By Kenneth Rapoza, CPA Industry Analyst
Why are we dependent on China’s pig population for a critical animal source material used in making heparin? Bovine heparin is the way to ween ourselves from that part of the medical supply chain, currently over-reliant on China.
It is found in hospital crash carts, is one of the essential lifesaving drugs in the world and there is a shortage of it – it’s called heparin. The anticoagulant (blood thinner) is used primarily to treat coronary disease, heart attacks – but it can be used as an input in therapeutics and found to assist in everything from common surgery to asthma medication and Covid-19.
For years we have been facing a heparin shortage and the future forecast only gets worse. In addition, there remains a serious question regarding the quality of crude heparin and all other animal sourced material imported from China. The solution to this shortage and the poor-quality issues can be found here, in the adoption of closed herd cattle protocols and getting the source material from American cattle rather than foreign pigs.
Heparin has long been used in patients vulnerable to blood clots in their legs, lungs, heart or other body parts. It is used to reduce their risk of heart attacks, strokes and pulmonary embolism. Millions of patients with critical illnesses, including those requiring kidney dialysis, are given heparin.
Most of the crude heparin and other animal sourced materials (ASM) come from pigs. And most of those pigs come from China with no regulatory oversight.
In fact, China is the source for 80 percent of the crude porcine-based heparin supply the US consumes.
A Local Supply Solution
Bovine heparin and other animal sourced material used to be considered the gold standard for 80 plus years until a cattle disease caused the US Food and Drug Administration to panic and look to porcine (pig) heparin instead. The FDA is strongly encouraging the conversation to bovine heparin as a local supply solution to the shortage, most of it due to health issues among China’s pig population. The FDA is encouraging bovine heparin development and use, though the roadblock is coming from the purchasers. If the government purchasers gave preference to bovine heparin then that would be the signal for the private market to start buying it again.
Drugs are dependent on two types of active ingredients: they are chemical and biological compounds commonly known as active pharmaceutical ingredients (API) and ASM. Your flu shot has chicken eggs in it, for instance.
API and ASM are the building blocks of the world’s pharmaceutical industry. ASM is often a key biological component of API mixtures, used to make important, daily-use drugs. They are part of the global pharmaceutical supply chain.
The heparin sodium API for injections made in India, for example, a key source of US pharmaceutical imports, mostly come from China. Some Indian companies have been saying that there are not enough alternative manufacturers for heparin. They’re stuck with China.
Prior to the early 1990s, bovine heparin was widely available and used here. The first bovine heparin in this country was approved in 1939, with several other heparins entering the market after that initial approval. The products were found to be safe and effective, and no adverse events associated with their use were ever reported.
It was a bovine spongiform encephalopathy outbreak – best known as “mad cow disease” – that spread from Brazil to the United Kingdom that generated concerns about the use of heparin from bovine sources. This concern led to the voluntary withdrawal by manufacturers of all bovine heparin products from the US. Since then, all heparin approved here and in Europe has been solely sourced from pigs, nearly all of them on Chinese farms, home to the Swine flu and other dastardly animal health problems. Yet, China is still winning the day on this. They are still the main source.
China has proven itself to be an unreliable partner, and can price gouge thanks to its total control of supply chains. On one occasion, when China was short of pig materials, they adulterated porcine heparin by adding a cheaper material to increase the product weight and increase their profits.
China’s Heparin Blunders
Heparin became global headline news from 2007-2008 when adulterated heparin was suspected of being connected to nearly 149 deaths (81 in the US) in 11 countries and over 500 hundred adverse reactions in the US. FDA investigators linked the cases to heparin from China. They concluded that over-sulfated chondroitin sulfate (OSCS) was used instead of the actual heparin. OSCS costs far less and was not being tested with the then existing USP quality control tests.
At that time, yet another viral infection known as “blue-ear disease” was sweeping through China’s pig herds. The disease drove up the price of porcine heparin as supply was constrained.
That wasn’t the last time.
In 2014, Beijing Shunxin Meihua Bio-technical Company, a manufacturer of heparin, received a warning letter after it barred FDA inspectors from accessing parts of its manufacturing site.
Questions of contamination also resurfaced in 2016 when French regulators and the FDA warned a Shandong-based company for using crude heparin batches that potentially were out of specification.
After the 2007 incident crude heparin prices went from $7,000 per kilogram to $36,000 in 2019.
In the last three months, prices of API from China have gone up between 20-35 percent, according to pharma industry associations in India, for instance.
Action on heparin shortages and alternatives is long overdue. It’s been over 6 years since the FDA encouraged the reintroduction of closed herd bovine heparin into the supply chain, but nothing has been done on this yet.
CPA wants to see the pandemic pushing the FDA, Health and Human Services and lawmakers in the right direction on protecting, and expanding, the adoption of closed herd protocols for local, animal sourced materials. As it now stands, pharmaceuticals are one of the key contributors to our trade deficit. We can make these products here and create much-needed middle class jobs and save American farms as we grind our way out of a global health crisis. We can establish manufacturing facilities in rural areas, economic development opportunity zones and Native American reservations as well.
Over the past 20 years, the vast majority of America’s ASM and API supply chain has been outsourced to foreign countries. Bovine heparin produced here will initially supplement the small amount (less than 20%) of domestically produced crude porcine heparin. It would replace, however, China imports.
Without adding bovine sourced heparin to the domestic mix, America will remain dependent on Chinese crude porcine heparin and India’s Injectable Porcine Heparin (made from Chinese crude porcine heparin). That poses a significant supply chain risk, and a meaningful risk to public health, especially if critical drugs become a bargaining chip in foreign policy matters or — in worst case scenarios — API gets used as a sort of weapon by adulterating it with deadly pathogens.
Due to the recent animal health crisis among China’s pig farmers, projections are that China will be short a whopping 500 million pigs, enough to produce over 80 metric tons of heparin. It takes somewhere between 6,000 and 8,000 pigs to produce just one kilogram of heparin. But it takes only 10 bovines to produce the same amount. This difference in the number of animals needed to produce heparin will help manufacturers comply with the traceability required by the FDA to ensure a faster response in case of pandemic outbreaks. The FDA has not been able to solve the American deaths caused by the Chinese adulterated heparin in 2008. Traceability and cooperation by the Chinese government are cited as the reason for being unable to close the case.
Closed herd cattle farms operate under a documented quality system. The farm and animals’ medical records and geographical history are required in order to be used for ASM. The animals are open field, grass feed, minimizing exposure to other chemicals. Bovine heparin is the safer than the ASM sourced from non-documented Chinese pig farms that come from more than 25,000 slaughter facilities in mainland China. Can we watch them all? Can we trust their quality?
An estimated 30 million Americans depend on heparin, including some 800,000 dialysis patients who use it regularly. We estimate that the US spends at least $2 billion dollars a year importing China heparin.
This is a call to Congress to get behind a movement to provide priority for traceable bovine heparin and the adoption of the closed herd quality system for all ASM used in pharmaceuticals. It’s safer, it’s local and it will provide needed support for American cattle farmers. Just as important, sourcing locally reduces, and maybe even ends, dependence on a foreign supply of critical inputs required to make critical medicine.