Impurity Characterization and qualification

Any component of the drug substance or drug product which is not the chemical entity as defined by the drug substance or excipient in the drug product has to be considered as an impurity.

The matter of impurities is a frequently debated issue. It is mainly focused on the validation of analytical methods and on the toxicology of potential impurities.

Our expert team will assist you in the process of the qualification of impurities and will provide safety limits of contaminants in your human or veterinary pharmaceuticals.

Our services include:

• Risk assessment and strategies for qualification of process impurities and other contaminants:

Potential genotoxic impurities: Toxicological Risk Assessment according to ICH M7 Guideline. In silico assessment (QSAR modelling) for genotoxicity alert identification using commercial tools such as Lhasa and Leadscope according to ICH M7 Guideline. ICH M7 compliant reports on assessment and control of mutagenic impurities in pharmaceuticals (services provided by partners).

Non genotoxic Impurities: Risk assessment and qualification strategies for normal impurities exceeding qualification thresholds in drug candidates and drug products in compliance with the ICH Q3A/B guidance’s.

Solvents: toxicological risk assessment for solvents not listed in the guideline ICH Q3C, defining safe levels in the drug product.

Elemental Impurities: definition of safe levels of elements including unusual routes of administration like intravitreal, dermal or mucosal.

Extractables & Leachables (E&L)

Cross-contamination: derivation of permissible daily exposure (PDE) levels of active ingredients (API) and isolated pharmaceutical ingredients (IPI) through cross-contamination in shared facilities.

• Derivation of permissible daily exposure (PDE) levels of active ingredients (API) and isolated pharmaceutical ingredients (IPI) through cross-contamination in shared facilities. The PDEs are prepared and reported in compliance with the “European Medicine Agency’s (EMA) guideline on setting health-based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities”.
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  For data-poor substances (IPI), in silico assessment (QSAR modelling, analogue identifications and read across justification) of toxicological endpoints using commercial tools such as Lhasa and Leadscope is proposed. The ICH M7 approach will be followed for the evaluation of genotoxicity potential. Other endpoints (e.g. skin sensitization) will be evaluated following a step-by-step approach (services provided by partners).

• Toxicological risk assessment of residual impurities from the manufacturing process (ISO 10993-18), degradation products (ISO 10993-13/14/15) and substances extracted and/or released by the primary packaging in the medical device (ISO 10993-17) including polymers (plastic/silicon), solvents, elemental and genotoxic impurities and definition of their safety limits.