In 2008, I got an unusual phone call from a guy named Joe Graedon. Joe said he was getting flooded with complaints from patients who had recently been switched to generic drugs. Joe was a trained pharmacologist and cohost of a radio show on NPR. Patient after patient said their generics were causing unwelcome side effects or even relapses. Joe believed the patients' claims. But when he reported these complaints to the FDA, officials there argued, "It was probably psychosomatic. Patients are upset by pills that look different from their old ones." Joe didn't buy it. He wanted someone with investigative firepower to dig into this, and since I was an investigative journalist, he called me. And then he posed a question that I couldn't get out of my head: "Katherine, what is wrong with the drugs?"
2008 年,我接到了 一通不同寻常的电话 是一个叫乔 · 格莱登 (Joe Graedon)的人打来的。 乔说,最近他收到了大量的投诉 来自近期改服仿制药的患者们。 乔是一位训练有素的药剂师, 同时,也搭档主持全国公共广播电台 (NPR)的一档电台节目。 一位又一位病人抱怨说, 仿制药带来了许多不良副作用, 甚至导致病情复发。 乔相信了病人的说法。 但当他把这些投诉上报给 美国食物及药品管理局(FDA)时, 那里的官员辩解说, “可能只是心理作用。 药片的样子和以前的不同, 病人因此觉得不满。” 乔没有买账。 他想请有调查火力的人 深挖这个情况, 因为我是一名调查记者, 他便联系了我。 然后他提出了一个问题, 一个在我脑海里挥之不去的问题: “凯瑟琳,这些药出了什么问题?”
I spent the next 10 years trying to track down the answer. Our health care system relies on generics. My family does, too. But a decade of interviews, meetings with whistleblowers, on-the-ground reporting across four continents and thousands of confidential files -- from the FDA, from generic drug companies and from the courts -- all pointed me in the same direction: a large number of generic drug manufacturers in certain overseas countries are passing off substandard drugs as legitimate generics for profit. They are deliberately flouting FDA regulations and standards. Basically, they are committing fraud.
接下来的十年里, 我试图追踪这个问题的答案。 我们的医疗系统依赖仿制药。 我的家人也是如此。 但经过十年的采访, 与知情者的会面, 跨越四大洲的实地探访, 以及数千份来自—— 美国食物及药品管理局, 来自仿制药公司, 以及来自法庭的机密文件—— 都将我指向了同一个方向: 在某些海外国家的 许多仿制药生产商 在把假冒伪劣的药品 伪装成合法仿制药出售 以攫取利润。 他们公然无视了 药监局的规章和标准。 本质上说,他们犯了欺诈罪。
In the process, they are risking the health of patients around the world. They may even be costing patient lives. One leading company in India has already shut down because of this activity. I wanted to know, was that company an outlier or the tip of the iceberg? What I uncovered is disquieting, and anyone who takes generic drugs has the right to be deeply concerned.
在这个过程中,他们让世界各地 患者的健康遭受威胁, 甚至有可能危及患者的生命。 印度有一家大型制药厂就 已经因为这些行为关闭。 我想知道, 那家公司是个例, 还是冰山一角? 我的发现令人不安。 任何服用仿制药的人 都有权对此深表忧虑。
If you're skeptical about any of this, that's fair. I saw generics as one of the world's great public health innovations, a giant win for patients worldwide. Ninety percent of our drugs today are generic. I knew generic HIV/AIDS medicine had saved many lives in Africa. Here at home, programs from Medicare to Medicaid and the Affordable Care Act depended on them. In an overpriced drug market, generics were the heroic underdog. But my biggest assumption was based on the FDA's reassurance that properly regulated generic drugs are not only safe and effective, but bioequivalent, interchangeable with the brand and with one another. Well, that's true -- if companies follow the rules on paper. But inside far-flung drug plants, I uncovered a different, unwritten set of rules.
如果你对我说的任何事表示怀疑, 那都是情有可原的。 我认为仿制药是世界上 非常伟大的公共医疗创举, 是对全球患者的巨大胜利。 今天,我们 90% 的药物是仿制药。 我知道非专利的艾滋病药物 在非洲拯救了无数生命。 在美国, 联邦医疗保险(Medicare)、 医疗补助(Medicaid) 和平价医疗法案 (Affordable Care Act) 都要依靠仿制药。 在定价过高的药品市场中, 仿制药可谓是失败的英雄。 但我最大的假设是 基于美国药监局的保证, 即正确监管的仿制药 不仅安全有效, 还具有生物等效性, 和品牌药以及其他 仿制药能够互换使用。 好,这点确实没错—— 前提是公司遵守了明文规定。 但在遥远的药厂里, 我发现了一套 不同的、不成文的规定。
I started my investigation by focusing on the regulatory framework. Right away, one fact surprised me: the FDA does not vet manufacturer applications by testing the drugs. Instead, it reviews company data. As the FDA's generic drugs director actually told me, "The approval system requires the ethical behavior of the applicant. Otherwise, the whole house of cards will fall down." Really? It's the honor system?
刚开始调查时, 我的注意力在监管框架上。 很快,有了一个另外吃惊的事实: 美国食物及药品管理局 筛查药物制造商的申请 依据的不是对药物的测试, 而是对公司数据的审核。 正如美国药监局 仿制药的主任告诉我的, “许可系统需要申请者的行为 合乎伦理道德规范。 否则,整个系统都会崩塌。” 真的?仅仅依靠自觉吗?
(Laughter)
(笑声)
After nine months of digging, I published my first article on generics. I wrote about patients who'd been switched to generic drugs and suffered medical setbacks. I quoted doctors who questioned whether generics really were bioequivalent to the brand. A month later, I got an anonymous email from someone calling himself "Four Dollar Refill."
经过九个月的调查, 我发表了第一篇关于仿制药的文章。 我讲述了改服仿制药的患者 如何遭受了病情恶化。 我引述了医生们的话, 他们质疑仿制药是否真的 具有与品牌药等同的生物等效性。 一个月之后, 我收到了一封匿名邮件 发件人自称 “四美元续药” 。
(Laughter)
(笑声)
Four dollars is what you'd pay to fill a generic prescription at Walmart. Four Dollar Refill worked inside the generic drug industry. He said if I really wanted to uncover the problem, I'd better go look where the majority of our generic drugs are made: in India and China. Four Dollar Refill was right; 80 percent of the plants making the active ingredient for all our drugs, brand or generic, are overseas, mostly in China and India. Any generic drug company anywhere in the world wanting approval to sell its drugs into our market has to follow elaborate rules known as "Good Manufacturing Practices."
四美元是你在沃尔玛 购买仿制处方药的价格。 “四美元续药” 在仿制药行业内工作。 他说,如果我真的想 调查这个问题的真相, 我最好应该去看看 大部分仿制药被生产的地方: 印度和中国。 “四美元续药” 是对的; 制造我们所有的药物, 包括品牌药和仿制药的 活性成分的工厂 有 80% 都位于海外, 主要在中国和印度。 在世界任何地方的任何仿制药公司 若是想得到向我们市场 出售其药物的许可, 都必须遵守一套被称为 《良好生产规范》的详尽法规。
I decided to learn every detail of how to manufacture a legitimate generic drug. At a top New Jersey lab, I watched as technicians ran tests on specialized machines and used flasks that mimic stomach conditions to measure drug dissolution. But one remarkable fact jumped out. The lab banned Wite-Out -- correction fluid -- across its facility. Under FDA rules, data serves as the cornerstone of quality. It has to be gathered at each manufacturing step, preserved and shared with regulators. Wite-Out was high-risk. It invited tampering. It was clear that for the FDA's regulatory regime to succeed, any company applying for approval had to be ethical, and its data had to be unaltered. But what if neither was true? What if the applicant was not ethical? What if the data was not pristine?
我决定去学习 如何生产合法仿制药的每一点细节。 在新泽西一间顶尖实验室, 我看着技术员在专业机器上进行测试, 用模仿胃部条件的烧瓶 测量药物的溶解过程。 但有一个细节引起了我的注意。 这间实验室—— 在所有设施中 禁用了涂改液。 在药监局的规章下, 数据是质量的基石。 在生产的每一步骤都必须收集、 保管数据, 并将其与监管者分享。 涂改液会带来很大风险。 它会引诱人篡改数据。 很明确的是, 药监局的监管制度想要成功实施, 任何申请许可的公司 都必须遵守伦理道德规范, 且其数据必须是未经改动的。 但要是两者都被违反了呢? 要是申请者并不道德? 要是数据并非原始版本?
I started to hear about a company in India called Ranbaxy, India's largest drug company, one of its first successful multinationals and one of the fastest-growing generic suppliers to the US market. A whistleblower was supplying internal Ranbaxy documents to the FDA. I got copies. Deciphering the company's charts, graphs and numbers unveiled a shocking swindle. They substituted unapproved, lower-purity ingredients. They invented documents like standard operating procedures, steaming them overnight in a sauna-like room to make them look old. They conjured up three-, six-, nine- and 18-month stability studies, all generated on the same day.
我开始听说一家位于印度叫 兰伯西(Ranbaxy)的公司, 它是印度最大的制药公司, 是印度首批成功的跨国公司, 也是美国市场中增长 最快的仿制药供应商。 一位知情者把兰伯西的内部文件 提供给了美国药监局, 我也得到了这些文件的副本。 解读了这家公司的图表和数据后, 我揭开了一个令人震惊的骗局。 他们替换了未经批准的、 低纯度的原料。 他们编造出类似 标准操作流程的文件, 在桑拿房一样的房间中 连夜干蒸这些文件, 让它们看上去像用旧了一样。 他们捏造出 3 个月、6 个月、 9 个月和 18 个月的稳定性研究, 结果全都是在同一天生成的。
Gradually, I was able to unearth the story behind this regulatory nightmare. In 2004, Ranbaxy hired a new research and development director. He suspected something was amiss. He ordered a young engineer named Dinesh Thakur to study the data in every drug application to find out if it was real or fake. Thakur eventually put together a devastating PowerPoint showing Ranbaxy had falsified data for over 200 products in more than 40 countries. The new R and D director showed this PowerPoint to a subcommittee of the board of directors. The subcommittee ordered the report and the laptop on which it was created destroyed. Then they forced Thakur out of the company. Thakur couldn't sleep, thinking about Ranbaxy's perilously bad drugs. So he risked his life to alert the FDA. After an eight-year investigation, Ranbaxy pled guilty to seven felonies for faking data.
渐渐地,我得以发掘出 这场监管噩梦背后的故事。 2004 年,兰伯西雇佣了 一位新的研发部主任。 他嗅到了猫腻, 于是便委任一位名叫迪内西·塔库尔 (Dinesh Thakur)的年轻工程师 研究每一份药物申请中的数据, 辨别数据的真伪。 塔库尔最后整理出 一份骇人听闻的 PPT 演示, 表明兰伯西在 200 多件 产品中伪造了数据, 波及 40 多个国家。 新任研发部主任把这份演示 拿给一个隶属董事会的委员会看。 这个委员会下令对这份报告, 以及编写报告所用的手提电脑 进行销毁。 然后他们强行把塔库尔开除了。 塔库尔夜不能寐, 满脑子都是兰伯西 充满危险的伪劣药物。 于是他冒着生命危险, 向美国药监局发出了警报。 经过一场为期八年的调查, 兰伯西承认了七项 伪造数据的重罪。
An FDA consultant taught me that just like cheap clothing made in distant factories, or "fast fashion," as she called it, there were fast drugs, too, made in pharmaceutical sweatshops overseas with low-quality ingredients and manufacturing shortcuts. In Mexico City, I sat in a bar with a whistleblower. He handed me documents revealing how the cost-cutting generic drug plant where he worked had knowingly released drug batches that contained glass particles. In Accra, capital of Ghana, doctors explained how low-cost Indian and Chinese medicine of all kinds barely seemed to work, even when they doubled and tripled the doses. In Mumbai, I met another whistleblower from a company that I had believed was ethical. He sat there and described the well-oiled machinery of data manipulation his company used to get compromised drugs approved fast. With tears running down his cheeks, he said, "What's going on in the industry is very, very, very dirty."
一位药监局的顾问告诉我, 就像在遥远工厂中 生产的廉价服装一样, 她将其称之为 “快餐时装” , 也有 “快餐药物” , 是在海外制药业的血汗工厂里, 用劣质原料和生产 “捷径” 制造的。 在墨西哥城, 我和一位知情者在酒吧里碰面。 他递给我的文件中揭露了他所工作的 削减成本的仿制药工厂 是如何在知情的情况下释出了 含有玻璃颗粒的药物批次。 在加纳的首都阿克拉, 医生们解释说, 各种廉价的印度和中国药物 几乎完全没效, 即使剂量已经翻了两倍或三倍。 在孟买,我见了另一位知情者, 他来自一个我曾以为 遵守道德规范的公司。 他坐在那里描述了 自己的公司如何熟练地运作 数据操纵的机制, 以便让有问题的药物能快速过审。 他泪流满面地说, “这个产业里发生的一切 非常、非常、非常肮脏。”
In the US, a confidential source who worked in the government handed me a thumb drive containing over 20,000 internal FDA documents. The emails and memos revealed how the agency's public health mission -- protecting consumers -- often clashed with its political mission -- showing Congress a steady stream of low-cost drug approvals. I also learned about the FDA's compromised inspection system for overseas drug plants. In the US, FDA investigators arrive unannounced to do surprise inspections. But overseas, the FDA gives manufacturing plants months of advance notice. It asks for the company's help arranging ground transportation and hotels. My sources also talked about staged inspections, where teams of data fabricators invent or alter needed documents to create a facade of compliance long before the FDA arrives.
在美国,一位在政府工作的线人 给了我一个 USB 闪存盘, 其中含有超过两万份 美国药监局的内部文件。 这些电子邮件和记事揭露了 该机构的公共卫生使命—— 保护消费者—— 常常和它的政治使命冲突—— 给国会呈现持续稳定的廉价药物许可。 我还得知,美国药监局 针对海外药厂的巡查系统 漏洞百出。 在美国,药监局调查员 会未经事前通知地 进行突击检查。 但在海外,药监局给生产厂商 长达数月的提前通知。 它要寻求海外公司的帮助 安排交通和住宿。 我的消息来源 还提到了预演好的检查, 几支篡改数据的队伍 对文件进行捏造或改动, 早在药监局到来之前 就制造好遵守规章的假象。
One intrepid FDA investigator named Peter Baker figured out how to find the truth. He ignored the data printouts, and he looked inside company computers. When files were deleted, he found metadata revealing hidden tests. The companies were prescreening their drugs, figuring how to alter the official tests so they would meet FDA specifications. As I said, this problem is more than a handful of bad actors. Over four years, Peter Baker inspected 86 plants in India and China. He found evidence of fraud in 67 of them.
一位彪悍的美国药监局调查员, 彼得 · 贝克(Peter Baker), 发现了该如何找到真相。 他无视了打印出的数据, 直接查看公司电脑。 当有文件被删除时, 他找到了元数据, 发现了隐藏起来的测试数据。 这些公司在预先审查它们的药物, 研究该怎样修改正式测试结果, 使其符合美国药监局的规章细则。 如我所说,这个问题 远比一群蹩脚演员要严重。 在四年时间里,彼得 · 贝克巡视了 位于印度和中国的 86 间工厂。 在其中 67 间工厂里, 他都发现了造假的证据。
Wonder what happens to a batch of drugs that fails testing? It should get thrown out. Instead, low-cost plants usually sell them into poorly regulated markets that don't realize what they're getting, places like Africa, Southeast Asia and India itself. The overseas generics industry calls this "dual-track production" -- better drugs for some, failed drugs for others. In the developing world, this corrupt system has flooded the market with so many bad drugs that public health researchers link them to the rise of drug-resistant infections.
你是否想过未能通过 测试的药物批次去了哪里? 它们本应被销毁。 然而,低成本工厂常常 把这些药物卖给监管不力、 并不知道入手了什么东西的市场, 比如非洲、 东南亚 和印度自己。 海外仿制药产业把这个 称为 “双轨生产”—— 给某些地方提供优质药物, 给其它地方提供劣质药物。 在发展中世界里, 这个腐败的系统导致市场上 充斥了如此繁多的劣质药物, 以至于公共卫生研究员认为 这些劣质药和耐药性 感染的增长有所关联。
But criminal behavior by overseas companies is only half the problem. Though some regulators apparently don't realize they're being conned, in the US, our regulators appear willing to overlook transgressions in order to continue green-lighting low-cost medicine. As a result, some American patients have gotten generic drugs with toxic impurities, unapproved ingredients, dangerous particulates or that are not bioequivalent. As the FDA investigator Peter Baker put it, if people actually understood, then nobody would take these drugs.
但海外公司的犯罪行为 仅仅是问题的一半。 虽然有些监管者明显 没有意识到自己受到了欺诈, 在美国,我们的监管者看上去 甘愿对违规行为视而不见, 以便继续放行廉价的药物。 结果,某些美国患者 拿到的仿制药中含有有毒杂质、 未经许可的成分、 危险的颗粒物, 或是不具有生物等效性的成分。 正如美国药监局的 调查员彼得 · 贝克所说, 如果人们真的理解其中利害, 那么没人会服用这些药物。
Are there ways to solve this global problem? Yes, there are. Solutions begin with recognizing that our current honor system for drug regulation is a relic of a bygone age. Science evolves. Medicine evolves. The global economy evolves. Shouldn't regulation evolve with them? Only one approach can guarantee quality generics: rigorous oversight, including unannounced inspections and systematic testing of drugs. Rigorous oversight means that regulators don't just look at printouts of data that may or may not be genuine. Effective solutions also depend on giving the average patient more information. We know where our breakfast cereal and our running shoes are manufactured. Why is it different for generic drugs?
有办法解决这个全球性的问题吗? 答案是肯定的。 想要开始解决问题,我们就要承认 目前药厂的自主药物监管系统 已不再属于这个时代了。 科学在进步,医药在进步。 全球经济在进步。 监管制度难道不应该也一起进步吗? 只有一种方法能保证仿制药的质量: 严格的监督, 包括突击检查, 以及对药物进行系统性测试。 严格的监督意味着 监管者不应只看打印出的、 可能真实也可能虚假的数据。 有效的解决方案也需要 给一般患者提供更多信息。 我们知道我们的早餐麦片和跑鞋 是在哪里生产的。 为什么仿制药要区别对待?
Patients can do something else. They can tell their elected officials and consumer organizations to speak up just as loudly to demand quality as they do to demand access. Consumer organizations can do their members a great service by testing and ranking generics, just like cars and washing machines. The big pharmacy chains owe it to the public to test the drugs they dispense. A trip to the pharmacy for affordable medicine shouldn't come with a hidden cost. Now is the time for all of us who care about patient safety to act on what we know.
患者还能做些别的事。 他们可以告诉选举出的 官员和消费者组织, 应像要求获取药物时一样 大声地呼吁要求质量。 消费者组织若是能 像汽车和洗衣机行业一样 对仿制药进行检测和分级排名, 会对其消费者大有裨益。 大型连锁药房应肩负对大众的责任, 检测它们出售的药品。 去药房购买负担得起的药品 不应有任何隐藏消费。 对于所有关心病人 安全的人而言,现在正是 根据我们了解的情况 采取行动的时刻。
Thank you.
谢谢。
(Applause)
(掌声)