英文文献：Generics substitution, bioequivalence standards, and oversight of international pharmaceutical producers: Complex issues facing the FDA-仿制药替代，生物等效性标准，以及对国际制药商的监督:FDA面临的复杂问题
英文文献作者：Aparna Mathur,Roger Bate
英文文献摘要：
The rules underlying the assessment of quality of generic drugs, and their bioequivalence to brand name products, have not changed significantly since the passage of the Hatch-Waxman Act in 1984. Yet the products on the market are significantly more complicated today, which may imply that two bioequivalent products are not identical to each other. Providing evidence from medications to treat epilepsy, depression and other serious conditions this paper shows that switching from an innovator brand to a generic may result in adverse consequences for patients. Moreover, the clinical impacts of shifting from one generic to another generic are also unknown. In a self-conducted survey, we provide original data to show that in only 10% of pharmacies surveyed over four consecutive months was the same generic (atorvastatin) available. Hence consumers often have less choice with respect to the generics they buy from brick and mortar pharmacies and we need more information to understand whether this type of enforced generic switching is advisable. Additionally, generic and brand name drugs source more ingredients and even final products from outside the U.S. especially India and China, countries with poor regulatory oversight. This would impact quality in US markets. The most notable failure in this regard was with the Indian firm Ranbaxy. Even after repeated failures to ensure quality at Ranbaxy and other Indian firms, and weak oversight in China, US patients are still prescribed their products. In this paper, we document these complex issues facing the FDA and conclude that transparency as well as updating of bioequivalence standards may be important to overcome some of these challenges. Further, transparency in labelling where products are sourced from could be a first step towards improving patient safety.

自1984年通过哈奇-韦克斯曼法案以来，非专利药品质量评估及其与品牌产品的生物等效性的基本规则并没有发生重大变化。然而，如今市场上的产品要复杂得多，这可能意味着两种生物等效产品并不完全相同。本文提供了治疗癫痫、抑郁症和其他严重疾病的药物证据，表明从创新品牌转向通用品牌可能会对患者造成不良后果。此外，从一种仿制药转向另一种仿制药的临床影响也是未知的。在一项自行开展的调查中，我们提供的原始数据表明，在连续四个月接受调查的药店中，只有10%的药店有相同的仿制药(阿托伐他汀)。因此，对于从实体药店购买的仿制药，消费者的选择往往较少，我们需要更多的信息来了解这种强制更换仿制药的做法是否可取。此外，仿制药和品牌药的成分甚至最终产品更多来自美国以外的国家，特别是监管不力的印度和中国。这将影响美国市场的质量。在这方面最明显的失败是与印度兰伯西公司的合作。尽管兰伯西和其他印度公司在保证质量方面一再失败，中国的监管也很薄弱，但美国患者仍会使用他们的产品。在本文中，我们记录了FDA面临的这些复杂问题，并得出结论，透明度以及生物等效性标准的更新可能对克服其中一些挑战很重要。此外，产品来源标签的透明度可能是改善患者安全的第一步。