As the number of cases of infection with the Wuhan coronavirus (formally SARS-CoV-2, with the illness itself designated COVID-19) continues to mount, and China and other countries aggressively perform screening, isolation, treatment, and tracking of patients' contacts, demand for various essential medical items is unprecedented. Ironically, most of the world's supply of masks and respirators, along with other materials essential for health care, comes from manufacturers in China. For example, American medical practitioners and dentists who go through large numbers of surgical masks daily had begun to find their supply chain interrupted by early February.
This situation reveals a vulnerable link in the global supply chain that supports everyday health care in hospitals around the world, and it has elicited concerns at the highest levels of the Trump administration. Peter Navarro, the president's senior trade adviser, urged the government to adopt policies that will limit U.S. involvement in global supply chains that could leave the country vulnerable to shortages in a medical crisis. "This is a wake-up call for an issue that has been latent for many years but is critical to U.S. economic and national security," Mr. Navarro said.
Even absent an aberration like the emergence of a new pandemic virus, drug shortages have plagued the practice of medicine in the United States. University of Chicago researchers in 2018 surveyed 719 pharmacists at large and small hospitals across the country and found that all of them reported experiencing at least one drug shortage in the past year, and 69 percent had experienced at least 50 shortages in that time.1 The majority were generic injectable pharmaceuticals commonly used in hospitals, including analgesics, cancer drugs, anesthetics, antipsychotics for psychiatric emergencies, and electrolyte solutions needed for patients on IV supplementation.
The FDA maintains a current list of drugs that are currently in shortage.2 As of March 11, 99 drugs were on it, and the list read like the contents of the pharmaceuticals cabinet of a hospital ICU or Emergency Room. As a result, hospitals are scrambling to assure adequate supplies of drugs that are in short supply, or to find substitutes for them. In the University of Chicago study, one-third of hospitals actually had to ration drugs at least once. That means that some patients got the second or third choice of a drug treatment, increasing the likelihood that the drug will be ineffective or only marginally effective, or have unwanted side effects.
Thus, the wake-up call that presidential adviser Mr. Navarro referred to is long overdue, and the pharmaceutical sector is particularly vulnerable: China has become the world's largest producer and exporter of the essential "active pharmaceutical ingredients" (APIs) used in the manufacture of drugs, not only in China but also in other countries, including the United States.
APIs in China are currently produced without sufficient quality control to ensure drug safety and efficacy, according to the findings of an important, recent report from the U.S.-China Economic Security Review Commission, which was established by Congress in 2000 when China was permitted to enter the World Trade Organization.3
The report's major points include:
- China is the world's largest producer of APIs, and the U.S. is heavily dependent on drugs that either come from China in finished form or from APIs sourced there.
- Because drug companies are not required to list the country of origin for APIs on drug labels, "U.S. consumers may be unknowingly accepting risks associated with drugs originating from China."
- The Chinese government promotes and protects the nation's pharmaceutical companies to the disadvantage of foreign competitors, as it does in other sectors, such as chemicals, electronics, and telecommunications.
- There are thousands of drug manufacturers in China, and the government's regulatory apparatus has insufficient resources to oversee them. Not surprisingly, it is ineffective, and failures of data integrity and drug safety scandals are common. In 2016, the China Food and Drug Administration investigated 1,622 drug clinical trial programs and rejected 80% of these applications after it found evidence of fraudulent data reporting or submissions of incomplete data, among other problems. (In the U.S. and Europe, the percentage would be in single digits.)
- The deficiencies in regulatory oversight of Chinese manufacturing also extend to the U.S. FDA. The report observed that the FDA deploys far too few inspectors to China for the large number of manufacturers there.
The report's conclusions are stunning:
1. "Because of U.S. dependency on China as a source of many critical drugs, banning certain imports due to contamination risks creating drug shortages in the United States." As discussed above, even in the absence of such bans, we are experiencing critical shortages of drugs, many of which are important and commonly used here. As a result, U.S. hospitals and EMTs must resort to second- or third-line medicines, because many drugs are produced only by a very limited number of foreign manufacturers.
2. "As a result of U.S. dependence on Chinese supply and the lack of effective health and safety regulation of Chinese producers, the American public, including its armed forces, are at risk of exposure to contaminated and dangerous medicines."
3. "Should Beijing opt to use U.S. dependence on China as an economic weapon and cut supplies of critical drugs, it would have a serious effect on the health of U.S. consumers." And, not only U.S. consumers: If China were to block or slow supplies of common, essential drugs, such as those to treat hypertension, high cholesterol, pain, stroke, cardiac disease, infections, pain and so on, morbidity and mortality would skyrocket worldwide – in effect, cause a policy-induced pandemic.
Complementing the findings of the Commission, a Government Accountability Office report released on Dec. 10, 2019, found that the FDA is not completing enough foreign drug inspections, cannot hire enough inspectors, and provides up to 12 weeks advance notice for some overseas inspections.4 "We have long-standing concerns about FDA's ability to oversee the global supply chain, a High Risk Series issue for 10 years," it concluded.
In summary, quite apart from the threat of disruption caused by the coronavirus outbreak, this is a prescription for disaster. To address the threats it identified, the Commission's report made several recommendations, which focus on congressional actions, including:
1. Congress should hold hearings to assess: (1) the capacity of the U.S. pharmaceutical industry to meet domestic demands; and (2) the extent of the United States' dependence on Chinese pharmaceuticals and active pharmaceutical ingredients; and (3) the ability of the U.S. FDA to guarantee the safety of such imports from China.
2. Congress should direct the Government Accountability Office to prepare a report on the U.S. FDA's ability to conduct inspections of Chinese drug manufacturing facilities.
3. Congress should pass legislation that would require drug companies to "list active pharmaceutical ingredients and their countries of origin on labels of imported and domestically produced finished drug products"; and that would create a "risk-based system making importers of active pharmaceutical ingredients (APIs) and finished products liable for any health risks incurred by consumers in the event the product is proven unsafe."
4. Congress should require Medicare, Medicaid, the U.S. Department of Veterans Affairs, the U.S. Department of Defense, and other federally funded health systems to buy pharmaceuticals only from domestic or foreign FDA-certified production facilities (unless the FDA finds that a specific drug is not available in sufficient quantities from such sources).
At least some members of Congress have gotten the message. Earlier this month, Senators Marco Rubio (R-Fla) and Chris Murphy (D-Conn) asked Dr. Stephen Hahn, the Commissioner of the Food and Drug Administration, whether the agency had the "necessary tools to ensure the safety and supply of pharmaceuticals, food and medical supplies" from China, worth $12.7 billion in 2018. We can now answer that question in the negative.
The supply chain disruptions from the COVID-19 outbreak are a reminder that the benefits of globalization of the production of vital medicines should not be compromised by reliance on a single, potentially unreliable source or country. The Commission's proposed sweeping changes are the minimum necessary to protect the health of Americans.
Henry I. Miller, MD, a physician and molecular biologist, is a Senior Fellow at the Pacific Research Institute in San Francisco, California. He was the founding director of the FDA's Office of Biotechnology. John J. Cohrssen, an attorney and psychologist, served in senior positions at White House agencies, including the office of the vice president.
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