Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993, USA.
Office of Bioequivalence, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire, Silver Spring, Maryland, 20993, USA.
AAPS J. 2017 Nov;19(6):1593-1599. doi: 10.1208/s12248-017-0137-x. Epub 2017 Sep 6.
Administration of proton pump inhibitors (PPIs) through nasogastric tubes may present risks. If the PPI drug products are not prepared properly, clogging or obstruction of nasogastric tubes can pose a safety concern. In addition, the integrity of the enteric coating of the drug product may be damaged resulting in reduced bioavailability of the active moiety. From the perspective of administration of generic PPIs when compared to the reference drug product, differences in formulation can potentially result in a greater relative risk for the generic drug product. As part of the assessment of bioequivalence, the Office of Generic Drugs (OGD) has developed a suite of in vitro testing to compare the delivery of the generic and reference products via nasogastric tubes. These in vitro tests assess essential attributes associated with the likelihood of clogging and maintenance of the enteric coating. These in vitro tests include studies evaluating sedimentation, granule size distribution, drug recovery, and acid resistance. One of the challenges is that while the administration of PPIs through nasogastric tubes is common in clinical practice, this issue is not uniformly addressed in the FDA approved label of the reference drug products. This paper discusses the design and rationale for in vitro testing of PPI formulations with respect to bioequivalence via nasogastric tube administration and in addition, it summarizes commonly occurring deficiencies in the in vitro nasogastric tube testing of 14 recent Abbreviated New Drug Applications (ANDA) submitted for five generic PPI drug products.
通过鼻胃管给予质子泵抑制剂（PPIs）可能存在风险。如果 PPI 药物产品制备不当，可能会堵塞或阻塞鼻胃管，从而带来安全隐患。此外，药物产品的肠溶包衣完整性可能会受损，导致有效成分的生物利用度降低。与参比药物产品相比，从给予通用 PPI 的角度来看，制剂差异可能会导致通用药物产品的相对风险增加。作为生物等效性评估的一部分，仿制药办公室（OGD）开发了一系列体外测试，以比较通过鼻胃管给予通用产品和参比产品的情况。这些体外测试评估了与堵塞和保持肠溶包衣的可能性相关的基本属性。这些体外测试包括评估沉淀、颗粒大小分布、药物回收和耐酸性的研究。其中一个挑战是，虽然通过鼻胃管给予 PPIs 在临床实践中很常见，但这一问题在参比药物产品的 FDA 批准标签中并未得到统一解决。本文讨论了针对通过鼻胃管给予生物等效性的 PPI 制剂的体外测试设计和原理，并总结了最近提交的五款通用 PPI 药物产品的 14 份简化新药申请（ANDA）中，在鼻胃管体外测试中常见的缺陷。
