Less than 24 hours after confirming his positive Covid-19 diagnosis, President Donald Trump received the first of five doses of remdesivir, a drug that hinders the ability of the coronavirus to replicate within the human body.
That same day, at the Erasmus University Medical Center in Rotterdam, the Netherlands’ second largest city, pharmacist Nicole Hunfeld sent out an email she had hoped never to write.
“Beste allen,” it began. “Dear all, we have just received a message from the RIVM that there will be a shortage of remdesivir.”
The Dutch National Institute for Public Health and the Environment, or the RIVM, is tasked with distributing remdesivir in the Netherlands. The drug is one of the few medications shown to help treat Covid-19, and for which there is “no adequate, approved and available alternative,” according to an Oct. 1 letter from the U.S. Food and Drug Administration’s chief scientist.
European authorities approved it for Covid-19 in the summer after the publication of successful trial data, and it has been frequently used in both Europe and the U.S. in conjunction with steroids, such as dexamethasone, and anticoagulants.
But as infection rates began rising precipitously across the continent once more in early October, demand in this small, northern European nation outstripped supply.
“No new courses can be started until we hear that there is stock again,” Hunfeld’s email continued. “Would you like to share this information with on-call colleagues and physician assistants?”
Hunfeld, who chairs a committee focused on drug shortages that forms part of the Netherlands’ national Covid-19 task force, told NBC News that it was the first time in her eight years as a specialized intensive care pharmacist that the responsibility for nationwide distribution of a drug in such high demand had been assigned to a centralized entity.
And now that the country’s entire stockpile was unexpectedly exhausted, she wanted to warn the eight doctors on her hospital’s Covid-19 task force immediately. By the next day, Oct. 3, her pharmacy team was unable to order more remdesivir on their internal system, with no fresh shipments expected for several days.
“We have no clue what’s going on in the Netherlands,” Hunfeld said of remdesivir’s interrupted supply. “We don’t have numbers, we don’t know how many vials there are, we don’t know how many orders are required. It’s a black box, so in a certain way it makes it really easy — you just order until they say no.”
The half-dozen patients at Erasmus on the medication that weekend were able to complete their prescribed five-day treatment course, but as Trump posed for photographs later that weekend inside the presidential suite at the Walter Reed National Military Medical Center in Bethesda, Maryland, newly admitted patients in several Dutch cities were unable to receive the antiviral as quickly as their doctors would have liked.
"We were telling everyone we had medication for Covid, among which is remdesivir, and then it’s not available,” Dr. Annelies Verbon, an infectious disease physician at Erasmus, said. “Kind of weird.”
Unlike most other high-demand drugs that physicians might prescribe to hospital patients, there is no generic alternative to remdesivir, Hunfeld, whose stock was replenished several days later, said. "You cannot exchange it at all. It's there or it’s not.”
“We’ve never had a shortage of medicine”
Experts say this recent shortfall in the Netherlands, however brief, is emblematic of the potential challenges to pharmaceutical supply chains that could dog doctors in Europe and beyond in the months ahead — with hospitalization numbers continuing to rise, and potentially lifesaving drugs and their ingredients produced in distant corners of the globe.
Remdesivir is typically prescribed for adolescent and adult Covid-19 patients with pneumonia-like symptoms who are receiving supplemental oxygen. This week, a large-scale World Health Organization trial — with results that are not yet peer-reviewed — has shown the drug does not have a statistically significant impact on mortality rates, but earlier trials have indicated that it can reduce patients’ hospital stays by several days.
Even in light of the disappointing WHO data, the pharmacists at Erasmus and one other Dutch hospital told NBC News that their teams did not immediately plan to change their treatment courses for Covid-19 patients. They explained that the new statistics did not sufficiently account for the other drugs prescribed in conjunction with remdesivir, the age and other demographic information associated with patients and the point of the disease’s development at which the antiviral was administered.
"Is it worth 2000 euros ($2340) per patient?” asked Hunfeld of her facility’s plans to continue using remdesivir. “Thats what we discussed today, but we need data that is peer-reviewed.”
Until now, physicians have employed the antiviral as one of the most important tools in their arsenal against Covid-19.
“As a doctor, I don't want to not be able to give a drug,” said Dr. Joachim Aerts, the head pulmonologist at Erasmus. “The very strange thing at this moment of time, we’ve never had a shortage of medicine in Western Europe — now we have to get used to being like a low-income country with a shortage of beds — and a shortage of medicine.”
European drug distribution and the sharing of data on a drug’s demand are conducted through a sometimes haphazard patchwork of doctors, hospitals, health ministries and the European Union’s centralized executive, the European Commission.
Gilead Sciences announced recently that it expected supply to “meet global demand by the end of this month,” and that it would begin fulfilling new remdesivir orders to Europe this week, after the signing of a new agreement with the commission — as the representative of multiple governments, including the United Kingdom. In Poland, the drug was recently in short supply, and in the U.K., it’s being rationed. Spain faced a shortage over the summer.
This agreement, Gilead said, should obviate the need for individual countries to stock up on the drug through the European Commission, headquartered in Brussels.
But the recent shortages have some European officials concerned that even if the supply of remdesivir is now more secure, a dramatic winter spike in infections could precipitate pressure on the continent’s sometimes opaque pharmaceutical supply chain.
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“A lot of good can be done with better data, and sharing some key statistics of how much hospitals have within the system,” said Oscar Guinea, a senior economist at the European Centre for International Political Economy think tank, who this summer co-authored a report on European pharmaceutical trade data.
He recalled that several European Union member states had restricted pharmaceutical shipments to neighboring nations at the start of the pandemic, and could do so again.
We don't have a clear vision of how many patients need what, where and when.
“If there’s another crisis, countries will again look to create stockpiles, and ask if they have enough reserves,” he said. “When the s--- hits the fan, countries often save themselves first.”
Drug shortfalls occur “when the level of collaboration isn't good enough, and when the data is not available, and when the forecasts are not reliable,” said Nathalie Moll, director general of the European Federation of Pharmaceutical Industries and Associations.
“One company supplying the whole world has to be able to foresee where to move things. And this is not always possible,” Moll said. “We don't have a clear vision of how many patients need what, where and when.”
“We have to improve on all of those areas. And I think it's very clear to everybody, that's a work in progress.”
A disjointed approach
Despite efforts by the European Commission to develop a new strategy that strikes a balance between more autonomous supply chains and an open market for free trade, the problems around pharmaceutical supply and distribution could extend beyond Europe’s borders.
“The crisis has shown that putting all your eggs in the same basket and relying solely on imports from one region of the globe can have dramatic consequences for the industry and the health care system,” said Marco Mensink, the director general of the European Chemical Industry Council, or Cefic.
In some countries like Spain, which also ran short on the drug in the late summer, remdesivir supplies have returned to a comfortable level, said Dr. Pablo Barreiro, an infectious disease specialist at the La Paz hospital in Madrid, which currently faces the highest reported infection rate in Europe.
“There’s specific criteria for use,” Barreiro said. “It’s not for everyone, only for special cases,” he said, adding that “nobody” lacked access to remdesivir, which he called “the most specialized drug required.”
“In some countries, these dialogues and coordinations are going quite well,” Adrian van den Hoven, the director general of generic developer and manufacturing industry body Medicines for Europe, said pointing to Italy where the first wave of infections was sudden and severe. “They learned the hard way and put everybody together in a group. But that's kind of the exception in most European countries.”
He said the approach was still too disjointed, and protectionist behavior — inside or outside the E.U. — remained highly problematic.
If a big wave happens, and there's a strong demand, a lot of governments will likely press the panic button.
“If a big wave happens, and there's a strong demand, a lot of governments will likely press the panic button,” he said.
Tom Elbersen, a spokesperson for the Dutch Health Ministry told NBC News that as the country now has “a lot of remdesivir — or if not a lot, enough.”
But several hospital pharmacists in the Netherlands’ largest cities described a time-consuming process whereby each patient requires an individual request form to be completed, before the appropriate six vials can be authorized and delivered to the relevant facility. And they expressed concern that this may disadvantage Dutch citizens if similar procedures are not adhered to elsewhere in Europe.
“My patient is not more or less important than a patient in Belgium or France,” said Reinier van Hest, the long-time chief pharmacist at one of Amsterdam’s largest hospital systems, who said he has no insight into drug requirements over the “next week, or the next months.”
“Doctors in the Netherlands, Germany, U.K., China, they all want to have remdesivir or the next new medicine that will work,” he said. “Demand is likely to be high, and stocks will be low, so the case of remdesivir, I can really imagine that it might be repeated for a new medicine.”
“We have to get used to the unpredictability.”
CORRECTION (Oct. 21, 2020, 11:20 a.m. ET): A previous version of this article misstated Nicole Hunfeld's position on the Netherlands’ national task force focused on drug supplies for Covid-19 treatment. She chairs a committee on the task force, she does not chair the task force.