Risk Management Strategies for Extractables and Leachables

FDA's Ingrid Markovic has just published in American Pharmaceutical Review on risk management for extractables and leachables. Here's a link (subscription required), and here is the abstract:

Extractables and leachables (E&L) are chemical entities, which can be released into intermediate material or final therapeutic biologic protein product at various times during upstream and/ or downstream manufacturing steps, packaging operations and/or storage. These substances may pose a safety risk to the patient by causing toxicity, carcinogenicity, immunogenicity and/or endocrine dysregulation. They may also alter product physico-chemical properties via direct interaction with the active pharmaceutical ingredient or, indirectly, by interacting with the excipients in product vehicle, thereby adversely affecting the product quality. Current paper will address a risk-based approach to conceptualizing, evaluating and executing identification and characterization of E&L along with regulatory considerations regarding the impact of these impurities on product quality, patient safety and clinical efficacy. Selected case studies are presented and discussed.