Kidney Microphysiological System Testing for Specific Contexts of Use in Drug Development

This project will evaluate kidney microphysiological system (MPS) platforms for their ability to predict clinically relevant toxicological responses and ADME properties, with the goal of assessing their readiness for fit-for-purpose applications in drug discovery and development.

About

The kidney is a common target organ for drug-induced toxicity and is poorly predicted in nonclinical in vivo studies. Furthermore, due to its critical secretory and filtration activities the kidney plays a role in both drug elimination and maintenance of overall body fluidic content. The structure of the nephron, the functional unit of the kidney and its role in maintaining whole body fluid and electrolyte balance lends the kidney well to MPS model design. Due to the specialized functions of each segment of the nephron (e.g., proximal tubule secretion versus distal tubule Na⁺/Cl^- reabsorption, and glomerular filtration), no single kidney model is required to represent the entirety of needs within pharmaceutical drug development. Rather, the ability to measure specific endpoints with clinical predictivity is of critical importance to the IQ MPS Affiliate and Critical Path Institute.

Technical Requirements

For the purposes of this RFI, MPS refers to models that encompass two or more of the following: multi-cellular/multi-layered tissue, microfluidics, derived of primary or stem cell-derived cells, or inclusion of an immune component. Specifically, this project seeks to investigate models such as organoids, microtissues, organs-on-a-chip, or a combination thereof.

The kidney MPS would ideally be viable and amenable to multi-day, repeated dosing, and exhibit segment (i.e., glomerulus, proximal, distal, collecting duct, etc.) appropriate function and key ADME-related gene expression, localization, and activity (e.g., CYP2B6, CYP2C8, OCT2, MATE1/2, etc.).

For specific technical and functional details of interest to the IQ MPS Affiliate and Critical Path Institute including and beyond minimal requirements, please refer to section 5.b of this RFI. Respondents are also encouraged to review recent manuscripts published by the IQ MPS Affiliate on kidney models and ADME requirements for microphysiological systems (Phillips, et al., Lab on a Chip, DOI: 10.1039/c9lc00925f, 2020; Fowler, et al., Lab on a Chip, DOI: 10.1039/c9lc00857h, 2020).

Application Process

Publication of the Request for Information (RFI) is the first step by the IQ MPS Affiliate and Critical Path Institute to solicit interest in collaborating on the testing of kidney MPS for specific contexts of use (e.g., pharmacology, drug metabolism, toxicology, etc.) in drug development. The information collected during the RFI process will be evaluated by IQ MPS Affiliate and Critical Path Institute members to aid in selection of respondent(s) to move forward to the Request for Proposal (RFP) stage. The IQ MPS Affiliate and Critical Path Institute may choose respondent(s) to move forward to the RFP stage based solely upon responses to the RFI, or may choose to request clarification on information provided by respondent(s) to the RFI, or request additional technical details. The IQ MPS Affiliate and Critical Path Institute will then release an RFP to selected respondent(s) detailing a study design for a specific context of use. Responses to the RFP will aid in determining study initiation.

**This project is no longer accepting applications.**

Download the Request for Information (RFI) here.

RFI ISSUED: June 3, 2021
DEADLINE TO RESPOND: Dec 31, 2021
RFP ISSUED: June 2022