Among the scientists across the world poised to rapidly produce data on SARS-CoV-2’s continued global proliferation is immunologist and virologist James Nyagwange of Kenya’s Medical Research Institute (KEMRI)-Wellcome Trust Research Program in Kilifi. He and his colleagues have planned a number of projects related to new variants and the human immune response to the virus, but over the past year, some of their COVID-19–related studies have stalled due to delays in getting the lab materials they need from abroad.
For a while, the researchers were precariously short on culture media, which they need to produce SARS-CoV-2’s spike protein in bulk for assays that detect virus-targeting antibodies in human blood samples. Fortunately, some orders arrived at the last minute before they ran out, Nyagwange says. But they have been less lucky with multiwell plates, which they need for another assay that assesses the antibodies’ ability to neutralize virus in vitro, bringing that project to a standstill. They’re also still waiting on special spike protein constructs that they need to make pseudoviruses—relatively harmless viruses engineered to carry mutated versions of the spike protein—so they can study the dangers posed by novel variants. They’re yet to receive one construct they ordered in January that encodes the spike protein of the B.1.351 variant, which has been circulating in Kenya for months, and another from a novel variant discovered more recently in the country.
Nyagwange says he’s heard from supply companies that the delays are related to reduced capacity as employees are working from home, or to holdups in getting the materials from their own suppliers. He adds that he worries the broken supply chains will delay key information for policymakers—such as whether the new variant has higher transmissibility or if the vaccines Kenyans are receiving are still effective against it. “You are just going by faith and not by science anymore,” he says. In general, “we are basically relying on data from other parts of the world to make policy right now.”
In developing countries, you have less funding for science, and then on top of that, these things are expensive.—Basant Giri, Kathmandu Institute of Applied Sciences
Even a year after the start of the pandemic, the supply chains that deliver lab materials to researchers are still faltering, slowing down the pace of both of COVID-19–focused studies and other research. To blame is not only increased demand for products related to COVID-19 research and testing, but also slowdowns in air traffic, as well as global disruptions in shipping. The challenges are affecting researchers everywhere but especially those outside the US and Europe who are often more reliant on importing lab materials. The delays are impeding access to all manner of lab supplies, and are often accompanied by a surge in prices, adding to the already high costs in some low- or middle-income countries.
“I think what COVID has shown us is that just-in-time supply management does not work when there’s a global pandemic,” remarks Victor Dieriks, who studies Parkinson’s disease at the University of Auckland in New Zealand and is also experiencing exacerbated supply delays. In other words, a system in which products are shunted along the supply chain only when they’re needed, rather than kept stocked, is proving to be ill-equipped for this time of crisis.
A year-long wait for a freezer
Many of the disruptions are caused by an overwhelming demand for COVID-19 related research, personal protective gear, and SARS-CoV-2 testing, which has driven a global shortage of plasticware, Jason Sutherland, the national sales and marketing manager of the life science supplier Celtic Molecular Diagnostics in Mowbray, South Africa, writes to The Scientist in an email. “Every plastic consumable that is required to run RT-PCR tests such as plates and pipette tips are being used in abundance and many of the suppliers are battling to keep up with the demand.”
Lab gloves can be particularly hard to come by, adds Sutherland. For more than a year, his company has been unable to procure any from its regular supplier in Germany as the country has stopped exporting them to prioritize domestic needs. Although companies have scaled up the production of certain products, plastic consumables remain in short supply, and Sutherland and his colleagues have been buying products in bulk to ensure their customers don’t run out, he says.
Even when products are available on the global market, the pandemic is stalling their delivery. A general drop in air traffic as well as a global shortage of shipping containers have meant both delays and inflated delivery prices. Staff shortages at ports and a congestion of container ships may have exacerbated the issue in New Zealand, Dieriks adds. In a country remarkably successful in swatting away COVID-19 outbreaks, the delays in lab supplies—pipette tips, the chemical xylene, and a new fridge for the lab, in Dieriks’s case—have become the main detriment to his research during the pandemic, he says. Ordering lab supplies has always been slower in New Zealand than it is in Europe, says Dieriks, who used to work in Belgium. But now, “some of the stuff is a few months before it comes in.”
As Nepal has now entered another major lockdown amid spiking cases and hospitalizations, Basant Giri of the Kathmandu Institute of Applied Sciences who specializes in developing low-cost analytical technology, says he worries that this could have long-term effects on lab supplies. During a four-month lockdown that ended in July 2020, air traffic stalled. He’s had to wait months for specific reagents for enzyme assays or standard reference materials for drug and antibiotic testing, and he’s been waiting on a new -80 °C freezer for about a year.
Under a new lockdown that began in late April, there are only chartered flights into Nepal, and there are also delays along certain shipping routes, notes Firoz Ahmad, the director of Helix Enterprises, which supplies labs across Nepal with molecular biology and life science equipment. Getting customers temperature-sensitive products, such as enzymes, poses a particular challenge “because there is a risk of longer transit,” he says. And due to limited space, the prices for air transport have increased by up to four times. His company honors price guarantees made before the lockdown—which has “really affected our business,” he notes—but extra costs get passed on to customers for new orders.
Giri says that certain enzymes were already around three times more expensive in Nepal than in the US before the pandemic began. “Obviously, that’s a big problem. In developing countries, you have less funding for science, and then on top of that, these things are expensive,” and sometimes even more so during the pandemic, he says. “So it’s very difficult to do science.”
Missing media, spoiled proteins, and other consequences
Some labs have been able to get around the supply challenges by bartering with colleagues, changing suppliers, or sourcing items locally, sometimes with a trade-off in quality, Dieriks says.
Earlier this year, virologist Alex Sigal’s lab at the Africa Health Research Institute in Durban, South Africa, was about to run out of critical supplies at the worst time—right when vaccine manufacturers tasked the researchers with investigating how effective SARS-CoV-2–targeting antibodies from the blood of vaccinated clinical trial participants would be against the B.1.351 variant. Luckily, they were able to scrounge up a box of 96-well microtiter plates from a neighboring institution, and collaborators in the US sent them a box of pipette tips, recalls virologist Shi-Hsia Hwa, a PhD student in Sigal’s lab. “If we had run short, then I think it [could have] slowed down the decision-making for a number of parties, in particular the South African government about what vaccines to try and purchase.” Fortunately, deliveries from their regular suppliers recovered, “but I think we do have a little bit of anxiety as to whether the famine situation is going to occur again,” Hwa says.
In Africa, most of these [supply] companies don’t even have distributor branches here. If they had that, for instance, you could be getting [things] locally. It wouldn’t take this long, even if they had to restock.—James Nyagwange, KEMRI-Wellcome Trust Research Program
Others don’t have any option but to wait. Tuberculosis researcher André Loxton of Stellenbosch University and the South Africa Medical Research Council’s Centre for Tuberculosis Research was able to source some items from colleagues. But he’s been waiting weeks for other products for which there are limited suppliers, he writes to The Scientist. That includes the tuberculosis vaccine BCG and 7h11 agar base used to grow tuberculosis-causing bacteria. As a result, he’s had to change some of his students’ projects, he adds.
Not being able to get the variant constructs in a timely manner, on top of delays in media, plates, and flasks, “[is] really impacting our daily work,” Nyagwange says. Many supply companies are prioritizing orders for COVID-19–related research, he adds. “So you can imagine how much more delays there are for things that are not COVID-related. There are many lab processes that are on hold right now.”
That includes the lab work needed to process samples that are part of a local surveillance project for arboviruses, which is experiencing long delays in delivery of the media necessary to grow the viruses and cell lines in vitro, he says. The team can archive the samples, “but it would be nicer to do this in real-time and inform policy.” He usually gives suppliers at least a month or so to deliver items to Kenya, he says, but with the pandemic, it’s sometimes taking almost four or five months.
In Auckland, it’s now been around three months since Dieriks ran out of his last stashes of a particular conformation of alpha-synuclein, a protein involved in Parkinson’s disease pathogenesis. A collaborator in Paris is “the only one that has this [specific] alpha-synuclein,” he says, but efforts to ship the protein to New Zealand or to research groups in the US have repeatedly failed; due to delays, the packages keep getting routed back to Paris. Once, when sending a package to the US, the process took so long the dry ice had evaporated by the time it arrived back in France, “so the whole package was basically ruined,” he says. Not having that protein “is really holding back my research. It’ll probably be another six months at least before we’re back on track.”
A need for home-grown supply and distribution
Manufacturers have taken several measures to adjust to the newfound demand for COVID-19–related products. Millipore Sigma, for instance, which makes various chemicals and reagents, has expanded its facilities, increased the stock of products, added the capacity to scale-up the production of critical products, and sourced more upstream supplies. “For other materials that are not pandemic related that are part of our core business, reagents, chemicals, sterile filtration, we are not seeing sustained availability issues,” a spokesperson for the company writes to The Scientist.
In Sutherland’s view, “many manufacturers now have the required infrastructure in place [to] ramp up production at a moment’s notice should any other pandemic suddenly arise in the future.” As for his business, Celtic has been keeping large stock reserves for its diagnostics customers and replenishing stockpiles as soon as products are sold.
To some scientists, the pandemic highlights the vulnerability of relying on distant countries for lab materials. “As it stands now, it all has to come from abroad,” Nyagwange notes. “In Africa, most of these [supply] companies don’t even have distributor branches here. If they had that, for instance, you could be getting [things] locally. It wouldn’t take this long, even if they had to restock.”
“It would be nice if some of the big biotech and pharma supply companies would start having more backups in terms of warehouses or stockpiles better distributed around the world,” adds Hwa, “so we’re not waiting for every single thing to come all the way from Europe or all the way from China.”
Hwa notes that the pandemic has sparked much discussion about how pharmaceutical manufacturing—particularly vaccine production—needs to be better distributed across the world. “But I think [the lab supply disruption] now makes it obvious that we need to also start looking into that with regards to the production of all the other stuff that goes into biological research,” she says. “Hopefully, the biotech industry ecosystem will start growing more here.”