Using microphysiological systems in regulatory applications is a nuanced process that has unique potential benefits and considerations. The 3Rs Collaborative’s MPS initiative works to advance the scientifically supported use of MPS in regulatory applications. We have given several presentations on this topic, have a publication under review about roles & responsibilities of various stakeholders, and work with the FDA-CDER on this topic via a consortium agreement. Right now the primary focus of our regulatory subgroup is on a cross-platform drug-induced liver injury (DILI) project and starting to benchmark current use of MPS in regulatory applications.
In late 2023, the 3Rs Collaborative requested participation from the FDA-CDER (Center for Drug Evaluation & Research) in a consortium activity with us. This request was approved in December of 2024.
This consortium activity seeks to address the public health need for more reproducible, predictive, and translational preclinical investigations and works to ensure the application of the 3Rs.
FDA-CDER’s is involved in the following ways:
An important issue in the implementation of microphysiological systems (MPS) in regulatory applications for drug safety assessment hinges on the confidence in the accuracy, reliability, and standardized characterization of such methods. Only through increased confidence in the performance of these platforms, can the industry rely on this data and specific regulatory guidance be created for its use in regulatory applications to the US Food & Drug Administration (FDA).
Co-creating a project with regulators, end-users, and manufacturers to evaluate a wide range of MPS for a particular context of use will help regulators gain confidence with these systems and develop guidance that can be applied to a variety of MPS. Similarly, with increased confidence in such platforms, MPS manufacturers may submit more qualification packages to the FDA, which would in turn further enhance confidence in these safety assessment tools.
This project is being done under a consortium agreement between the FDA’s Center for Drug Evaluation Research (CDER) and the 3Rs Collaborative (3RsC). Its main goal is to build confidence in using MPS for a particular regulatory context of use by conducting a cross-platform research project of drug induced liver injury (DILI), using the same compounds and general design across platforms. This project is expected to highlight expected variabilities across platforms that might be observed in study reports. This project is further meant to support a letter of intent to the ISTAND qualification program. Ultimately we hope to identify best practices for the conduct and reporting of safety studies and facilitate future qualification platforms.