Using the monocyte activation test as a stand-alone release test for medical devices

Abstract

Monocyte activation tests (MAT) are widely available but rarely used in place of animal-based pyrogen tests for safety assessment of medical devices. To address this issue, the National Toxicology Program Interagency Center for the Eval­uation of Alternative Toxicological Methods and the PETA International Science Consortium Ltd. convened a workshop at the National Institutes of Health on September 18-19, 2018. Participants included representatives from MAT testing laboratories, medical device manufacturers, the U.S. Food and Drug Administration’s Center for Devices and Radio­logic Health (CDRH), the U.S. Pharmacopeia, the International Organization for Standardization, and experts in the development of MAT protocols. Discussions covered industry experiences with the MAT, remaining challenges, and how CDRH’s Medical Device Development Tools (MDDT) Program, which qualifies tools for use in evaluating medical devices to streamline device development and regulatory evaluation, could be a pathway to qualify the use of MAT in place of the rabbit pyrogen test and the limulus amebocyte lysate test for medical device testing. Workshop outcomes and fol­low-up activities are discussed.

Synthesis of a biocompatible benzophenone-substituted chitosan hydrogel as novel coating for PEEK with extraordinary strong antibacterial and anti-biofilm properties

“…The pyrogenicity of the coating surface and/or the presence of potential pyrogenic residues or contaminants was elucidated by a monocyte activation test using the Mono Mac-6 cell line and an enzyme-linked immunosorbent assay (ELISA) for quantitative detection of IL-6 secretion [84,85]. An approximately two-fold increase in IL-6 was detected in the medium of cultures grown in wells with 625 mg/cm 2 of 100%-BPCS, 50%-BP-CS, 12%-BP-CS and 7%-BP-CS coatings compared to negative controls (Fig.…”

A worldwide survey on the use of animal‐derived materials and reagents in scientific experimentation

“…LAL and TAL [57] are cell extracts from the hemolymph of different horseshoe crab species, at least two are already considered vulnerable [58] or even endangered [59] by the International Union for Conservation of Nature's Red List of Threatened Species, respectively. However, the European Pharmacopoeia included a synthetic substitute (recombinant Factor C, rFC) in 2016 [57] and a method containing reagents deriving from human blood (Monocyte‐Activation Test, MAT) in 2010 [60]. MAT and rFC will hopefully eliminate the need for harvesting horseshoe crab hemolymph and end the use of the RPT [61, 62].…”

Nanosafety: An Evolving Concept to Bring the Safest Possible Nanomaterials to Society and Environment

“…At the present, the Limulus Amebocyte Lysate (LAL) assay is considered the golden standard for assessing and quantifying endotoxin content in pharmaceutical products and medical devices; nevertheless, there are a few limitations for its application [ 74 ]. For that reason, it is important to use a second method to validate our results, such as the monocyte activation test [ 75 ], especially in the case of preparations containing nanomaterials, considering that interferences with toxicological assays are a concern [ 76 ], as discussed in the previous section.…”