Wittayanukorn Saranrat, Rosenberg Matthew, Schick Andreas, Hu Meng, Wang Zhong, Babiskin Andrew, Lionberger Robert, Zhao Liang
Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center of Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, USA.
Office of Program and Strategic Analysis, Center of Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, USA.
Ther Innov Regul Sci. 2020 Nov;54(6):1372-1381. doi: 10.1007/s43441-020-00163-x. Epub 2020 Jun 3.
Increasing generic drug price competition by facilitating abbreviated new drug applications (ANDA) submission may help patients have access to affordable care. This study examined factors associated with first ANDA submission for the brand drug to be copied [the "reference listed drug" (RLD)].
This study used several data sources from 1/1/2011 to 12/31/2017, including FDA's Approved Drug Products With Therapeutic Equivalence Evaluations (the Orange Book), internal ANDA submission data, FDA's Product-Specific Guidances (PSGs), National Drug Code, and IQVIA National Sales Perspectives. Two Cox proportional hazard models were separately performed to determine factors associated with first ANDA submissions for groups of ANDAs for RLDs with "new chemical entity" (NCE) exclusivity that were submitted on the first lawfully permissible date NCE ANDAs, and non-NCE ANDA groups.
For NCE group, annual market sales were the only factor associated with increased likelihood of first ANDA submission. Specifically, adjusted hazard ratio (HR) for RLDs with annual sales > $250 million was nearly 5 times higher than those with annual sales < $10 million (HR 4.74; Confidence Interval [CI] 1.85-12.13) suggesting RLDs with higher sales are more likely to have ANDA submissions. For the non-NCE group, annual market sales (HR 2.40; CI 1.09-5.25, sales > $100-250 million compared with sales < $10 million) and PSG availability were associated with increased likelihood of first ANDA submission. Being an ANDA for a complex drug product was associated with decreased likelihood of submission for both NCE (HR 0.51; CI 0.26-0.99) and non-NCE groups (HR 0.62; CI 0.39-0.98).
Given the impact of regulatory-related factors, particularly PSG availability prior to ANDA submission, the findings provide opportunities to address high drug prices with specific FDA actions. Specifically, timely development of PSGs, including those for complex generics, and research prioritizing complex generics may facilitate ANDA submission; and thus, promote drug price competition.
通过简化新药申请（ANDA）提交流程来增强仿制药价格竞争，可能有助于患者获得可负担的医疗服务。本研究调查了与首个针对待仿制品牌药（“参考上市药物”[RLD]）提交ANDA相关的因素。
本研究使用了2011年1月1日至2017年12月31日的多个数据源，包括美国食品药品监督管理局（FDA）的《具有治疗等效性评估的已批准药品》（橙皮书）、内部ANDA提交数据、FDA的特定产品指南（PSG）、国家药品代码以及艾昆纬全国销售视角数据。分别进行了两个Cox比例风险模型，以确定与在首个合法允许日期提交的具有“新化学实体”（NCE） exclusivity的RLD的ANDA组、NCE ANDAs组以及非NCE ANDA组的首个ANDA提交相关的因素。
对于NCE组，年度市场销售额是与首个ANDA提交可能性增加相关的唯一因素。具体而言，年销售额>2.5亿美元的RLD的调整后风险比（HR）几乎是年销售额<1000万美元的RLD的5倍（HR 4.74；置信区间[CI] 1.85 - 12.13），这表明销售额较高的RLD更有可能有ANDA提交。对于非NCE组，年度市场销售额（HR 2.40；CI 1.09 - 5.25，年销售额>1亿 - 2.5亿美元与年销售额<1000万美元相比）和PSG的可用性与首个ANDA提交可能性增加相关。作为复杂药品的ANDA与NCE组（HR 0.51；CI 0.26 - 0.99）和非NCE组（HR 0.62；CI 0.39 - 0.98）的提交可能性降低相关。
鉴于监管相关因素的影响，特别是在ANDA提交之前PSG的可用性，研究结果为FDA采取特定行动应对高药价提供了机会。具体而言，及时制定PSG，包括针对复杂仿制药的PSG，以及将复杂仿制药作为研究重点，可能会促进ANDA提交；从而促进药品价格竞争。
