Wilson L G
Department of History of Medicine, University of Minnesota, Minneapolis, USA.
Arch Surg. 1995 Oct;130(10):1035-9. doi: 10.1001/archsurg.1995.01430100013002.
The indictment of John Najarian, MD, and Richard Condie at Minneapolis, Minn, on April 10, 1995, was a defining episode in the prolonged agony that has ensued since August 1992, when the federal Food and Drug Administration (FDA) placed Minnesota Anti-Lymphocyte Globulin (MALG) on clinical hold, bringing to an end its use as an immunosuppressive agent for patients undergoing transplantation. The principal charge in the indictment is that from about 1968 until 1992--the whole period of the development and use of MALG--Dr Najarian and Mr Condie conspired to defraud the United States by impeding the FDA in its oversight of biological drugs and that they did so for the purpose of financial gain. If the charges can be considered seriously, they mean that Dr Najarian's purpose in the development and manufacture of MALG was to make money, presumably for himself, and that the possible benefit of MALG to the patients was of secondary concern to him. Several difficulties arise immediately. In 1968, MALG offered a promising new approach to immunosuppression. In a relatively crude form, it had been used at the University of Colorado with striking improvement in the survival of patients undergoing transplantation and transplanted organs, but it was painful to administer by intramuscular injections and, in addition to other side effects, produced muscular spasms. Dr Najarian and his colleagues succeeded in purifying MALG so that the pure globulin could be injected into a central vein. The process of purification was complicated and expensive, so it was hardly practical for each transplant center to produce MALG for itself. Thus, in 1969, when Dr Najarian submitted an investigational new drug application (IND) to the FDA, he stated that his purpose was to manufacture MALG not only for patients at the University of Minnesota Hospital but also for patients at other transplant centers, which were not in a position to make it for themselves. He asked the FDA to approve recovery of the cost of providing MALG to other institutions. The FDA approved Dr Najarian's IND application early in 1970 but did not respond to his request for cost recovery--then, or for the next 15 years. Dr Najarian was free to manufacture MALG and to distribute it to other transplant centers for investigational use, but as for paying for it, that was his problem. The FDA offered no suggestion.
1995年4月10日，明尼苏达州明尼阿波利斯市的医学博士约翰·纳贾里安（John Najarian）和理查德·康迪（Richard Condie）被起诉，这是自1992年8月以来漫长痛苦历程中的一个决定性事件。当时，联邦食品药品监督管理局（FDA）暂停了明尼苏达抗淋巴细胞球蛋白（MALG）的临床试验，使其作为移植患者免疫抑制剂的使用画上句号。起诉书中的主要指控是，从大约1968年到1992年——MALG整个研发和使用期间——纳贾里安博士和康迪先生合谋欺骗美国，妨碍FDA对生物药品的监管，目的是获取经济利益。如果这些指控被认真对待，那就意味着纳贾里安博士研发和制造MALG的目的是赚钱，大概是为了他自己，而MALG对患者可能带来的益处对他来说是次要考虑因素。立即出现了几个难题。1968年，MALG提供了一种有前景的免疫抑制新方法。以相对粗糙的形式，它已在科罗拉多大学使用，接受移植的患者和移植器官的存活率有显著提高，但通过肌肉注射给药很痛苦，除了其他副作用外，还会引起肌肉痉挛。纳贾里安博士及其同事成功提纯了MALG，这样纯球蛋白就可以注入中心静脉。提纯过程复杂且昂贵，所以每个移植中心自行生产MALG几乎不切实际。因此，1969年，当纳贾里安博士向FDA提交一份研究性新药申请（IND）时，他表示自己的目的不仅是为明尼苏达大学医院的患者生产MALG，也为其他无法自行生产的移植中心的患者生产。他请求FDA批准收回向其他机构提供MALG的成本。FDA在1970年初批准了纳贾里安博士的IND申请，但对他收回成本的请求未作回应——当时没有，在接下来的15年里也没有。纳贾里安博士可以自由生产MALG并将其分发给其他移植中心用于研究，但至于付费问题，那是他自己的事。FDA没有给出任何建议。
