Improving Biopharmaceutical Safety through Verification-Based Quality Control

摘要

Biopharmaceuticals and small-molecule drugs have different approval pathways but the same quality control (QC) paradigm, where the quality of released but untested units is inferred from that of tested but destroyed units. This inference-based QC will likely miss rare prerelease defects, and defects emerging after product release. The likelihood for such defects is heightened for biopharmaceuticals due to their complexity, which makes manufacturing errors more likely, and fragility, which makes postrelease damage more likely. To improve biopharmaceutical safety, we suggest transitioning their QC from inference- to verification-based practice by developing inspection technologies that can nondestructively verify the quality of every vial from the point of release to the point of care. One candidate, water proton NMR (wNMR), is briefly discussed.TrendsMore biopharmaceuticals, including biosimilars, are coming to the market. Many recent approvals are biosynthesized using genetically modified bacteria, yeasts, cells and animals.Biopharmaceuticals are getting more complex to include live viruses and cells.More and more biopharmaceuticals are formulated as injection-ready liquids, often at high protein concentration.The manufacturing of more biopharmaceuticals is outsourced to foreign countries, where FDA oversight is challenging.The 21st Century Cures Act encourages more data collection by nonexperts in nontraditional clinical trial settings (Real-World Data).Nondestructive inspection technologies, like wNMR, are being developed.]]>