Regulators are increasingly signalling that new approach methodologies (NAMs) are not just acceptable, but actively encouraged as a route to more predictive, ethical and efficient drug development. For many organisations, this shift translates directly into competitive advantage: earlier and more reliable decision making, leaner and less animal intensive non-clinical packages and the potential to shorten development timelines and reduce late stage failures. Download poster, ‘Action Potential Waveform Analysis in Human iPSC-Cardiomyocytes Enables Mechanistic Assessment of Multichannel Cardiac Effects’, which highlights how NAM-based approaches can deliver this type of efficient, mechanistic insight in practice.
The key question is no longer whether to adopt NAMs, but how to implement them with confidence while continuing to meet evolving regulatory expectations and protecting programme value.
Recent FDA communications and guidance emphasise the role of NAMs such as computational models, human relevant in vitro systems and organoid technologies in reducing reliance on animal testing while maintaining, or even improving, the quality of safety and efficacy data. This direction is reinforced by initiatives including the FDA’s roadmap to reducing animal testing in preclinical safety studies and clarification of NAM use in recent US legislation.
The FDA‘s increasing acceptance of alternatives to animal testing for monoclonal antibodies and other selected drug classes marks an important milestone. By explicitly recognising NAMs, including AI enabled in silico models and advanced human cell based systems, as potentially viable alternatives in Investigational New Drug (IND) packages, regulators are signalling that sponsors who invest in validated, human relevant models can benefit from more streamlined, future proof development strategies.
As this regulatory shift accelerates, many drug developers are moving from debating whether to use NAMs to addressing practical questions around implementation. Organisations must determine where NAMs can feasibly replace, reduce or refine existing animal studies. They must also understand how to build weight-of-evidence packages that integrate NAM data with pharmacology and other non-clinical findings and how to document validation and translational relevance so that regulators can confidently interpret the results.
Regulatory guidance consistently emphasises early engagement with agencies, incremental integration of NAMs alongside legacy approaches and careful attention to assay qualification and context of use. In this environment, robust human based assays that map clearly onto clinically relevant safety endpoints are particularly valuable.
Metrion’s cardiomyocyte assay shows how a well designed, human relevant NAM can support the new regulatory paradigm for cardiac safety assessment. The assay uses human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with high-frequency optical recording to capture human cardiac electrophysiology in a scalable, quantitative format, enabling detailed analysis of action potential characteristics and rhythm.
In a 96-well format using a voltage-sensitive fluorescent dye and high speed recording on the Lumencor VOLTA platform, the assay measures key cardiac endpoints such as action potential duration (for example APD90), rise time, beat rate and parameters linked to QRS and QTc interval liabilities. These end points are mechanistically linked to biomarkers traditionally assessed using in vivo animal telemetry or ex vivo heart preparations, but here they are produced in a human cellular background with improved scalability and reproducibility, positioning the assay as a central element in a NAM based cardiac safety strategy.
To be adopted with confidence, NAMs must align with recognised regulatory frameworks such as ICH E14/S7B and the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. The hiPSC-CM platform can be used to assess a compound’s propensity to prolong repolarisation-associated markers linked to QTc liability and to support assessment of exposure margins associated with a 10 ms QTc increase, a threshold recognised by regulators as a signal for clinical concern.
Because hiPSC-CMs capture integrated electrophysiological responses, they can reveal proarrhythmic risk arising from both direct ion channel modulation and more complex, indirect mechanisms that single ion channel assays might miss. This enables mechanistic assessment of depolarisation, repolarisation and rhythm-related perturbations within a human cellular background. While hiPSC-CMs do not fully recapitulate the electrophysiological maturity of adult ventricular cardiomyocytes, they provide a translationally relevant platform that can complement established in vitro and in vivo cardiac safety approaches within a defined context of use. This broader physiological coverage may be especially relevant for biologics such as monoclonal antibodies, which may not follow classical small-molecule toxicity patterns but can still affect cardiac electrophysiology through downstream pathways.
Regulators have made it clear that successful NAM adoption will depend on careful validation, transparent documentation and a strong scientific rationale for each assay’s context of use. Metrion’s cardiomyocyte assay supports these expectations by offering quantitative, human derived data, standardised 96 well throughput for reproducibility and the ability to run longer term, serum free exposures to investigate delayed or cumulative cardiotoxicity.
Despite strong regulatory momentum, many organisations remain cautious about moving away from entrenched animal models. Here, Metrion’s cardiomyocyte assay provides a pragmatic bridge: it can be introduced alongside existing studies to build internal confidence, demonstrate predictive performance and progressively replace or refine legacy assays as evidence accumulates. In parallel, it supports the principles of Replacement, Reduction and Refinement and aligns with ethical and societal expectations to reduce animal use while enabling earlier detection and prioritisation of safer candidates.
Selecting the right partner is critical when introducing NAMs into your development pipeline. At Metrion we:
This combination of depth, precision and applied expertise is what distinguishes Metrion as a trusted partner for organisations looking to implement NAMs confidently and effectively.
Regulators are increasingly signalling that new approach methodologies (NAMs) are not just acceptable, but actively encouraged as a route to more predictive, ethical and efficient drug development. For many organisations, this shift translates directly into competitive advantage: earlier and more reliable decision making, leaner and less animal intensive non-clinical packages and the potential to shorten development timelines and reduce late stage failures. Download poster, ‘Action Potential Waveform Analysis in Human iPSC-Cardiomyocytes Enables Mechanistic Assessment of Multichannel Cardiac Effects’, which highlights how NAM-based approaches can deliver this type of efficient, mechanistic insight in practice.
The key question is no longer whether to adopt NAMs, but how to implement them with confidence while continuing to meet evolving regulatory expectations and protecting programme value.
Recent FDA communications and guidance emphasise the role of NAMs such as computational models, human relevant in vitro systems and organoid technologies in reducing reliance on animal testing while maintaining, or even improving, the quality of safety and efficacy data. This direction is reinforced by initiatives including the FDA’s roadmap to reducing animal testing in preclinical safety studies and clarification of NAM use in recent US legislation.
The FDA‘s increasing acceptance of alternatives to animal testing for monoclonal antibodies and other selected drug classes marks an important milestone. By explicitly recognising NAMs, including AI enabled in silico models and advanced human cell based systems, as potentially viable alternatives in Investigational New Drug (IND) packages, regulators are signalling that sponsors who invest in validated, human relevant models can benefit from more streamlined, future proof development strategies.
As this regulatory shift accelerates, many drug developers are moving from debating whether to use NAMs to addressing practical questions around implementation. Organisations must determine where NAMs can feasibly replace, reduce or refine existing animal studies. They must also understand how to build weight-of-evidence packages that integrate NAM data with pharmacology and other non-clinical findings and how to document validation and translational relevance so that regulators can confidently interpret the results.
Regulatory guidance consistently emphasises early engagement with agencies, incremental integration of NAMs alongside legacy approaches and careful attention to assay qualification and context of use. In this environment, robust human based assays that map clearly onto clinically relevant safety endpoints are particularly valuable.
Metrion’s cardiomyocyte assay shows how a well designed, human relevant NAM can support the new regulatory paradigm for cardiac safety assessment. The assay uses human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with high-frequency optical recording to capture human cardiac electrophysiology in a scalable, quantitative format, enabling detailed analysis of action potential characteristics and rhythm.
In a 96-well format using a voltage-sensitive fluorescent dye and high speed recording on the Lumencor VOLTA platform, the assay measures key cardiac endpoints such as action potential duration (for example APD90), rise time, beat rate and parameters linked to QRS and QTc interval liabilities. These end points are mechanistically linked to biomarkers traditionally assessed using in vivo animal telemetry or ex vivo heart preparations, but here they are produced in a human cellular background with improved scalability and reproducibility, positioning the assay as a central element in a NAM based cardiac safety strategy.
To be adopted with confidence, NAMs must align with recognised regulatory frameworks such as ICH E14/S7B and the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. The hiPSC-CM platform can be used to assess a compound’s propensity to prolong repolarisation-associated markers linked to QTc liability and to support assessment of exposure margins associated with a 10 ms QTc increase, a threshold recognised by regulators as a signal for clinical concern.
Because hiPSC-CMs capture integrated electrophysiological responses, they can reveal proarrhythmic risk arising from both direct ion channel modulation and more complex, indirect mechanisms that single ion channel assays might miss. This enables mechanistic assessment of depolarisation, repolarisation and rhythm-related perturbations within a human cellular background. While hiPSC-CMs do not fully recapitulate the electrophysiological maturity of adult ventricular cardiomyocytes, they provide a translationally relevant platform that can complement established in vitro and in vivo cardiac safety approaches within a defined context of use. This broader physiological coverage may be especially relevant for biologics such as monoclonal antibodies, which may not follow classical small-molecule toxicity patterns but can still affect cardiac electrophysiology through downstream pathways.
Regulators have made it clear that successful NAM adoption will depend on careful validation, transparent documentation and a strong scientific rationale for each assay’s context of use. Metrion’s cardiomyocyte assay supports these expectations by offering quantitative, human derived data, standardised 96 well throughput for reproducibility and the ability to run longer term, serum free exposures to investigate delayed or cumulative cardiotoxicity.
Despite strong regulatory momentum, many organisations remain cautious about moving away from entrenched animal models. Here, Metrion’s cardiomyocyte assay provides a pragmatic bridge: it can be introduced alongside existing studies to build internal confidence, demonstrate predictive performance and progressively replace or refine legacy assays as evidence accumulates. In parallel, it supports the principles of Replacement, Reduction and Refinement and aligns with ethical and societal expectations to reduce animal use while enabling earlier detection and prioritisation of safer candidates.
Selecting the right partner is critical when introducing NAMs into your development pipeline. At Metrion we:
This combination of depth, precision and applied expertise is what distinguishes Metrion as a trusted partner for organisations looking to implement NAMs confidently and effectively.
Regulators are increasingly signalling that new approach methodologies (NAMs) are not just acceptable, but actively encouraged as a route to more predictive, ethical and efficient drug development. For many organisations, this shift translates directly into competitive advantage: earlier and more reliable decision making, leaner and less animal intensive non-clinical packages and the potential to shorten development timelines and reduce late stage failures. Download poster, ‘Action Potential Waveform Analysis in Human iPSC-Cardiomyocytes Enables Mechanistic Assessment of Multichannel Cardiac Effects’, which highlights how NAM-based approaches can deliver this type of efficient, mechanistic insight in practice.
The key question is no longer whether to adopt NAMs, but how to implement them with confidence while continuing to meet evolving regulatory expectations and protecting programme value.
Recent FDA communications and guidance emphasise the role of NAMs such as computational models, human relevant in vitro systems and organoid technologies in reducing reliance on animal testing while maintaining, or even improving, the quality of safety and efficacy data. This direction is reinforced by initiatives including the FDA’s roadmap to reducing animal testing in preclinical safety studies and clarification of NAM use in recent US legislation.
The FDA‘s increasing acceptance of alternatives to animal testing for monoclonal antibodies and other selected drug classes marks an important milestone. By explicitly recognising NAMs, including AI enabled in silico models and advanced human cell based systems, as potentially viable alternatives in Investigational New Drug (IND) packages, regulators are signalling that sponsors who invest in validated, human relevant models can benefit from more streamlined, future proof development strategies.
As this regulatory shift accelerates, many drug developers are moving from debating whether to use NAMs to addressing practical questions around implementation. Organisations must determine where NAMs can feasibly replace, reduce or refine existing animal studies. They must also understand how to build weight-of-evidence packages that integrate NAM data with pharmacology and other non-clinical findings and how to document validation and translational relevance so that regulators can confidently interpret the results.
Regulatory guidance consistently emphasises early engagement with agencies, incremental integration of NAMs alongside legacy approaches and careful attention to assay qualification and context of use. In this environment, robust human based assays that map clearly onto clinically relevant safety endpoints are particularly valuable.
Metrion’s cardiomyocyte assay shows how a well designed, human relevant NAM can support the new regulatory paradigm for cardiac safety assessment. The assay uses human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with high-frequency optical recording to capture human cardiac electrophysiology in a scalable, quantitative format, enabling detailed analysis of action potential characteristics and rhythm.
In a 96-well format using a voltage-sensitive fluorescent dye and high speed recording on the Lumencor VOLTA platform, the assay measures key cardiac endpoints such as action potential duration (for example APD90), rise time, beat rate and parameters linked to QRS and QTc interval liabilities. These end points are mechanistically linked to biomarkers traditionally assessed using in vivo animal telemetry or ex vivo heart preparations, but here they are produced in a human cellular background with improved scalability and reproducibility, positioning the assay as a central element in a NAM based cardiac safety strategy.
To be adopted with confidence, NAMs must align with recognised regulatory frameworks such as ICH E14/S7B and the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. The hiPSC-CM platform can be used to assess a compound’s propensity to prolong repolarisation-associated markers linked to QTc liability and to support assessment of exposure margins associated with a 10 ms QTc increase, a threshold recognised by regulators as a signal for clinical concern.
Because hiPSC-CMs capture integrated electrophysiological responses, they can reveal proarrhythmic risk arising from both direct ion channel modulation and more complex, indirect mechanisms that single ion channel assays might miss. This enables mechanistic assessment of depolarisation, repolarisation and rhythm-related perturbations within a human cellular background. While hiPSC-CMs do not fully recapitulate the electrophysiological maturity of adult ventricular cardiomyocytes, they provide a translationally relevant platform that can complement established in vitro and in vivo cardiac safety approaches within a defined context of use. This broader physiological coverage may be especially relevant for biologics such as monoclonal antibodies, which may not follow classical small-molecule toxicity patterns but can still affect cardiac electrophysiology through downstream pathways.
Regulators have made it clear that successful NAM adoption will depend on careful validation, transparent documentation and a strong scientific rationale for each assay’s context of use. Metrion’s cardiomyocyte assay supports these expectations by offering quantitative, human derived data, standardised 96 well throughput for reproducibility and the ability to run longer term, serum free exposures to investigate delayed or cumulative cardiotoxicity.
Despite strong regulatory momentum, many organisations remain cautious about moving away from entrenched animal models. Here, Metrion’s cardiomyocyte assay provides a pragmatic bridge: it can be introduced alongside existing studies to build internal confidence, demonstrate predictive performance and progressively replace or refine legacy assays as evidence accumulates. In parallel, it supports the principles of Replacement, Reduction and Refinement and aligns with ethical and societal expectations to reduce animal use while enabling earlier detection and prioritisation of safer candidates.
Selecting the right partner is critical when introducing NAMs into your development pipeline. At Metrion we:
This combination of depth, precision and applied expertise is what distinguishes Metrion as a trusted partner for organisations looking to implement NAMs confidently and effectively.