Extractables & Leachables

During manufacture and use, pharmaceutical products and medical devices make contact with processing equipment, packaging and delivery device components. Small amounts of chemicals may leach from any or all of these into the pharmaceutical product, and subsequently be delivered to the patient along with the dose. It is critical for all parties that such leaching does not occur in quantities that significantly alter the safety, identity, strength or quality of the drug. Extractables and Leachables (E&L) studies play a critical role in quality control and monitoring.

ToxHub toxicological risk assessment follow a tiered approach based on the Extractables and Leachables study results. The exposure, including treatment dose, dosing route, dosing frequency and its likely duration are key elements of the assessment. We combine the hazard evaluation of the individual chemicals with exposure information to assess whether any significant health risks exist.

The evaluation of Extractables & Leachables (E&L) is also an important part of verifying the safety of a medical device product.

Our activities include:

  • Toxicological risk assessment for Extractables & Leachables (E&L) in active pharmaceutical ingredients from manufacturing equipment and in pharmaceutical products from primary packaging, including polymers (plastic/silicon), lubricants, pigments, solvents, inks, adhesives, surface coatings, elemental and genotoxic impurities (ICH M7, ISO 10993, ISO 11040, ISO 11979, ISO 14971, ISO 20072, ISO 27427, USP <1663>, USP <1664>, PQRI recommendations, upcoming ICH Q3E);
  • Derivation of Safety Concern Thresholds (SCT) considering route of administration, frequency and duration of drug product administration, posology, dosages;
  • Toxicological risk assessment of substances extracted and/or released by the primary packaging in the MD (E&L, ISO 10993-17) including polymers (plastic/silicon), solvents, elemental and genotoxic impurities and definition of their safety limits;
  • For unknown substances 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).