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RSS订阅Expect a lot more pharmaceutical makers here to get the green light over the next few years. Even as Chinese products are drawing increased scrutiny, the nation's generic-drug industry is gearing up for the export of finished medicines. It is still small -- India's generics-export powerhouse is 10 times as big. But China is already the world's largest producer of raw materials for drugs, and manufacturing those raw materials is a stepping-stone to making the completed product.
That is what happened at Ranbaxy Laboratories Ltd. India's biggest Indian pharmaceutical company by sales started out in 1961 making drug ingredients. In 1988, a Ranbaxy plant in Toansa, India, won FDA approval to export raw pharmaceutical ingredients to the U.S. Ten years later, Ranbaxy launched the first of its own products, the antibiotic cefaclor, in the U.S. following FDA approval. Now, North America is the company's largest market, contributing $391 million in revenue to its $1.34 billion total for last year.
Zhejiang Huahai Pharmaceutical Co., the domestically listed Chinese drug maker that won FDA approval this summer, is 'exactly an example of a Chinese company today attacking the developed markets,' says Yusuf Hamied, chairman of Cipla Ltd., one of India's top drug companies.
Dr. Hamied calls the Chinese 'brilliant scientists and brilliant chemists' and warns that 'India is no match for them if they pick up their English language and pick up a little on regulatory approvals, which they're doing very fast anyway. They are a major, major threat to India, no doubt about it.'
To export its medicine, Huahai must wait until May 2012, when a U.S. patent held by Boehringer Ingelheim GmbH for the AIDS drug nevirapine, which the German company markets under the brand name Viramune, is set to expire. But the FDA imprimatur will make it easier for Huahai to get other approvals and attract American drug partners. Huahai now hopes to replicate its FDA performance with other pharmaceutical products and to start exporting a finished-dosage Alzheimer's drug to Europe as early as next year.
Huahai, for the time being, doesn't plan on following in the footsteps of the Indian generics titans that revolutionized an industry by actively challenging the patents of blockbuster drugs in the courts. 'Currently, we don't think we have that kind of capability or technical knowledge of doing a patent,' says Jessica Yu, Huahai's regional representative for North American and Japanese drug sales. 'It costs a lot of money and what we are focusing so far is manufacturing.'
Huahai currently sells nevirapine to the Chinese government for around $3.50 for one bottle of 60, 200-milligram pills. The company hopes to bid through the Clinton Foundation to sell drugs to Africa. The Clinton Foundation didn't reply to a request for comment.
Whether or not it meets that goal of exporting finished products, the Huahai nevirapine approval is likely to be the starting point of any time line drawn years from now, when China's finished-generics industry is likely to have become a force to reckon with.
Major markets already depend on China for raw drug ingredients, as well as for commodities like vitamin C, for which Chinese manufacturers provide more than 85% of the supply used in the U.S. With it's low costs, China has become the world's largest exporter of raw ingredients for pharmaceuticals. Indeed, China's growing dominance in manufacturing is steadily increasing its power to set the prices of a wide variety of industrial and consumer products. Konda Reddy, a health-care analyst in India for Frost & Sullivan, a research and consulting firm, says Chinese prices for raw pharmaceutical materials are already 10% to 15% below those of their Indian rivals.
Previously 'the Europeans were afraid of India,' says Jinsong Du, a health-care analyst in Hong Kong with Credit Suisse. Now, he says, 'it's China; the growth is so huge.'
The current alarm over toxic drugs, toiletries and toys from China could pose a major marketing challenge to China's would-be generics-export industry. For the past year, China's own drug-regulatory agency, the State Food and Drug Administration, has been embroiled in a huge corruption investigation, culminating in the execution of its former chief, Zheng Xiaoyu, in July for taking bribes from drug companies to speed approvals, the same month Huahai won its FDA approval.
In the spring of 2006, at least 11 people fell ill and five of them died after taking injections of a medicine used to treat inflammation of the gallbladder made by Qiqihar No. 2 Pharmaceutical Co. because the company, to save money, had used diethylene glycol -- the same chemical that the FDA said recently might be in toothpaste produced in China.
Increased scrutiny of goods made in China could complicate the effort of Huahai and other Chinese companies to sell their products overseas. One Huahai customer, Kraemer & Martin GmbH in Germany, declined to comment on its relationship with the company, while another prospective partner didn't reply to a request for comment.
Still, the green light for Huahai's AIDS drug, granted even amid the outcry over the Chinese exports, suggests the mechanism is in place for the country's pharmaceutical-export industry to grow. The raw materials so far have continued to flow, and major companies stand by their Chinese sourcing.
'Our global head of operations comes here every year just to make sure that this relationship and this supply are reliable,' says Yin Xudong, AstraZeneca PLC's vice president of primary care for in China. Chinese drug companies are the main suppliers of the raw ingredients needed to make AstraZeneca's Seroquel, a blockbuster that is used to treat schizophrenia and other mental disorders, according to Mr. Yin. Sales of the drug were $3.4 billion last year.
China is struggling to stem a steady flow of counterfeit drugs; fake Viagra tablets, for instance, can be bought in airport lounges here. But even though enforcement can be spotty or even nonexistent, the country does have relatively strict laws that, at least on paper, protect drug patents. That situation stands in stark contrast to lax patent laws that were the norm for years in India and allowed a generation of Indian drug companies to thrive by churning out cheap copycat pills with impunity.
'Inside China, the intellectual-property rights, as far as the drug patents are concerned, are actually good in terms of the actual laws,' says Mr. Yin. 'The enforcement may have a problem. We will see counterfeits. But the Chinese SFDA will not issue a new drug license for a compound that we already have a patent for. That will not happen.' As a result, he says, 'We don't see this as a major threat to us.'
Over the past three decades, Indian generic-drug makers such as Cipla, Ranbaxy and Dr. Reddy's Laboratories Ltd. have made over the industry by competing fiercely with Western multinationals over drug pricing. The implications have been profound not just for the industry but for consumers, who can purchase cheaper Indian versions of the drugs their doctors prescribe.
India's share of the finished-generics export market, at around $4 billion in 2005, still dwarfs China's, which was $380 million for the same period. But because it had such a small base in 2004, that was up 23%, according to figures compiled by Credit Suisse.
China also had 14% of the $31 billion market for raw pharmaceutical materials, known as active pharmaceutical ingredients, or APIs, as of 2005. That compares with India's 6%. China's rise could threaten other countries, too. Italy, for example, at 10%, is the second-biggest producer of raw pharmaceutical materials.
The pharmaceutical food chain consists of companies that manufacture the chemicals needed to produce ingredients, the ingredients themselves, the finished generic drugs -- China's new horizon -- and, finally, the companies that invent new drugs. There are 906 Chinese companies with active pharmaceutical ingredients listed in the FDA's drug-registration database, according to Christopher C. Kelly, a spokesman for the FDA in Washington.
There are other Chinese companies hoping to win a share of the generics market. Most, like Huahai, are raw-materials exporters aiming to travel up the food chain. For example, Hisun Pharmaceutical Co., established in 1956, is now one of China's largest producers of APIs. And Shanghai Desano Chemical Pharmaceutical Co. exports materials for AIDS drugs to India, Thailand and Brazil.
Huahai, based in Linhai, on China's eastern coast, was founded by Chen Baohua in 1989. He started the company with an initial investment of around $5,000 and 12 employees mixing chemicals in a one-room warehouse. The 44-year-old Mr. Chen now owns 27% of the company's stock and manages Huahai's 2,200 employees.
Huahai used to focus on hypertension drugs but now makes a stable of generic medicines. Though still very small, it saw sales nearly triple to 557 million yuan ($74.2 million) last year from 187 million Chinese yuan in 2002. The company's profit has more than doubled in that same period, rising to 110 million yuan from 50 million yuan. The stock price has also soared in recent years. Huahai currently gets 90% of its revenue from APIs, most of which are exported to drug companies in more than 30 countries.
In April, the FDA sent two officials to inspect Huahai's finished-dosage factory. Xu Pijie, the 42-year-old plant manager, remembers the officials asking hard questions and giving specific advice on how to improve the manufacturing processes.
'They had very detailed specifications about how to wash all the equipment,' Mr. Xu says. 'I was a little nervous.'
今年夏季，中国浙江临海的一家小药厂──浙江华海药业股份有限公司(Zhejiang Huahai Pharmaceutical Co., 简称：华海药业)生产的抗艾滋病药物获得了美国食品和药物管理局(FDA)的认证，不经意间，中国的制药业也平静地通过了一个重要的里程碑。FDA迄今为止的数据显示，这是中国制药企业首次获准向美国出口成品药。
预计今后几年里将有更多的中国制药企业获得FDA的绿灯。尽管中国产品的质量引起了越来越多的关注，但中国的仿制药行业正在大力推进成品药的出口。中国在这方面刚刚起步──印度的仿制药出口规模是中国的10倍。不过，中国已经是世界上最大的原料药生产国，而原材料加工是生产成品药的基础。
这也是印度Ranbaxy Laboratories Ltd.走过的道路。这家印度销售额最大的制药企业成立于1961年，当初也是主要生产原料药。1988年，Ranbaxy在印度Toansa的一家工厂获得了FDA的认证，得以向美国出口原料药。10年后，在得到FDA批准后，Ranbaxy在美国推出了首个自己的产品──抗生素头孢克洛。如今，北美已成为这家企业最大的市场，去年该公司的总收入为13.4亿美元，其中有3.91亿美元来自北美。
印度最大制药企业之一Cipla Ltd.的董事长尤素福•哈米德(Yusuf Hamied)说，华海药业是中国企业进军发达国家市场的一个缩影。
哈米德称中国人是最有才华的科学家和化学家。他警告说，如果中国人的英语水平进一步加强，并获得更多监管认证──他们在这方面进展很快，那么印度将无法与之抗衡。毋庸置疑，他们会给印度造成非常非常大的威胁。
广告华海药业需要等到2012年才能出口这种药品，届时德国公司Boehringer Ingelheim GmbH拥有的这种抗艾滋病药品nevirapine（品牌名Viramune）在美国的专利才会失效。但FDA的认证将使华海药业能够更加容易地获得其它批准，并吸引美国的制药合作伙伴。华海药业现在希望其它药品也能获得FDA的批准，同时最早能在明年开始向欧洲出口治疗阿尔茨海默症(Alzheimer's)的成品药。
华海药业暂时还没有步印度仿制药巨头后尘、在法院上挑战畅销药品专利权的计划。华海药业负责北美和日本市场销售的区域代表Jessica Yu说，目前，我们认为还不具备从事专利药研究的能力或技术知识。这要投入大量资金，而我们目前关注的重点是生产。
华海药业目前向中国政府出售nevirapine的价格为每瓶（200毫克60片装）3.50美元左右。该公司希望参与克林顿基金会(Clinton Foundation)的采购招标，向非洲出售这种药品。克林顿基金会没有回复记者的置评要求。
无论是否实现了出口成品药的目标，华海药业的nevirapine获得认证都可能成为该公司今后几年内发展轨迹的起点，中国的成品仿制药行业也很可能将成为人们不可小视的力量。
世界主要市场目前已经依靠中国提供原料药，以及维他命C等商品。目前，美国市场上的维他命C有85%以上都是中国生产的。由于成本较低，中国已成为全球最大的原料药出口国。的确，中国在制造业中的重要程度与日俱增，这也使其在众多工业产品和消费品上的定价权越来越大。研究咨询机构Frost & Sullivan驻印度的医疗保健业分析师昆达•雷迪(Konda Reddy)称，中国原料药的价格已比印度竞争对手的价格低了10%至15%。
瑞士信贷(Credit Suisse)驻香港的医疗保健研究分析师杜劲松（音）说，以前欧洲害怕印度企业。现在轮到它们害怕中国企业了，这些企业的发展势头非常迅猛。
目前对中国生产的有毒药品、化妆品和玩具的担忧可能会给未来中国仿制药出口业的营销增加难度。过去一年里，中国药品监管机构国家食品药品监督管理局(State Food and Drug Administration)一直在接受反腐败调查，其前局长郑筱萸因在药品审批过程中收受贿赂而在7月份，也就是华海药业获得FDA认证的同一月被判处死刑。
2006年春季，至少有11人在注射了齐齐哈尔第二制药有限公司(Qiqihar No. 2 Pharmaceutical Co.)生产的治疗胆囊炎的药物后患病，其中5人死亡，原因是该公司为了省钱而在药品中添加了二甘醇。FDA称，最近在中国产牙膏中也发现了同样的化学物质。
对中国产商品越来越严格的审查可能会令华海药业和其它中国企业向海外销售产品的努力更加复杂化。华海药业的客户之一德国Kraemer & Martin GmbH对与该公司的关系不予置评，另一家潜在业务伙伴没有回复记者的置评请求。
不过，在对中国出口产品感到恐慌的背景下，华海药业的抗艾滋病药物仍获得了绿灯，这表明中国制药业增长的机制已经开始发挥作用。迄今为止中国的原料药仍在不断出口到海外，而主要跨国巨头也在纷纷从中国采购。
阿斯利康(AstraZeneca)中国区普药业务副总裁尹旭东说，我们的全球运营负责人每年都来这里，就是为了确保这种关系和供应是可靠的。尹旭东称，中国的制药企业是阿斯利康治疗精神分裂症等疾病的畅销药思瑞康(Seroquel)的主要原料药供应商。去年这种药品的销售额为34亿美元。
中国一直在努力遏制仿冒药品的流通。比如，在中国的机场大厅就能买到假冒的万艾可(Viagra, 又名：伟哥)。不过，尽管执法情况并不理想，甚至根本不存在，中国至少在纸面上制定了比较严格的保护药品专利的法律。与此形成鲜明对比的是，多年来印度的专利法形同虚设，众多印度制药企业大肆生产廉价仿制药，却没有受到任何处罚。
尹旭东说，在中国，知识产权乃至药品专利都受到了关注，从法律角度来说保护的力度并不差。执行可能存在问题。我们还将会看到仿冒品。但中国国家食品药品监督管理局不会对我们已经拥有专利的药品发放新药许可。这种情况不会再发生了。因此，我们认为这不是一个主要威胁。
在过去30年里，Cipla、Ranbaxy和Dr. Reddy's Laboratories Ltd.等印度仿制药生产商通过在药品定价上与西方跨国公司展开激烈的竞争推动了该行业的转变。这不但对该行业，而且对消费者也都具有深远的意义，使患者能够以更低的价格购买处方药的印度仿制品了。
印度2005年在成品仿制药出口市场所占的规模为40亿美元左右，远远超过了中国同期的3.80亿美元。但根据瑞士信贷汇编的数据，由于2004年中国的基数很低，这个数字比上一年增长了23%。
到2005年为止，中国在310亿美元的原料药（即API, 活性药用成分）市场占有14%的份额，印度的市场占有率为6%。中国的崛起还可能危及到其他国家。比如，意大利目前是第二大原料药生产国，所占份额为10%。
药品链条中包含生产原料药所需的化学物质的公司、原料药生产公司、成品仿制药公司（中国目前所处的环节）以及开发新药的公司。FDA在华盛顿的发言人克里斯托弗•凯利(Christopher C. Kelly)说，FDA的药品登记数据库中共有906家生产原料药的中国公司。
其它一些中国公司也希望能在仿制药市场上占据一席之地。其中大多数企业都象华海药业一样属于希望向链条上游发展的原料药出口商。比如，成立于1956年的浙江海正药业股份有限公司(Zhejiang Hisun Pharmaceutical Co., 简称：海正药业)现在就是中国最大的原料药生产商之一。上海迪赛诺(Shanghai Desano Chemical Pharmaceutical Co.)则向印度、泰国和巴西出口抗艾滋病药品的原料药。
华海药业是由陈保华在1989年创立的。他对该公司的初期投资约为5,000美元，由12名员工在一个仓库中配制化学品。现年44岁的陈保华目前持有该公司27%的股份，管理着2,200名员工。
华海药业过去的业务重点是高血压药物，但现在已开始生产多种仿制药。尽管规模依然很小，但2006年该公司的销售额已经达到人民币5.57亿元（7,420万美元），比2002年的1.87亿元增长了近两倍。同期该公司的利润增长了一倍多，从5,000万元增加到1.10亿元。华海药业的股票在中国A股市场上市交易，股价近年来也持续走高。华海药业有90%的收入来自于原料药，其产品出口到了30多个国家。
今年4月份，FDA派出两名官员检查了华海药业的成品药工厂。42岁的药厂经理许匹杰（音）回忆道，这些官员询问了一些很难的问题，对如何改进生产工艺也提出了具体建议。
他们对如何清洗所有这些设备提出了非常详细的指标。我感到有些紧张。