Some answers here. This is about as efficient/swift as I expect the federal government to be (which is to say not very):
Quote:
January 31: HHS Secretary Alex Azar declared a public health emergency, which initiated a new requirementlabs that wanted to conduct their own coronavirus tests must first obtain an emergency use authorization (EUA) from the FDA. According to reporting from Reuters, the emergency declaration made it more difficult to expand testing outside the CDC:This was the moment when the wheels came off the bus. Keith Jerome, the lab director at the University of Washington Virology Lab in Seattle, told The New Yorker how perverse this heightened standard was from a public health perspective:Quote:
That's because the declaration required diagnostic tests developed by individual labs, such as those at hospitals or universities, to undergo greater scrutiny than in non-emergenciespresumably because the stakes are higher.
"Paradoxically, it increased regulations on diagnostics while it created an easier pathway for vaccines and antivirals," said Dr. Amesh Adalja, a senior scholar at the Johns Hopkins University Center for Health Security. "There was a real foul-up with diagnostic tests that has exposed a flaw in the United States' pandemic response plan."EUAs were intended to speed up the normal authorization process. But in this case, labs that were already conducting their own coronavirus tests needed to cease operations until they were granted an EUA. By declaring a public health emergency and not waiving EUA requirements, the FDA was actually slowing down the testing process.Quote:
From the point of view of the academic labs, we look at it, like, when there's any run-of-the-mill virus that people are used to, they trust us to make a test. But when there's a big emergency and we feel like we should really do something, it gets hard. It's a little frustrating. We've got a lot of scientists and doctors and laboratory personnel who are incredibly good at making assays. What we're not so good at is figuring out all the forms and working with the bureaucracy of the federal government.
Obtaining an EUA is no quick task. The FDA requires new protocols to be validated by testing at least five known positive samples from a patient or a copy of the virus genome. Most hospital labs have not even seen coronavirus cases yet. An article in GQmagazine detailed how Alex Greninger, an assistant director of the clinical virology laboratories at the University of Washington Medical Center, was forced to navigate a regulatory morass:But submitting the physical application wasn't the end of the process. Before granting the EUA, the FDA wanted Greninger to run his testing protocol against the MERS and SARS viruses:Quote:
After emailing his application to the FDA, Greninger discovered that it was incomplete. It turned out that in addition to electronically filing it, he also had to print it out and mail a physical copy along with a copy burned onto a CD or saved to a thumb drive. That package had to be shipped off to FDA headquarters in Maryland. It was a strange and onerous requirement in 2020, but Greninger complied. He had no choice. On February 20, he overnighted the hard copies of his application to the FDA.February 3: The FDA hosted a previously scheduled all-day conference at its headquarters with regulators, researchers, and industry leaders to "discuss the general process for putting diagnostic tests cleared under emergencies on the path to permanent approval by the FDA," according to reporting by Reuters. "Though coronavirus was now the hottest topic in global medicine, a broadcast of the meeting conveyed little sense of urgency about the epidemic sweeping the globe" and the virus was only mentioned "in passing."Quote:
Greninger complied. He called the CDC to inquire about getting some genetic material from a sample of SARS. The CDC, Greninger says, politely turned him down: the genetic material of the extremely contagious and deadly SARS virus was highly restricted.
"That's when I thought, 'Huh, maybe the FDA and the CDC haven't talked about this at all,'" Greninger told me. "I realized, Oh, wow, this is going to take a while, it's going to take several weeks."
February 4: The FDA issued an emergency use authorization (EUA) for the CDC's test to be used at any CDC-qualified lab. Prior to issuing the CDC an EUA, all tests had been collected in the field and then shipped to CDC headquarters in Atlanta for analysis. During this time period, the CDC was able to run only about 500 tests (12 of which came back positive). To implement nationwide testing, the CDC would need to distribute its testing kits to partner labs across the country.
In a declared emergency, the FDA has broad discretion about which laboratory-developed tests will be permitted to be used. By only issuing a single EUA to the CDC, the FDA put all its eggs in one basket. Alan Wells, the medical director for the University of Pittsburgh Medical Center's clinical laboratories, told the Wall Street Journal: "We had considered developing a test but had been in communication with the CDC and FDA and had been told that the federal and state authorities would be able to handle everything."
February 5: The CDC began shipping test kits to about 100 state, city, and county public-health laboratories across the country, which would have allowed 50,000 patients to be tested. However, most of the partner labs ran into problems during the validation stage (which is necessary to ensure the tests were functioning properly), according to a ProPublica investigation:The specific cause of these problems is still under investigation, but the initial findings suggest there were problems with one or more of the reagents used in the CDC testing kits. The CDC paused testing at its partner labs and resumed exclusive and very limited testing at its Atlanta headquarters.Quote:
The [CDC] shunned the World Health Organization test guidelines used by other countries and set out to create a more complicated test of its own that could identify a range of similar viruses. But when it was sent to labs across the country in the first week of February, it didn't work as expected. The CDC test correctly identified COVID-19, the disease caused by the virus. But in all but a handful of state labs, it falsely flagged the presence of the other viruses in harmless samples.
February 10: The CDC notified the FDA about the reagent problems in the testing kits it had shipped to its partner labs. By not allowing private companies or public labs to use their own tests, the FDA had created a single point of failure and ultimately delayed large-scale testing by weeks. Keith Jerome, the lab director at the University of Washington, explained to The New Yorker why the FDA's plan was vulnerable from the outset:February 21: Nancy Messonnier, the director of the National Center for Immunization and Respiratory Diseases (NCIRD) at the CDC, told journalists that the issues with the reagents were still not resolved.Quote:
The FDA's exclusive authorization to the CDC to conduct COVID-19 tests ended up creating "what you'd think of as an agriculture monoculture. If something went wrong, it was going to shut everything down, and that's what happened." Jerome said that his lab has taken its own steps to mitigate this problem. "We've built three completely independent testing pathways in our laboratory, so that if there's a shortage of a reagent or a bit of plastic, we have other ways to do the testing."
February 24: An association of more than 100 state and local health laboratories sent a letter to the FDA commissioner asking for "enforcement discretion" to use their own lab-developed tests. The chief executive of the association that sent the letter called it a "Hail Mary" pass and an act of desperation. The FDA directed the labs to submit an EUA application instead.
Between mid-January and February 28, the CDC produced more than 160,000 tests but used fewer than 4,000.
February 29: Facing a backlash to its rollout of testing, the FDA reversed its position and removed the requirement that advanced laboratories obtain prior emergency use authorization before using their own tests. At the time, this exemption applied only to "laboratories that are certified to perform high-complexity testing consistent with requirements under Clinical Laboratory Improvement Amendments." One researcher estimated 5,000 virology labs in the country met this standard. For context, U.S. testing capacity includes approximately 260,000 laboratory entities.
March 3: Vice President Pence announced the CDC was lifting all federal restrictions on who can be tested for COVID-19: "Any American can be tested, no restrictions, subject to doctor's orders." Previously, testing was limited to only those who were exhibiting symptoms and had recently traveled to China or had been exposed to a known case. However, the supply of tests in particular regions would continue to be the most common binding constraint.
March 12: The FDA issued an EUA to Roche. Paul Brown, the head of Roche's Molecular Solutions division, told The New Yorker, that "the company had been working on a test since February 1st" and that "the new tests, which are mostly automated, can make it possible for large testing companies such as Quest and LabCorp to test for COVID-19." The CDC and state and local public health labs have been running tests manually. Reaching the scale of millions of tests will require automated tests on high throughput machines at large testing companies.
March 13: President Trump declared a national emergency. The FDA issued an EUA to Thermo Fisher.
March 15: HHS Secretary Azar waived sanctions and penalties against any covered hospital that does not comply with various provisions of the HIPAA Privacy Rulerelated to patient privacy and consent, including the need "to obtain a patient's agreement to speak with family members or friends involved in the patient's care." Previously, HIPAA privacy provisions and the Common Rule were holding up testing and the dissemination of information. According to an article in the New York Times, these kinds of requirements prevented labs from conducting coronavirus tests on samples collected for research purposes:They were not to test the thousands of samples that had already been collected.Quote:
Federal and state officials said the flu study could not be repurposed because it did not have explicit permission from research subjects; the labs were also not certified for clinical work. While acknowledging the ethical questions, Dr. Chu and others argued there should be more flexibility in an emergency during which so many lives could be lost. On Monday night, state regulators told them to stop testing altogether.
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On a phone call the day after the C.D.C. and F.D.A. had told Dr. Chu to stop, officials relented, but only partially, the researchers recalled. They would allow the study's laboratories to test cases and report the results only in future samples. They would need to use a new consent form that explicitly mentioned that results of the coronavirus tests might be shared with the local health department.
