The goals of preclinical studies are to identify the initial safe dose and dose escalation schemes in humans, to identify target organs for toxicity, and to identify safety parameters for clinical monitoring. The U.S. Food and Drug Administration (FDA) requires preclinical study researchers to use good laboratory practices (GLP)—defined in medical product development regulations—for preclinical laboratory studies.
There is currently an outbreak of respiratory disease caused by a novel coronavirus. The virus has been named “SARS-CoV-2”, and the disease it causes has been named COVID-19. On January 31, 2020, the U.S. Department of Health and Human Services (HHS) issued a declaration of a public health emergency related to COVID-19 and mobilized the Operating Divisions of HHS (1). In addition, on March 13, 2020, the President declared a national emergency in response to COVID-19 (2).
In order to continue valuable preclinical research during the COVID-19 outbreak, modifications in GLP study operations are essential. In the laboratory, the number of workplaces at each bench could be limited and plexiglass plates could be placed between the workspaces for protection. Contingency plans should be in place in the case of a worker becoming infected with COVID-19. Contact between departments could minimized using separate entrances and staircases. Onscreen sharing, share points, data processing, and review activities could be performed remotely. Other challenges include the potential need to store study samples for extended periods until they can be analyzed. In such cases, it is important to evaluate the long-term stability of stored samples to ensure data quality once they are analyzed.
For preclinical studies, it is important to build in additional pre-study time to account for delays in making and receiving supplies and drugs. Preclinical studies using animal models have continued throughout the COVID-19 pandemic with study modifications to maintain critical samples and animal populations. Securing the supply chain to ensure adequate food, bedding, enrichment, and chemicals for cage wash and disinfection are essential. Animal care personnel could be classified as “essential personnel” and could utilize split schedules, staggered shifts, and restricted hours in the vivarium to maintain social distancing and keep personnel safe.
Enhanced sanitation in the common areas at the start and end of each shift is key to ensuring personnel safety. Conducting critical maintenance procedures should be continued including maintaining shared computational equipment and equipment that requires gas or cryogen monitoring/service, such as deep storage freezers, electron microscopes, mass spectrometers, and incubators.
Maintaining an adequate Quality Assurance (QA) program is essential and it is recommended that QA activities are prioritized using a risk-based approach. The use of remote technology such as video calls as an alternative to physical presence would be considered acceptable provided there is enough detail within study records to describe the method of observation. The use of remote observation methods should be fully risk-assessed to ensure they provide a similar level of oversight as a physical audit.
Operation Warp Speed & Its Effects
On May 15, 2020, the White House announced Operation Warp Speed to accelerate the development, production, and distribution of COVID-19 vaccines, therapeutics, and diagnostics in order to produce and deliver 300 million doses of safe and effective vaccines. The most promising candidates were selected and provided coordinated government support for their development. Protocols for the demonstration of safety and efficacy were aligned, which allowed clinical trials to proceed more quickly. The protocols for the clinical trials were overseen and set by the federal government. Some preclinical testing was done in parallel to the clinical trials. Manufacturing capacity for selected candidates were advanced while they were still in development. There was an expansion of supplies for specialized materials and resources, such as cold-chain storage, glass vials, and other materials, that can be necessary for distribution of the vaccines. Once a vaccine was ready, the Department of Defense's involvement enabled fast distribution and administration.
Operation Warp Speed has demonstrated that the government and industry can work together to facilitate drug development during the COVID-19 pandemic. What will drug development activities look like post-pandemic? Biopharmaceutical companies will place greater attention on early detection and prevention, which means the onset of some diseases could be delayed or prevented. Artificial intelligence could help speed drug discovery by analyzing research data more effectively and screening chemical libraries, de-novo drug design, drug repurposing, and preclinical testing. Biopharmaceutical companies are quickly learning how much work can be done remotely, or with fewer onsite employees. Many aspects of a clinical trial could be done remotely using connected digital devices and the internet. Virtual clinical trials could lead to larger pools of potential candidates, improve convenience for patients, and lead to more efficient trials. Furthermore, some companies are now delivering clinical supplies directly to a patient’s home rather than from the site of the clinical study. The COVID-19 pandemic has increased the pace of drug development and regulatory approval dramatically, accelerating activities in ways that shorten the time needed to deliver safe, effective therapeutics, vaccines, and diagnostics to patients.
1. Secretary of HHS Alex M. Azar, Determination that a Public Health Emergency Exists (originally issued Jan. 31, 2020, and subsequently renewed), available at https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx.
2. President Donald J. Trump, Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus Disease (COVID-19) Outbreak (Mar. 13, 2020), available at https://www.whitehouse.gov/presidentialactions/proclamation-declaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/.