Monocyte Activation Test (MAT) Batch Release Testing
- Which products is the MAT suited to as a batch release test?
- How does the monocyte activation test work during batch release testing?
- Comparing the different batch release testing MAT methods
- What steps do you need to take to start release testing using MAT?
- Why is the monocyte activation test ideal for batch release testing parenterals?
Pyrogen testing a must for many products at batch release.
The unique characteristics of many finished products have regulatory submission bodies mandate them to be tested for both endotoxins and non-endotoxin pyrogens. Examples of such products include medical devices, drugs that themselves impact body temperature regulation, intrinsically pyrogenic vaccines, drugs which stimulate immunological reactions, blood derived products as well as those which interfering factors when tested with LAL assays.
MAT the only recommended in-vitro pyrogen test alternative.
While the Rabbit Pyrogen Test (RPT) has long been the gold standard of the comprehensive pyrogen test during the process of batch release testing, the global transition away from in-vivo assays in pharmaceutical testing at large has led pharmacopoeial bodies like Ph. Eur. to specifically point to the use of the in-vitro Monocyte Activation Test (MAT) as a required pyrogen test, where applicable and after product-specific validation.
What is the Monocyte Activation Test and how does it work?
Very simply, the MAT test is a simulation of the human immune system response to endotoxin, non-endotoxin pyrogenic contamination. Broadly, the test method is carried out as follows:
The process of employing MAT as your pyrogen test release assay.
Which MAT method is best suited for my product at batch release testing?
METHOD A Quantitative test
Involves comparing the IL-6 release of a non-spiked product preparation with the LPS standard endotoxin dose response curve to determine the concentration of endotoxin equivalent units of contamination present in the product preparation. When lower than the product’s CLC, the MAT is passed.
METHOD B Sem-quantitative test
Employed if non-linearity between dose response curve and standard endotoxin curve. Involves comparing IL-6 release of a spiked product preparation with equivalent points of LPS standard preparation. Here, the concentration of endotoxin equivalent units of contamination present in the product preparation is equal to the difference between that of the spiked and non-spiked product preparations. If lower than its CLC, the MAT is passed.
METHOD C Ref. lot comparison
For products that are intrinsically pyrogenic. The contaminant concentration (in endotoxin equivalent units) present in the product preparation is compared with that of a reference lot. If lower or comparable to reference lot, the MAT is passed.
Benefits of using the Monocyte Activation Test as your batch release assay
Get a head start on Ph. Eur. mandated RPT transition
In June 2021, the Ph. Eur. Commission announced plans to completely replace the rabbit pyrogen test (RPT) in the Ph. Eur., within approximately 5 years. There are 59 Ph. Eur. texts for vaccines for human use, blood products, antibiotics, radiopharmaceuticals and containers which specify the use of RPT and will thus be expected to transition to an in-vitro alternative in the next five years. The Ph. Eur. specifically recommends the use of MAT as a replacement.
Suitability to all product categories
The rabbit pyrogen test is suitable for testing general pharmaceuticals and biologics, while it fails as an assay for cell therapeutics and cannot be applied to all medical devices. The LAL and rFC are also effective for general pharmaceuticals but their enzymatic nature means they cannot be counted on for all medical devices, biologics or cell therapeutics. It is only the Monocyte Activation Test that is suitable and successful when batch release testing any product category
Reflects human biological reaction
The unique characteristics of many finished products have regulatory submission bodies mandate them to be tested for both endotoxins and non-endotoxin pyrogens. Examples of such products include medical devices, drugs that themselves impact body temperature regulation, intrinsically pyrogenic vaccines, drugs which stimulate immunological reactions, blood derived products as well as those which interfering factors when tested with LAL assays.
"But what will we need at our site to get started with our MAT testing?"
Check out our neat overview of all the supporting materials, equipment and reagents you'll need on your end to make sure you're MAT battle-ready.
