Shortages of widely prescribed drugs are endemic in the U.S. To address the problem, we need a policy change that would enable overseas manufacturers to sell products in the U.S. that already have received marketing approval from certain foreign governments with standards comparable to ours and vice versa. In other words, there should be reciprocity of drug approvals.
A pediatrician in South Carolina, Dr. Deborah Greenhouse, recently tweeted:
Today: I tried to prescribe amoxicillin for an ear infection: The pharmacy didn't have it. I tried to prescribe Tamiflu for flu. The pharmacy didn't have it. I tried to prescribe Adderall for ADHD. The pharmacy didn't have it. If that doesn't bother you, it should.
It does bother me. These are important drugs, and such shortages are neither new nor rare. Several years ago, University of Chicago researchers 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 previous year, and 69% had experienced at least 50 shortages in that time. 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. As of January 19, 123 drugs were on it, including two (amoxicillin and Adderall) mentioned by Dr. Greenhouse. The list includes much of the contents of the medicines cabinet of a hospital ICU or emergency room and many drugs used by paramedics.
Hospitals are scrambling to ensure adequate supplies of drugs that are in shortage or to find substitutes for them. In the University of Chicago study, one-third of hospitals had to ration drugs at least once. That means that some patients, like Dr. Greenhouse’s, got the second or third choice of drug treatment, increasing the likelihood that the drug will be ineffective or only suboptimally effective or have unwanted side effects.
The pandemic has contributed to drug shortages in other countries. The U.S. and other governments have expressed interest in increasing domestic manufacturing to provide additional and more diverse global manufacturing capability. Concerns have been raised about reliance on any single country, especially China, the world’s largest producer of active pharmaceutical ingredients (APIs). A 2019 report from the U.S.-China Economic Security Review Commission concluded that the United States is heavily dependent on drugs that are either sourced from China or include APIs sourced from China. This is especially true for generic drugs, which comprise most prescriptions filled in the United States.
The FDA does not track the volume of specific APIs produced by specific manufacturing facilities in China or other countries. It has, however, counted the number of facilities registered by the agency for the U.S. market and found that the vast majority are in the U.S., Europe, India, Canada, and other countries. “As of August 2019, only 28 percent of the manufacturing facilities making APIs to supply the U.S. market were in our country. By contrast, the remaining 72 percent of the API manufacturers supplying the U.S. market were overseas,” with 13 percent in China.
Accordingly, FDA has cautioned that “because of the limitations of available data, we cannot assess the extent of U.S. dependence on China. For instance, we do not have information about the volume of API produced in China or even in the United States, or how much of China’s API output reaches the U.S. market through other countries.”
To ameliorate drug shortages, we need a policy change that would enable overseas manufacturers to sell products in the U.S. that already have received marketing approval from certain foreign governments with standards comparable to ours and vice versa. In other words, approval in one country would be reciprocated automatically by the others (subject to the creation of approved labeling in an appropriate format and other formalities). That would afford drugmakers in those countries rapid access to the U.S. market, helping to alleviate our shortages and preventing future ones.
In effect, the stage has been set for such an advance. The United States has been a leader in the deliberations of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), which has led to harmonized standards among the FDA and its foreign counterparts. These countries now have a standardized dossier for seeking approval of new drugs, the U.S. accepts research conducted in other countries to support applications for the approval of new drugs and devices, and the FDA has established Current Good Manufacturing Practices for foreign production facilities.
Lacking specific legal authority for importing needed unapproved products, the FDA tried to improvise procedures based on its “enforcement discretion,” a practice disallowed by the U.S. Federal District Court for the District of Columbia when it was challenged.
The bottom line is that Americans need to be assured of the availability of pharmaceuticals in the marketplace so that healthcare providers have more reliable inventory and choices when shortages arise. Reciprocity of drug regulatory decisions would help to achieve that, and the White House and Congress should make it happen without delay.