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.

生物制药和小分子药物具有不同的批准途径，但具有相同的质量控制（QC）范式，其中已释放但未经测试的单元的质量是从经过测试但被破坏的单元的质量推断出来的。这种基于推论的质量控制可能会错过罕见的预发布缺陷，以及产品发布后出现的缺陷。由于生物药品的复杂性，这种缺陷的可能性增加，这使得制造生物药品的可能性更高，而由于易碎性，使得生物药品的释放后损坏的可能性更高。为了提高生物制药安全性，我们建议通过开发可以无损验证每个小瓶从释放点到护理点质量的检查技术，将其QC从推论转变为基于验证的实践。简要讨论了一种候选物质，水质子NMR（wNMR）。