LCDB Plus

LCDB Plus is a decision support tool developed by Lhasa Limited for carcinogenicity risk assessment. It features an expanded TD₅₀ dataset compared to its predecessor, enabling scientists to identify and evaluate the reliability of existing carcinogenicity data for a given compound, or to calculate new TD₅₀ values for proprietary compounds. LCDB Plus is designed for use within broader in silico carcinogenicity assessment workflows, supporting regulatory submissions and acceptable intake (AI) limit determinations across the life sciences industry.

LCDB Plus sits within Lhasa's wider suite of carcinogenicity assessment tools — alongside Vitic, Derek Nexus, and Kaptis — which together support a flexible, evidence-based approach to carcinogenicity safety assessment. Each tool can be used independently or in combination, depending on the scientific question, regulatory context, and available data.

Key Features of LCDB Plus

• Intelligent searching and transparent data quality: LCDB Plus is presented within a user-friendly, standardised interface that facilitates structure, substructure, and similarity searches. TD₅₀ values are presented alongside an enhanced Lhasa Letter Graded Reliability Scoring system to help users assess the quality of individual studies.
• TD₅₀ calculation for proprietary compounds: The tool provides a transparent methodology for calculating TD₅₀ values from experimental data, enabling bespoke TD₅₀ calculations for proprietary compounds while remaining consistent with original Carcinogenic Potency Database (CPDB) values established by Lois Gold and her team.
• Expanded carcinogenicity data coverage: LCDB Plus aggregates 127% more available carcinogenicity data values compared to the original LCDB, supporting more informed determinations of acceptable intake (AI) limits and carcinogenic potency assessments.
• ICH M7 alignment: The tool offers validated data and methodology for efficient ICH M7 assessment of Class 1 impurities, with a regulatory-aligned approach to TD₅₀ calculation.
• Access to maintained public carcinogenicity data: The original Lhasa Carcinogenicity Database (LCDB), founded in 2016, remains freely accessible and serves as a significant source of long-term carcinogenicity studies for academics and researchers.

Recommended Carcinogenicity Assessment Workflow

1. Define the substance and assessment context: Access curated in vivo and in vitro carcinogenicity data via LCDB Plus and Vitic, bringing together regulatory studies, legacy datasets, and expert-reviewed evidence to inform early risk understanding.
2. Predict carcinogenic potential and interpret mechanistic evidence: Identify structural alerts associated with carcinogenic mechanisms using Derek Nexus, and contextualise findings using mechanistic knowledge and adverse outcome pathways (AOPs) with Kaptis to connect molecular events with potential carcinogenic outcomes.
3. Integrate all evidence streams: Bring together experimental data, in silico predictions, and mechanistic insight using Kaptis to assess relevance, uncertainty, and confidence in the overall evidence base. Lhasa tools support — rather than replace — expert scientific judgement, enabling transparent and auditable assessments.
4. Support regulatory decision-making: Derive an overall carcinogenicity position with clearly defined confidence levels, documented uncertainties, and recommended next steps. Generate transparent, traceable reports to support weight-of-evidence submissions and regulatory discussions, including those aligned with ICH S1B(R1).

Regulatory Alignment

• ICH S1 & S1B(R1): Guidance on when and how to conduct carcinogenicity studies for pharmaceuticals, including weight-of-evidence frameworks for waiving or tailoring 2-year rat carcinogenicity studies.
• ICH S2: Guideline for genotoxicity testing and interpretation of results to support pharmaceutical safety evaluation.
• ICH S8: Guidance on assessing immunotoxicity during pharmaceutical development.
• ICH M7: Framework for assessment of mutagenic impurities, including Class 1 impurities where TD₅₀ data from LCDB Plus is directly applicable.
• REACH (EC) 1907/2006: European regulation designed to protect human health and the environment from risks posed by chemical substances.

LCDB Plus is part of Lhasa Limited's integrated in silico platform for carcinogenicity assessment. It can be used as a standalone tool or in combination with Vitic, Derek Nexus, and Kaptis to support comprehensive, mechanism-based, and regulatory-aligned carcinogenicity risk assessments. The platform is designed to reduce reliance on long-term animal studies by enabling robust weight-of-evidence approaches grounded in curated data, structural knowledge, and adverse outcome pathway frameworks.