安全の落差

 フランス南リヨンの工業地帯でアスピリン製造工場が閉鎖し、欧州・米国ではアスピリン製造設備が無くなる。中国によってその製造は引き継がれ、バイエルでさえ中国から供給を受けている。
 リヨンプラントは、1908年以来ずっとアスピリンを製造し、それでも、世界のアスピリン市場の25パーセントより多くを占めているRhodiaというフランス化学会社の巨人が所有しているが、100年目にして製造を中止する予定だ。Rhodia は約40マイル南にある、西ヨーロッパの最後の鎮痛剤アセトアミノフィン工場を閉鎖した。
 中国は現在世界のアスピリンの約2/3を製造し全世界に供給している。中国の工場は安全だろうか?
 ジェネリック製品の価格に敏感なことが、供給業者の品質保証を困難にしている。数千の中国製薬メーカーの利ざやは薄く、偽造と汚染は珍しくない。2002年に中国で売られた薬剤の8%が偽造であると概算された。
 3週間前にFDAが北京・上海・広州に事務所を開設すると発表した。昨年FDAはジェネリック薬品の有効成分を提供している1,154のプラントのリストを発表したが、43%は中国に39%はインドにあり、米国にあるのはわずか13%だった。
 ブランド薬剤メーカーは長年中国からの成分輸入に反対してきたが、製造のアウトソーシングは大手企業でも始まった。
画像 FDAは1兆ドル以上の消費財の管理監督をしている。米国の消費の約25%にのぼる。食物販売における4660億ドル、薬の2750億ドル、化粧品の600億ドル、およびビタミン剤など180億ドルを含んでいる。全ての輸入品の1/3を監視しなければならない。高々500人の検査官と古いコンピュータシステムではますます無力感に襲われる。
 今年の夏には汚染トマト問題でFDAは汚染源の特定がなかなかできず、壊れた組織であることが証明された。2002年の法律で食物の生産から消費までのトラッキングが必要とされたはずだが、政府は未だに記録の規格化を義務づけていない。
(書きかけ)
----------------
汚染ヘパリン製剤問題の核心はFDAにある/米国
http://kurie.at.webry.info/200803/article_28.html
FDAは医薬品の安全性保証はできない
http://kurie.at.webry.info/200711/article_4.html
世界を危険にさらす薬剤の恐怖
http://kurie.at.webry.info/200804/article_3.html
拙速な審査で治療が患者に提供される/米国
http://kurie.at.webry.info/200810/article_65.html
--------------------------------------------------
The Safety Gap
http://www.nytimes.com/2008/11/02/magazine/02fda-t.html
By GARDINER HARRIS
Published: October 31, 2008

In the belly of an industrial district south of Lyon, France, just past a sulfurous oil refinery and a synthetic vanilla plant, sits a run-down, eight-story factory that makes aspirin, the first pharmaceutical blockbuster. The Lyon factory is the last of its kind. No other major facility in Europe or the United States makes generic aspirin anymore. The market has been taken over by low-cost Chinese producers. Even Bayer, the German company that created aspirin in the 1890s and has fought for more than a century to distinguish its product as the most trustworthy one, now has backup supplies from China.

The Lyon plant is owned by a French chemical giant named Rhodia that has been making aspirin since 1908 and still accounts for more than 25 percent of the world’s aspirin market. But now a century after its entry into the business, the company intends to quit making aspirin altogether. The plant was last renovated in 1992, and it would need an upgrade to continue operating, an investment the company can no longer justify in what has become a cutthroat business. In fact, Rhodia is closing another factory about 40 miles to the south. This one makes the painkiller acetaminophen, which is found in Tylenol. It, too, is the last such facility in Western Europe.

In some ways, this is a nonevent. European factories close; Chinese ones open. Consumers like their commodities cheap, in the case of aspirin as with everything else. China now produces about two-thirds of all aspirin and is poised to become the world’s sole global supplier in the not-too-distant future. But are the Chinese factories safe? Who knows? The U.S. Food and Drug Administration, the European Medicines Agency and other competent government regulators rarely, if ever, inspect them. (By contrast, Rhodia’s plant was last inspected by the F.D.A. in July and is routinely inspected by one country or another.) Companies that import Chinese pharmaceutical ingredients, including aspirin, are required to test the supplies before using them, and some send private inspectors to China to ensure that suppliers use adequate controls. No pharmaceutical maker wants its name to become synonymous with disaster, and the vast majority of drugs that are consumed in the United States are safe. But some industry executives told me that price sensitivity in the generics industry makes it more difficult to fully vet their low-cost suppliers.

In China, where thousands of drug manufacturers sell products in the local markets, profit margins are razor thin, and counterfeiting and contamination are common. In 2002, the Pharmaceutical Association, a Chinese trade group, estimated that as much as 8 percent of over-the-counter drugs sold in China are counterfeit. Contaminated products extend beyond drugs, as was made tragically clear this fall when four Chinese babies died and 53,000 were sickened by melamine, a toxic chemical illegally added to watered-down baby formula to artificially increase the protein count and fool quality tests.

Though no melamine-tainted baby formula from China was found in the United States, it has shown up in other countries. This is the latest in a series of food- and drug-safety scandals. China has in recent years exported poisonous toothpaste, deadly dog food, toys made with lead paint and tainted fish. In one infamous example this spring, Chinese manufacturers substituted a cheap fake for the dried pig intestines used to make the drug heparin, which is given to dialysis and surgery patients to prevent blood clotting. As deaths among those taking the drug mounted, the F.D.A. discovered the taint and banned the contaminated drug. In the end, 81 people may have died from allergic reactions, and tens of thousands around the world were exposed to danger. F.D.A. officials admitted that the agency should never have approved the Chinese-made heparin for sale in the United States; the agency, it turned out, had never inspected the Chinese plant making it.

Concerns about Chinese drugs have become so intense that just three weeks ago, the Health and Human Services secretary, Michael O. Leavitt, announced that the F.D.A. would open an office in Beijing by the end of the year and offices in Shanghai and Guangzhou next year. The agency still plans to send inspectors to China from the U.S., but the offices will provide “an infrastructure that will make those people more effective,” Leavitt said at the time of the announcement.

China’s leap to one of the biggest suppliers of pharmaceutical ingredients in the world happened over the last decade, as the Chinese government subsidized the construction of manufacturing plants that have undercut prices everywhere. Generic drug makers in the United States, where price competition is fierce, were the first to seek cheaper drug ingredients in China. Last year, generic drug applications to the F.D.A. listed 1,154 plants providing active pharmaceutical ingredients: 43 percent of them were in China, and another 39 percent were in India. Only 13 percent were in the United States. Branded drug makers, with their fatter profit margins, resisted buying ingredients from China for years, but with their businesses now suffering, even major pharmaceutical companies like AstraZeneca, Bayer, Baxter and Pfizer have announced deals to outsource manufacturing to China.

I have been writing about the drug industry for more than a decade, but I have rarely written about a subject that both branded and generic drug makers wanted to discuss less. Nearly all of the industry executives who spoke for this article did so anonymously. Even the Generic Pharmaceutical Association, a normally loquacious trade group, was largely silent on the issue. Not one of them, it seems, wants to talk too much about the difficulty of regulating factories across several times zones, 6,000 miles and a vast linguistic and cultural divide.

The F.D.A. regulates more than $1 trillion worth of consumer goods, which amounts to about 25 cents of every consumer dollar spent in this country. This includes $466 billion in food sales, $275 billion in drugs, $60 billion in cosmetics and $18 billion in vitamin supplements. The agency is responsible for monitoring a third of all imported goods, from eggplant to eyeliner, microwave ovens to monoclonal antibodies, slaughterhouses to cellphones. But with fewer than 500 import inspectors and computer systems so old that repairmen must be called out of retirement to fix them, the agency is increasingly beset by a sense of futility.

Even the F.D.A.’s staunchest defenders now acknowledge that something is terribly wrong. Among them is Peter Barton Hutt, who served as the agency’s general counsel during the Nixon administration and is widely considered the dean of the F.D.A. bar in Washington. I’ve interviewed Hutt dozens of times over the years, and he has always defended the F.D.A. No more. “This is a fundamentally broken agency,” Hutt told me earlier this year, “and it needs to be repaired.”

The breakdown is not simply about money. This summer 1,442 people around the country were sickened by tainted tomatoes ― or possibly jalepeño peppers. Such scares have become familiar, and the inability to quickly find the sources of contamination has been one of the agency’s signal failures. A 2002 law requires produce processors and distributors to keep track of where food goes and comes from, but the government has yet to mandate standardized record-keeping. As a result, in response to a scare, investigators must pour over a blizzard of contradictory packing slips and incompatible computer programs as they race to save people.

To ensure the safety of imported drugs, the F.D.A. relies almost entirely on its own inspections of foreign plants. This was not much of a problem 30 years ago, when most medical products consumed in the United States were made here and F.D.A. inspectors could drive around to plants in their district. Most of those plants have since moved abroad, and now decades can pass between inspections. Testifying before Congress in April, Dr. Janet Woodcock, director of the F.D.A.’s drug center, spoke with rare frankness about the ability of the agency to do its job abroad. “The F.D.A. of the last century is not configured to regulate this century’s globalized pharmaceutical industry,” she testified.

Other current and former F.D.A. officials I talked to echoed Woodcock’s warning. Tim Wells, who was a field investigator and then a compliance officer for 24 years at the F.D.A., now does private audits of drug plants and sees the holes in the agency’s safety net. “A company I recently visited abroad hasn’t been inspected for 10 years,” he told me.

Besides being more frequent, domestic inspections are unannounced and more intense. And when inspectors find dangerous conditions at domestic plants, they generally return promptly to ensure that those conditions get fixed. Not so in foreign plants. In a report released Oct. 22, government auditors reported that between 2002 and 2007, F.D.A. inspectors found dangerous conditions in 15 foreign plants. Only one of those plants was reinspected within two years, the auditors found. In every other case, the agency took foreign managers at their word that promised changes were made.

The record is particularly bad in China. Over the past six years, the F.D.A. has managed to inspect annually an average of just 15 of the 714 Chinese drug plants that export to the United States. At its present pace, the F.D.A. would need more than 50 years to visit all of these Chinese plants. By contrast, the F.D.A. inspects domestic drug plants every 2.7 years.

Inspectors volunteer for the grueling overseas assignments, and, it turns out, they don’t much like traveling to parts of Asia. “I went to Taiwan once, and after initially spending a night in a very nice hotel, I was transferred several hours by car to a hotel closer to the plant,” recalls DeVaughn Edwards, who worked as an F.D.A. inspector for 14 years until he left in 2006. “The bed consisted of two mattresses on the floor. There was no lock on the door. You had to hope that no one came in. It was dark; there were no amenities, no TV that worked. There was a shared restroom down the hall. It was only one night there, but it was enough to make you not want to revisit the plant or spend too much time there.”

When inspectors do go to China, their reports sometimes read like a bureaucratic rendering of Mark Twain’s “Innocents Abroad.” During a 2001 trip, for example, two F.D.A. inspectors visited a plant that was exporting acetaminophen to the United States. The plant had never been inspected. “The F.D.A. inspection team was met at the hotel in Wenzhou by representatives from Wenzhou No. 3 Pharmaceutical Factory and . . . transported by public ferry and then company vehicle to the manufacturing facility on Dong Tou Island off the coast of Wenzhou,” their report states. “There is no street address or plot number, and the address of the facility is given only by the county and province.”

Once the team arrived in what seemed like the middle of nowhere, the inspectors learned the drug was being manufactured at another plant ― one that once had a similar name but had recently changed it. “In fact,” the report continues, “inspection found that there were initially three separate and independent firms operating under the names Wenzhou No. 1 Pharmaceutical Factory, Wenzhou No. 2 Pharmaceutical Factory and Wenzhou No. 3 Pharmaceutical Factory. The location of Wenzhou No. 1 Pharmaceutical Factory was also determined by the F.D.A. inspection team during the visit to Wenzhou, and it was learned that the firm is operating under a new Chinese name; however, the English translation of that name was not available.” So the two inspectors flew back to the

United States ― at taxpayers’ expense ― never having inspected a thing.

The F.D.A.’s apparent inability to keep names straight is no trivial matter. One reason the agency failed to inspect the Changzhou plant that produced deadly heparin, for instance, was that someone mixed up the facility’s name and concluded that the plant had already been inspected. Chinese plant names, a vestige of its once strictly controlled economy, are often very similar, and translations can vary. For instance, there are 57 separate drug master files ― the basic F.D.A. record of a plant’s name, location and approved product ― with “Shanghai” in the name. Some are obvious repeats, like the ones for “Shanghai No. 6 Pharmaceutical Factory” and “Shanghai Number 6 Pharmaceutical Factory.” But others could be separate plants. Or maybe not. It’s just too hard to tell.

Compounding the problem is the F.D.A.’s antiquated technology. Its computer systems are so awful that officials have no way of knowing which names, or which plants, are real. To determine which factories need to be inspected, agency investigators must consult two incompatible databases, one of which lists 3,000 foreign drug plants exporting to the United States and the other 6,800. Which number is right? Nobody really knows. Officials have told House investigators that their best guess for the number of foreign drug plants exporting to the United States is 2,967, while the Government Accountability Office recently guessed 3,249. Neither can the agency tell in many cases when the plants were last inspected (or, more important, which have never been inspected), where they are located or what products they make.

The combined ports of Los Angeles and Long Beach receive about 45 percent of all ship-borne trade that comes to the United States, or some 5.2 million containers a year. When I visited one day in May, giant cranes were unloading and loading more than 30 ships, each bearing about 2,500 containers. Some 40 to 50 of those containers ― a tiny fraction of the total ― were trucked to a gigantic warehouse about a half-mile from the ports. There the F.D.A. and Customs and Border Protection cracked open shipping containers that they considered suspicious and then emptied the containers into a large examination area in front of the bays, arranging the boxes and crates as if they were pathologists lining up organs from an autopsy.

Just about every crate I saw contained some kind of food product. One crate came from Indonesia, and its manifest said it contained products with chicken inside. Indonesia plus chicken suggests avian flu to F.D.A. officials. So they decided to take a look. The crate turned out to contain chicken seasoning, but no actual chicken. Still, the cans were sent off for testing. Deeper into the guts of the container were glass jars of sambal terasi, a hot sauce. They would probably be sent back because the F.D.A. requires makers of low-acid foods in jars or cans to register with the agency.

The labels on high-end olives from Italy were lacking the required nutritional information, so back to Italy they went. Jars of jam made of figs and tangerines indicated they were produced close to Ukraine, so an F.D.A. inspector said that he wanted to sample the product for radioactive fallout from the 1986 Chernobyl disaster.

As I wandered through this cornucopia, I realized that I had seen similar products at specialty grocery stores all over New York. My brother is a gourmet chef, and I bet an F.D.A. inspection of his kitchen cabinets would net a sizable seizure of improperly labeled food of suspicious provenance. The F.D.A., after all, inspects less than 1 percent of all imports.

This year, 18.2 million shipments of food, devices, cosmetics and drugs are expected to enter more than 300 U.S. ports; the F.D.A. had 454 investigators in 2007 ― one and a half per port ― to scrutinize them. Theirs is an almost hopeless task, made even more frustrating by the inability of one part of the F.D.A. to share even its most basic information with another. Inspectors in Los Angeles, for instance, have no way of knowing which Chinese drug or device imports really ought to be reviewed because they do not have access to records of F.D.A. plant inspections. If the agents knew, for example, that an F.D.A. inspector had found significant problems at a particular facility, they could be sure to check for the maker’s name on a shipping manifest. But they have no way of knowing where to focus their attention. “Our current nonautomated approach to entry screening cannot continue,” Woodcock of the F.D.A. told Congress. “We need to be able to assure that both the product and site of manufacture are acceptable before a drug gets into our country.”

I met Yusuf K. Hamied in the lobby of the Waldorf-Astoria Hotel, where he likes to stay when visiting New York City from his home in Mumbai. He greeted me warmly and turned quickly to the matter at hand. “Let’s go eat,” he said, steering me to a nearby Chinese restaurant where the maître d’ greeted him by name and showed us to a quiet table.

Hamied is the chairman and managing director of Cipla, the giant Indian generic drug manufacturer. A small man with thinning white hair and well-tailored suits, Hamied has become something of an international public-health hero. In September 2000, Hamied walked into an international meeting on AIDS and other diseases and promised to sell a cocktail of AIDS drugs for about $600 per patient per year, a fraction of the price then being offered by large drug makers. “Friends,” he told the crowd, “I represent the needs and aspirations of the third world. I represent the capabilities of the third world, and above all I represent an opportunity.”

Until Hamied’s announcement, most leaders and even many charitable organizations had dismissed the possibility of treating impoverished Africans and Asians who were infected with H.I.V. Drug combinations that kept the infection at bay cost upward of $15,000 per year, a price even those in rich nations strained to bear. But by defying Western companies that held the patents on the medicines, Hamied, whose offer was later lowered to $350 and then to $80, changed everything.

この記事へのコメント

2008年11月03日 18:39
私はあまり薬はのまないけれど、
そんな私が一番たくさんのむ薬は
鎮痛剤です。

私は中国を信用できないでいるので
この記事を読んですごく不安です。

中国のさまざまな問題の原因は、
教育不足による視野の狭さからくる
知識不足だと思います。

人口が多いと、教育も広く浅くに
なってしまうのかも知れませんが、
容易にコントロールするためには
知らない方が良いという点を悪用
しているような感じもするし。
そんな現実に、急激な経済発展が
その人間性すらねじ曲げてしまって。

長い歴史の中で数々の偉大な人物を
送り出してきた中国の指導者たちの
本当にしたいことがこの現実なのか。
とても信じられない気持ちでいっぱい。

私は、今の中国には、はっきりNO!
と言わなくてはいけないと思います。

この記事へのトラックバック