Wednesday, August 14, 2019

CHINA RX or in other words, Stupid USA and Stupid India?

For an idea of how China might leverage our dependence, consider what happened in 2010 when China, the dominant global producer of rare earth metals, allegedly halted shipments to Japan. Toyota', one of Japan's biggest car makers, depends on rare earth metals to make its popular hybrid cars. China reportedly didn't end the embargo until Japan released the captain of a Chinese fishing boat that had collided with Japanese coast guard vessels in the East China Sea.6 The world can do without hybrid cars for a while, but in a public health emergency there is no time to wait for medicines. Despite the national security risk our dependence on China represents, US pharmaceutical companies have advocated for making it easier for the Department of Veterans Affairs to buy drugs made in China. Even now, if an altercation in the South China Sea causes Americans to be wounded, military doctors may have to rely on medicines with essential ingredients made by the adversary.

Enterprising minds figured out a way to make a cheap substitute that mimicked the real product, stretching a limited supply of the authentic product. The cheap knockoff, added somewhere during manufacturing, cost nine dollars a pound while the real product cost nine hundred dollars a pound, signaling the contamination was intentional and economically motivated. 49 Dr. Janet Woodcock, director of the FDA's Center for Drug Evalu- ation and Research that oversaw the agency's response to the contamination, said that because the contaminant comprised one-third of some batches of heparin, "it does strain one's credulity to suggest that it might have been done accidentally."50

Federal officials determined that contaminated heparin had been shipped to eleven countries: Australia, Canada, China, Denmark, France, Italy, Japan, the Netherlands, New Zealand, Germany, and the United States.' I lhe former FDA associate commissioner for policy and planning, William Hubbard, said Germany had several deaths. S2 The total number of people harmed globally has never been publicly reported. Chinese officials denied that its companies were responsible. "The oversulfated chondroitin can ... not be a suspected root cause of heparin adverse events as reported in the US media previously," said Jin Shaohong, deputy director general for China's National Institute for the Control of Pharmaceutical and Biological Products, at a news conference at the Chinese embassy in Washington.53 He placed blame on the US manufacturer and wanted to inspect Baxter's Cherry Hill plant.

At 1 a.m. on February 27, the day after FDA officials finished inspecting Changzhou SPL, Charlisa Allen's phone rang." It was Bob calling with good news. A match for a new heart and kidney was found. He told her to come quickly and to bring the kids. Four hours later, as he was being wheeled into the operating room, he pulled her close and whispered, "One of the doctors told me I got the contaminated heparin. I didn't want you to worry, so I didn't tell you. If I don't make it, go after Baxter."55 
itting at a desktop computer in a small, windowless office in a well- known hospital, a pharmacist we'll call Barbara was on the phone with drug company giant Pfizer'* when a curious thing happened. "Where is the doxycycline made ? " she asked, referring to the common antibiotic the hospital buys for conditions ranging from teenage acne to toxic anthrax. "Is it from the United States or coming from another country?" I While on hold, she turned her head away from the receiver and said in a hushed voice, with an air of incredulity, "They were asking me if I was a member of the press. I've never had a drug company ask me that before." After a minute or two, the call ended. Swiveling around in her chair, she was miffed. "They're not going to tell us." The company rep read from a prepared statement, saying that the company is global, its manufacturing is complex and includes numerous suppliers, and it does not provide information on their manufacturing locations because they are subject to change. "I think it means they know people will be concerned based on where they may be getting it," she said. Four months later, we called Pfizer and asked the same question: where is the doxycycline made that it sells? A customer service representative gave us the same answer. "I do not have a specific site for that product.... We are a global company so we have sites all over the world, and we source ingredients from all over the world."2

It's almost impossible to find out where prescription drugs are made. Millions of people are ingesting drugs made in China and don't know it. Hundreds of thousands of physicians are prescribing them, and they don't know it either. The medicines are packaged to look like an all-American product. Information about where drugs are made is kept secret behind a Berlin-type wall. We looked for cracks in the wall and found them. While browsing the internet, we stumbled upon a paper prepared in 2012 by an employee of Thomson Reuters% a business intelligence company, that listed generic drugs including birth control pills, HI V/ AIDS medicine, and medicines for Alzheimer's and Parkinson's diseases made in China and sold in America, and the names of US-based sales partners-3 Ihe document shined a rare light on an opaque market, and it is the only publicly available information we could find that named generic drugs made in China and their distributors in the United States. Here are some of the generic drugs on the list: BIRTH CONTROL PILLS A birth control pill, Levonest", is made in China by Novast Laboratories-.i It is sold in the United States under the name Northstar R.xo located in Memphis, Tennessee: Online pharmacy GoodRx• lists this generic drug made by this company for sale at big-box stores and retail pharmacies including Walgreens% Walmart, Rite-Aid¯, Safeway'S M, CVS% and TargeÜ.6 We verified the information about the country of origin on DailyMed, an authoritative website maintained by the National Library of Medicine located on the campus of the National Institutes of

origin on DailyMed, an authoritative website maintained by the National Library of Medicine located on the campus of the National Institutes of Health. It is the official source of information printed on the drug pack- aging. -Ihe FDA provides and updates the information, which is supplied by manufacturers:  even this not  true as many relabled  meds do not  say where the  original came  from

DailyMed usually has pictures of the drug package, and some images may show the name of the country where the product is made. For Levonest, the photo of the package says the pills are manufactured by Novast Laboratories in Nantong, China, for Northstar Rx in Memphis, Tennessee.8 HIV/AIDS An HI V/ AIDS drug, nevirapine, made by Zhejiang Huahai, is marketed by a privately held US firm Breckenridge Pharmaceutical Inc: that sells drugs to wholesalers, managed care companies, and retail drugstores.9 Breckenridge issued a press release in 2012 to announce the marketing and distribution agreement. 10 Nevira ine was the first eneric dru made in China to receive FDA

Nevirapine was the first generic drug made in China to receive FDA approval. n The Wall Street Journal predicted correctly that its approval was the likely "starting point of any timeline drawn years from now, when China's finished-generics industry is likely a force to reckon with." 12 DISEASE A drug for disease, donepezil, the generic for the brand-name drug Aricept', is made by Zhejiang Huahai Pharmaceuticals. 13 The drug is distributed by Solccf in Cranbury, New Jersey. Solco is the sales and marketing arm of Prinston Pharmaceutical, a spin-off from Zhejiang Huahai. BIPOLAR DISORDER ANO SCHIZOPHRENIA

A drug to treat bipolar disorder and schizophrenia, risperidone, the generic for brand-name Risperdar, is made by Zhejiang Huahai and dis- tributed by Solco.16

HIGH BLOOD PRESSURE A generic, amlodipine besylate, for reducing high blood pressure and relieving chest pain, is made by China Resources Saike Pharmaceutical Company in Beijing for Secan Pharmaceutical< in Malvern, Pennsylvania.17 According to the Secan Pharmaceuticals website, the company name was Beijing Pharma USA but changed its name to Secan Pharmaceuticals in 2007.1* 'Thomson Reuters reported it is not uncommon for Chinese companies to use more Western-sounding names when selling generic drugs in the United States. 19 A high blood pressure medicine, losartan potassium, is made by Zhejiang Huahai and distributed by Rising Pharmaceutical

Company press releases, consumer websites, and DailyMed are other sources ofinformation about drugs made in China and sold in the United States. CANCER A drug to treat metastatic colon and rectal cancer, made in China by Jiangsu Hengrui Medicine Company, is marketed by Sagent Pharmaceuticalsw, a company located in the Chicago suburbs, according to a press release.21 A chemotherapy drug to treat leukemia, lymphoma, and myeloma in children and adults, made in China by Jiangsu Hengrui Medicine Company, is sold in the United States by Swiss drugmaker Sandoz".22

ANTIDEPRESSANTS Solco is selling the generic for Wellbutrin', an antidepressant, according to a press release issued by Prinston Pharmaceutical.23 EPILEPSY An epilepsy medicine for seizures, levetiracetam, is made by Zhejiang Huahai Pharmaceuticals for Prinston Pharmaceuticals.24 ANTIBIOTICS

Doxycycline is being sold by Solco, according to a press release.2S An anti- biotic cream, clindamycin, is sold by Pfizer's generic subsidiary, Green- stone¯. The drug is made in China, according to DailyMed.26 This list is hardly exhaustive, and while China makes a small number of generic drugs for sale in the United States, it is ramping up fast to make even more. Solco is one example, with thirty-four generic drugs pending approval from the FDA, according to the company's website.27 Eighty-nine percent of prescriptions filled in the United States are generic.28 Consumers and doctors can choose among different manu- facturers ofa generic drug. When we searched DailyMed for companies that sell lisinopril for high blood pressure, for example, many options 29 came up. 

As revealed in the following chapters, if China accelerates generic drug production and undercuts other sellers on price and drives them out of the market, Americans may eventually be unable to live without generics made in China. For now, the United States is much more dependent on China for the
active ingredients needed to make many generic and brand-name drugs, over-the-counter products, and vitamins. WHAT'S INSIDE YOUR MEDICINES? Inside every pill are active and inactive ingredients. The active ingredient creates the therapeutic effect. The inactive ones are dyes, preservatives, flavorings, and binders that form the tablet. In regular strength Tylenol• tablets, the active ingredient is acetaminophen. Without it, pills would be as effective as a candy pill. The  inactive active ingredients needed to make many generic and brand-name drugs, over-the-counter products, and vitamins. WHAT'S INSIDE YOUR MEDICINES? Inside every pill are active and inactive ingredients. The active ingredient creates the therapeutic effect. The inactive ones are dyes, preservatives, flavorings, and binders that form the tablet. In regular strength Tylenol• tablets, the active ingredient is acetaminophen. Without it, pills would be as effective as a candy pill. The inactive ingredients are magnesium stearate, modified starch, powdered cellulose, pregelatinized starch, and sodium starch glycolate, according to Tylenol .com. China is the largest global supplier of the active ingredients and  inactive ingredients are magnesium stearate, modified starch, powdered cellulose, pregelatinized starch, and sodium starch glycolate, according to Tylenol .com. China is the largest global supplier of the active ingredients and

China is the largest global supplier of the active ingredients and chemical building blocks needed to make many prescription drugs, over- the-counter products, and vitamins." For specific generic and brand-name drugs, it isn't easy to find where the active ingredients, also called bulk pharmaceuticals or bulk drugs, are made. Drugmakers say the information is proprietary and therefore a trade secret. Companies that manufacture them for generic and brand- name companies are typically required to sign nondisclosure agreements that prevent them from giving out the information to those like us who ask about the ingredients. By scouring the pharmaceutical industry trade press and company press releases, we found drugs, sold by big-name pharma companies, made with active ingredients from China. Here are just a few: active ingredient in Imbruvica•, a medicine for treating lym-

Ihe active ingredient in Imbruvica•, a medicine for treating lym- phoma and leukemia marketed by Janssen", a subsidiary of Johnson & Johnson", is made in China.32 lhc active ingredient in a breast cancer and lung cancer drug, gem- citabine, sold by Hospira", is made in China by Jiangsu Hansoh.33

The active ingredient in vancomycin, an antibiotic of last resort to treat infections that have become resistant to other antibiotics, sold by Hospira, is made in China by Zhejiang Medicines. THE BIG SHIFT In the 1990s, the United States, Europe, and Japan manufactured 90 percent of the global supply of the key ingredients for the world's medi- cines and vitamins.3S Now, China is the largest global supplier. American dependence on China for the active ingredients in many medicines is so significant that a headline in a 2012 pharmaceutical industry newsletter, FiercePharma, blared, "Dangers Aside, Drugmake rs Can't Live without Chinese Active Ingredients."36 The accompanying

When it comes to Chinese-made active pharmaceutical ingredients, Western drugmakers are between a rock and a hard place.... They know Chinese oversight of ingredient manufacturing is insufficient to snuff out substandard producers but that has not deterred companies from buying them anyway." Former federal official Ted Kirk acknowledged, "l think there are active ingredients out there that we basically only get from China, which is a little bit scary." 38 Tie centralization of the global supply for essential ingredients for drugs in China makes it vulnerable to interruption, whether by mistake or design. lfdisruptions occur for an essential ingredient made in China, the United States will wait in line along with Europe, India, and other countries to obtain it. If a global public health crisis occurs, China will Mish

countries to obtain it. If a global public health crisis occurs, China will likely keep its domestically produced medicines at home and stockpile them to secure access for its citizens before seeing to the needs of other nations.

India makes generic drugs for the United States, but it, too, is depen- dent on China for key ingredients to make drugs such as penicillin, according to a Boston Consulting GroupSM study." Unlike the main- stream media in the United States, the Indian press doesn't hesitate to report the health and national security risks of dependence on China. A Financial Express headline blared, "Indian [active ingredient] Industry Faces Chinese Threat," because of its dependence on China. 40 The Eco- nomic Times published a story about the risks to national security, and the opening line was, "Imagine a situation where a soldier's medical kit is running out of essential drugs on a battle front." 41 A deterioration in India's relationship with China could trigger China to withhold supplies of vital components in essential medicines. Indonesia is another country dependent on China, and the soaring prices of materials from there have increased the cost ofdrugs, the Jakarta Post reported. 42 The Indonesian government is having a harder time

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