How blackouts, fires, and a pandemic are driving shortages of pipette tips — and hobbling science

The humble pipette tip is tiny, cheap, and utterly essential to science. It powers research into new medicines, Covid-19 diagnostics, and every blood test ever run.

It is also, ordinarily, abundant — a typical bench scientist might grab dozens every day.

But now, a series of ill-timed breaks along the pipette tip supply chain — spurred by blackouts, fires, and pandemic-related demand — have created a global shortage that is threatening nearly every corner of the scientific world.

The pipette tip shortage is already endangering programs across the country that screen newborn babies for potentially deadly conditions, like the inability to digest sugars in breast milk. It is threatening universities’ experiments on stem cell genetics. And it is forcing biotech companies working to develop new drugs to consider prioritizing certain experiments over others.

Right now, there’s no sign that the shortage will end soon — and if it gets worse, scientists might have to start postponing experiments or even abandoning parts of their work.

“The idea of being able to do science without them is laughable,” said Gabrielle Bostwick, a lab manager at California-based synthetic biology startup Octant Bio.

Of all the scientists unnerved by the shortage, researchers responsible for screening infants have been the most organized and outspoken.

Public health laboratories screen infants within hours of their delivery for dozens of genetic conditions. Some, like phenylketonuria and MCAD deficiency, require doctors to immediately change how they’re caring for the baby. Even just delays in the screening process has resulted in some infant deaths, according to a 2013 investigation.

Each child’s screening requires about 30 to 40 pipette tips to complete the dozens of diagnostic tests, and thousands of children are born each day in the United States.

As early as February, these labs were making it clear they did not have the supplies they needed. Labs in 14 states have less than a month’s worth of pipette tips left, according to the Association of Public Health Laboratories. The group was so concerned that it has, for months, pressured the federal government — including the White House — to prioritize the pipette tip needs of newborn screening programs. So far, the organization says, nothing has changed; the White House told STAT that the government is working on several ways to increase the availability of tips.

In some jurisdictions, the plastics shortage has “almost caused parts of the newborn screening programs to shut down,” said Susan Tanksley, a branch manager in the Texas health department’s laboratory services section, during a February meeting of a federal advisory committee on newborn screening. (Tankskey and the state health department did not respond to a request for comment.)

Some states are receiving batches of tips with just a day left to spare, leaving them little choice but to beg other labs for backup, according to Scott Shone, the director of North Carolina’s state public health laboratory. Shone said he had heard of some public health officials calling around “saying, ‘I’m running out tomorrow, can you overnight me something?’ Because the vendor says it’s coming, but I don’t know.’”

“Trusting when that vendor says, ‘Three days before you run out, we’re going to get you another month’s supply’ — it’s anxiety,” he said.

Many labs have turned to jury-rigged alternatives. Some are washing tips and then reusing them, increasing the potential risk of cross-contamination. Others are running newborn screenings in batches, which could increase the time it takes to deliver results.

So far, these solutions have been enough. “We are not in a situation where there’s immediate jeopardy to newborns,” Shone added.

Beyond labs that screen newborn babies, biotech companies working on new therapeutics and university laboratories doing basic research are also feeling the squeeze.

Scientists at PRA Health Sciences, a contract research organization that is working on clinical trials for hepatitis B and several Bristol Myers Squibb drug candidates, say supplies running out is a constant threat — though they haven’t yet had to formally delay any readouts.

“At times, it gets down to one rack of tips sitting on the back shelf, and we’re like ‘Oh my goodness,’” said Jason Neat, the executive director of bioanalytical services at PRA Health’s lab in Kansas.

The shortage has become alarming enough at Arrakis Therapeutics, a Waltham, Mass. company working on potential treatments for cancer, neurological conditions, and rare diseases, that its head of RNA biology, Kathleen McGinness, created a dedicated Slack channel to help her colleagues share solutions for conserving pipette tips.

“We had a realization that this was not acute,” she said of the channel, #tipsfortips. “A lot of the team have been very proactive about solutions, but we didn’t have a centralized place to share that.”

Most of the biotech companies interviewed by STAT said they were taking steps to conserve limited pipettes and, thus far, have not had to halt work.

Octant’s scientists, for example, are being very selective about using filtered pipette tips. These tips — which are particularly difficult to source lately — offer samples an extra layer of protection against outside contaminants, but can’t be sanitized and reused. So they’re dedicating them to activities that might be particularly sensitive.

“If you’re not paying attention to what’s running out, you could very easily run out of things,” said Danielle de Jong, a lab manager at the University of Florida’s Whitney Laboratory; the lab she works in studies how stem cells work in small marine animals related to jellyfish that can regenerate parts of themselves.

Scientists at the Whitney Laboratory have, at times, bailed out their neighbors when supply orders didn’t arrive in time; de Jong has even caught herself eyeing other labs’ shelves for any unused pipette tips, just in case her lab need to borrow some.

“I’ve been working in a lab for 21 years,” she said. “I’ve never encountered supply chain issues like this. Ever.”

There’s no singular explanation for the shortage.

The sudden explosion of Covid-19 tests last year — each of which relies on pipette tips — certainly played a role. But the effects of natural disasters and other freak accidents further up the supply chain have also cascaded down to laboratory benches.

The devastating statewide blackouts in Texas, which killed more than 100 people, also broke a critical link in the complex pipette supply chain. Those power outages forced ExxonMobil and other companies to temporarily close plants in the state — some of which made polypropylene resin, the raw material for pipette tips.

According to a March presentation, ExxonMobil’s Houston-area plant was the company’s second-largest producer of polypropylene in 2020; only its Singapore plant made more. Two of ExxonMobil’s three biggest polyethylene plants were also located in Texas. (In April 2020, ExxonMobil even increased polypropylene production at two U.S.-based plants.)

“After the winter storm in February this year, it is estimated that over 85% of the polypropylene production capacity in the U.S. was adversely affected due to a variety of issues such as broken pipes at the production plants as well as the loss of electricity and vital raw materials needed to restart production,” said a spokesperson for Total, another Houston-based oil and gas company that produces polypropylene.

But supply chains have been stressed since last summer — well before February’s deep freeze. Lower-than-usual amounts of raw materials isn’t the only factor that’s throttling supply chains — and pipette tips aren’t the only plastic-based piece of lab gear that’s been in short supply.

A manufacturing plant fire also knocked out 80% of the country’s supply of the containers for used pipette tips and other sharp objects, according to a document posted on the University of Pittsburgh’s website.

And in July, U.S. Customs and Border Protection began blocking products from a major glove manufacturer suspected of forced labor practices. (CBP issued the findings of its investigation last month.)

“What we’re seeing is really anything in the plastics-related side of the business — polypropylene, specifically — is either on backorder, or in high demand,” said PRA Health Sciences’ Neat.

The demand is so high that the price of some scarce supplies has gone up, according to Tiffany Harmon, a procurement administrator at PRA Health Sciences’ bioanalytics lab in Kansas.

The company is now paying 300% more for gloves through its usual supplier. And PRA’s pipette tip orders now have an extra fee tacked on. One pipette tip manufacturer, which announced a new 4.75% surcharge last month, told its customers that the move was necessary because the price of the raw plastic materials had almost doubled.

Adding to the uncertainty for laboratory scientists is the distributors’ process for determining which orders will be filled first — the workings of which few scientists said they fully understood.

“The lab community has been asking from the beginning to help us understand how these decisions are made,” said Shone, who referred to vendors’ formulas for determining allocations as “black box magic.”

STAT contacted more than a dozen companies that manufacture or sell pipette tips, including Corning, Eppendorf, Fisher Scientific, VWR, and Rainin. Just two responded.

Corning declined to comment, citing proprietary agreements with its customers. MilliporeSigma, meanwhile, said that it allocates pipettes on a first-come, first-serve basis.

“Since the outbreak of the pandemic, the entire life science industry has experienced unprecedented demand for Covid-19 related products, including MilliporeSigma,” a spokesperson for the major scientific supplies distribution company told STAT in an emailed statement. “We are working 24/7 to meet this increased demand for these products and as well as those used in scientific discovery.”

Despite attempts to bolster the supply chain, it’s not clear how much longer the shortages will last.

Corning received $15 million from the Department of Defense to make 684 million more pipette tips per year at its facility in Durham, N.C. Tecan, too, is building new manufacturing facilities with $32 million from the CARES Act.

But that won’t fix the problem if plastics production remains lower than expected. And neither of those projects will actually be able to produce pipette tips before the fall of 2021, anyway.

Until then, laboratory managers and scientists are bracing for more shortages of pipettes and just about anything else.

“We started this pandemic short of swabs and media. And then we had shortages of reagents. And then we had shortages of plastics. And then we had shortages of reagents again,” North Carolina’s Shone said. “It’s like Groundhog Day.”

Update: After this story was published, MilliporeSigma explained that it uses a first-come, first-serve system for allocating pipette tips, not the four-tier system it had first described. The story now reflects the company’s update.

Read the original article here.