Toxicology Evaluation/Safety Assessment

Services – Based on decades of experience and success

  • Evaluation of both known and novel compounds
  • Screening for developmental candidates (“Fail Early, Fail Economically” model)
  • Calculation of safe and allowable levels and qualification of process impurities, residual solvents, degradants, and excipients
  • Design of further safety testing based on known or predicted toxicology
  • Identification of compounds of regulatory concern
  • Assessment of the potential hazard of batch-to-batch or scale-up changes in drug composition
  • Estimation of the risk from leachables and extractables
  • Answering regulatory questions and concerns for both active and inactive compounds
  • Pharmaceutical active ingredient occupational / manufacturing hazard categorization (OELs/HHAs)
  • Impurities qualification for pesticides as per FAO/WHO (international)
  • Preclinical study design
  • Assessment of changes to manufacturing process
  • Design and evaluation of stability studies
  • Recommendation of preclinical and analytical CROs (global experience and current status)
  • More than 1,500 successful evaluations (view List of Compounds Assessed)

Information Sources

Derek (Lhasa, Ltd.)

  • Assessment of risk levels in both humans and animals using QSAR methods
  • Accepted as a predictive model by the FDA
  • Prediction of multiple toxicity endpoints: carcinogenicity, chromosome damage, genotoxicity, hepatotoxicity, HERG channel inhibition, irritation, mutagenicity, ocular toxicity, reproductive toxicity, respiratory sensitization, skin sensitization, thyroid toxicity, and other miscellaneous or custom endpoints
  • Estimation of safety testing outcomes (e.g. Ames, CHO, etc.)
  • High-throughput screening for all assessed endpoints
  • Meteor (Lhasa, Ltd.)
  • Predicted metabolites for drugs, impurities, degradants, or any other compound
  • Estimation of metabolic pathways and their likelihood
  • Recursive evaluation for estimation of full metabolic tree

STN

  • STN is a multiple-database search service from CAS, a division of the American Chemical Society
  • Includes RTECS, HSDB, TOXCENTER, AGRICOLA, BIOSIS, BIOTECHNO, DDFB, DDFU, DISSABS, DRUGB, DRUGU, EMBAL, EMBASE, ESBIOBASE, HEALSAFE, IMSDRUGNEWS, LIFESCHI, MEDLINE, MSDS-CCOHS, MSDS-OHS, PHARMAML, SCISEARCH, TOXCENTER, VETB, and VETU.
  • Structure searches using multiple criteria

INSTEM (previously Leadscope Enterprise)

  • Full search of published FDA data on marketed drugs, excipients, food chemicals, including SBAs
  • Full search of multiple other FDA databases: FDA SAR Carcinogenicity Database, FDA SAR Genetox Database, FDA CDER 2011 Chronic/Subchronic Database, FDA CDER (Center for Drug Evaluation and Research) reviews, FDA CDER 2011 Genetox Database, FDA CDER 2011 Repro-Developmental Database, FDA CFSAN 2011 Acute Toxicity Database, FDA CFSAN 2011 Chronic/Subchronic Database, FDA CFSAN 2011 Genetox Database, and the FDA CFSAN 2011 Repro-Developmental Database
  • Toxicity data for more than 163,000 chemical structures (data primarily from RTECS)
  • Predictive toxicology using structural similarity searches

Leadscope Model Applier

  • Compound assessment using the QSAR models that the FDA uses for predictive toxicology (models under development may not be available)
  • Prediction of rodent carcinogenicity, non-human genetic toxicity, non-human reproductive toxicity, non-human developmental toxicity, non-human neurotoxicity, non-human miscellaneous toxicity endpoints, human adverse hepatobiliary effects, and human adverse urinary tract effects

Literature, Databases, and Experience

  • Gad Consulting Services initiated and continues to update the vehicles project to identify safe levels of vehicles and excipients for nonclinical studies. The source for pre-clinical CRO’s (new expanded edition in preparation)
  • GCS has experienced researchers with access to both public and fee-based toxicology, medical device, biomaterial, chemical, and biochemical databases
  • We have licensed copies of multiple chemical entity search programs and a vast library, including the Merck Index, USP, Martindale’s, PDR, an excipient database, and other similar products
  • Gad Consulting Services has internal databases of evaluated drugs, excipients, polymers, and biomaterials (view List of Compounds Assessed)
  • Extensive library access: NLM, universities, publishers, internet journals holdings, and an extensive internal library
  • Dr. Gad has authored or edited 53 books, 80 independent chapters, and more than 400 papers and abstracts and has more than 47 years of experience in compound risk and safety assessment