Life Sciences / Pharmaceuticals
Toxicological Assessment of Pharmaceutical Impurities and Components
Pharmaceutical manufacturers face many challenges regarding safety of their ingredients and products. During the manufacture, transfer, packing, distribution, and administration of drug products, chemicals can leach into the product from external sources, including manufacturing components, drug delivery devices, and final container closures. Chemicals can alsobe introduced from other sources, creating a potential hazard to patients. Manufacturers are also challenged with establishing the safety of other non-active ingredients, including excipients and other impurities, as well as residual processing components at applied doses.
Extractables and leachables (E&L) testing of pharmaceutical products is critical to characterize the potential hazards of leachable impurities and establishing patient safety.
Our Experience
Intertox helps clients understand, describe, and document the potential toxicological hazards of drug product impurities and other components, to meet the requirements of regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for establishing drug product safety prior to achieving product approval. We have over 35 years of experience conducting toxicological assessments to support the pharmaceutical, medical device, and other industries, and are deeply familiar with regulatory processes and how to help our clients’ meet challenges on the path to successfully developing new medical products and bringing them to market.
We have completed toxicological assessments for hundreds of pharmaceutical E&Ls and other impurities and ingredients, including complex polymers, degradants, solvents, and elements, as well as long applied and newer excipients and biological components, for all routes of exposure including injection/parenteral, oral, topical, inhalation, nasal/ mucosal, and ocular routes. toxicological assessments and support services are consistent with guidance and recommendations from International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) (e.g., ICH M7, Q3B, Q3C); ISO 10993-17 and 18; United States Pharmacopeial Convention (USP; e.g., Chapters <232>, <467>, <1663>, <1664>); and Product Quality Research Institute (PQRI), and standard and accepted toxicological assessment principles and methodologies.
We utilize our extensive database of knowledge on these substances to help clients quickly ascertain potential concerns and demonstrate product safety. In cases where the availability of toxicological data is limited, we are skilled in the application of read-across methodologies or in silico approaches to predict the biological activity or toxicity of chemical compounds based on their chemical structure.
Our Services
- Identification of Analytical Evaluation Thresholds (AETs)
- Development of Permissible Daily Exposure (PDE) levels per ICH, USP, and PQRI guidance and recommendations
- Establishment of Tolerable Intakes (TIs), Tolerable Exposure (TEs), and Margins of Safety (MoS) per ISO 10993-17 and 18 guidance
- Screening potential extractable or leachable targets to prioritize potential hazards (e.g., whether chemicals may be mutagenic/ carcinogenic or sensitizers) and support identification of analytical targets
- Assessment of the safety of excipients or other “inactive” ingredients or residual processing components in drug products
- Assistance in setting material safety tolerances
Our Process
We consult with you to determine your specific project goals and objectives and understand how your product will be used, who the patient population is, how they may be exposed, and what existing data has been collected. In conducting our assessments, we consider the potential implications of patient profiles to establish appropriate safe levels. You can be assured that our assessments focus on your specific needs.
Our assessments are conducted by DABT-certified toxicologists with extensive experience in assessment of E&Ls and other pharmaceutical impurities and ingredients, and undergo a rigorous QA/QC process. Consistent with FDA recommendations, we emphasize acquiring and understanding source literature and study documentation. For compounds with limited data, we leverage computational models and predictive methologies to anticipate potential toxicity based on chemical structure and biological activity.