Risk-based scientific approach for determination of extractables/leachables from biomanufacturing of antibody-drug conjugates (ADCs).

Recent developments in biopharmaceutical processes twined with a desire to remove cleaning and cross-contamination issues from drug production have led to the widespread introduction of single-use technologies and systems within operations. One key area that end users need to address with the advent of these single-use solutions is the potential for increased levels of extractables and leachables within a process, which need to be evaluated and understood as part of any regulatory submission. A science-based and practical method for characterization of extractables and leachables from single-use systems used in manufacturing antibody-drug conjugates has been developed and described in detail. This risk-based approach minimizes the amount of test work while meeting the regulatory requirements to ensure the drug safety and quality. The test design is optimized and the analytical methods (gas chromatography/mass spectrometry, liquid chromatography/mass spectrometry, and inductively coupled plasma/mass spectrometry) are shown to be suitable for quantifying and identifying the extracted chemical compounds. Application of this characterization method speeds up the filing process for qualification and validation of single-use systems used in bioprocesses.