, pumps, hardware and accessories. [Shop Products](https://www.sigmaaldrich.com/FR/en/products/industrial-microbiology/sterility-testing-consumables-media-and-filtration) [](https://www.sigmaaldrich.com/FR/en/products/industrial-microbiology/microbial-filtration) [Microbial Filtration](https://www.sigmaaldrich.com/FR/en/products/industrial-microbiology/microbial-filtration) Speed up your time-to-result with rapid microbial testing using our complete membrane filtration systems; used in bioburden testing, food and beverage analysis, and cannabis microbiology testing. [Shop Products](https://www.sigmaaldrich.com/FR/en/products/industrial-microbiology/microbial-filtration) Overview Related Articles & Protocols Support  ## [](https://www.sigmaaldrich.com)What is a Pyrogen? A pyrogen is a substance that causes a rise in temperature (fever reaction) in a human or animal through the activation of the innate immune system. They constitute a heterogeneous group of contaminants comprising microbial and non-microbial substances. Pyrogens can be classified into two groups: endotoxins and non-endotoxin pyrogens (NEPs). Endotoxins are substances found in Gram-negative bacteria. Non-endotoxin pyrogens are other microbial substances, including those derived from Gram-positive bacteria or viruses and pyrogens originating from yeasts and fungi. Non-microbial pyrogenic substances can also originate from rubber particles, microscopic plastic particles, or metal compounds in elastomers. Several test methods are available for the detection of pyrogens. They can be classified based on the type of contaminant they detect, and the need for animal materials to perform the test as described in the below table: | | | | |---------------------|--------------------------------------|--------------------------------| | | Detection of Broad Range of Pyrogens | Detection of Endotoxins Only | | Animal-based method | Rabbit pyrogen test (RPT) | Bacterial endotoxin test (BET) | | *In vitro* method | Monocyte activation test (MAT) | Recombinant factor C (rFC) | ## [](https://www.sigmaaldrich.com)Rabbit Pyrogen Testing The rabbit pyrogen test (RPT) involves measuring the rise in temperature of rabbits following the intravenous injection of the tested product. The RPT gives qualitative results and the sensitivity is quite low. The robustness of the test is also limited, due to development of pyrogen tolerance in rabbits after repeated injections, or stress from the rabbits when performing the assay. Note: Rabbit Pyrogen Testing (RPT) is now forbidden in Europe, and the Monocyte Activation Test (MAT) is the method of choice for detecting both endotoxin and non-endotoxin pyrogens. ## [](https://www.sigmaaldrich.com)Monocyte Activation Test The [Monocyte Activation Test (MAT)](https://www.sigmaaldrich.com/FR/en/products/industrial-microbiology/pyrogen-testing) is an alternative to animal-based methods for the detection of both endotoxin and non-endotoxin pyrogens. The monocyte activation test mimics the human immune reaction by incubating monocytes with the tested sample. If pyrogens are present, monocytes are activated and produce inflammatory molecules, cytokines, responsible for the febrile reaction. The cytokines are then detected using an immunological assay (ELISA) involving specific antibodies and an enzymatic color reaction.  Note: As of July 2025, the European Pharmacopoeia (Ph. Eur.) Commission recommends using the Monocyte Activation Test (MAT) as the preferred method for pyrogen testing. The Rabbit Pyrogen Test (RPT) is now banned in Europe. [Read the article](https://www.edqm.eu/en/-/ph.-eur.-bids-adieu-to-rabbit-pyrogen-test-in-its-monographs) and [discuss further with our Experts](https://www.sigmaaldrich.com/FR/en/campaigns/pyrogen-testing) to move to the MAT detecting endotoxin and non-endotoxin pyrogens and to follow the regulatory trend.  ## [](https://www.sigmaaldrich.com)Bacterial Endotoxin Testing (LAL test) The most common method for endotoxin testing is the Limulus amoebocyte lysate test (LAL test); an assay based on the lysate of amoebocytes from the horseshoe crab blood. The lysate from horseshoe crab blood cells naturally reacts with bacterial endotoxins in a coagulation reaction. This method has a high sensitivity for the quantification of endotoxins, but it does not detect non-endotoxin pyrogens. ## [](https://www.sigmaaldrich.com)Recombinant Factor C (rFC) Testing The recombinant Factor C is a genetically engineered protein normally found in the Limulus amebocyte lysate cascade. In this test, Factor C reacts with endotoxin and couples with a marker to produce a quantifiable, fluorescent end product. The recombinant Factor C test uses the same principle as the LAL test, but without the need for animal-derived material.  [Shop All Products](https://www.sigmaaldrich.com/search/pyrogen-testing?focus=products&page=1&perpage=30&sort=relevance&term=Pyrogen%20Testing&type=product) [](https://www.sigmaaldrich.com/documents-search) [Looking for More Specific Information?](https://www.sigmaaldrich.com/documents-search) Visit our document search for data sheets, certificates and technical documentation. [Find Documents](https://www.sigmaaldrich.com/documents-search) * * * - [Cell Culture FAQs: Bacterial Endotoxin Contamination](https://www.sigmaaldrich.com/FR/en/technical-documents/technical-article/microbiological-testing/pyrogen-testing/what-is-endotoxin) FAQs on bacterial endotoxin contamination, details on endotoxin testing using the LAL assay, and tips to avoid contamination in cell cultures. - [See All (1)](https://www.sigmaaldrich.com/FR/en/search/facet-search?focus=sitecontent&term=facet-search) ### Find More Articles and Protocols Enter Keywords Search * * * ## Related Webinars [](https://www.sigmaaldrich.com/FR/en/collections/webinars/w924713416) [Monocyte Activation Test: A Powerful Tool to Assess Pyrogenic Risk in Pharmaceutical Process](https://www.sigmaaldrich.com/FR/en/collections/webinars/w924713416) In this webinar, we discuss how monocyte activation tests performed with the PyroMAT® System detect endotoxin and non-endotoxin pyrogens. [](https://www.sigmaaldrich.com/FR/en/collections/webinars/w877364779) [*In Vitro* Pyrogen Detection in Pharma](https://www.sigmaaldrich.com/FR/en/collections/webinars/w877364779) Learn how our PyroMAT® System provides a robust solution for in vitro Pyrogen Test in pharma with a ready-to use kit. [](https://www.sigmaaldrich.com/FR/en/collections/webinars/w343863313) [Risk Considerations for the Presence of Pyrogens and the Need for the MAT Test in Pharmaceutical Processing](https://www.sigmaaldrich.com/FR/en/collections/webinars/w343863313) In this lecture, you will learn how to test for pyrogen (including non-endotoxin pyrogens) in your pharmaceutical samples, what are the existing methods in order to have a controlled process. ## How Can We Help In case of any questions, please submit a [customer support request](https://www.sigmaaldrich.com/FR/en/support/customer-support) or talk to our customer service team: Email [[email protected]](mailto:[email protected]) or call +1 (800) 244-1173 ## Additional Support - [Chromatogram Search](https://www.sigmaaldrich.com/chromatogram-search) Use the Chromatogram Search to identify unknown compounds in your sample. - [Calculators & Apps](https://www.sigmaaldrich.com/FR/en/support/calculators-and-apps) Web Toolbox - science research tools and resources for analytical chemistry, life science, chemical synthesis and materials science. - [Customer Support Request](https://www.sigmaaldrich.com/FR/en/support/customer-support) Customer support including help with orders, products, accounts, and website technical issues. - [FAQ](https://maestro.my.site.com/knowledgeportal/s/) Explore our Frequently Asked Questions for answers to commonly asked questions about our products and services. __Featured Articles__ [Cell Culture FAQs: Bacterial Endotoxin Contamination](https://www.sigmaaldrich.com/FR/en/technical-documents/technical-article/microbiological-testing/pyrogen-testing/what-is-endotoxin) FAQs on bacterial endotoxin contamination, details on endotoxin testing using the LAL assay, and tips to avoid contamination in cell cultures. [In Vitro Pyrogen Detection in Pharma](https://www.sigmaaldrich.com/FR/en/collections/webinars/in-vitro-pyrogen-detection-in-pharma) *In Vitro* Pyrogen Detection in Pharma [Monocyte Activation Test: A Powerful Tool to Assess Pyrogenic Risk in Pharmaceutical Process](https://www.sigmaaldrich.com/FR/en/collections/webinars/monocyte-activation-test) In this webinar, we discuss how monocyte activation tests performed with the PyroMAT™ System detect endotoxin and non-endotoxin pyrogens. [Risk Considerations for the Presence of Pyrogens and the Need for the MAT Test in Pharmaceutical Processing](https://www.sigmaaldrich.com/FR/en/collections/webinars/pyrogens-and-mat-tests) In this webinar, Tim Sandle will explain why the presence of pyrogens could be harmful for pharmaceutical processes, and how to control and limit their presence. Haut __Connectez-vous pour continuer__ Pour continuer à lire, veuillez vous connecter à votre compte ou en créer un. 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