Carcinogenicity assessment

Lhasa combines in silico models, in vitro data, existing animal studies, and expert knowledge within an adverse outcome pathway (AOP) framework to predict carcinogenicity using a weight-of-evidence (WoE) approach, without relying on additional animal studies. Predictions and experimental findings are mapped onto a comprehensive network of carcinogenicity AOPs in Kaptis, supporting transparent, human-relevant assessments that can help replace or reduce traditional long-term rodent carcinogenicity studies.

Lhasa tools support carcinogenicity risk assessment across the full decision-making process, for both main ingredients and impurities, by:

• Characterising hazard and potency for relevant modes of action, such as genotoxicity, hormonal or immune-mediated mechanisms, and secondary pharmacology, using a combination of in silico predictions, curated experimental data, and public sources.
• Evaluating human relevance of findings and translating from experimental systems using adverse outcome pathways (AOPs) and mode-of-action analysis.
• Supporting exposure and dose-response considerations, where data are available (e.g., TD50 values in LCDB Plus), to inform human risk, particularly in high-exposure scenarios.
• Highlighting data gaps and suggesting targeted follow-up studies to refine the risk assessment.

Together, these capabilities provide a robust, transparent basis for human-relevant carcinogenicity risk assessment and informed regulatory decision-making, whether evaluating main ingredients with high exposure potential or impurities with genotoxic concerns under frameworks such as ICH M7.

Kaptis is an in silico decision-support solution by Lhasa for carcinogenicity weight-of-evidence (WoE) assessment. It helps scientists determine the carcinogenic potential of a compound by capturing and connecting data from diverse sources (e.g. primary and secondary pharmacology, genotoxicity, hormonal perturbation, immune modulation, and repeat-dose toxicity) within a curated network of carcinogenicity adverse outcome pathways (AOPs). By organising evidence around biological mechanisms and human relevance, and embedding best-practice assessment principles, Kaptis supports transparent, human-relevant evaluations of cancer risk, including clear confidence in conclusions and suggested next steps. For example, Kaptis can facilitate more informed WoE assessments under ICH S1B(R1).

Kaptis is designed to operationalise the weight-of-evidence framework described in ICH S1B(R1). It:

• Aligns data with the key ICH S1B(R1) factors, including primary and secondary pharmacology, genotoxicity, hormonal perturbation, immune modulation, repeat-dose toxicity, and histopathology.
• Organises evidence within an adverse outcome pathway (AOP) network to clarify biological plausibility and human relevance, while helping identify data gaps, links between factors, consistency across datasets, and hypotheses for further investigation.
• Provides a transparent structure for documenting scientific reasoning, including uncertainty, confidence in conclusions, and proposed next steps.

This structured approach helps justify the waiving or tailoring of 2-year rat carcinogenicity studies and supports clear, evidence-based communication between sponsors and regulators.

Lhasa tools such as Kaptis, Derek Nexus and Sarah Nexus enable an integrated, mechanism‑based approach to carcinogenicity. They:

1. 1. Aggregate and structure data from in vitro, in vivo and in silico sources – Derek Nexus, Sarah Nexus, Vitic, LCDB Plus.
   2. Contextualise those data on carcinogenicity AOP networks – Kaptis.
   3. Help identify modes of action, key events and human relevance – Kaptis.
   4. Define confidence in assessments and support confident decision‑making – Kaptis.

This supports robust, transparent and reproducible weight‑of‑evidence (WoE) assessments that align with ICH S1B(R1) expectations and make better use of non‑animal methods.

Using the Lhasa in silico suite for carcinogenicity assessment, users can generate well‑structured, narrative reports suitable for inclusion in ICH S1B(R1) carcinogenicity submissions and more.

Where needed, Consult Lhasa can prepare complete submission‑ready dossiers and support interpretation with expert consultation.

Manual carcinogenicity assessments require searching, extracting, and reconciling large volumes of heterogeneous data. Lhasa tools streamline this process by:

• Using structured workflows to search for and collate relevant data from both public and internal sources.
• Providing in silico predictions to complement experimental data and help prioritise or target further testing efficiently.
• Structuring evidence in Kaptis around adverse outcome pathways (AOPs), enabling coherent, mechanism-based narratives while helping identify data gaps, links between evidence streams, and inconsistencies.

This approach supports faster assessments, clearer scientific rationales, and more consistent, auditable decisions compared with purely manual approaches. It can also help facilitate greater alignment between sponsors and regulators, reducing the risk of unexpected challenges during regulatory review.