From 1968 to 2020, Americans experienced a remarkable increase in life expectancy, from 70 to 78 years. Much of that was due to advances in drugs and vaccines, many of which are now unavailable because of shortages. FDA Commissioner Robert Califf called recently for Congress to give his agency more power to address them. The FDA can’t remedy underlying market conditions, he said, but it can help to avert supply-chain issues if manufacturers let regulators know about problems.
However, it’s not the actions or inactions of the FDA that’s the problem, and Califf intimated as much by referring to the importance of market conditions. Congress could, and should, act to take advantage of market forces.
Shortages of important drugs 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 percent had experienced at least 50 shortages in that time. Most 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. Hospitals are scrambling to ensure adequate amounts of drugs in short supply or to find substitutes. In the University of Chicago study, one-third of hospitals had to ration drugs at least once. That means some patients got the second or third choice of a drug treatment, increasing the likelihood that the drug will be ineffective or only suboptimally effective or have unwanted side effects.
Much of this is preventable. In order to ease 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 those of the FDA, and vice versa. In other words, reciprocity.
Approval in one country on the list would be automatically reciprocated by the others (subject to the creation of approved labeling in the appropriate format, language, 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. It might even put downward pressure on drug prices.
Reciprocity would also ameliorate other problems, such as the FDA dragging its feet on the approval of important drugs and vaccines that have been given the green light elsewhere. For example, Bexsero, a vaccine to prevent meningitis B, was approved in 2013 by the European Union, Australia, and Canada but not by the FDA until 2015.
Another example was the long delay before the FDA’s 2015 approval of Fluad, a flu vaccine containing an adjuvant that boosts the immune response. It is used primarily in the elderly, whose immune response to flu vaccines typically is poor. Fluad has been used in Italy since 1997 and approved in more than three dozen countries. The 18‐year delay in availability in the United States undoubtedly resulted in many avoidable hospitalizations and deaths.
The stage is set for reciprocity of approvals. The U.S. has been a leader in international deliberations that have led to harmonized standards among FDA and its foreign counterparts. Many countries now have a standardized dossier for seeking approval of new drugs, the U.S. accepts research conducted in other countries to support drug and medical device approvals, and the FDA has established Current Good Manufacturing Practices for foreign production facilities. Thus, we’re already part of the way there.
Admittedly, not all drug shortages would be addressed by reciprocity of approvals. Part of the problem is that 90 to 95 percent of generic sterile injectable drugs, which are heavily represented on the FDA’s shortage list, depend on starting materials from China and India. Still, reciprocity would help in the short term.
Americans need to be assured of the availability of pharmaceuticals in the marketplace so healthcare providers have more reliable inventory, experience fewer shortages, and more 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. FDA Commissioner Califf should be urging them to do so.
