Case Analysis - Environment, The 2019–20 coronavirus pandemic is an outbreak

Case Analysis

Environment. The 2019–20 coronavirus pandemic is an outbreak caused by the severe acute respiratory syndrome coronavirus 2 (COVID 19)1. Its origins are difficult to pinpoint. Early reports linked 28 of the first 41 cases to a “wet market” in Wuhan, China2. The first case reported in the US occurred on January 22, 2020. As the table suggests, confirmed US cases reached an inflection point near the end of February3.

Capacity for Covid-19 testing in California surged, especially as the two largest commercial labs - Quest Diagnostics and Lab Corps – began to take samples. But the state still had a major backlog when it came to processing the samples. As of April 1, 87,000 tests had been collected but more than 57,000 of those were still pending results4. Meanwhile, as they waited for test results, many patients were taking up space in isolation wards and disrupting hospital operations.

During the early days of the outbreak, when containment would have been easier, the Federal government appears to have missed a series of opportunities to ensure more widespread testing6. On February 12, the CDC announced that a faulty reagent was causing a problem with its diagnostic Covid 19 test. Certified labs in the US having the right equipment could have used any of the protocols publicized by the WHO, ordered primers from any number of DNA synthesis companies, and pushed forward with testing. But federal regulations required that labs had to perform a number of validation studies and to submit data for FDA review. This required viral specimens, which could be hard to obtain if you were not the CDC.

Thus, by February 25, only 12 US labs outside the CDC, in just five states, had the ability to test for the virus. At the time, only 426 people in the US had been tested. Meanwhile, South Korea was reportedly testing 15,000 people per day. Furthermore, under the CDC’s narrow testing guidelines, only people with symptoms and a history of travel to China were eligible to receive a test. This meant many infectious people were missed during the crucial early days of the virus’s spread in the US5.

On February 29, facing mounting pressure, the FDA changed its regulations to allow certified clinical labs to develop and begin using their own tests to detect Covid-19 without prior approval. The two largest diagnostic commercial labs began conducting a few thousands tests a day, and a spokesperson for Quest said the company expected to have the capacity to conduct “tens of thousands of tests per week” by the end of March. Universities and hospitals also booted up. However, while on March 1 the CDC still claimed that only 15 Americans were sick with the coronavirus, even rudimentary models suggest that roughly 10,000 Americans may have been infected at that time5.

The Innovative Genomics Institute (IGI)4

On March 13, Jennifer Doudna was giving a rousing speech to the core members of the IGI, a three-year-old CRISPR research hub where Doudna is the executive director. The usually understated CRISPR/Cas 9 co-discoverer looked up at her colleagues seated in the auditorium and said, “Folks, I have concluded that the IGI must rise and take on this pandemic.”

“When I heard that, I had a vision of Lady Liberty not lifting up a torch but raising a micropipette,” said Fyodor Urnov, the IGI’s scientific director. Doudna deputized Urnov to put together a new team to tackle the testing issue from scratch. But how does a crew of CRISPR researchers with no prior clinical diagnostic experience make this leap?

On March 16, the FDA shifted responsibility for regulating clinical testing sites to individual states. In California, an executive order from Governor Newsom had removed state licensing requirements for Covid-19 tests in CLIA-certified labs. Thus, at Berkeley, there was one lab that had the right certifications to process samples from patients: the student health center.

While the clinical testing lab at the UCSF, a major medical center, had 40 technicians working around the clock in shifts, Berkeley’s student health center had just two. It also lacked the required biosafety infrastructure to test for Covid-19. Its two technicians had been sending samples to a nearby commercial laboratory; however, it was taking a week to get results back to UC Berkeley. Guy Nicollette, assistant vice chancellor of the university’s health services, said “In a perfect world we’d be able to test everyone who wants to get tested, which is why we are thrilled to partner with researchers that will expand our testing capacity.” Thus, the student health center extended its CLIA certification to a 2,500-square-foot lab on the first floor of the IGI.

RNA extraction can be done by hand, which is often the case at public health labs and other smaller operations. It requires the carefully orchestrated additions of different chemicals, enzymes, and tiny beads that catch the virus’s RNA. But doing these steps over and over for hundreds of samples consumes time and increases the potential for making errors. To minimize both, IGI officials decided to buy a new robot. They chose one from Hamilton, the STARlet, that can handle 100 patient sample tubes and transfer the liquid inside each one into its own barcoded dimple on a 96-well plate.

Newer PCR machines can run four times more samples - 384 at a time - faster and more accurately than the older ones recommended by the CDC. To extract RNA at that scale, the IGI crew pinched a different liquid-handling robot - the $400,000 Hamilton Vantage - from one of the now silent CRISPR labs upstairs. For 96-well patient sample plates, it purifies out the viral RNA and converts it into PCR-ready 384-well plates without any human intervention.

An evolutionary biology professor at UC Berkeley, Noah Whiteman, had put out a Twitter call on March 9 asking for an inventory of PCR machines in case the area’s Covid-19 testing facilities ran short. He quickly compiled a list of about 30 machines. The IGI crew scanned the list for newer machines capable of running 384 samples at a time. The ancillary equipment was also important. They needed to have a ready store of reagents, swabs, and tubes in which to store the swabs so that the lab wouldn’t run into shortages.

The IGI testing protocol team, led by Lin Shiao, settled on a kit from Thermo Fisher that had already been authorized for emergency use by the FDA. The company had produced a million kits upfront. So IGI - along with some individual professors - plowed its own funds into stockpiling tons of the kits. “We are literally burning cash,” he said, adding that sitting on its donor-provided funds in a time of pandemic would be “a violation of everything we stand for.”

But to make these kits run on the newer machines required adapting them, miniaturizing them for the more densely packed 384-well plates. “We wouldn’t use them if we were doing RNA extraction manually because the liquid sizes are so small that they’re very prone to human error,” says Lin Shiao. “The robot is way more accurate. That’s what is going to allow us to eventually scale up to 4,000 samples a day.”

As the robotics team was programming the robots and the protocol team was miniaturizing the protocols, other volunteers - including executives from SalesForce and laboratory information firm Third Wave Analytics - were busy setting up and testing the electronic chain of custody software that would keep track of each sample according to its unique barcode. This HIPAA-compliant code will ultimately be responsible for transmitting information about where each sample was in the testing process, including the test’s eventual result, back to the doctor who ordered it.

Meanwhile, the health center brought a former technician back out of retirement to oversee the lab’s usual operations, while a certified lab director came in from UC Davis to oversee the Covid-19 testing. In addition to Lin Shiao, within a few hours 861 other people had responded to the IGI’s call for volunteers. Several dozen of the more qualified ones - people with prior RNA extraction and PCR experience – needed training on CLIA compliance. They learned how to properly wear masks and gloves and other safety protocols for working with patient samples. They learned how to work in a biosafety cabinet - a sterile, negatively pressurized workspace - that had been dragged down from a different lab and reassembled on the first floor.

Volunteers will work in three teams to cover two 5-hour daily shifts, with socially distanced “battle lieutenants” positioned to step up if anyone falls ill. In early April, the teams will run a few hundred tests per day using manual protocols on two of the older PCR machines. Later in the month, once the robots are fully validated, they expect to ramp up to as many as 4,000 daily tests, as needed, says Urnov.

Volunteers like Lin Shiao don’t hope to still be running Covid-19 testing six months from now. Someday he’d like to get back to CRISPR. But for now, he’s grateful for a chance to chip in and, despite the 12- to 16-hour days, happy to have a reason to spend less time on Twitter. And it’s the first time he’s felt like all those years spent moving tiny bits of liquid around might actually directly change someone’s life for the better. “It feels good not to sit around but rather do my part to hopefully help curb this pandemic,” he says.

QUESTIONS

1. What is the “opportunity” that caused the IGI to diversify into diagnostic testing?

2. Use the PESTEL model to describe how the firm’s environment may have contributed to the “opportunity.”

3. Describe any “inertia” among incumbent diagnostic testing firms that also may have contributed to the “opportunity.”

4. Describe how IGI’s core competence in process technology expands testing capacity (addresses the “opportunity”).

5. How is the leader’s mission (rise and take on this pandemic) interpreted into different justifications (purposes) by members of the senior team?

6. How is the senior team empowered and transformed?

7. The $64,000 question is whether Jennifer’s Doudna’s leadership, that of subordinates, or self-selection is responsible for the above. What questions would you ask to resolve this issue?

8. IGI’s entry into diagnostics is an example of the corporate strategy of related diversification. How does it leverage its own strengths (internal development) to exploit this “opportunity?” Are any of these strengths unique and/or difficult-to-imitate?

9. Make recommendations for the future strategy of IGI.

REFERENCES

1. https://en.wikipedia.org/wiki/2019%E2%80%9320_coronavirus_pandemic

2. https://www.wbur.org/hereandnow/2020/02/13/new-coronavirus-origins-deaths

3. Source: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html

4. https://www.wired.com/story/crispr-lab-turned-pop-up-covid-testing-center/

5. https://www.theatlantic.com/health/archive/2020/03/next-covid-19-testing-crisis/609193/

6.

https://www.nytimes.com/2020/03/10/us/coronavirus-testing-delays.html

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