Review on organs-on-chips for medicines safety assessment: A European regulatory perspective

Area of Science:

• Biomedical Engineering
• Toxicology
• Drug Development

Background:

• Organ-on-chip (OoC) technology has emerged as a promising alternative to traditional animal testing for drug safety assessment.
• The period between 2010-2020 saw substantial development in OoC models, mimicking various human organs and their interactions.
• Existing safety assessment methods face challenges in accurately predicting human responses to medicinal products.

Purpose of the Study:

• To review the development and applications of organ-on-chip technology in non-clinical drug safety assessment from 2010-2020.
• To identify the most frequently modeled organs, common safety endpoints, and tested compounds in OoC studies.
• To discuss regulatory challenges and opportunities for the acceptance of OoCs in medicinal product safety evaluation.

Main Methods:

• Comprehensive literature review of organ-on-chip studies published between 2010 and 2020.
• Analysis of organ systems modeled, types of OoCs, biological safety endpoints, and medicinal compounds tested.
• Examination of regulatory discussions and qualification considerations for OoC technologies.

Main Results:

• Liver, kidney, and heart were the most commonly mimicked organs in OoCs, with a focus on hepatotoxicity and metabolism-induced toxicity.
• The majority of reviewed OoCs utilized a single endpoint, often cell viability or death, for toxicity measurement.
• A wide range of biological safety endpoints and medicinal compounds have been tested across various OoC platforms.

Conclusions:

• Organ-on-chip technology shows significant potential for enhancing non-clinical drug safety assessment, particularly for liver-related toxicity.
• Standardization of endpoints and further validation are crucial for increasing regulatory acceptance of OoCs.
• Regulatory agencies, such as the European Medicines Agency, are actively exploring the integration of new approach methodologies (NAMs) like OoCs into regulatory submissions.