Here we go again. A recent Bloomberg article once again cited the potential shortage of Heparin, a critical blood-thinning medication. Attached is the recent article, as well as a case study/excerpt from my book, “Single Point of Failure: The 10 Essential Laws of Supply Chain Risk Management”. Once again, the importance of collecting, monitoring and managing critical supply chain data by the products/value you produce comes front and center. Over the past decade, I’ve worked with more than 50 organizations to design, apply, improve, and deploy activity-based risk management. Contact me @ gary.lynch@theriskproject.com if you’d like to learn more.
Deadly Pig Disease Sparks Fear of a Heart Drug Shortage
By
A case study demonstrates how a critical supply chain can be more vulnerable
than anyone thinks. The drug heparin is derived from animal liver cells and
is a vital anticoagulant (formula C12H19NO20S3). It prevents blood clots and is
used to treat acute coronary disease, a trial fibrillation, thrombosis, and pulmonary
embolism; clinical trials for the treatment of arthritis, asthma, cancer, and
even organ transplants are promising. It is also used in bypass and other heart
surgery operations. In other words, it is a vital drug. David Strunce, president
of Scientific Protein Laboratories, Baxter Lab’s main supplier of heparin, says
that the Yuan Intestine and Casing Factory is not in his company’s supply
chain. Scientific Protein can’t trace its supplies in China in as much detail as it
can in the United States. “We’re all dealing with the China collection system,”
Mr. Strunce reported.
China is the world’s largest heparin exporter, shipping more than $100 million
of the substance a year. China’s lack of consistent oversight of its heparin
industry highlights a regulatory gap that’s opening as drug makers increasingly
go shopping globally for ingredients. 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 2008, more than 85 percent of these
heparin exports went to the United States, Austria, France, Italy, and Germany,
according to an industry trade group.
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 that a drug company or the FDA could
later tap into. Many heparin processors, including Changzhou Scientific Protein
Laboratories (SPL), the plant that supplies Baxter, are registered as chemical or
agricultural-byproducts companies and weren’t checked by health authorities.
Abraxis Pharmaceutical Products, or APP Pharmaceuticals, Baxter’s main rival,
says its Chinese supplier, Shenzhen Hepalink, is able to trace refi ned heparin
back to individual pigs. Shenzhen Hepalink also says it requires suppliers of raw
heparin to follow rules designed to minimize the chances of contamination.
The agency did, at most, 21 inspections of Chinese drug-making facilities
annually in fiscal years 2002 through 2007, according to the U.S. Government
Accountability Office (GAO). That represents a fraction of the 714 Chinese facilities
that, as of the end of fiscal 2007, the GAO says were involved in making
drugs or drug ingredients for the U.S. market. FDA Commissioner Andrew von
Eschenbach has said he would like to station inspectors in China.
Because heparin 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 may contain active viruses or bacterial toxins. Since
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192 Single Point of Failure
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 drugmakers 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 business people
and middlemen can easily “provide buyers with fake records.”14
By 2010, China is expected to produce nearly 25 percent of the world’s
pharmaceutical ingredients, according to a recent study by the investment firm
Credit Suisse. “If you haven’t been in a plant for the last two or three years,
you don’t have any clue what’s going on in those places,” said a congressional
source familiar with investigative work into the FDA by the House Commerce
Committee’s subcommittee. “They could be running monster truck rallies on
the plant floor, and we wouldn’t know about it.”
“The computer infrastructure is outdated, it’s not stable, there is insufficient security and capability,” said Dale Nordenberg, a Science Board member
who specialized in the computer systems. “The FDA is still relying on
an amalgamation of paper-based records and poorly integrated electronic
platforms.” The two main FDA databases cannot agree on how many foreign
companies are subject to FDA inspection. One claims the number is 3,000,
the other 6,800. Compounding the confusion, the FDA uses corporate
names, rather than identification numbers, to track production plants and
registration information. For an agency monitoring the operations of companies
in dozens of countries worldwide, this creates confusion. Indeed,
Scientific Protein’s China operation slipped through the FDA’s inspection
regimen primarily because of confusion over the company’s name. But
Nordenberg is hardly encouraged by the agency’s admission this was at the
root of the FDA’s failure to inspect the plant. “That’s just another heparin
timeline,” he said.15
One expert says as much as 70 percent of China’s crude heparin—for
domestic use and for export—comes from small factories in poor villages. One of
the biggest areas for these workshops is in coastal Jiangsu Province, north
of Shanghai, where entire villages have become heparin production centers.
In a village called Xinwangzhuang, nearly every house along with a narrow
street double as a tiny heparin operation, where teams of four to eight
women wearing aprons and white boots wash, splice, separate, and process pig
Law #6: Managing Production Risk Is a Dirty Job 193
intestines into sausage casings and crude heparin. The floors had large puddles
and drainage channels; the workshops were dilapidated and unheated;
and steam from the production process fogged up the windows and soaked the
walls. There were large ovens to cook ingredients and halls lined with barrels
to store enzymes, resins, intestines, and wastewater. “This is our family-style
the workshop,” said Zhu Jinlan, the owner of one heparin operation, who stopped
sorting pig intestines and invited visitors to a back room, where she lives with
her husband and child. “We’ve been doing this for about ten years.”
Experts say the small, unregulated factories could pose dangers because
they do not have the same controls and rules as large slaughterhouses, which
also produce crude heparin. “If you don’t control the incoming source, it’s very
hard to get rid of the contaminants,” says Liu Jian, a heparin expert at the
The University of North Carolina. Mr. Strunce of SPL says his company never buys
directly from the crude-heparin producers, only through its wholesalers, which
he called “consolidators”—Changzhou Techpool, its Chinese joint venture
partner, and Ruihua. His company, he said, has records documenting all the
transactions. But in Rugao, producers of crude heparin tell a different story.
A sales manager for a major supplier, Nantong Koulong, said he sells directly
to SPL without going through either of the two wholesalers. “We provided crude
heparin to Changzhou SPL,” said the sales manager, Chen Jianjun. Some of
Koulong’s stock comes from the unregulated workshops, he said. The owner
of one such workshop, Ms. Zhu in Xinwangzhuang, said she sold to SPL two
years ago. She also sells to Koulong. “We are really a traditional family-style
plant,” she said. “We have no certificate.”
After an outbreak of blue-ear pig, the disease swept through 25 of China’s 31
provinces and regions in 2008, prices soared and many drug suppliers had to
look to the small workshops. The epidemic said Cui Huifei, a heparin expert at
the Shandong University School of Medicine, “made those biotech companies
inevitably purchase from the family-style plants, for cheaper prices.”16
SINGLE POINT OF FAILURE 