NEW YORK – According to an audit released last week by the US Department of Health and Human Services (HHS) Office of Inspector General (OIG), the US Centers for Disease Control and Prevention's (CDC) failure to develop a working SARS-CoV-2 molecular test in the early days of the COVID-19 pandemic stemmed from a variety of factors ranging from inexperienced and insufficient staff to a lack of quality safeguards and physical resources.
In its report, the OIG recommended several steps the CDC should take to improve its processes, including establishing more rigorous processes for test development, implementing lab quality management systems, and ensuring that the agency has the personnel and lab space needed for developing tests in future emergencies.
Following the first reports of COVID-19 in China toward the end of 2019, the CDC began developing a molecular test for SARS-CoV-2 with the goal of sending test kits to public health labs around the country so that they could test for the disease. The agency launched its test development efforts in mid-January 2020 and received Emergency Use Authorization from the US Food and Drug Administration at the beginning of February. It then began sending test kits to public health labs with the expectation that the CDC and public health labs would perform SARS-CoV-2 testing while academic and industry clinical labs and in vitro diagnostic manufacturers developed their own tests and moved them through the FDA EUA process.
The CDC test was flawed, however, due to contamination during the production process, which caused it to fail in the hands of some public health laboratories. This meant that the country's testing capacity was extremely limited as the virus began to spread rapidly in the weeks to follow.
In its audit, the OIG aimed to review the CDC's SARS-CoV-2 test development process to identify the factors that led to the process's initial failure.
One of the main issues identified by the office's report was that the respiratory virus diagnostic (RVD) lab, which was primarily responsible for developing the test kits as well as the strategy for producing and distributing it, had limited experience in test development and lacked formal policies and procedures for such a process.
"Without established policies and procedures at RVD lab, the [RVD lab] lead scientist had to create the processes and procedures for developing the COVID-19 test kit while the test kit was being developed," notes the OIG report, adding that this "created a high-risk environment that allowed for incomplete processes to occur," including distribution of test kits to public health labs before the CDC had determined that all the kits worked properly.
OIG found that the RVD lab's lack of experience in test development was compounded by the lab's relatively limited resources. Prior to the COVID-19 pandemic, the lab had a staff of two to three scientists and an annual budget of between $200,000 and $300,000 a year. During planning meetings in January 2020, the lab's lead scientist told management at the CDC's National Center for Immunization and Respiratory Diseases (NCIRD) that to develop a SARS-CoV-2 test, the RVD lab would need "approximately 20 additional personnel with experience in project management, regulatory affairs, quality assurance, quality control, manufacturing, laboratory testing, and information management."
This scientist requested help from the agency's Influenza Division, which develops test kits for flu annually and so had considerably more test development experience than did RVD. Ultimately, however, the RVD lab received assistance from only 13 employees, a mix of full- and part-time staff.
The OIG report notes that CDC personnel interviewed for the audit "recalled RVD lab's lead scientist calling and pleading with individuals" in other parts of the agency for help with development of the test kit.
Adding to the RVD lab's difficulties was a lack of physical lab space and capacity at the CDC. At the time the lab began its development efforts, the CDC had not yet obtained virus samples that could be used for test development and verification. Instead, the RVD lab requested that the agency's Biotechnology Core Facility Branch (CORE) lab create viral material based on the SARS-CoV-2 genome sequence released by China.
The CORE lab was already making reagents for the RVD lab's test kit and typically would not produce both test reagents and materials for test verification in the same space at the same time due to the possibility of contamination. However, OIG found that due to the urgency of the situation and the lack of lab space and resources needed to segregate these two processes, the CORE lab violated this policy, exposing its processes to the contamination that ultimately undermined the agency's SARS-CoV-2 test.
The report also identified failures of oversight that contributed to the test's initial failure, noting that the RVD lab operated without performance measures that could be used for tracking its test development progress and with "minimal oversight" from NCIRD. Gaps in oversight remained after the CDC's COVID-19 response was elevated from an NCIRD-led effort to an agencywide response in late January 2020.
The agency's test development effort also suffered from the lack of an agencywide document control system and the lack of an agencywide laboratory quality management system, both of which made it difficult to track and manage the test's development and to obtain and share data relevant to that process.
In light of these failures, OIG recommended that the CDC take a number of steps to improve its test development procedures, including creating processes for test development with defined "roles, responsibilities, and oversight"; creating processes to "ensure adequate staffing and laboratory space can be obtained for future responses"; revisit the agency's incident management system (IMS) to ensure effective oversight of a response effort; implement an agencywide lab document control system; and have all agency infectious disease labs implement a quality management system.
In an addendum to the OIG report, the CDC said it has addressed a number of the office's recommendations, noting that it has developed a laboratory quality plan (LQP) intended to ensure the agency produces "high-quality test methods and test results in both routine and emergency operations." It added that it has "revised internal controls, plans, and procedures to improve the separation of duties and laboratory capacity" and has reorganized its IMS to "ensure a consistent approach for all response activities, including laboratory-based efforts."
The CDC said it is still in the process of implementing an agencywide document control system and quality management systems in its infectious disease labs.