New approach methodologies applied where they belong — alongside traditional data, supporting toxicological judgement. Read-across, in silico prediction, in vitro evidence and exposure-led NGRA where the regulatory question warrants it.
NAMs integrated into weight-of-evidence reasoning.
NAMs are integrated into weight-of-evidence reasoning when their foundations are right. A read-across needs biological similarity, not just structural overlap. A (Q)SAR prediction needs to fall within the model's applicability domain. An NGRA case needs to be exposure-led, with a clear problem formulation. Our work is structured around getting these foundations right before the dossier or assessment is put together — with scientific judgement, applicability domain assessment and uncertainty handling central to every evaluation.
(Q)SAR, read-across, in vitro evidence, PBPK and NGRA — integrated into a coherent weight-of-evidence, not assembled in parallel.
From early NAM strategy through to file review and regulatory response — concrete points where NAM-derived evidence and NGRA reasoning support the assessment.
From NAM strategy to NGRA case — structured weight-of-evidence reasoning the regulator can read.
REACH registrants whose read-across has been challenged at substance evaluation or compliance check. Cosmetic ingredient teams building NGRA cases for novel ingredients without traditional in vivo data. Active substance dossiers where mode-of-action arguments need strengthening at peer review. We also support clients screening candidate libraries early in development, using NAM data to prioritise compounds before committing to in vivo studies.
A REACH registrant's read-across for repeated-dose toxicity had been challenged at compliance check. The initial hypothesis had been built primarily on in silico structural similarity, with limited biological evidence. ECHA flagged the read-across as insufficiently anchored in mechanistic data.
An in silico-based read-across ECHA had questioned in the draft decision, an OECD 422 combined repeated-dose and reproductive/developmental toxicity screening study identified as the alternative information requirement, and a 30-day comment period to submit substantive justification.
Outcome. Strengthened read-across submitted with bridging NAM data and absorption evidence demonstrating biological and kinetic similarity. The bridging strategy addressed the in vivo testing requirement for repeated-dose and DART endpoints (OECD 422). The targeted approach was applicable to other analogue groups in the client's portfolio facing similar challenges.
Most NAMs conversations start in one of these five places. If yours doesn't fit, send it through anyway — we'd rather hear the question than guess at it.
When the question is one a NAM can credibly answer, the file is anchored to mechanistic evidence, and the weight of evidence addresses the regulator's specific concern. NAM data alone are not enough — the file has to explain why the NAM evidence is fit for the regulatory question.
Biological similarity, not structural similarity alone. The case needs biological or mechanistic anchoring (AOP, mode of action, key events), in vitro data to confirm biological similarity where available, and kinetic and metabolic comparability between source and target substances. Structuring under the ECHA RAAF framework, with transparent uncertainty analysis, is what holds up under regulatory scrutiny.
Not yet. NGRA is a developing framework, and regulatory acceptance is limited. Cosmetics is most advanced — Article 18 drives NAM use, and a small number of NGRA case studies have been published — but formal SCCS acceptance of NGRA conclusions remains case-by-case. Outside cosmetics, NGRA application is largely conceptual. What is growing rapidly is the use of NAMs themselves — read-across, in vitro evidence, in silico predictions, mechanistic data — within traditional risk assessment and weight-of-evidence frameworks.
An Integrated Approach to Testing and Assessment — combining (Q)SAR, in vitro and existing in vivo data to answer a regulatory question with traceable reasoning. A Defined Approach has a fixed combination of methods and decision logic; an IATA is the broader framework that may include one or more Defined Approaches alongside expert judgement.
Yes. We assess whether the NAMs applied are fit for purpose, identify elements likely to face regulatory challenge, and strengthen applicability domain reasoning, mechanistic anchoring or weight-of-evidence integration as needed. Regulatory acceptance is shaped by the regulator's questions and the dossier as a whole — our role is to make sure the NAM-based file is technically robust and addresses the assessment elements that matter most.
Tell us the substance, the data gap and the deadline. We'll come back with an initial scope and a fit assessment.