Less than 24 hours after confirming his positive diagnosis of Covid-19, President Donald Trump received the first of five doses of remdesivir, a drug that prevents the coronavirus from replicating in the human body.
On the same day, pharmacist Nicole Hunfeld at the Erasmus University Clinic in Rotterdam, the second largest city in the Netherlands, sent an email that she had hoped she would never be able to write.
“Best of all,” it began. “Dear Sir or Madam, we have just received a message from the RIVM that there will be a shortage of remdesivir.”
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The Dutch National Institute for Public Health and the Environment (RIVM) has the task of distributing Remdesivir in the Netherlands. The drug is one of the few drugs that are used to treat Covid-19 and for that There is “no adequate, approved and available alternative”. According to a letter from the chief scientist of the US Food and Drug Administration dated October 1.
The European authorities approved it for Covid-19 in the summer after the publication of successful trial data. In both Europe and the US, it has been widely used in conjunction with steroids such as dexamethasone and anticoagulants.
But when the infection rates rose sharply again across the continent in early October, the demand in this small northern European nation exceeded the supply.
“New courses cannot be started until we hear that stocks are back,” continued Hunfeld’s email. “Would you like to share this information with on-call colleagues and medical assistants?”
Hunfeld, who also chairs the Netherlands’ national task force that focused on drug supplies for treatment for Covid-19, told NBC News that it was the first time in her eight years as a specialist critical care pharmacist that the responsibility for the nationwide distribution of a drug in this high demand was assigned to a central office.
And now that the entire supply in the country was unexpectedly exhausted, she wanted to warn the eight doctors of the Covid-19 task force at her hospital immediately. The next day, October 3rd, her pharmacy team was unable to order more remdesivir on her internal system as no new deliveries were expected for several days.
“We have no idea what’s going on in the Netherlands,” said Hunfeld of the remdesivir interruption in supply. “We don’t have numbers, we don’t know how many vials there are, we don’t know how many orders it takes. It’s a black box, so in a way it makes it really easy – you just order until they say no . “
The half-dozen Erasmus patients taking medication that weekend were able to complete their mandatory five-day treatment course, but when Trump posed for photos later that weekend in the presidential suite of Walter Reed National Military Medical Center in Bethesda, Maryland, newly admitted patients in several Dutch cities were unable to get the antiviral as quickly as their doctors would have liked.
“We told everyone that we had drugs for Covid, including remdesivir, and that they weren’t available,” said Dr. Annelies Verbon, Infectious Disease Doctor at Erasmus. “Somehow strange.”
Unlike most other high-demand drugs that doctors might prescribe to hospital patients, there is no generic alternative to remdesivir, said Hunfeld, whose inventory was replenished a few days later. “You can’t change it at all. It’s there or not.”
“We never had a shortage of medicines.”
Experts say this latest shortage in the Netherlands, as brief as it may be, symbolizes the potential challenges to pharmaceutical supply chains that doctors in Europe and beyond could haunt in the coming months – as hospitalizations continue to rise and possibly life-saving drugs and their ingredients are manufactured in distant corners of the world.
Remdesivir is typically prescribed for adolescent and adult Covid-19 patients with symptoms of pneumonia who are given extra oxygen. This week a big one World Health Organization study – with results that have not yet been peer-reviewed – showed that the drug did not have a statistically significant effect on the death rate, but earlier studies did have specified that it can cut patients’ hospital stays by several days.
Even given the disappointing WHO data, pharmacists from Erasmus and another Dutch hospital told NBC News that their teams had no immediate plans to change their treatment courses for Covid-19 patients. They said the new statistics did not adequately take into account other remdesivir-related drugs prescribed, age and other demographic information related to patients, and when the disease progressed when the antiviral drug was administered.
“Is it worth 2000 euros per patient?” Hunfeld asked about her facility’s plans to continue using Remdesivir: “We discussed that today, but we need data that will be peer-reviewed.”
So far, doctors have used the antiviral agent as one of the most important tools in their arsenal against Covid-19.
“As a doctor, I don’t want to be able to give medication,” said Dr. Joachim Aerts, the senior pulmonologist at Erasmus. “The strange thing about this moment is that in Western Europe we’ve never had a drug shortage – now we have to get used to being like a low income country with a shortage of beds – and a shortage of drugs. ”
The European distribution of medicines and the exchange of data on the demand for medicines are carried out by a sometimes random patchwork of doctors, hospitals, health ministries and the central executive of the European Union, the European Commission.
Gilead Sciences recently announced that it expects the offering “to meet global demand by the end of this month” and that it will begin new remdesivir contracts in Europe starting this week following the signing of a new agreement with the Commission to represent it will meet several governments, including the UK. The drug has recently been in short supply in Poland and is being rationed in the UK. Spain had a shortage in the summer.
This agreement, Gilead said, should avoid the need for individual countries to obtain the drug through the European Commission based in Brussels.
Due to the recent shortages, some European officials have concerns that a dramatic spike in infections during winter could put pressure on the continent’s sometimes opaque pharmaceutical supply chain, even if supplies of remdesivir are now safer.
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“A lot of good can be done with better data, and it shares some vital statistics on how many hospitals there are in the system,” said Oscar Guinea, senior economist at the European Center for International Political Economy think tank who contributed this summer a report on European data on pharmaceuticals trade.
He recalled that at the beginning of the pandemic, several member states of the European Union had restricted the supply of medicines to neighbors and could do so again.
We do not have a clear idea of how many patients need what, where and when.
“If there is another crisis, countries will try again to create stocks and ask if they have enough reserves,” he said. “When that s — hits the fan, countries often save themselves first.”
Drug shortages occur “when the level of collaboration is not good enough and when the data are not available and when the forecasts are not reliable,” said Nathalie Moll, General Director of the European Federation of the Pharmaceutical Industry and Associations.
“A company that supplies the whole world needs to be able to predict where things are going to be moved. And that’s not always possible, ”said Moll. “We don’t have a clear idea of how many patients need what, where and when.”
“We have to improve in all of these areas. And I think it is clear to everyone that this is still a work in progress. “
A disjointed approach
Despite efforts by the European Commission to develop a new strategy that will strike a balance between more autonomous supply chains and an open market for free trade, problems with the supply and distribution of medicines 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 world can have dramatic consequences for industry and the health system,” said Marco Mensink, General Director of European Chemical Industry Council or Cefic.
In some countries like Spain that too The drug ran low in late summerAccording to Dr. Pablo Barreiro, an infectious disease specialist at La Paz Hospital in Madrid, which currently has the highest reported infection rate in Europe, remdesivir supplies have returned to comfortable levels.
“There are specific criteria for its use,” said Barreiro. “It’s not for everyone, just in special cases,” he said, adding that “nobody” had no access to remdesivir, which he called “the most specialized drug”.
“In some countries these dialogues and coordination are going quite well,” said Adrian van den Hoven, general director of the generic drug development and manufacturing industry Medicines for Europe, pointing to Italy, where the first wave of infections was sudden and severe. “They learned the hard way and put everyone in a group. But this is an exception in most European countries. “
He said the approach is still too incoherent and protectionist behavior – inside or outside the E.U. – remained very problematic.
When a big wave happens and there is strong demand, many governments are likely to press the panic button.
“When a big wave happens and there is strong demand, many governments are likely to press the panic button,” he said.
Tom Elbersen, a spokesman for the Dutch Ministry of Health, told NBC News that the country now has “a lot of remdesivir – or if not much, enough”.
However, several hospital pharmacists in the largest cities in the Netherlands described a time-consuming process whereby each patient had to fill out an individual application form before the corresponding six vials could be approved and delivered to the appropriate facility. And they expressed concern that this could put Dutch citizens at a disadvantage if similar procedures are not followed elsewhere in Europe.
“My patient is no more or less important than a patient in Belgium or France,” said Reinier van Hest, the longtime chief pharmacist in one of the largest hospital systems in Amsterdam, who said he had no insight into drug needs for the “next” week or the next few months. “
“Doctors in the Netherlands, Germany, the UK and China all want remdesivir, or the next new drug that will work,” he said. “Demand will likely be high and inventory will be low. In the case of remdesivir, I can really imagine that it could be repeated for a new drug.”
“We have to get used to the unpredictability.”