Recommended Guidelines for Developing, Qualifying, and Implementing Complex In Vitro Models (CIVMs) for Drug Discovery

Ekert, Jason E.; Deakyne, Julianna S.; Pribul-Allen, Philippa; Terry, Rebecca; Schofield, Christopher; Jeong, Claire G.; Storey, Joanne; Mohamet, Lisa; Francis, Jo; Naidoo, Anita A.; Amador, Alejandro; Jl, Klein; Rowan, Wendy C.

doi:10.1177/2472555220923332

Cited by 39 publications

(50 citation statements)

References 89 publications

(115 reference statements)

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“…7 In addition, MPS are also responsive to the 3R principles of animal use in research -refinement, reduction, and replacement -and offer a way for significant reduction on the use of animals or animal models for preclinical studies. 8,24 It is now becoming increasingly clear that MPS can serve as in vitro tools within many areas of drug development, 25,26 including serving as physiologically-relevant platforms for early lead compound target validation and therapeutic safety and toxicity assessment during the preclinical phase. 12,[27][28][29] In addition, MPS can be used for modeling of both common and rare diseases, 7 with successful modeling of a number of rare disorders, such as Progeria, 30,31 Barth syndrome, 32 and hereditary hemorrhagic telangiectasia.…”

Section: Impact Statementmentioning

confidence: 99%

“…88,91 In addition to the need for further MPS characterization, the IQ MPS Affiliate have identified a variety of other hurdles impeding MPS adoption in the pharmaceutical industry including the need for standards, bridging and comparing pre-clinical animal model data with tissue chip data, providing enough data to increase confidence in the technology, and increasing throughput for specific applications. 25,91 For example, the level of throughput needed varies widely based on CoU, e.g. the quantity of actively investigated compounds and the degree of certainty required to inform data-driven decisions.…”

Section: Impact Statementmentioning

confidence: 99%

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Microphysiological systems: What it takes for community adoption

Hargrove-Grimes

Low

Tagle

2021

Exp Biol Med (Maywood)

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Microphysiological systems (MPS) are promising in vitro tools which could substantially improve the drug development process, particularly for underserved patient populations such as those with rare diseases, neural disorders, and diseases impacting pediatric populations. Currently, one of the major goals of the National Institutes of Health MPS program, led by the National Center for Advancing Translational Sciences (NCATS), is to demonstrate the utility of this emerging technology and help support the path to community adoption. However, community adoption of MPS technology has been hindered by a variety of factors including biological and technological challenges in device creation, issues with validation and standardization of MPS technology, and potential complications related to commercialization. In this brief Minireview, we offer an NCATS perspective on what current barriers exist to MPS adoption and provide an outlook on the future path to adoption of these in vitro tools.

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Section: Impact Statementmentioning

confidence: 99%

Section: Impact Statementmentioning

confidence: 99%

Microphysiological systems: What it takes for community adoption

Hargrove-Grimes

Low

Tagle

2021

Exp Biol Med (Maywood)

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“…A standard approach for the validation of a novel safety model, is to determine the sensitivity and specificity of the model with a set of compounds that have a large body of preclinical and clinical data available [ 41 , 42 ]. Once the dynamic range of the model is established, clinical safety outcomes are then replicated in an acute or chronic state.…”

Section: Evaluating Drug Safety and Efficacymentioning

confidence: 99%

Organ-on-chip applications in drug discovery: an end user perspective

Clapp

Amour

Rowan

et al. 2021

Biochemical Society Transactions

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Organ-on-chip (OoC) systems are in vitro microfluidic models that mimic the microstructures, functions and physiochemical environments of whole living organs more accurately than two-dimensional models. While still in their infancy, OoCs are expected to bring ground-breaking benefits to a myriad of applications, enabling more human-relevant candidate drug efficacy and toxicity studies, and providing greater insights into mechanisms of human disease. Here, we explore a selection of applications of OoC systems. The future directions and scope of implementing OoCs across the drug discovery process are also discussed.

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“…This recognition has led to the development of increasingly sophisticated 3D cell cultures to more accurately reproduce the complexity of an in vivo environment. Using scaffolds, hydrogels, and microfabricated devices, 3D cell culture technology has rapidly developed as a promising assay for testing of drug delivery, metabolism, pharmacology, and toxicity 16 . MALDI IMS has the potential to be a key part of the analytical strategy for assessing 3D cell cultures by measuring drug penetration, distribution, and cellular response to the drug and other stimuli.…”

Section: Study Conductmentioning

confidence: 99%

“…Using scaffolds, hydrogels, and microfabricated devices, 3D cell culture technology has rapidly developed as a promising assay for testing of drug delivery, metabolism, pharmacology, and toxicity. 16 MALDI IMS has the potential to be a key part of the analytical strategy for assessing 3D cell cultures by measuring drug penetration, distribution, and cellular response to the drug and other stimuli. The ability to assess multiple treatment conditions across several time points on a well‐controlled, yet biologically relevant, sample is highly attractive.…”

Section: Study Conductmentioning

confidence: 99%

The emergence of imaging mass spectrometry in drug discovery and development: Making a difference by driving decision making

2021

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The pharmaceutical industry is a dynamic, science-driven business constantly under pressure to innovate and morph into a higher performing organization. Innovations can include the implementation of new technologies, adopting new scientific methods, changing the decision-making process, compressing timelines, or making changes to the organizational structure. The drivers for the constant focus on performance improvement are the high cost of R&D as well as the lengthy timelines required to deliver new medicines for unmet needs. Successful innovations are measured against both the quality and quantity of potential new medicines in the pipeline and the delivery to patients. In this special feature article, we share our collective experience implementing matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) technology as an innovative approach to better understand the tissue biodistribution of drugs in the early phases of drug discovery to establish pharmacokinetic-pharmacodynamic (PK-PD) relationships, as well as in the development phase to understand pharmacology, toxicology, and disease pathogenesis. In our experience, successful implementation of MALDI IMS in support of therapeutic programs can be measured by the impact IMS studies have on driving decision making in pipeline progression. This provides a direct quantifiable measurement of the return to the organization for the investment in IMS. We have included discussion not only on the technical merits of IMS study conduct but also the key elements of setting study objectives, building collaborations, data integration into the medicine progression milestones, and potential pitfalls when trying to establish IMS in the pharmaceutical arena. We categorized IMS study types into five groups that parallel pipeline progression from the earliest phases of discovery to late stages of preclinical development. We conclude the article with some perspectives on how we see MALDI IMS maintaining relevance and becoming further embedded as an essential tool in the constantly changing environment of the pharmaceutical industry.

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Recommended Guidelines for Developing, Qualifying, and Implementing Complex In Vitro Models (CIVMs) for Drug Discovery

Cited by 39 publications

References 89 publications

Microphysiological systems: What it takes for community adoption

Microphysiological systems: What it takes for community adoption

Organ-on-chip applications in drug discovery: an end user perspective

The emergence of imaging mass spectrometry in drug discovery and development: Making a difference by driving decision making

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