As the United States struggles to keep pace with the rapidly escalating COVID-19 pandemic, demand for healthcare services and supplies has revealed the precariousness of our healthcare system and supply chains in the face of such extreme challenges. Shortages of ICU beds, ventilators, and proper personal protective equipment for healthcare providers have been a frequent point of discussion. Shortages of these items will have very visible and immediate impacts on public health, but as the number of COVID-19 hospitalizations increases, another growing threat to the US healthcare system’s ability to respond to the pandemic is emerging: shortages of essential drugs diverted from patients with their primary indications to treat patients infected with COVID-19.
On March 31st two anti-malaria drugs, hydroxychloroquine (which is also used to treat lupus and rheumatoid arthritis) and chloroquine, were added to the FDA’s drug shortages webpage due to a “significant surge in demand.” This surge in demand is driven by the fact that these drugs are viewed as potential treatments for COVID-19, a stance that is only based on the results of small clinical studies with conflicting results and anecdotal evidence (double-blind randomized controlled trials have not yet been conducted). Both drug products were recently granted emergency use authorization by the FDA, which allows for the drugs to be “donated to the Strategic National Stockpile to be distributed and prescribed by doctors to hospitalized teen and adult patients with COVID-19, as appropriate, when a clinical trial is not available or feasible.” The US Department of Health and Human Services (HHS) has already accepted 30 million doses of hydroxychloriquine sulfate and one million doses of Resochin (medical grade chloroquine phosphate) for this purpose. Due to this surge in demand, per an FDA New Release, “The agency is working with manufacturers to assess their supplies and is actively evaluating market demand for patients dependent on hydroxychloroquine and chloroquine for treatment of malaria, lupus and rheumatoid arthritis. All manufacturers are ramping up production, and…the FDA is working with manufacturers to ensure this can happen expeditiously and safely.”
While drug shortages of hydroxychloroquine and chloroquine dominate the news, there are shortages of other essential drugs that are equally concerning. As the demand for ventilators has increased, so has the demand for drugs associated with their use. Intubation is incredibly uncomfortable, and requires adequate sedation to ensure proper placement of a breathing tube while avoiding damage to the patient’s vocal cords during placement. Intubated patients are typically given strong sedatives and pain medicine (such as propofol and fentanyl), and also paralytics, to keep them comfortable. Data released from healthcare companies reveal dramatic spikes in demand for sedatives, pain medications, paralytics, and other drugs often required for patients on ventilators. This demand is driven not only by the overwhelming number of COVID-19 patients, but by the prolonged duration of a typical COVID-19 ICU stay - two weeks or more - as opposed to the average stay of one week. Some of these drugs, including midzaolam and fentanyl, are now listed on FDA’s drug shortages webpage.
Ramping up the manufacturing of drugs experiencing shortages will not be easy. Contributing to the shortage is that most of drug manufacturing is on a “just-in-time” schedule; although manufacturers typically have 2-3 months of safety stock on hand, with the increased utilization of these drugs for COVID-19 patients, these stores will be depleted at an expedited rate. As drug manufacturing is highly regulated, ancillary manufacturers cannot readily be converted to drug manufacturers. Increasing domestic manufacturing will be contingent upon currently available manufacturing capacity and the availability of active pharmaceutical ingredient (API).
Rho is actively monitoring drug shortages, as well as additional new information as it is released from the FDA regarding the current COVID-19 pandemic.
Charity Duran, PhD, RAC, Integrated Product Development Associate, works with companies at all stages of development to support their regulatory submissions. She has over a decade of experience in scientific and regulatory writing. Her experience includes the development and production of documents supporting regulatory submissions (modules of NDAs and INDs), the preparation of briefing packages to support regulatory meetings, and the development of clinical study documents, including clinical study protocols and clinical study reports.