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CEHTRA - Consultancy for Environmental & Human Toxicology and Risk AssessmentCEHTRA assess the Safety of Pharmaceutical Substances
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Pharmaceuticals / Human Health

CEHTRA assess the Safety of Pharmaceutical Substances CEHTRA can assist you in the profiling of the safety of early candidates, the monitoring of studies and in dealing with Investigator Brochures, CTD Dossiers, Permitted Daily Exposure (PDE) monographs and with the Safety Qualification of impurities in drug substance/products.

Early candidate safety profiling

In early drug development, identifying predictable safety issues of pharmaceutical lead candidates is crucial for reducing safety-related attrition later in the process. Approximately 75% of all adverse drug reactions have been dose-dependent, which can be predicted on the basis of pharmacology profiling and safety evaluation studies. The safety hazards that most frequently impact drug development are related to liver, cardiac and target/off target effects. Because it is impossible to assess the risk of all the potential adverse drug reactions during the early drug discovery stage, a clear strategy must be in place to understand potential development limiting liabilities so that an appropriate risk management plan can be implemented early in drug development. Early knowledge of the toxicities will enable companies to build customized testing schemes to discover superior candidates for advancing in to development

CEHTRA has a team of experienced drug discovery and development scientists who can provide expert guidance on the following aspects of safety assessment during lead identification stage of drug discovery:

  • Computational prediction of possible chemical scaffold related safety issues
  • Prediction of potential target related safety issues based on target biology and published data
  • Provide an integrated safety assessment plan for lead selection

 Study placement and monitoring

CEHTRA has strong working relationship with several non-clinical CROs across the world. Our experience can assist the sponsors to ensure proper execution of the non-clinical study protocols and successful regulatory filing. We can assist sponsors in the following specific areas:

  • Develop study protocols that are compliant with international regulations
  • Identify the right place to conduct the non-clinical studies
  • Serve as the study monitors on behalf of the sponsor for the outsourced studies
  • Assist in data review and report preparation and finalization

Preparation of non-clinical sections for Investigator Brochures

The Investigator's Brochure (IB) is a comprehensive compilation of clinical and non-clinical data on the investigational product. The IB is a document of critical importance throughout the drug development process and is updated with new information as it becomes available. The purpose of the IB is to compile data relevant to studies of the investigational product in human subjects gathered during preclinical and other clinical trials to provide the investigator with information necessary for the management of study conduct and study subjects throughout a clinical trial. An IB facilitates understanding of the rationale for, and their compliance with, many key features of the protocol, such as: dose of the study drug, dose frequency and dosing interval, methods of administration and safety monitoring procedures.

CEHTRA team has experience in preparing the IBs for multiple indications in compliance with ICH guidance (ICH E6 (R1): Guideline for Good Clinical Practice June 2015. CEHTRA can assist sponsors:

  • Review of non-clinical pharmacology, pharmacokinetic (PK) and toxicology study reports 
  • Author no-clinical pharmacology, PK and Toxicology sections of the IB
  • Prepare integrated assessment of pharmacology, PK and toxicology findings to derive specific study conclusions and guide human starting dose selection and escalation plan.

Preparation of CTD Dossiers for CTA/NDA (Modules 2 & 4)

CEHTRA have the expertise to prepare nonclinical sections of the Common Technical Document according to the M4S Guideline. We can also provide support to review the individual study reports for accuracy, completeness and thus ensure high quality dossier for regulatory submission.

Preparation of Permitted Daily Exposure (PDE) monographs for active pharmaceutical ingredients

The European Medicines Agency’s (EMA) new good manufacturing practice (GMP) requirements is set forth in Chapters 3 and 5 in the EU GMP Guideline and is effective from March 1st, 2015. In Chapter 3, one of the important change is the requirement for the prevention of cross-contamination by appropriate design and operation of manufacturing facilities. Additionally, each medicinal product will require a toxicological evaluation based on scientific data, in order to appropriately determine the hazard. The purpose of this toxicological evaluation is to determine the health-based permissible daily exposure (PDE) limit for each pharmaceutical product.

CEHTRA scientific team has significant experience to prepare regulatory complaint PDE monographs on various categories of pharmaceuticals in a cost effective and timely manner.

Safety Qualification of impurities in drug substance/products

Impurities, degradants, residual solvents, and leachable can become part of a drug product or substance in multiple ways. But the extent of their presence is strictly governed by a series of International Conference on Harmonization (ICH), U.S. Food and Drug Administration (FDA), and European Medicines Agency (EMA) guidelines.

CEHTRA has the expertise to provide a comprehensive impurity safety assessment and qualification assistance. CEHTRA uses a combination of methods that include full literature searches (for known molecules), QSAR (Quantitative Structure-Activity Relationship) evaluations (for novel compounds), develop and execute product specific impurity qualification protocols, assist in study execution by CROs and finally safety assessment and compilation for regulatory submissions that can satisfy world-wide regulatory agencies.

CEHTRA can provide Computational Toxicology Assessment of the impurities in compliance with ICH M7 guidance (March 2015). We use Derek Nexus (expert rule-based) and Sarah Nexus (statistical-based) combined predictions to assess the mutagenic potential of Pharmaceutical Impurities.

 
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®Cehtra • July 2017