COVID-19 diagnostic developers could gain financial and operational manufacturing assistance and a regulatory fast-track through a new program announced by the NIH in collaboration with FDA and BARDA. While the Rapid Acceleration of Diagnostics (RADx) program is intended to incent developers to come up with novel solutions to ongoing testing capacity issues, the project’s success will depend on the regulatory competencies of participants.
By Laura DiAngelo, MPH
Executive IQ Brief
- How things work now: Diagnostics that can detect the virus that causes COVID-19 are required to submit an Emergency Use Authorization (EUA) to the FDA for review and authorization before heading to market. While the FDA has authorized 42 EUAs for these types of diagnostics, reports still indicate that the diagnostic capacity is lacking in the US. Without widespread testing, policymakers may have difficulties tracking the virus through the population.
- What’s new: The RADx program is intended to provide technical, scientific and financial support for diagnostic developers selected for the program. Led by the NIH with support from the FDA and other agencies, the program will provide selected companies scientific support in developing their product, expedited review by the FDA, and financial support to scale-up manufacturing and distribution.
- Impact: A key challenge for manufacturers with COVID-19 products has been scaling up manufacturing as public pressure and need increases. The financial and operational assistance of RADx could be a significant incentive for manufacturers to develop and deploy products.
- Additionally, the program will prioritize diagnostics that won’t face similar supply chain challenges to those already on the market. Current issues include shortages of necessary accessories (e.g., swabs, reagents), a lack of laboratory capacity for testing, or the need for a patient to be in the hospital to be tested for COVID-19. These projects would likely significantly scale up the number of tests available and used in the US.
- What’s next: The NIH is currently accepting applications. The announcement states that it expects to have “millions” of tests deployed each week by late summer/early fall. Currently, the only EUA template for viral tests available from the FDA is for molecular diagnostics, which could limit the types of products that could apply for the project. However, the agency is expected to issue an EUA template for antigen tests in the near future.
Regulatory Background and Context
Manufacturers of diagnostics that can detect SARS-nCOV-19, the virus that causes COVID-19, are eligible for an expedited path to market by seeking an Emergency Use Authorization (EUA) rather than full approval from the agency.
Under the COVID-19 Public Health Emergency (PHE), the FDA can issue these authorizations based on whether there is reason to believe that an unapproved product may be effective in responding to a serious or life-threatening condition and there is no approved product available. This is a lower standard for market access compared to the standard for full FDA approval, which requires “substantial evidence” of a drug’s safety and efficacy—or “substantial equivalence” to a predicate device for moderate-risk medical devices like diagnostics.
The FDA issued its first EUA for a diagnostic to detect COVID-19 on February 4. That test was submitted and manufactured by the CDC. However, issues with the test’s manufacturing led to a slow and shaky roll out of the test, with “the delay in testing capacity…slow[ing] the US response to the coronavirus,” as POLITICO reported.
While the agency has since issued 42 EUAs for molecular diagnostics to identify the novel coronavirus, additional problems related to shortages of necessary accessories, such as nasopharyngeal swabs, continues to limit testing capacity.
On April 29, NIH Director Francis Collins announced a new program to expedite and incent COVID-19 diagnostic development and market deployment, the Rapid Acceleration of Diagnostics (RADx). This program will be sponsored by the NIH but include close involvement by FDA, CMS, BARDA and ASPR.
Under RADx, manufacturers and developers can submit test proposals to the NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB). If selected, the NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) and Point-of-Care Technology Research Network (POCTRN) will support both pre-market and post-market functions—including clinical testing, validation, commercialization and scaling up of manufacturing for the tests selected for the fast-track program.
Although the final decision about accepting a proposal will come from the NIH, an “external panel of experts” will review applications on four distinct criteria:
- Regulatory: Does the proposal include a feasible plan for submitting for both an EUA and “to subsequently obtain FDA clearance”?
- Technical: Are any of the product’s proposed design features an improvement over current approaches? These include high levels of analytical performance, including specificity, sensitivity, reliability, and dynamic range, or operational factors such as using alternative sampling strategies (e.g., saliva), flexibility in the swabs used, mobile-device integration, or site of use?
- Clinical: Could the test realistically be integrated into clinical workflow?
- Commercialization: If the test works, how can it be implemented/scaled in an economically viable way?
Testing proposals that meet these criteria will be considered for scientific, technical and financial assistance by the agencies. The program has $1.5 billion in funding, according to Dr. Collins, and on the NIH’s Point of Care Technology Research Network (POCTRN) website it states that they will provide “up to $500 million” per project. Depending on whether the projects receive the full $500 million available per project, at least three could be selected.
This program provides a significant financial incentive for diagnostic developers to submit their tests for review under the program. The availability of funding to support commercialization and rapid manufacturing scale-ups, as well as technical assistance on reimbursement and coverage policies, is likely to appeal to test manufacturers.
Diagnostic tests are typically regulated as Class II devices by the FDA, which means that the proposals would need to include a plan to support the market clearance of a Class II medical device submission, known as a 510(k). However, given the inherently increased risk profile of a diagnostic for COVID-19, the FDA may determine that the product is Class III, and therefore subject to the Premarket Application (PMA) pathway.
While the NIH blog post announcing RADx states that the program is open to proposals “from the basement to boardrooms,” it’s unlikely that “basement” projects would be selected, as proposals that will be prioritized are those that have “feasible plans” for both an EUA and “eventual clearance” from the FDA. It’s unlikely that a diagnostic developed by a non-traditional manufacturer would have a plan in place as part of their proposal to submit a test through the 510(k), or potentially PMA, process.
However, while the announcement states that diagnostics selected for the program will receive “accelerated timelines,” with the tests targeted to be available widely by the end of the summer, it’s not clear what flexibilities the FDA will leverage to expedite their review. As long as the COVID-19 PHE is still in effect, tests do not need to be formally cleared or approved to be marketed if they have an EUA.
The NIH said in a statement to AgencyIQ that projects would be expedited using “other biomedical technology accelerator and entrepreneurship networks it supports around the country; partnerships with other agencies within HHS, such as ASPR/BARDA, FDA, CDC, and CMS; and NSF, among others, to support the validation, clinical testing, regulatory review, and commercialization of COVID-19 tests selected by RADx.”
NIH did not clarify which authorities the FDA would use to expedite testing review. The FDA did not respond to AgencyIQ request for comment.
Out of the currently available medical device review pathways, the most obvious choice for accelerating review of a diagnostic for COVID-19 under RADx would be the Breakthrough Device Program, which replaced the FDA’s Expedited Access Pathway and Priority Review program for medical devices in 2018. The criteria for eligibility for a breakthrough device designation are similar to those for an EUA, including the requirement that the device is intended for use in a life-threatening or irreversibly debilitating disease for which there is no approved or clear alternatives exist. However, a device can also be designated a breakthrough if it represents “breakthrough technology,” offers a significant advantage over an already available alternative or is in found to be in the best interest of patients.
A key consideration: If a diagnostic is cleared by the FDA for the identification of COVID-19, the existing EUAs for similar diagnostic products could be revoked. A main condition of the granting of an EUA is that there must be no FDA-approved product that could potentially substitute for the non-approved one. If a diagnostic receives an expedited clearance through the RADx, the 42 other diagnostics may have to be removed from market. There are a few exceptions to this policy, however, including if “there are insufficient supplies of the approved” (or in this case, cleared) “alternative to fully meet the emergency need.”
The program website indicates that NIH expects to “deploy millions of tests per week” by the end of the summer 2020 or early fall.
The RADx program could effectively function as a way to incent diagnostic developers to voluntarily submit their novel diagnostics for review by relieving the financial burden associated with managing a huge manufacturing scale-up. As AgencyIQ has previously covered, both the development of a new technology for COVID-19 and the ability to quickly scale up manufacturing at population-wide levels has been a significant challenge for industry.
The RADx websites says that:
“Budgets for this second phase [approval and scale up] of the work are expected to be substantial. Budgets will include funding for scale-up and manufacturing to enable large-scale distribution by late summer 2020 or as early as feasible for the proposed solution. NIH will supply the needed budget, partnerships and other resources to fully deploy successful tests to the public on the shortest possible timeline. NIH will negotiate cost sharing with for-profit institutions as appropriate.”
The rolling submission and selection process is currently underway and will “continue until further notice.”
The FDA’s Dr. Stenzel has been indicating that an inter-agency program was in the works to improve regulation and oversight of diagnostic tests since early April. Dr. Stenzel stated at a town hall meeting on April 22 that “we thank our interagency partners for coming together in this awesome way to be able to assess the performance capabilities—at least at certain levels—on these voluntary manufacturers to come in.”
Tests authorized under this program are likely to be viewed as more reliable and accurate than those under just an EUA.
Currently, however, the only EUA template available for diagnostic tests to identify the COVID-19 causing virus is for molecular diagnostics, which are complex kinds of test. Although the agency has been expected to issue an EUA template for antigen tests, a comparatively simpler type of diagnostic, it has yet to do so. Operationally, this could limit the kinds of projects that can be submitted for consideration.
The RADx program also doesn’t address a significant issue in COVID-19 diagnostic regulation: serological testing. There are more than 100 non-reviewed serological tests thought to be on the market under the FDA’s current policies.