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[丹麦制药行业的早期成就 - 7]

[Early achievements of the Danish pharmaceutical industry-7].

作者信息

Grevsen Jørgen V, Kirkegaard Hanne, Kruse Edith, Kruse Poul R

出版信息

Theriaca. 2014(42):31-62.

PMID:25816561
Abstract

A/S GEA Farmaceutisk Fabrik was established as a family business in 1927 by the pharmacist Knud L. Gad Andresen who until then had been employed in the pharmaceutical industry. Gad Andresen wanted to run a company focusing on the development of generics, and he wanted this development to take place in a close cooperation with Danish physicians. This has indeed been achieved with success. In 1995 GEA was purchase'd by the American pharmaceutical company Bristol-Myers Squibb who in a press release characterized GEA as Denmark's second largest manufacturer of generics. Immediately after this takeover GEA's R&D department ceased the research in innovative products and from now on exclusively focused on the development of generics. Three years later GEA was sold to the German generic company Hexal who later on resold GEA to the Swiss generic company Sandoz. GEA changed ownership another couple of times until the last owner went bankrupt in 2011. GEA is yet again a model example of an early Danish pharmaceutical company which was established as an individual company, and which had a long commercial success with the production and marketing of generics. GEA's earliest products, the organotherapeutics, were not innovations. The innovative products were developed already in the 1890s in Denmark by Alfred Benzon, and later on copies followed a.o. from Medicinalco and from foreign companies before GEA marketed their generics. Therefore GEA had to promote their preparations as especially qualified medicinal products and to intimate that the products of the competitors were less "active'". At the end of the 1920s the Ministry of Health became aware of the fact that there might be health problems related to the none-existing control of both the or- ganotherapeutic preparations and actually also the other medicinal products of the pharmaceutical industry. Therefore the Ministry had requested the National Board of Health for a statement regarding this problem. The National Board of Health was, however, at that time of the opinion that there were no serious problems with organotherapeutics from those companies marketing such products. It requires studies in the unprinted journals of the Ministry of Health and the National Board of Health to find the background for and the causes of the request from the Ministry at this point concerning the control of the organotherapeutic products of the pharmaceutical industry. Neither were GEA's barbiturates innovative products. The "Gad Andresen Case" is interesting for two reasons. Firstly, it illustrates that the development of generics at this stage could not always take place exclusively in a pharmaceutical-chemical laboratory, but also required a certain minimum of clinical trials including human beings. Secondly, it shows that the industrial products had now slowly, but surely gained market shares and displaced the pharmacy-produced medicinal products to such an extent that it did not only worry the pharmacy owners and their trade orga- nization. Now this concern had also resulted in a counteract so that the pharmacies in the manufacture of their products had to copy the industrial products, however, in certain cases with a dubious result. Gealgica tablets and especially their content of fenacetine is not only a model example of how the opinion of the positive and negative properties of a medicinal product changes over time. It also shows how long time could pass before the health authorities took measures against a substance with problematic side effects in spite of the fact that less damaging substances had been available for a long time, in this case paracetamol. Medicinal products containing fenacetine were on the market for almost 100 years. On the contrary meprobamat is a model example of a drug substance where the opinion of its positive and negative properties changed essentially over a relatively short period. In spite of this it remained on the market for a little less than 40 years. Restenil and Trihistan are mentioned on Knud & Dagny Gad Andresen's homepage (in 2014) as new medicinal products developed by GEA. This is not quite correct. Both drug substances in these preparations had been developed in the USA. In Denmark GEA had the possibility to market these substances under GEA's own brand names along with corresponding foreign brand names. It can be concluded that GEA's own research on the whole was confined to the development of own patentable syntheses of already known drug substances. During the later marketing of generics GEA appealed to the national feeling of the Danish population in the same way as a.o. Pharmacia did in the 1920s. From the very start GEA specialized in the manufacture of generics, and GEA was able to follow this way with commercial success--as a Danish alternative--for almost 90 years.

摘要

A/S GEA制药厂由药剂师克努德·L·加德·安德森于1927年作为家族企业创立,在此之前他受雇于制药行业。加德·安德森希望经营一家专注于仿制药开发的公司,并且希望这种开发能与丹麦医生密切合作进行。这确实成功实现了。1995年,GEA被美国制药公司百时美施贵宝收购,该公司在一份新闻稿中将GEA描述为丹麦第二大仿制药制造商。此次收购后,GEA的研发部门立即停止了创新产品的研究,从那时起专门专注于仿制药的开发。三年后,GEA被出售给德国仿制药公司赫克塞尔,赫克塞尔后来又将GEA转售给瑞士仿制药公司山德士。GEA又经历了几次所有权变更,直到最后一任所有者在2011年破产。GEA再次成为丹麦早期制药公司的一个典型例子,它作为一家独立公司成立,并在仿制药的生产和营销方面取得了长期的商业成功。GEA最早的产品,即器官疗法药物,并非创新产品。创新产品早在19世纪90年代就由阿尔弗雷德·本宗在丹麦开发出来,后来在GEA销售其仿制药之前,Medicinalco和外国公司等纷纷进行了仿制。因此,GEA不得不将其制剂宣传为特别优质的药品,并暗示竞争对手的产品活性较低。20世纪20年代末,卫生部意识到,由于对器官疗法制剂以及制药行业的其他药品缺乏监管,可能存在健康问题。因此,卫生部要求国家卫生局就该问题发表声明。然而,当时国家卫生局认为,销售此类产品的公司生产的器官疗法药物不存在严重问题。需要查阅卫生部和国家卫生局未公开的期刊才能找到此时卫生部要求对制药行业的器官疗法产品进行监管的背景和原因。GEA的巴比妥类药物也不是创新产品。“加德·安德森案”之所以有趣有两个原因。首先,它表明在这个阶段,仿制药的开发并非总是能完全在药物化学实验室进行,还需要一定数量的包括人体试验在内的临床试验。其次,它表明工业产品现在虽然缓慢但确实获得了市场份额,并在很大程度上取代了药店生产的药品,这不仅让药店老板及其行业组织感到担忧。现在这种担忧也导致了一种抵制行为,以至于药店在生产产品时不得不仿制工业产品,然而在某些情况下结果令人怀疑。Gealgica片剂,尤其是其中的非那西丁成分,不仅是一个药品正负属性的看法如何随时间变化的典型例子。它还表明,尽管早已存在危害较小的物质,如对乙酰氨基酚,但卫生当局在针对一种有问题副作用的物质采取措施之前,可能会经过很长时间。含非那西丁的药品在市场上销售了近100年。相反,甲丙氨酯是一种药物物质的典型例子,其正负属性的看法在相对较短的时间内发生了根本变化。尽管如此,它在市场上销售了不到40年。在克努德和达格尼·加德·安德森的主页(2014年)上提到Restenil和Trihistan是GEA开发的新药。这并不完全正确。这些制剂中的两种药物物质都是在美国开发的。在丹麦,GEA有机会以自己的品牌以及相应的外国品牌销售这些物质。可以得出结论,GEA自身的研究总体上局限于对已知药物物质进行可申请专利的合成开发。在后来仿制药的营销过程中,GEA以与20世纪20年代法玛西亚等公司类似的方式唤起丹麦民众的民族情感。从一开始GEA就专门从事仿制药的生产,并且作为丹麦的一个选择,GEA能够在这条道路上取得近90年的商业成功。

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