Critical Drugs for Critical Care: Protecting the US Pharmaceutical Supply in a Time of Crisis

Epidemics shine a bright light on the weak spots in our social structures, and in recent months COVID-19 has pointedly exposed the fragility of the US pharmaceutical supply chain. A single announcement from the White House prematurely claiming the safety and efficacy of hydroxychloroquine (Plaquenil) as a “game changer” for COVID-19 infection was enough to trigger a shortage of this drug.¹ Hospitals treating severe COVID-19 cases now face significant challenges in maintaining supplies of far more essential critical care drugs, such as vasopressors, sedatives, and bronchodilators.² In turn, many states have sought access to Strategic National Stockpile supplies only to find that such life-saving therapies were not available or had not been included in this portfolio.³ With the long bulge of the pandemic curve still to follow, it is likely that other commonly used drugs will face shortages in months to come.

The logistical challenges of the response to the COVID-19 pandemic recall a set of similar problems experienced as the United States responded to the anthrax bioterror attacks of September 2001. After the antibiotic ciprofloxacin was pronounced as vital to national security in the face of the acute infectious threat, the supply of this pharmaceutical agent was likewise immediately threatened by hoarding and stockpiling.⁴ Although several initiatives have been developed to strengthen US public health preparedness since then, it is clear that the fundamental problem of securing a supply of pharmaceutical agents key to public health in a time of national crisis has not been resolved.

CHALLENGES TO THE PHARMACEUTICAL SUPPLY CHAIN

Two main characteristics of the COVID-19 pandemic have contributed to the failure of the public health response and the potential for pharmaceutical shortages. First, unlike the supplies mobilized in response to bioterrorism, a single curative therapy cannot be the focus of the biomedical response to the COVID-19 pandemic. COVID-19 patients require a range of therapeutic and preventive agents, and as the pandemic has unfolded the types of drugs, devices, and supplies needed to provide an adequate response have only expanded. In the absence of a single “magic bullet,” the most important influence on mortality seems to be access to good supportive care, which requires a more general set of medical products: intravenous fluids, bronchodilators, sedatives, antipyretics, antithrombotics, and more.

Second, most biopreparedness exercises have prepared for an infectious disease threat, such as the anthrax scare, to be a singular and acute event. The chronic nature of the COVID-19 pandemic—which has unfolded slowly, with long incubation periods, asymptomatic spread, and no clear end in sight—has further contributed to the depletion of supplies intended for the response to acute and short-term public health threats. The unknown duration of this condition challenges planning capacity, as manufacturers and suppliers are unsure of how long they will need to respond to the increased demand.

Making matters worse, COVID-19 struck a nation already reeling from an escalating series of shortages of basic medical inputs that had become evident in prepandemic times. The drugs that have been historically most affected by shortages are low-cost generics and drugs for intravenous infusion, drug classes that are now essential to the supportive care and intensive management of COVID-19 cases.⁵ Although most drug shortages recorded in recent years were driven by manufacturing problems, crisis-related shortages are characterized by surges in demand that are often region and facility specific, reflecting the need not only for increasing supply but also for facilitating drug distribution.

PROTECTING THE SUPPLY CHAIN DURING CRISES

The federal government has mechanisms to protect the public’s health in the face of a crisis, but its ability to protect the pharmaceutical supply chain has been shown by the COVID-19 pandemic to be anemic at best. Even though some emergency measures have been implemented in the present pandemic, the need for new institutional processes to strengthen and increase the responsiveness of the US pharmaceutical supply chain in the face of a public health emergency still remains.

A solution would be to empower a new office in the Food and Drug Administration (FDA) to identify and safeguard the supply of essential drugs at special risk of shortage in times of crisis. Protecting the supply of critically needed drugs would focus on two dimensions: increasing manufacturing capacity and facilitating distribution.

Enhancing Manufacturing Capacity

Increasing manufacturing capacity to meet surges in demand is costly and time consuming, as it may require expanding facilities or changing the source of active pharmaceutical ingredients, both of which require FDA approval. Certain drugs have additional production challenges, for example intravenous solutions are required to pass 14-day sterility tests before commercialization, which may further slow these drugs becoming available in the market. Manufacturing drugs such as sedatives and anesthetics depends on quotas allocated by the Drug Enforcement Administration (DEA).

To enhance the manufacturing capacity of critically needed drugs in advance of crises, the FDA could require manufacturers to maintain extra inventory or even to build in additional manufacturing capacity for scaling-up. Once a crisis begins, the FDA could provide faster approval of new active pharmaceutical ingredient sources and of repurposing production facilities and could reconsider, on a drug-by-drug basis, certain manufacturing requirements such as the 14-day sterility test for injectables. Based on the FDA’s list, the DEA could provide a responsive review of the production quotas allocated to manufacturers, and the secretary of Health and Human Services could review the need for additional manufacturers to enter the market for certain products, in which case the secretary might consider invoking policies such as Section 1498.⁶ Under this law, the Secretary can authorize manufacturers to produce an emergency supply of a drug under patent without the patent holder’s approval (but providing fair compensation to the patent holder).

Improving Distribution

Another challenge is distribution. A recent survey found that hospitals treating many patients with acute COVID-19 in New York City had greater need for life-supporting pharmaceuticals and were therefore at greater risk for shortages than other facilities in New York City or acute care hospitals located in other regions.⁷ Distributing the existing supply of pharmaceutical products to the neediest facility types and geographic areas may be limited by contractual agreements and FDA regulations. Redistribution restrictions may be even stricter when transporting products across state lines is involved.

To improve distribution in advance of a crisis, the FDA should create a centralized information source to monitor drug shortages at regional or local levels. Once a crisis begins, the FDA could temporarily waive regulations that limit the transfer of drug inventory across facilities. Temporarily waiving contractual provisions that limit procurement between facilities, wholesalers, and pharmacies could also be explored. Other measures could focus on preventing hoarding, for example by requesting that drug prescriptions above a certain quantity be justified.

Although some of these actions have been employed on a piecemeal basis, to date their implementation has been reactive and not part of a concerted, proactive strategy. In the long term, this moment of crisis offers an opportunity for the federal government to exercise stronger oversight of the drug supply for the future, so that none of our patients will suffer harm from lack of access to the medicines that form the bedrock of supportive care.