FDA helps protect the United States from chemical, biological, radiological, nuclear, and emerging infectious disease threats by ensuring that medical countermeasures (MCMs—for example, drugs, vaccines, and diagnostic tests) to counter these threats are safe, effective, and secure.
Scientists working to develop MCMs against several high-priority biological threat agents are at high risk of aerosol-transmitted laboratory infection and life-threatening disease, as there are no vaccines or treatments for these agents. Accordingly, much of the work to develop MCMs for these high-priority agents must be done in high and maximum biosafety level (BSL)-4 laboratories to prevent the agents from being released into the environment, and to provide maximum safety for the scientists.
The unique challenges of BSL-4
While necessary to ensure lab worker safety and prevent accidental release of dangerous pathogens, BSL-4 environments pose unique challenges to developing MCMs. For example, data generated to support a regulatory submission to FDA must be collected in accordance with quality systems, like good laboratory practice (GLP) regulations, to be useful and reliable, and to facilitate FDA review to ensure safety and efficacy.
However, meeting data quality and integrity standards like GLP in a BSL-4 environment is challenging. Current practice is often inconsistent among laboratories due to technological infrastructure, available internal standard operating procedures, level of regulatory awareness, and individual breadth of experience and training. And completing even routine lab tasks in a protective BSL-4 suit can be difficult—imagine, for example, trying to pick up a small item, like a toothpick, while wearing two pairs of thick gloves.
To help address the challenges associated with ensuring data quality and integrity in regulated studies conducted in BSL-4 laboratories to support MCM development, FDA and the University of Texas Medical Branch, Galveston National Laboratory (UTMB) collaborate to provide an annual training course on how to meet GLP requirements in BSL-4 facilities (“data quality course”).
This popular course offers a unique opportunity for the regulatory and scientific communities to discuss complex issues in an interactive environment and identify and share best practices for ensuring data quality and integrity in BSL-4 facilities.
In addition to UTMB and FDA, other federal partners from the National Interagency Confederation for Biological Research (NICBR ) provide support and resources for this course. These partners include:
- From the National Institutes of Health
- Office of the Director
- National Institute of Allergy and Infectious Diseases (NIAID)
- National Cancer Institute (NCI)
- From the Department of Defense
- U.S. Army Medical Research and Materiel Command (USAMRMC)
- From the Department of Homeland Security
- National Biodefense Analysis and Countermeasures Center (NBACC)
History and new additions
Since the data quality course began in 2013, it has quickly reached capacity each year. In its first five years, 269 participants completed the course.
In September 2017, the FDA Medical Countermeasures Initiative (MCMi) renewed the grant to continue the data quality course for an additional five years, from 2018-2022. UTMB and FDA will also expand on-demand online offerings, adding data quality-related good clinical practices (GCP) training and other courses to meet the needs of researchers responding to emerging infectious disease outbreaks.
The week-long, data quality course is designed to help researchers who conduct studies intended to support approval under the Animal Rule, which may be used to grant marketing approval of certain products when human challenge studies would not be ethical or feasible.
The course includes expert lectures and hands-on laboratory activities conducted in BSL-2 and BSL-4 training laboratories to emphasize the differences between biosafety levels, and the complexity of conducting laboratory activities in a BSL-4 environment.
Topics covered include:
- Animal Rule regulations, and clinical applications of Animal Rule studies
- Assay validation
- BSL-2/3/4 comparison, with hands-on simulations
- BSL-4 equipment, with hands-on work in a BSL-4 training lab
- Disease agent characterization
- GCP and GLP regulations
- Good documentation practices
- Institutional Animal Care and Use Committee (IACUC) protocols
- Supportive care
- Surrogate endpoints
- Testing facility management
- Veterinary pathology
Learning objectives for participants:
- Determine requirements needed to conduct high-quality studies to develop appropriate MCMs
- Identify criteria used to evaluate MCMs in animal models that reflect human disease
- Examine modern methods to comply with data quality standards when conducting nonclinical studies in maximum containment
The FDA/UTMB collaborative course, “Achieving Data Quality and Integrity in Maximum Containment Laboratories,” was held from April 23-27, 2018. More than fifty scientists and regulators from industry, academia and government attended the 2018 course predominantly held at the National Institutes of Health (NIH) in Bethesda, Maryland. Participants also attended lectures and tours at BSL-4 laboratories in Fort Detrick at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) and NIAID’s Integrated Research Facility (IRF) in Frederick, Maryland.
Lectures covered challenges of Ebola human clinical trials, the Animal Rule, Institutional Animal Care and Use challenges and best practices to achieve Good Laboratory Practices(GLP) in managing BSL-4 laboratory studies. Participants—including international public health agency collaborators from the United Kingdom, Canada, Germany, China, Italy, Venezuela, and Singapore - completed practice exercises while wearing full high containment BSL-4 suits.
New this year was a Good Clinical Practice (GCP) focus group, “Achieving Data Quality and Integrity in Clinical Trials Involving High Consequence Pathogens.” The focus group was held to support the expansion of the course for 2019 at the NIH Clinical Center and in 2020 at the new University of Nebraska Training Center partnering with Dr. Christopher Kratochvil and the National Ebola Training Education Center. In addition to Dr. Kratochvil, notable focus group participants included Dr. Aloysius Hanson (Medical School faculty from Liberia), Dr. Ian Crozier (NIAID IRF), Dr. Colleen Kraft (Emory University), Dr. Lisa Hensley (IRF Associate Science Director), RADM Denise Hinton (FDA’s Chief Scientist), Dr. Christoph Conrad (Paul Erlich Institute), NIAID’s Kevin Barrett, and Dr. Richard Rupp (UTMB).
The 2018 course closed with distinguished faculty, NIAID Director, Dr. Anthony Fauci, who discussed the challenges of pandemic preparedness. He oversees an extensive portfolio of basic and applied research to prevent, diagnose, and treat established infectious diseases.
Who may attend?
FDA welcomes participants from government, industry, and academia. We welcome international participation as well; attendees in previous years have included representatives from international public health agencies. Attendees typically include:
- Product sponsors (industry)
- Quality assurance personnel
Pre-requisites include GLP and IACUC training that are available to course attendees.
What do attendees say about the course?
Participants overwhelmingly share that they will apply knowledge gained during this course, ultimately resulting in improved patient and public health outcomes. In recent years, 96% of participants indicated that they would like to attend this course again in the future, and 94% would recommend the course to a colleague.
"The collection of knowledge from the government and industry compiled for this course is unparalleled. For those who work with developing MCMs, this is the most relevant training course that I have ever seen.”
How much does it cost?
There are no registration fees for this course, however, seats are limited and course attendees are invited based upon diversity of roles, responsibilities, and organization.
Registration information will be updated in the beginning of 2020.