The U.S. capacity for SARS-CoV-2 testing is limited by several items, including the swabs used to collect patient specimens, but the supply of reagents has been front and center recently. Despite those concerns, several private test makers said they are quickly ramping up production, including Thermo Fisher Scientific Inc., of Waltham, Mass., which said it has enough supplies of all types on hand to provide 2 million reactions per week, a volume that should increase to 5 million per week in April.

FDA commissioner Stephen Hahn said in a March 11 congressional testimony that there was some strain on the supply of reagents, but that the agency was working with labs on alternative reagents. Rep. Ted Lieu (D-Calif.) resurrected the issue in a March 17 letter to Vice President Mike Pence, citing a statement by CDC director Robert Redfield in March 13 congressional testimony about the reagent problem. Lieu also referenced a March 10 statement by the American Society for Microbiology about the situation, which said that the CDC decision to require only one specimen swab instead of two has reduced the required volume of reagents by half.

Thermo Fisher told BioWorld that the company had 1.5 million tests available to ship under the emergency use authorization (EUA) as of March 16, a volume the company expects to rise to 2 million per week. Thermo Fisher spokesperson Ron O’Brien said the company has enough consumables to address both extraction of RNA and the positive controls for that 1.5 million reactions. Those supplies will also be sufficient to handle the 2 million tests that will be made available in the coming weeks.

O’Brien said the next phase of the company’s effort is to ramp up to 5 million reactions per week in April, adding that these tests are optimized for the Applied Biosystems 7500 analyzer. The 7500 polymerase chain reaction (PCR) system is specifically listed in the EUA for the Thermo Fisher test, and O’Brien said a number of labs have the sample prep and instrumentation to run the test. Thermo Fisher is also working with the FDA to expand the number of instruments that can be used with both the sample prep and the PCR system, O’Brien said.

Quest Diagnostics Inc., of Secaucus, N.J., said it had expected to ramp up testing capacity for its tests to 20,000 per day based on the use of high-throughput testing platforms. That volume should reach 280,000 tests per week by the beginning of April, although this is contingent on a steady supply of swabs, reagents and other instruments and supplies.

Quest said it currently performs its tests at its lab in San Juan Capistrano, Calif., but that an additional eight sites should come online by the end of March, including sites in Dallas, Los Angeles and Chicago. Quest had not forwarded an update for March 18 prior to press time.

U.S. lab system hampered by many factors

In a March 14 investor note by William Blair Equity Research of Chicago, analysts Brian Weinstein and Andrew Brackman noted that one of the more pressing supply chain issues at play is that of swabs used to obtain samples. The largest manufacturer that supplies the U.S. market with both the swabs and the transport media is located in northern Italy, however.

There is also a pinch on RNA extraction kits, including the extractors, and the analysts cited back-orders on extractors priced at $100,000 each, units that can prepare a “few hundred samples a day,” the analysts said.

Brackman and Weinstein cast doubt on comparisons between the U.S. and South Korea, given that testing components were available much earlier in the spread of the virus in South Korea. “South Korea was not fighting with other countries to get what they needed in terms of the raw materials” to make the supplies and instruments, they said, adding that South Korea has a centralized lab infrastructure. In contrast, the U.S. has roughly 11,000 labs that enjoy “varying degrees of capabilities in microbiology and molecular diagnostics.”

The situation is further exacerbated by cuts to Medicare rates for diagnostics, which Weinstein and Brackman blamed for a shortage of lab personnel capable of assembling an assay and running it on instruments that are not fully automated. That has forced many labs with testing capacity to wait for kits developed and approved for their fully automated systems, while “some of the largest regional labs do not have any LDT capabilities,” they said.

Sen. Paul drops new LDT legislation

Rep. Rand Paul (R-Ky.) has unveiled legislation that would bar the FDA from exercising any regulatory authority over lab-developed tests. The Verified Innovative Testing in American Laboratories (VITAL) Act of 2020 specifically states that “no aspects of laboratory-developed testing procedures shall be regulated” via the Food, Drug and Cosmetic Act, essentially cutting the FDA entirely out of the picture.

In response, the Association for Molecular Pathology (AMP) said in a March 18 statement that it applauds the legislation, which AMP said would modernize regulation of tests via the Clinical Laboratory Improvement Act of 1988. AMP said “the current coronavirus pandemic highlights the inefficient FDA oversight process” while simultaneously highlighting the vital role played by a variety of lab types, including public health labs. The FDA’s initial emergency use authorization policy “prevented many laboratories from fixing the flaw in the first test kit” provided by the CDC, and imposed needless drag on the efforts of private and academic labs to ramp up their own testing protocols.

AMP President Karen Weck said the bill “will provide clinical laboratories with clarity and predictability in federal oversight of testing programs.” Weck also said the delayed response by the FDA and the CDC “perfectly illustrates the importance of clinical laboratories in being able to provide novel testing services.”

Dramatic change from slow start by FDA, CDC

Scott Danzis, a partner in the D.C. office of Covington & Burling LLP, told BioWorld that while the FDA and the CDC struggled to move testing forward in the early days, “things have shifted dramatically” since that time. Danzis said the issue of FDA regulation of lab-developed tests is of long standing, but that the Verifying Leading-edge IVCT Development (VALID) Act, first proposed in December 2018, has at least some support from the clinical lab community.

“I think we should probably avoid taking away specific lessons from this situation” in terms of what should be a regulatory scheme in a more normal situation, Danzis said. However, he added that any legislative response “needs to be carefully tailored” to ensure there can be rapid rollouts of countermeasures in a public health crisis.

With regard to items such as N95 masks, Danzig said, “what the agency is trying to do is work with companies to ensure that what is produced is to specifications.” However, “they do relax the quality systems requirements in this time of emergency,” he said. There are masks available that are manufactured under regulations administered by the National Institute for Occupational Health and Safety, which are not intended for medical settings, but rather are for uses such as construction work.

“That’s not to say they don’t have standards attached to them,” Danzig said, but federal government agencies are more comfortable deploying them in this situation than would otherwise be the case. The CDC has updated its recommendations to state that such a face mask would be acceptable for health care professionals when an N95 respirator mask is unavailable. Danzig said that a manufacturer simply needs to document a NIOSH authorization for the mask.

The updated FDA policy on testing allows the states to oversee testing during the COVID-19 crisis, but Danzig said, “I think there are some questions that need to be worked through.” He noted that while the state of New York has a long history of regulation, not all state governments are thus staffed, and consequently, “it remains to be seen which states will exercise this authority.” Those states do have options, however, such as using the test authorization scheme in place in New York as a method of enabling testing capacity.

Telehealth waiver loosens geographic restrictions

The Centers for Medicare and Medicaid Services announced March 17 a telehealth waiver that covers hospital, office and other visits effective March 6. The waiver covers professional services to Medicare beneficiaries in all areas of the nation for the duration of the Public Health Emergency. This covers telehealth in any facility and the beneficiary’s home, Providers can waive the co-insurance that would ordinarily be required, and the Department of Health and Human Services will not audit such transactions for whether a previous relationship had existed between the patient and the health care professional.

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