Ingenuity, collaboration, and expertise create a game-changing COVID-19 test swab
Swabs typically don't attract much attention. Small, simple, inexpensive, quickly used and discarded, they hardly seem to merit their title of "medical device." But amid the COVID-19 pandemic, the lowly swab has gained enormous importance. Without it, testing grinds to a halt and detecting the virus becomes extremely difficult.
So when demand for swabs exploded last spring and supplies became scarce, Paul Jannetto, Ph.D., a laboratory director in Mayo Clinic's Department of Laboratory Medicine and Pathology who serves as vice chair of the department's Supply Chain Management Committee, faced a serious problem.
There are two main manufacturers of flocked nasopharyngeal swabs — the standard swab for molecular SARS-CoV-2 testing. While the manufacturers worked to ramp up production to meet demand, Dr. Jannetto and his colleagues in Supply Chain Management were tasked with the job of looking for alternative vendors and swab types.
What sounded like a straightforward assignment — find more swabs — became a massive effort that involved numerous departments and experts, and culminated in Mayo Clinic, for the first time, designing, testing, and mass-manufacturing a new medical device listed with the Food and Drug Administration (FDA): the 3D-printed mid-turbinate swab.
That achievement reinforced a critical link in the supply chain, allowing Mayo Clinic to press forward with confidence as it develops an at-home COVID-19 test and easing the burden on health care teams who administer in-person tests.
"Trusted vendor partnerships combined with the ability to self-manufacture crucial products like these swabs gives us the ability to weather this pandemic," Dr. Jannetto says. "It gives us choices, so we don't have to compromise on the high-quality care Mayo Clinic delivers."
Uncovering an appealing alternative
One of the first people to weigh in on the swab dilemma was Bobbi Pritt, M.D., chair of Mayo's Division of Clinical Microbiology. She knew from previous research that nasal mid-turbinate swabs could be as effective as nasopharyngeal swabs in detecting viral infections of the upper respiratory tract.
"Dr. Jannetto and I started communicating early on and, based on my prior work with mid-turbinate swabs for influenza diagnosis, we searched the literature and found that mid-turbinate swabs looked good for COVID-19, as well," she says.
Dr. Pritt saw benefits to pursuing the use of mid-turbinate swabs. First, they are more comfortable for patients because they don't need to reach as far back into the nasal passage as nasopharyngeal swabs to obtain a sample. Second, patients can collect a sample themselves with a mid-turbinate swab for COVID-19 testing, while self-collection is not an option with nasopharyngeal swabs. That means patients can collect their sample at home, or they can come to a clinical setting and perform self-collection with supervision from a health care professional who can coach them on proper technique from a safe distance.
Mayo Clinic already has implemented self-collection at a number of sites. Once FDA emergency use authorization is received, at-home collection will roll out.
"Observed self-collection using mid-turbinate swabs is a big step forward," Dr. Pritt says. "It doesn't have to be a nurse collecting the sample, as is the case with nasopharyngeal swabs. Our nurses are in high demand, so being able to have other staff observe self-collection is a big plus. Observed self-collection also requires less personal protective equipment, so this allows us to conserve valuable resources. Lastly, patients prefer the mid-turbinate swabs because they're not as invasive and are more comfortable."
Turning to in-house know-how
To move forward, Dr. Jannetto established a connection with Copan Diagnostics, Inc. to supply Mayo Clinic with mid-turbinate swabs. But there was still a concern. Copan is the world's only mid-turbinate swab manufacturer. Although Dr. Jannetto was confident that Mayo Clinic and Copan had a solid partnership, there was no guarantee the company would be able to consistently supply enough swabs to meet the high clinical demand. As a result, he began looking for a backup.
That's when Dr. Jannetto discovered Mayo Clinic's 3D Anatomic Modeling Laboratory, and another idea began to form. What if Mayo could make its own swabs to supplement the commercial supply?
Housed in Mayo Clinic's Department of Radiology, the 3D Anatomic Modeling Laboratory takes radiological data, such as CT scans and MRI images, and converts it via 3D printing into replicas of anatomy to aid surgical planning. Lab staff also create patient-specific tools that can be sterilized and used in the operating room.
Jonathan Morris, M.D., the lab's medical director, learned of the interest in 3D printing swabs and was confident it could be done. "That's right up our alley. We invent things. We print things. That's where our expertise is," Dr. Morris says. "And we've built an ecosystem in our lab that has a quality management system for 3D printing Class 2, sterilizable, biocompatible devices. Because we already had that set up, inventing a mid-turbinate swab based on the criteria Dr. Jannetto gave us was right in our wheelhouse."
Enter Amy Alexander, a senior biomedical engineer in the lab. Her job was to design the swab and determine the feasibility of mass production. Although a 3D-printed nasal mid-turbinate swab had not been developed previously, research into 3D-printed nasopharyngeal swabs was already in process.
"The national 3D-printed nasopharyngeal swab study, led by 3D-printing experts at University of South Florida, Northwell, and advised by Formlabs, gave us the confidence to try," Alexander says.
With input from Mayo Clinic Laboratories, Clinical Microbiology, and Clinical Biochemistry, Alexander and the team working with her went through four iterations of the swab design and then several versions of the build.
"Once the swab design was finalized, my role was to help plan and develop a mass manufacturing system, which I had never done before," she says. "But COVID has given us all opportunities to expand on skill sets we didn't know we had."
Investigating the accuracy
After the lab team created the swabs and showed they could be printed, it was time to test them. Joseph Yao, M.D., a Mayo Clinic clinical microbiologist, conducted initial studies on the swabs. Then Dr. Pritt, Dr. Yao, and their team designed a clinical study to see if the mid-turbinate swabs could be relied on for accurate COVID-19 testing. The Department of Laboratory Medicine and Pathology's Research Innovation Office oversaw patient recruitment, consent, and collection. Nurses at Mayo Clinic Health System in Mankato, Minnesota, managed most of the patient swab collections.
For the study, 318 patients were swabbed with the Mayo-manufactured mid-turbinate swabs and the nasopharyngeal swabs. Testing the nasopharyngeal swabs produced 37 positive results. Testing the mid-turbinate swabs produced 38 positive results. When comparing the mid-turbinate swab to the nasopharyngeal swab, there were five mid-turbinate swabs results that came back with either a false negative or a false positive result — an overall agreement of 98.4%. That favorably compared to the testing gold standard of 95%. In a separate part of the study, participants were asked to collect their specimens with both the Copan and Mayo swabs. Eighty-five percent reported the process was easy or very easy.
"We were pretty confident, based on the literature we saw before we got to SARS-CoV-2, that mid-turbinate swabs would be a good way to go," Dr. Pritt says. "But having our own data to show that the mid-turbinate swabs detected just as many positive cases as the nasopharyngeal swabs was extremely helpful. And more data that's come out since then has continued to support use of mid-turbinate swabs."
Armed with that data, Alexander registered Mayo's 3D Anatomic Modeling Lab as a medical device manufacturing facility and listed the 3D-printed mid-turbinate swab as a medical device with the FDA. Mass production began in November.
"That's an incredibly fast timeline in the medical device design and production world, and it never would have been possible if Mayo leadership in all the areas involved hadn't come to together to make it happen safely and effectively," Alexander says.
Relying on a tradition of teamwork
Today, the 3D Anatomic Modeling Lab produces approximately 32,000 mid-turbinate swabs in a five-day span. Although the swabs from Copan are the primary mid-turbinate swab Mayo Clinic uses, the Mayo 3D-printed swabs are available to supplement that supply. And they serve as a backup if the Copan supply is disrupted.
"Having the ability to manufacture what we need gives us stability, and it puts Mayo Clinic in the driver's seat," Dr. Jannetto says. "Now we're not dependent on a single source producing the swabs and shipping them to us. This innovation gives us redundancy and allows us to maintain our vital operations."
Reflecting on the effort it took to pull off the swab manufacturing, Dr. Morris credits Mayo Clinic's commitment to teamwork. "We have a culture of true, fluid, multidisciplinary interaction," he says. "We work together to find a solution that's best for the patient. We're not stuck in silos. When you put that culture in the middle of a crisis like COVID, it really shines."
From her perspective in Laboratory Medicine, Dr. Pritt sees the project's success in similar terms. "This was completely dependent on Mayo Clinic's culture of collaboration, and it's one of the best examples of collaboration I've seen at Mayo," she says. "We involved teams in Microbiology, the Anatomic Modeling Lab, the practice, Supply Chain Management, Central Services, and leadership. If any of those had fallen through, the project would have fallen apart. But everyone was so supportive, and the result was a win all the way around."