Objectives To evaluate whether off-patent prescription drugs at risk of sudden price increases or shortages in the United States are available from independent manufacturers approved in other well regulated settings around the world.

Design Observational study.
Setting Off-patent drugs in the USA and approved by the Food and Drug Administration, up to 10 April 2017.
Study cohort Novel tablet or capsule prescription drugs approved by the FDA since 1939 that were no longer protected by patents or other market exclusivity and had up to three generic versions.
Main outcome measures Number of additional manufacturers that had obtained approval from any of seven non-US regulators with similar standards (European Medicines Agency (European Union), HealthCanada (Canada), Therapeutic Goods Association (Australia), Medsafe (New Zealand), Swissmedic (Switzerland), Medicines Control Council (South Africa), and the Israel Health Ministry). Association with drug characteristics including US orphan drug designation for drugs treating rare diseases, World Health Organization essential medicine designation, treatment area, drug product complexity (that is, with attributes that could complicate establishing bioequivalence or manufacturing), and total Medicaid spending in 2015.
Results Of 170 eligible study drugs, more than half (109, 64%) had at least one manufacturer approved by a non-US regulator and 32 (19%) had four or more. Among 44 (26%) drugs with no FDA approved generic versions, 21 (48%) were available from at least one manufacturer approved by one of the seven non-US regulators, and two (5%) by four or more manufacturers. Across all drugs and regulators (including the FDA), 66 (39%) drugs were available from four or more total manufacturers. Of 109 drugs with at least one non-US regulator approved manufacturer, 12 (11%) were approved for patients with rare diseases and 29 (27%) were WHO designated essential medicines; only 12 (11%) were complex products that might be more complicated to import. The highest numbers of drugs were indicated for treating cardiovascular diseases, diabetes, or hyperlipidemia (19, 17%); psychiatric disease (16, 15%); and infectious diseases (15, 14%). In 2015, Medicaid alone spent nearly US$700m (£508m; €570m) on generic drugs without adequate US competition that could have had a manufacturer approved by non-US peer regulatory agencies.
Conclusion In this study, more than half the off-patent drugs with no generic competition in the USA had at least one independent manufacturer approved by a non-US peer regulatory agency; slightly fewer than half had four or more total manufacturers. Facilitating US patient access to such manufacturers could help sustain affordable access to essential off-patent drugs.

目的为了评估在美国是否有可能出现价格突然上涨或短缺的非专利处方药，可从世界各地其他受到良好监管的环境中批准的独立制造商获得。

设计观察研究。
设置在美国的非专利药物，并通过美国食品和药物管理局批准，到4月10日2017年
研究组自1939年被FDA批准新型片剂或胶囊处方药已不再受专利或其它市场独占保护，并有最多三个通用版本。
主要观察指标已获得七个具有类似标准的非美国监管机构（欧洲药品管理局（欧盟），加拿大卫生署（加拿大），治疗药物协会（澳大利亚），医疗保险（新西兰），瑞士医疗（瑞士））中的任何一家的批准的其他制造商的数量，药品管制委员会（南非）和以色列卫生部）。与药物特征相关联，包括用于治疗罕见病的美国孤儿药物名称，世界卫生组织的基本药物名称，治疗区域，药物产品复杂性（即可能会使建立生物等效性或制造复杂化的属性）以及2015年医疗补助总支出。
结果在170种合格的研究药物中，一半以上（109，64％）具有至少一家经美国以外的监管机构批准的制造商，而32种（19％）具有四种或以上。在没有FDA批准的非专利版本的44种（26％）药物中，至少有7种非美国监管机构之一批准的制造商有21种（48％），有4种以上的制造商提供了2种（5％）。在所有药物和监管机构（包括FDA）中，共有四个或更多制造商提供了66种药物（占39％）。在至少有一家未经美国监管机构批准的制造商的109种药物中，有12种（11％）被批准用于罕见病患者，而29种（27％）是WHO指定的基本药物；只有12种（11％）是复杂的产品，进口可能会更加复杂。指出用于治疗心血管疾病，糖尿病或高脂血症的药物数量最高（19％，17％）；精神病（16，15％）; 和传染病（15，14％）。在2015年，仅Medicaid就在仿制药上花费了近7亿美元（5.08亿欧元； 5.7亿欧元），而美国却没有足够的竞争，这可能会使制造商获得非美国同行监管机构的批准。
结论在这项研究中，超过一半在美国没有仿制药竞争的非专利药物中至少有一个由非美国同行监管机构批准的独立制造商。略少于一半的制造商总数达到四个或更多。便利美国患者接触这些制造商，可以帮助维持负担得起的基本非专利药物的获取。