Toxicology Evaluation

Services

  • 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
  • Impurities qualification for pesticides as per FAO/WHO (international)
  • Preclinical study design
  • Assessment of changes to manufacturing process
  • Design of stability studies
  • Recommendation of preclinical and analytical CROs
  • More than 1500 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

Leadscope Enterprise

  • Full search of published FDA data on marketed drugs, excipients, and food chemicals
  • 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.
  • 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 mutiple chemical entity search programsand 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 and internet journals holdings.
  • In addition, Dr. Gad has authored or edited 44 books, 52 independent chapters and more than 400 papers and abstracts and has more than 34 years of experience in compound risk assessment.