Scientifically Robust. Expert Software. Improving efficiency and aiding regulatory submission for over 30 years

Transcription

1 Scientifically Robust Expert Software Improving efficiency and aiding regulatory submission for over 30 years

2 Innovation through collaboration Lhasa Limited is a not-for-profit organisation and registered educational charity that provides decision support tools for use in the investigation of toxicology, metabolism and degradation. Established in 1983, Lhasa continues to draw on over 30 years of experience to create user-friendly, state-of-the-art in silico prediction and database systems. Representing Lhasa's Members

3 Becoming a member Lhasa Products Becoming a member of Lhasa Limited presents a valuable opportunity to participate in the development of computer-aided reasoning and information systems for the advancement of chemistry and the life sciences. Lhasa s members include the world s top 20 pharmaceutical organisations, leading companies in the chemical and cosmetics industries, as well as many of their relevant regulatory bodies and academic institutions. Lhasa Limited is widely recognised for the high quality of its software and Lhasa s dedicated employees work proactively towards the discovery of improved solutions for problems and issues faced by its members. Through regular scientific and software updates, Lhasa continues to deliver accurate, transparent knowledge to its solutions, to make them more comprehensive, as well as easier and faster to use. Future Drive our Lhasa is owned and funded by its members and recognises that member needs must be the priority in order to be successful. As a member of Lhasa, your organisation has the opportunity to influence the development of our products and services. shared knowledge shared progress

4 Extensive Metabolism Knowledge Lhasa expert scientists implement Meteor biotransformations utilising public and proprietary data, ensuring vast coverage of biotransformations. Reduces Risk in R&D Save time and money by identifying reactive, potentially adduct-forming intermediates and quickly assessing their toxicity through Derek, Sarah or Vitic Nexus. Accurate Metabolite Ranking The methodologies in Meteor rank predicted metabolites by taking into account experimental data and the chemical environment of the site of metabolism. Greater Efficiency Eliminates the need to set up costly and time consuming analytical methods to measure impurities that are unlikely to be present in the final drug product. Using structure activity relationships and a dictionary of biotransformations, Meteor provides transparent Phase 1 and 2 metabolism predictions. An expert, knowledge-based system for the prediction of metabolic fate Industry-standardised software tool for the calculation of purge factors of potentially mutagenic impurities in a synthetic route Transparent Predictions Predictions are clearly represented and supported by a measure of confidence. This high level of transparency facilitates expert review. A statisticalbased system for the prediction of mutagenicity Using a unique machine-learning methodology, Sarah provides statistical-based predictions for mutagenicity. Sarah can be used as part of an ICH M7 workflow and predictions are accepted by regulators under the ICH M7 guideline. The preferred expert rulebased system for toxicity prediction. Winner of the Queen s Award for Enterprise: Innovation 2016 Confident Predictions Skin Sensitisation Predictions Using a Nearest Neighbour approach, EC3 values are predicted for compounds that fire a skin sensitisation alert. The Sarah model is built upon a large, high-quality dataset that has been curated by Lhasa experts. Derek can be used as part of an ICH M7 workflow and predictions are accepted by regulators under the ICH M7 guideline. The ICH M7 Guideline specifically allows for a control strategy that relies on an understanding of process controls in lieu of analytical testing. Transparent Predictions Provides expert commentary and detailed supporting information for calculated purge factors, enabling improved and justifiable decision making. Aiding Submission to Regulators Mirabilis provides a report which includes the purge calculation, scientific rationale and supporting evidence to aid in the submission to regulators. Rapidly find relevant supporting examples for your impurities by structure, substructure or similarity searching. A semi-automated approach, built on expert knowledge, Mirabilis improves the efficiency of purge analysis. A toxicity database and information management system The Vitic database contains expert curated, high-quality and peer reviewed toxicity data from both published and unpublished sources. The only actively maintained system for the prediction of degradation, Zeneth uses structure activity relationships to provide forced degradation predictions for query compounds. Using structure activity relationships created by Lhasa s scientific experts, Derek provides scientifically robust and transparent toxicity predictions for query compounds. An expert, knowledgebased system for the prediction of degradation pathways Variety of Endpoints Covered Derek predicts for various endpoints including carcinogenicity, mutagenicity, genotoxicity, teratogenicity, irritation and more. Reducing Risk in R&D Save time and money by identifying potentially toxic chemicals early, thereby reducing risk in research and development. Advanced Warning System Provides an instant understanding of what results might be expected when running stress tests. Transparent Predictions Current Toxicological Data Regular updates by Lhasa s dedicated expert data team ensures access to the latest toxicology data. Meeting Regulatory Requirements Analysis of actual and potential impurities by conducting database and literature searches across carcinogenicity and mutagenicity data. Meeting Regulatory Requirements Numerous guidelines (including RDC 53) stipulate the need to understand the consequences of degradation, and focus on impurities and stability testing. Predictions are clearly represented and contain detailed supporting evidence associated with the degradation pathway.

5 Production Intermediates A database for sharing Ames mutagenicity results of production intermediates. Excipients A database for the sharing of excipient vehicle toxicity data. MIP DILI Aromatic Amines A database to improve the understanding and predictability of primary aromatic amines. A consortium with the objective of developing novel modelling approaches and enhancing shared understanding of drug induced liver injury. Elemental Impurities A database to share analytical data on the levels of trace metals within batches of excipients used in the formulation of pharmaceutical drug products. ipie A database to support the environmental testing of pharmaceuticals. Committed to Collaboration The current Research Collaboration Agreement (RCA) is an extension to previous agreements, and will last until November Lhasa Limited works cooperatively with FDA/CDER (US Food and Drug Administration/Center for Drug Evaluation and Research) to develop prediction software that is consistent with FDA/CDER regulatory activities. Lhasa contributes software and scientific expertise and the FDA/CDER provides toxicological and human adverse effect information and scientific expertise. Lhasa Limited members benefit from the advances and improvements to the Lhasa software as a result of the RCA. FDA RCA An agreement to use publicly releasable FDA data to construct, improve and validate Lhasa s software for toxicity, metabolism, chemical degradation and impurity purge factor prediction. Lhasa Limited believes in Shared Knowledge, Shared Progress. Its not-forprofit, member driven and honest broker status is designed to facilitate collaborative working and confidential data sharing between organisations. Lhasa runs collaborative projects with industry, academia and regulatory bodies to continually advance science for the benefit of its members, the wider scientific community and the public. Typically delivering secure systems for the management of proprietary data, Lhasa also provides scientific expertise to interpret the data for computer modelling.

6 A free, online database for the retrieval of relevant carcinogenicity data. Founded on the Carcinogenic Potency Database (CPDB), Lhasa has used its knowledge in the field of user experience to add new functionality, building on the excellent work of the team behind the original database. Structure searchable The ability to easily build complex queries around both structures and associated data, which allows for the retrieval of specific information, aiding decision support and improving productivity. Lhasa Freely available online There is no need to install the database, it can be easily accessed online at any time. Carcinogenicity Database Attractive user interface The redesigned user interface is clear, intuitive and easy to use.

7 Working together for a better future When asked why people choose to work with Lhasa Limited, the common responses are: Software is easy to use and well supported. Transparency of Lhasa systems allows trust and confidence in the science presented. Over 30 years of experience in developing state-of-the-art in silico prediction and database systems. All science is developed in-house, providing the opportunity to discuss directly with Lhasa expert scientists. Lhasa collaborates with the wider scientific community to advance the understanding and performance of in silico technology. Feedback from members is encouraged and listened to, and drives the future development of Lhasa products. shared knowledge shared progress Lhasa Limited Registered Office Granary Wharf House, 2 Canal Wharf, Leeds LS11 5PS Registered Charity (290866) Reference 01/ (0) info@lhasalimited.org ISO 9001: CERTIFIED