Scientifically Supported Best Practices in Leachable Screening Studies for Pharmaceutical and Parenteral Drug Products

Purpose: Pharmaceutical parenteral drug products (PDPs) and orally inhaled nasal drug products (OINDPs) are critical medications for patient care, for which the route of administration is intravenous or oral/nasal inhalation, and the drug products directly infuse into the bloodstream or lungs, but they are categorized as high-risk for leachables. Method: These external foreign chemical substances (leachables) may adversely affect and alter patient safety. Results: These primary container closure systems and manufacturing process equipment mainly comprise rubber elastomers, polypropylene, resin, ink, adhesives, glass, or plastic material. To establish the ID of detected compounds and their quantity in the finished parenteral drug formulation and then to assess the formulation for toxicological safety, broad-scope non-specific analytical screening methods are required that are capable of screening out and quantifying the predicted/unpredicted leachable compounds at the levels that pose anticipated toxicological concerns for human patients. Before the selection of the final primary packaging system for the parenteral drug product, their extractable screening profile/knowledge is required to minimize leachable compounds in the finished drug product formulation and to develop and manufacture a safe product for human patients. The adverse effect or toxicity of leachables proportionally increases with an increase in the dose of the drug product or the duration of therapy because the volume of the drug product administered to a patient in a larger quantity is directly proportional to the concentration of the detected leachable. Conclusion: This document outlines the detailed process/scientific approach for conducting an organic leachable screening profile for parenteral drug products with respect to the chemical nature of leachables, i.e., polarity, propensity, volatility, and techniques.