Impurities

The examination of extractable and leachable substances (such as plasticizers, antioxidants, stabilizers and dyes) is extremely important for the protection of patients and for regulatory documentation destined for authorities such as the FDA and EMA. In recent years, the pharmaceutical industry has developed a better understanding of the impact of extractables and leachables on patient safety and drug product interaction, leading to increased scrutiny by the regulators. When there is a change in a drug product’s immediate packaging materials, there is a regulatory requirement to assess the impact of the change. Testing is conducted to ensure that the materials are not leaching into a pharmaceutical or from a medical device to a patient. Typically, the testing is done on rubber and polymer materials or components used in medical device and pharmaceutical packaging. Analytical Testing Service providers offers a number of services for Extractables and Leachables such as: Test strategy planning and data evaluation based on the available information; Supporting of risk analysis procedures; Development of a tailored study design for extractables and leachables or chemical characterization, according pharmaceutical standards and ISO 10993 part 12/18; Extractables profiling (inorganic and organic extractables); Sequential extractions and alternative extraction techniques for isolating extractables in materials made from polymers, metals and ceramics; Characterization of extractables by chromatographic and spectroscopic investigations; Identification of a material and the identification and quantitation of the chemicals present in materials by chemical characterization; Identification and evaluation of the physico-chemical, mechanical, morphological and topographical properties of materials; Chemical and structural changes (e.g. by DSC) on polymeric materials after stressing by temperature or irradiation; Determination of the Analytical Evaluation Threshold (AET); Calculation of the AET based on Safety Concern Threshold (SCT) or Threshold of Toxicological Concern (TTC) and ICH M7 guideline; Biocompatibility: USP<87> and USP <88>; Toxicological assessments and method development and validation of potential leachables in pharmaceutical products and from medical devices; Performing leachables studies or simulated use studies on pharmaceutical products and medical devices; Reporting and evaluation of results within the current guidelines. Extractable and Leachable testing also is expanding in the extent and complexity of testing, which requires comprehensive design of the E&L program based on sound scientific principles. Trending from just detecting and quantifying the known and expected leachables has transitioned to now addressing the issues of unknown and unexpected leachables. The complexity of the E&L study program poses significant challenges for pharmaceutical product development, and requires significant expertise for the successful design and execution of an E&L program.