Another drug contamination has been reported in the news lately. This time it's Heparin, a blood thinning drug that is used to prevent clots from forming in renal dialysis machines, administered during open-heart surgery, or to treat deep vein thrombosis.
Here's an interesting (and heavily truncated) article from the Wall Street Journal.
The Heparin Trail: China's Role In Supply Of Drug Is Under Fire
By GORDON FAIRCLOUGH and THOMAS M. BURTON
February 21, 2008; Page A1
YUANLOU, China -- In a small, damp factory here, blood-smeared men wring pulp from pig intestines, then heat it in concrete vats.
The activity at Yuan Intestine & Casing Factory is the first step in the poorly regulated process of making raw heparin, the main ingredient in a type of blood-thinning medicine that in recent days has come under suspicion in the deaths of four Americans.
More than half the world's heparin comes from China. The chemical is often extracted from pig entrails in small factories -- many as rudimentary as this one, which also manufactures sausage casings from intestines. The heparin eventually ends up in drugs used world-wide by patients having surgery or who need dialysis.
(For a fascinating slide show: http://online.wsj.com/article/SB120352438415380201.html)
Heparin goes through extensive processing in its journey from abattoir to IV bag. Nevertheless, because some of it originates in tiny Chinese factories like these, if there's a problem with the final medication, it can be nearly impossible to trace the raw heparin back to the source, the pigs whose tissue was used to make it.
The lack of a well-documented supply chain for medicines such as heparin is a problem that has come under the spotlight with last week's announcement of four deaths and some 350 allergic reactions among patients who received heparin sold in the U.S. by Baxter International Inc. Yesterday the Food and Drug Administration, which is trying to pinpoint the cause of the deaths, inspected a heparin-production facility in China.
[…]
The growing concern over heparin's safety brings to the forefront the question of whether the raw materials from which it is made -- for that matter, the raw materials for any drug derived from animals -- should be more tightly controlled. The FDA's position is that the purification steps in the drug-making process are sufficient to produce a pure product from pig tissue, and that 'companies are responsible for sourcing the materials' and 'appropriately processing the material.'
Heparin goes through numerous, intensive purification steps before reaching medicine cabinets. However, some doctors and industry executives say it's still essential that even raw materials be consistent, clean and traceable so that if a problem arises it can quickly be contained.
[…]
Heparin makers in China readily acknowledge the lack of oversight. Yuan Changkun, the owner of the small factory here, says health regulators don't visit his plant. Mr. Yuan doesn't keep records of where he acquires the intestines he uses. Nor is he sure who the end customers are.
'Basically, it goes overseas. It's for foreigners,' he says.
Selling to Middlemen
Like many small producers, Mr. Yuan sells his output to middlemen, making it tough to know where in the world it eventually ends up.
[…]
In contrast with the FDA's position that the heparin-purification process alone may be sufficient, Patrick Soon-Shiong, APP's chairman, contends that the ability to trace back to individual animals is important. Heparin is extracted from the guts of the animal, he notes, 'and lymph nodes in the bowel may harbor contaminants from infections.'
The raw heparin made by China's myriad small producers ends up in the hands of about 50 export companies, which sell to customers overseas. In the first half of last year, more than 85% of these heparin exports went to the U.S., Austria, France, Italy and Germany, according to an industry trade group.
[…]
Supply Workshops
[…]
An ideal system for tracing heparin back to the barnyard would involve tagging individual pigs, then keeping files detailing each animal's record of vaccination, feed and overall health. That record could follow the animal to the slaughterhouse, providing a paper trail which a drug company or the FDA could later tap into.
[…]
China Jurisdiction
[…]
A spokesman for the Chinese government's main product-safety watchdog, the General Administration of Quality Supervision, says his agency 'is not responsible for anything related to drug issues.'
That leaves makers of raw heparin with no regular government supervision, many manufacturers say.
[…]
Purifying Heparin
Heparin itself is a molecule related to sugar that's present in pigs, sheep and other animals. Because it is derived from living tissue, companies that purify raw heparin follow a range of steps -- filtration, heat treatments and other processing -- to reduce the risk that it contains active viruses or bacterial toxins.
Since mid-2006, China's pig herds have suffered serious outbreaks of porcine reproductive and respiratory syndrome, a viral illness commonly known as blue-ear disease. Sick animals are supposed to be rejected by slaughterhouses, but enforcement can be lax. Also, infected animals may be slaughtered before symptoms are recognized.
Some drug makers say it's important to be able to trace back to the pigs that served as raw materials. That way, if patients have adverse reactions to a drug, the root problem can be discovered and other possibly tainted batches can be pulled from the market.
Many Chinese heparin manufacturers say this is a very difficult standard to meet in China's business and agriculture environment. Wang Shengfu, manager of another raw-heparin maker in China's Shandong province, Linyi Meiyuan Seasoning Co., notes that unscrupulous businesspeople and middlemen can easily 'provide buyers with fake records.'
His firm uses pig intestines only from slaughterhouses owned by its parent company, he says, so it can keep accurate records.
Mr. Yuan, the owner of the heparin and sausage-casing factory in the village of Yuanlou, is a gregarious man who takes pride in the business he has built. Now 57 years old, he has earned enough money from heparin to send his two sons to university.
Mr. Yuan himself never graduated from high school because his family was too poor to pay for school.
He launched the original business in the mid-1980s making sausage casings from intestines. Later he added heparin production.
Mr. Yuan's four-room factory, which has a roof made of tile and thatch, is part of the compound in which he also lives. In a central courtyard, raw heparin -- a brown-and-white powder -- air-dries on a table.
Every day, his company collects barrels of pig intestines from slaughterhouses in the region. 'They give us a commodity. I give them money. We don't keep records,' he says. The intestines of about 3,000 pigs are required to produce a kilogram of heparin.
In his factory, men in thick aprons untangle intestines at a bench, flush them with water and pass them through a wringer. The resulting slurry is dumped into concrete vats, where it gets heated. Because coal is expensive, the factory sometimes burns rubbish -- old shoes and clothing -- to heat the slurry.
The slurry is later mixed with a resin that adheres to heparin. That mix passes through several more steps. Toward the end of the process the raw heparin is stored in old-fashioned, Chinese-style ceramic pots on the floor.
Mr. Yuan produces about six kilograms of the stuff a month, which he sells to middlemen. Recently it has been selling for 6,500 yuan, or about $900, a kilogram.
Not all factories are so primitive. Mr. Wang, the owner of the Anhui plant, recently invested in a larger facility that uses stainless-steel tanks and other more modern equipment. There, workers on three assembly lines process the intestines of 6,000 pigs a day.
[…]
Ellen Zhu in Yuanlou, China, and Anna Wilde Mathews in Washington contributed to this article.
Write to Gordon Fairclough at gordon.fairclough@wsj.com and Thomas M. Burton at tom.burton@wsj
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