In the newest "COVID-19: The CIDRAP Viewpoint" report from the Center for Infectious Disease Research and Policy (CIDRAP), researchers lay out not only how the US drug supply chain has been vulnerable for years, but how those vulnerabilities are exacerbated by the COVID-19 pandemic.
To transform what the authors call a "fail and fix" approach to a "predict and prevent" paradigm, they offer nine specific recommendations that involve a more coordinated national policy framework to track, identify, mitigate, and prevent drug shortages using a transparent database of drug supply chains. This public database would encompass all prescription drug products in the US market, and analysis of the data would focus on the most critical drugs and the consequences that would likely be experienced if there is a shortage.
Titled "Part 6: Ensuring a Resilient US Prescription Drug Supply," the report points out that 29 (72.5%) of the 40 critical drugs for COVID-19 patients are experiencing shortages, according to the American Society of Health-System Pharmacists (ASHP). When these drugs are not available, healthcare providers have to consider rationing existing drug supplies, if any, finding therapeutic substitutes, or even having the patient go without treatment.
"Our focus on drug supply chains started in 2018—well before this pandemic, and what we're seeing fits right in," CIDRAP Director Michael Osterholm, PhD, MPH, says, referencing the center's Resilient Drug Supply Project (RDSP), for which he is co-principal investigator (PI). RDSP scientists produced today's report.
"At this point it's fair to say that the pandemic is clearly showing the real challenges that the drug shortages represent," Osterholm adds.
CIDRAP publishes CIDRAP News, but its news operation functions independently from its research efforts.
Shortages to continue until supply system changes
For some doctors, intubation-related drugs have become the rate-limiting factor for COVID-19 care, and not the ventilators or personal protective equipment (PPE, such as N95 respirators, surgical masks, and gowns) that grabbed headlines at the beginning of the pandemic.
In the spring, for instance, orders for the heart medication norepinephrine spiked by 122% across the nation, with Premier reporting a 421% increase in New York, with the supplier able to fill only 55% of the orders. Shortages of this drug affect COVID-19 patients, but they also affect non–COVID-19 patients who have septic shock. A 2011 norepinephrine drug shortage led to a 3.7% increase of the in-hospital rate of death for patients with septic shock.
A crucial drug cited in the report, propofol—a sedative to calm patients while they are intubated—has no close substitute, in part because of how quickly it can be adjusted to suit changes in the patient's status. It, too, has been plagued by shortages.
Another affected drug product has been albuterol inhalers. Their use for COVID-19 patients has created supply issues for patients using these inhalers for asthma or chronic obstructive pulmonary disease.
Also, antibiotics such as azithromycin or the combination drug piperacillin-tazobactam have experienced shortages in the past few months. Whether local or nationwide, drug shortages relating to intubation, sedation, paralytics, pain, antivirals, antibiotics, and more affect not only COVID-19 patients but also those who need the same drugs for elective surgery or other reasons.
"Last spring when we had a few states hitting their peak COVID-19 demand, the wholesalers and manufacturers were able to adjust by shipping supplies from the Midwest to the Northeast when New York and New Jersey needed it, or from the South to California and Washington," says Stephen Schondelmeyer, PharmD, PhD, MPubAdm, senior author of the report and co-PI of the RDSP.
"But when you have 30 to 35 states or more all hitting a peak at one point in time," he adds, "there's a much higher peak and really no place with excess drug supply to redistribute. Complicating the situation, the United States cannot expect to draw upon drug supplies from other parts of the world when most other countries are also facing increased need and demand due to COVID-19."
Call for national policy, new entity
To meet the demand, manufacturers have taken steps to ramp up production, and the FDA has adjusted its regulations, allowing some drugs to be made by compounding facilities, others to go to market with incomplete labels, and still other drugs to have extended expiration dates.
These changes have helped, although they will not provide a complete or immediate fix. Changing drug production takes time and resources, and both are already stretched thin. COVID-19 outbreaks have led to factory production slowdowns and shutdowns, shipping disruptions, and export bans and barriers. Unexpected increases of drug production may take 2 or 3 months to a year rather than just a few weeks, as with PPE supplies.
Schondelmeyer says, "Even though we can talk about the US demand and supply of drugs, when one works with the upstream drug supply chain, one quickly realizes that more than 70% of the drugs used in the United States are made outside of the country. So we are actually dealing with a global drug supply chain."
Among the key recommendations in the report:
- The United States should have a national process and infrastructure for analyzing, predicting, managing, and preventing shortages of critical medications.
- An in-depth map of the US drug supply chain is needed to identify where each drug product in the US market was made, including where the starting materials, active pharmaceutical ingredients, and finished drug product were produced.
- Congress should authorize and fund a national entity to build the map noted above, publish information on each drug's supply chain, acquire and analyze prescription drug data, estimate the consequences of failing to address drug shortages, and coordinate national policy.
- This national entity could be an existing agency or a new federal start-up.
- Prescription drug profiles for each drug should be made publicly available on a consumer-friendly website and include key information.
Issues that demand response
Unraveling the full journey of a drug product is one of the first steps to help people predict where supply is vulnerable and could break down. Right now, the RDSP is working to build a database that gathers, maps, and house such information.
To truly prevent shortages, though, the "Viewpoint" recommendations align knowledge with action to create a national entity that proactively tracks the US drug supply and has the power to make sure supply needs are met. As Schondelmeyer puts it, "Traditional market forces may level out supply and demand in the long run, but when drug shortages occur, a patient who needs a life-saving drug now will not be able to wait for a long-run solution."
"These solutions aren't going to happen overnight," Osterholm says, "but hopefully this pandemic has provided a spotlight on a number of issues that demand response."