Tailored advisory for Pharmaceuticals.

“Impurities, PDEs, OELs/OEBs, ERA, and more”

Impurity Characterization and Qualification Assessment

Our expert team provides comprehensive support in the qualification of impurities and the establishment of safety limits for contaminants in your human and veterinary pharmaceuticals. Our services include risk assessment and tailored strategies for the 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 (performed via a partner).
  • ICH M7 compliant reports on assessment and control of mutagenic impurities in pharmaceuticals.
  • Toxicological Risk Assessment and determination of Acceptable Intakes for nitrosamines.
  • Purge factor calculation.

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

• Solvents: Toxicological risk assessment for solvents in human and veterinary drug substances according to ICH Q3C and VICH GL18 guidelines, with the establishment of safe levels.

• Elemental Impurities: Toxicological assessment and definition of safe levels of elements in human and veterinary drug products according to ICH Q3D, including unusual routes of administration like intravitreal, dermal or mucosal.

• Extractables & Leachables (E&L) toxicological evaluation: definition of safe levels and Margins of Safety.

Permitted Daily Exposures (PDEs), Occupational Exposure Limits (OELs) and Bandings (OEBs)

PDEs and OELs are critical for ensuring patient safety and maintaining a safe work environment for pharmaceutical manufacturing. Our PDE/OEL evaluations are conducted and signed by certified experts with decades of industry experience and have consistently accepted by authorities.

• Estimation of PDEs for human and veterinary active ingredients and manufacturing intermediates in compliance with the “European Medicine Agency’s (EMA) guideline on setting health-based exposure limits for use in risk identification in the manufacturing of different medicinal products in shared facilities” (EMA/CHMP/ CVMP/ SWP/169430/2012).

• Establishment of OEL/OEB for active ingredients, intermediates, and reagents.

• PDEs and OELs are determined based on the toxicological properties and the available pharmacological data (if relevant), or in silico predictions for substances with limited data.

Environmental Risk Assessment (ERA)

Including an ERA in your marketing authorization dossier is not only mandatory but essential for safeguarding ecosystems. For our pharmaceutical industry clients, we assess the necessary data, prepare the ERA in accordance with regulatory requirements, and assist with compiling all essential documentation. Our expertise ensures compliance and thorough evaluation:

• Regulatory compliance: EMEA/CHMP/SWP/4447/00 Rev 1 (2024) for Human Medicinal Products and VICH GL6 and VICH GL38 for Veterinary Medicinal Products.

• Comprehensive evaluation: Conducting a systematic or targeted literature review on endpoints of relevance for the ERA including physico-chemical, ecotoxicological, and fate properties to assess risks of active ingredients for the environment.

• Testing strategies: Developing tailored testing solutions for marketing authorization; waiving possibilities for required tests; study design and monitoring to meet all testing requirements in compliance with the relevant guidelines and regulations.