Section of Child Neurology, Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, United States of America.
Section of Child Neurology, Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, United States of America.
Seizure. 2024 Apr;117:83-89. doi: 10.1016/j.seizure.2024.02.003. Epub 2024 Feb 5.
Generic drug manufacturing has shifted away from the U.S. in the last few decades. The medication supply chain, from manufacturers to resellers, has become increasingly globalized and complex. This has led to bottlenecks in their manufacture resulting in medication shortages. Review of this process as it pertains to antiseizure medications (ASM) shows gaps in our comprehension of its complexities. Understanding these processes will be essential for preventing medication shortages.
The aim of this research is to examine the generic ASM supply with an emphasis on production, labeling, and repackaging.
Data from the United States Food and Drug Administration (FDA) and the National Library of Medicine (NLM) website DailyMed was used to evaluate supply chain details to gather information on antiseizure medication formulations, manufacturing locations, and labeling.
Out of 3142 ASM-related active National Drug Code (NDC-9) codes, 2663 NDC-9 codes with Abbreviated New Drug Application (ANDA) status were included in the analysis. Most (94.8 %) were enteral, with only 5.2 % being parenteral (intravenous and intramuscular route). We identified the manufacturing country for 82 % of these codes, corresponding to 306 unique ANDA numbers. 119 manufacturing sites in 12 countries produce generic ASM Finished Dosage Forms (FDF): 103 for enteral and 21 for parenteral. India is the main producer of enteral ASM FDFs with 49 sites, followed by the US with 36. Regarding parenteral formulation, five countries had 21 unique manufacturing locations. 42 % of the 103 enteral ASM FDFs manufacturing sites produced multiple ASM FDFs, with one facility making eight distinct ASMs. 34.4 % of facilities were associated with over 3 ANDAs, and 15.1 % with more than 5. 22.7 % of ANDAs lacked a manufacturing facility identifier. Repackaged ASM FDFs constituted 48 % of NDC-9 s. Gabapentin and pregabalin were the most common oral ASMs.
India is the major source for generic ASM FDFs manufacturing, leading to concerns about overall supply dependency on that country. There is a paucity of facilities for the global supply of parenteral ASM FDFs. There is missing data for many NDC-9 codes emphasizing urgency for transparency in the supply chain.
在过去几十年中，仿制药制造已经从美国转移出去。从制造商到转售商的药物供应链已经变得越来越全球化和复杂。这导致药物制造出现瓶颈，从而导致药物短缺。审查与抗癫痫药物（ASM）相关的这一过程表明，我们对其复杂性的理解存在差距。了解这些过程对于预防药物短缺至关重要。
本研究的目的是检查仿制药 ASM 的供应情况，重点是生产、标签和重新包装。
使用美国食品和药物管理局（FDA）和国家医学图书馆（NLM）网站 DailyMed 的数据评估供应链细节，以收集有关抗癫痫药物制剂、制造地点和标签的信息。
在 3142 个与 ASM 相关的活跃国家药物代码（NDC-9）中，有 2663 个 NDC-9 代码具有简略新药申请（ANDA）状态被纳入分析。大多数（94.8%）是肠内的，只有 5.2%是肠胃外的（静脉和肌肉内途径）。我们确定了这些代码中 82%的制造国家，对应于 306 个独特的 ANDA 编号。12 个国家的 119 个制造工厂生产通用 ASM 成品剂型（FDF）：103 个用于肠内，21 个用于肠胃外。印度是肠内 ASM FDF 的主要生产商，有 49 个生产基地，其次是美国，有 36 个。关于肠胃外制剂，有五个国家有 21 个独特的制造地点。103 个肠内 ASM FDF 制造工厂中有 42%生产多种 ASM FDF，一个工厂生产八种不同的 ASM。34.4%的工厂与 3 个以上的 ANDA 相关联，15.1%的工厂与 5 个以上的 ANDA 相关联。22.7%的 ANDA 缺乏制造设施标识符。重新包装的 ASM FDF 占 NDC-9 的 48%。加巴喷丁和普瑞巴林是最常见的口服 ASM。
印度是仿制药 ASM FDF 制造的主要来源，这导致人们对该国整体供应的依赖性感到担忧。全球供应肠胃外 ASM FDF 的工厂数量较少。许多 NDC-9 代码的数据缺失，强调了供应链透明度的紧迫性。
