With the increasing emphasis on the 3Rs (Replacement, Reduction, & Refinement), read-across remains a central strategy for delivering scientifically robust, animal-free safety assessments.

To ensure we remain aligned with evolving regulatory expectations and methodological advances, we recently attended the Die Akademie Fresenius Online Conference, “Read-Across: Recent Developments & Regulatory Implications.”

The event brought together regulators, industry and academic experts, offering valuable insight into not just current practice – but the direction of travel.

Where the Regulatory Science is Moving

Presentations highlighted rapid advances in analogue and category formation, including:

• Grouping strategies based on shared structural, mechanistic, metabolic, or functional features.
• Chemical fingerprinting and hybrid similarity metrics integrating structural, physicochemical, and biological descriptors.
• Matched molecular pair (MMP) approaches.
• Integration of QSAR, omics, AOP and MoA information to strengthen biological plausibility.
• Metabolic similarity and metabolite driven read-across.
• Use of virtual control groups to support similarity arguments and reduce reliance on in vivo data.

There was also strong emphasis on:

• Harmonised workflows (including OECD Toolbox-based approaches and EFSA’s structured read-across framework).
• NAMs integration to reduce uncertainty.
• Cross-sector case studies covering industrial chemicals, plant protection products and pharmaceuticals.

• Regulatory updates from EFSA (2025 guidance), OECD (3rd edition grouping guidance) and ECHA (acceptance under REACH and CLP).

   

Clear Regulatory Signal for Read-Across

A consistent message across agencies was unmistakable:

Read-across is accepted – but only when uncertainty is clearly characterised, transparently justified, and supported by multiple independent lines of evidence.

The era of narrative justification is closing. The era of structured, reproducible, mechanistically coherent read-across has arrived.

What This Means for Industry

For companies relying on read-across to:

• Fill data gaps under REACH or UK REACH.
• Support classification and labelling decisions.
• Strengthen plant protection or biocide submissions.

The expectations are rising.

Regulators increasingly expect:

• Explicit uncertainty mapping.
• Endpoint-specific biological plausibility.
• Integration of NAMs data.
• Transparent workflows capable of independent scrutiny.

Read-across remains a powerful tool – but it isn't just a cost-saving shortcut. It’s a strategy that must be designed with regulatory defensibility in mind from the outset.

Our Perspective on Read-Across

The conference reinforced something we see daily in practice:

Successful read-across depends less on similarity alone, and more on how coherently the scientific narrative is structured around mechanistic understanding and uncertainty management.

Staying at the forefront of methodological and regulatory developments is not optional – it is essential for ensuring assessments remain compliant, defensible, and future-proof.

As regulatory reliance on NAMs continues to grow, the companies that invest early in structured, transparent read-across strategies will be best positioned to avoid delays, minimise challenges, and secure smoother dossier progression.

Regulators are no longer asking whether read-across is possible – they are asking whether it is defensible.

If your business depends on read-across to support registration, classification or authorisation decisions, now is the time to ensure your approach aligns with where regulatory science is heading.

If you’re preparing a submission or reassessing an existing read-across justification, call or email and we’ll help ensure a defensible read-across strategy.