Pyrogen Testing Services
We have conducted in vivo pyrogen testing with speed and accuracy for over 30 years, offering rapid sample turnaround and technical expertise. We perform this critical component of our clients’ quality control program in our dedicated Good Manufacturing Practice (GMP)-compliant facilities using our own specific-pathogen-free (SPF) rabbits. Test items include protein-based material, non-protein material, and blood products. Tests for pyrogenicity can be performed for both Investigational Medicinal Products (IMP) and authorized drug products.
The rabbit pyrogen test (RPT) remains a viable mammalian test model when testing for non-endotoxin pyrogens and a variety of products for which LAL is limited. One-time pyrogen testing may also be required by regulatory authorities to support routine use of endotoxin tests. All in vivo rabbit pyrogen tests are performed according to USP, European, and/or Japanese Pharmacopeia.
We also offer in vitro bacterial endotoxin testing. Assays are performed to meet all pharmacopoeia requirements, including gel-clot (qualitative) and turbidimetric kinetic and chromogenic (quantitative) methods. We also provide preliminary screening and validation of products as well as a backup technical service to clients.
Monocyte Activation Testing (MAT)
Reflecting our commitment to the 3Rs, we’re continuously seeking new methods and technologies to provide clients with viable in vitro alternatives to in vivo tests. As part of this commitment, we offer the Monocyte Activation Test (MAT) according to EP 2.6.30. The MAT is based on the human reaction to pyrogens that cause a fever and may be used as an alternative to the rabbit pyrogen test. This method can be used to detect a wide range of pyrogens, including Gram-positive and Gram-negative organisms, parasitic, viral, and other biological pyrogens (e.g., yeast).
It also offers a solution for testing products that prove to be problematic in other in vitro endotoxin tests, such as drugs that affect body temperature regulation (e.g., antipyretic drugs and steroids), drugs that cause immunological reactions (e.g., immunoglobulins), detergents, some blood-derived products (e.g., stem cells), and other products that are turbidimetric, strongly colored, or interfere with clotting.
When required, our scientific staff can work with clients to develop other approaches to the MAT to satisfy testing objectives.
Pyrogen Detection Application Suitability
|Rabbit Pyrogen Test||Endotoxin (LAL)||MAT|
|Principle of Test|
|Fever Reaction Mammal||Defense Mechanism
|Fever Reaction Human|
|Air pollutants||+3||+/– 3||+|
|Medical devices||+3||+/– 3||+|
|1 Variable pyrogenic responses
2 Rabbit testing often required
3 Can only be tested indirectly by extracting device or filter with pyrogen-free water or saline
Frequently Asked Questions (FAQs) About Pyrogenicity Testing
What are the different types of pyrogen tests?
Currently, the regulations encourage sponsors to use in vitro methods (e.g., MAT or LAL) to evaluate the presence of such molecules. However, for some products, there is still a need to continue using in vivo methods for pyrogenicity (e.g., rabbit pyrogen test). We have several options available for pyrogen testing, including MAT, LAL, and rabbit pyrogen tests – all done in accordance with GMP guidelines.
What are pyrogens?
Pyrogens are fever-inducing substances usually derived from microorganisms (endotoxins or lipopolysaccharide [LPS]) and, when present systemically in sufficient quantities, can lead to severe signs of inflammation, shock, multi-organ failure, and sometimes even death in humans. Furthermore, pyrogens can be classified into these two groups – endotoxin and “NEP” (non-endotoxin pyrogen). The human body can suffer symptoms ranging from fever to septic shock depending on the concentration of the pyrogen molecules present in the drug. Pyrogenicity testing is important for determining if pyrogens are present in your product.
What are the endotoxin limits for medical devices?
Endotoxin limits are 20 EU/mL or 2.15 EU/mL for devices in contact with cerebrospinal fluid.