On March 13, 2020, leaders from CSU’s Office of the Vice President for Research and the CSU Health Network scheduled a call with representatives from the Larimer County Department of Health and Environment and the Colorado Department of Public Health and Environment. Members of the call explored whether CSU’s extensive biomedical capabilities, talents, and investigators could be leveraged to provide on-campus Reverse Transcriptase, Real-Time Polymerase-Chain-Reaction (RT-PCR) clinical testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) – the virus that causes COVID-19. Facing a severe shortage of testing capabilities and mounting state-wide cases, the County and State officials expressed interest, but this would be no small task. Human clinical testing for COVID-19 requires not only that the test itself be authorized by the US Food and Drug Administration (FDA), but the clinical laboratories responsible for performing the test are certified by the Centers for Medicare and Medicaid Services (CMS) under the Clinical Laboratory Improvement Amendment (CLIA) regulations.   

CSU had proposed to use a Laboratory-Developed Test (LDT), which according to the FDA, “is a type of in vitro diagnostic test designed, manufactured and used within a single laboratory.” ^1 Under regular (pre-COVID-19 pandemic) circumstances, CLIA certification of a research laboratory to perform clinical testing with an FDA 510(k) cleared LDT would be a big lift.   

Compliance with these regulatory requirements would take substantial effort, hundreds of millions of dollars, and significant infrastructure capital investments. In practice, the FDA has had a policy of enforcement discretion, rarely enforcing LDT regulatory requirements provided that LDTs were not used outside of a single laboratory. Although FDA reserves the right to offer formal regulatory oversight, in the past, the laboratories were left to self-regulate at their own risk. 

Circumstances changed with the arrival of SARS-CoV-2 and a sudden need across the US for expanded clinical testing, including at CSU. Despite a previous lack of enforcement, the FDA began issuing Emergency Use Authorizations (EUAs) to individual labs for LDTs related to SARS-CoV-2 testing, clearly indicating that it considers these tests to be subject to FDA oversight. Simultaneously, the FDA also gave broad discretionary authority to individual states and territories utilizing guidance regarding COVID-19 testing published on March 11, 2020. ^5 The Guidance stated, “a State or territory choosing to authorize laboratories within that State or territory to develop and perform a test for COVID-19 would do so under the authority of its State law, and under a process that it establishes.”   

What ensued was a jumble of approaches in which some labs around the country requested EUAs from FDA for their testing processes. Others received authorization to conduct COVID-19 testing from their state governments, and some even proceeded under the authority of their county health departments. CSU’s unique approach, and in consort with its land grant heritage, was to take advantage of existing EUAs covering the testing for SARS-CoV-2 at CSU’s Veterinary Diagnostic Laboratory. However, that was not the end of the story because the FDA is not the only agency regulating in vitro diagnostic tests. Suppose even a single test result is to be released to an individual (instead of publishing unidentified group results as part of a study). In that case, CMS oversight is required to ensure compliance with CLIA regulations.  While the CMS website cites a 4-12-week turn-around time for certification, this does not account for the time needed to prepare the application, which can take six months to a year. Preparation requires testing laboratories to demonstrate compliant processes and procedures, provide extensive training to the staff and set up HIPAA-compliant data systems. However, the CSU’s Veterinary Diagnostic Laboratory already adheres to similar standards as those required by CLIA regulations due to its work with the Centers for Disease Control and Prevention (CDC). Thus, it was already in the position to apply for necessary permits for operation. Additionally, reduced data system requirements to facilitate the pandemic response further expedited the application process. Remarkably, within three weeks of applying for access to gain critical capacity for our community, the CSU team received approval from the Colorado CLIA office to move forward with clinical testing.    

The team that supported this effort included a diverse group of CSU researchers, administrative leaders, and lawyers who were joined by representatives from the Larimer County Department of Health and Environment and the Colorado Department of Public Health and Environment. Over those three weeks, this group convened weekly for online video chats. A Brady Bunch-like panel of participants discussed the logistical, regulatory, scientific, and legal aspects of the project and worked together to identify resources and share expertise.    

This same multidisciplinary team approach has been expanded to a variety of other innovative efforts on campus. Groups are coming together to address the myriad, often urgent unmet medical needs related to the COVID-19 pandemic, overcoming considerable hurdles and navigating the complex regulatory landscape of biomedical research. Their success is evidenced by the diversity and the sheer number of projects that are underway on campus. This section of the magazine will highlight several multidisciplinary teams leveraging the University’s unique research talent and advanced technological capabilities to develop solutions across a whole spectrum of challenges posed by this pandemic.   

With more than 25 projects and more than 100 CSU researchers and staff working on antivirals, vaccine development, and other technologies to combat SARS-CoV-2, the University is poised to significantly impact this effort at a local, state, and federal level. Some of the innovative projects highlighted in this section of the magazine include the SolaVAX™ vaccine development effort, led by the Executive Director of the Infectious Disease Research Institute, Dr. Ray Goodrich, which has garnered significant government funding. The vaccine candidate uses a novel process effective against Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which is in the same coronavirus family as SARS-CoV-2. Another team, led by CSU Professor Dr. Rushika Perera, is testing drugs and chemicals to see if they might be effective against SARS-CoV-2. Dr. Bryan Willson, Executive Director of CSU’s Energy Institute and a team of engineers from CSU, collaborated with the Fort Collins-based Woodward, Inc. to submit a EUA to FDA for a novel emergency ventilator using parts more available in the supply chain.   

The diversity of efforts at CSU brings a wealth of ground-breaking solutions to the challenges posed by the COVID-19 pandemic and, but these efforts will also require careful navigation of the complex mix of regulatory, operational, and technical difficulties. The situation is further complicated by dynamic changes in FDA regulations and fast-paced guidance at a rate that has not been seen in many decades. While regulatory consultants, clinical research coordinators, and researchers struggle to understand how to understand an often-changing regulatory landscape and stay on the right side of compliance, FDA is signaling that at least some of its modifications in response to the pandemic may become permanent. FDA needs to ensure it can continue to be responsive as this pandemic unfolds and that it remains prepared for future public health emergencies, should they arise. As CSU multidisciplinary teams increasingly place their knowledge, experience, and innovative solutions in service of the broader community’s needs, they will require more support in regulatory assistance, clinical research support, and an expanded compliance system. The ultimate success of these initiatives at CSU will be measured in lives saved and our broader Colorado community’s improved health and safety.