Zeneth

Zeneth is an in silico software solution developed by Lhasa Limited, designed to identify forced degradation pathways of organic compounds and predict likely degradation products of drug substances and formulated drug products. It is intended for pharmaceutical scientists and formulation teams involved in drug development, stability assessment, and regulatory submission, helping them to characterise degradant structures quickly and make informed decisions throughout the development workflow.

Identification and control of degradants in active pharmaceutical ingredients (APIs) and drug products is a critical aspect of chemical safety assessment. Mutagenic impurities and degradation products can complicate formulation, extend development timelines, and impact shelf life. Zeneth addresses these challenges by providing comprehensive knowledge of degradation pathways and supporting compliance with key regulatory guidelines including ICH M7, ICH Q3B, and RDC 964.

Core Capabilities

• Identify and assess degradants: Zeneth uses its comprehensive knowledge of degradation pathways to swiftly predict likely degradation products of drug compounds. Drug-excipient interactions can also be assessed to understand potential stability issues in the final formulated product.
• Enable informed decision making: Zeneth can be used in exploratory formulation departments to identify potential degradation problems at an early stage in the drug development workflow. This early understanding aids future decisions around experimental requirements and excipient selection.
• Manage regulatory submission: After processing a drug compound through Zeneth, a range of filters can be applied to produce a results tree that can be compared to experimental findings. The customisable report feature allows users to create reports suitable for regulatory submission.

Regulatory Alignment

• ICH M7: Under ICH M7, potential degradation products likely to be present in the final drug product must be evaluated for mutagenic potential. Zeneth's comprehensive knowledge of degradation pathways ensures structure elucidation of experimentally observed degradants. Its predictions are consistent with the conditions required to be tested under ICH guidelines: thermolytic, hydrolytic, oxidative, and photolytic.
• ICH Q3B: Zeneth supports requirements under ICH Q3B (Impurities in New Drug Products) by predicting forced degradation pathways of organic compounds under various environmental conditions, and by supporting the identification and assessment of potential degradants whilst considering the effect of excipients and impurities.
• RDC 964: Zeneth supports many requirements under the RDC 964 guideline, which establishes general requirements for forced degradation studies on medicines containing synthetic and semi-synthetic APIs. Zeneth can provide a potential degradation profile of the drug, consider the effect of different excipients and impurities in the final formulated product, help identify chemical structures of detected degradants, and demonstrate chromatographic separation of degradation products to support regulatory submission.

Workflow Integration

• Zeneth is applicable across early-stage exploratory formulation through to late-stage regulatory submission activities.
• Predictions consider reaction conditions aligned with ICH-mandated forced degradation study parameters.
• The software supports structure elucidation of experimentally observed degradants, enabling comparison of predicted and observed results.
• Customisable reporting functionality allows users to generate documentation ready for inclusion in regulatory dossiers.

Zeneth is part of Lhasa Limited's broader suite of in silico tools for impurity and degradant control, which also includes Mirabilis for mutagenic impurity purge factor calculations and Vitic Q3D for elemental impurity assessments. Together, these tools support pharmaceutical organisations in meeting the increasing regulatory demands for impurity reporting and control across the drug development lifecycle.