Opening Session: Introduction to Emergency Outbreak Situations and Data Collection
Keynote: National Preparedness and Response in the 21st Century
Luciana Borio, MD
Vice President of Technical Staff, In-Q-Tel
The novel coronavirus, which hadn’t yet become a global pandemic at the time of the workshop, highlights the importance of diagnostic tests in outbreak management and control. Through EUAs, the FDA has provided timely access to diagnostic tests during the 2009 H1N1 influenza pandemic, the 2014 West African Ebola epidemic, and the 2016 Zika epidemic in the Americas. The agency worked alongside IVD developers in real time to validate and authorize these tests. In 2013, EUA authority was expanded to allow the FDA to act based on the threat of an emergency, instead of waiting until after the emergency has occurred.
Yet advancing EUA IVD products to full marketing status has been a struggle, due to lack of incentive for the commercialization of many diagnostic tests and government policies that prioritize therapies over diagnostic tests as countermeasures. Progress will require collaboration and funding by the U.S. government and other partners to promote the systematic collection of RWD that could be used to support FDA approval of IVDs.
The necessary collaboration can only take place if partners frankly discuss obstacles, understand the capability of each partner, and develop shared responsibility for advancing EUA IVD products to full marketing status.
Watch this presentation in Morning Sessions 1, starting at 7:14.
Keynote: Evaluating Novel Diagnostics in an Outbreak Setting: Lessons Learned from Ebola
Nira Pollock, MD, PhD
Associate Medical Director of Infectious Diseases, Diagnostic Laboratory, Boston Children’s Hospital
Faculty Member, Division of Infectious Diseases, Beth Israel Deaconess Medical Center
During the Ebola outbreak in West Africa in 2014-2016, Pollock’s research team worked with Partners in Health to develop field studies in Sierra Leone to evaluate promising Ebola diagnostics. Challenges from evaluating novel diagnostics in the Ebola emergency setting can be applied to the COVID-19 pandemic. These challenges are related to:
• Ownership of samples and data
• Patient consent and approval of research protocols
• Regulatory authority
• Identifying a “gold standard” reference technology
• Communicating effectively.
A vision of a Global Emergency Diagnostic Framework emerged as a way to address these challenges. Such a framework would include standards for diagnostic evaluation (or, optimally, also development and evaluation) in an outbreak setting set in advance by an international expert committee.
Also, An R&D Blueprint for Action to Prevent Epidemics; Plan of Action came out of the Ebola outbreak (published by WHO in 2016 and updated in 2017 and 2018). If development efforts during outbreaks use
fair and transparent principles which will have been negotiated before the emergency by all stakeholders, the global community will benefit, according to the blueprint. Stakeholders must work together to develop a framework for development and evaluation of diagnostics in an outbreak setting.
Watch this presentation in Morning Sessions 1, starting at 23:38.
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Four representatives of the FDA shared the agency’s perspective on EUAs.
Perspective from the FDA Chief Scientist
Rear Admiral Denise Hinton
FDA Chief Scientist
Collaboration and coordination are mandatory to expedite the development and availability of safe and effective medical countermeasures, such as diagnostic tests, for use during a potential public health emergency. FDA collaborates with interagency partners, product developers, international partners, and global regulators to help drive and foster innovation to advance public health and strengthen national security.
At the onset of an outbreak such as the novel coronavirus, there are typically no legally-marketed tests for clinical use. FDA experts collaborate with other U.S. government agencies and international partners to speed the processes necessary to make tests available for emergency use under FDA’s EUA authority. Since 2009, FDA has issued more than 60 EUAs for diagnostic tests for infectious diseases such as H1N1, MERS, coronavirus, Ebola, and Zika.
Within days of receiving the genetic code for the 2019 novel coronavirus FDA drafted EUA review templates for CDC and other test developers. The agency is also developing reference materials for developers to use to validate their diagnostic tests (as of February 2020).
Watch this presentation in Morning Sessions 1, starting at 1:03:21.
Timothy Stenzel, MD, PhD
Director, OHT7: Office of In Vitro Diagnostics and Radiological Health, CDRH
With an EUA, FDA can authorize the use of an unapproved medical countermeasure or the unapproved use of an approved medical countermeasure for serious or life-threatening diseases or conditions caused by threat agents. Of the 57 EUAs that FDA has approved only 4—less than 10%—have progressed to De Novo or 510(k) status. There is an urgent need for more EUA products to progress to full authorization.
RWD and RWE may be one solution to removing barriers to full authorization. In 2017, the FDA published Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices: Guidance for Industry and Food and Drug Administration Staff. This guidance document highlighted the importance of relevance and reliability in using RWE. Establishing pathways for the use of RWD and RWE would remove inhibitions about using these. CDRH/OIR is committed to working with all stakeholders to advance EUA products to full marketing status as efficiently and effectively as possible.
Watch this presentation in Morning Sessions 1, starting at 1:12:05.
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Transitioning Diagnostics from Emergency Use Authorization (EUA) to Marketing Applications
Uwe Scherf, MSc, PhD
Director, Division of Microbiology Devices, OHT7, Office of In Vitro Diagnostics and Radiological Health, CDRH
FDA encourages sponsors to interact with the agency during the EUA process and to transition EUAs to marketing applications. Under the right conditions, RWD—data relating to patient health status and/or the delivery of health care that are routinely collected—can potentially be used to support regulatory decisions. Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices: Guidance for Industry and Food and Drug Administration Staff describes FDA’s thinking about RWD and RWE. RWD must demonstrate relevance and reliability. Uses of RWE, the clinical evidence about the use and potential benefits or risks of a medical product derived from analysis of RWD, include:
• Expanded indications of use
• Post-market surveillance studies
• Post-approval device surveillance as a condition of approval
• Control group
• Supplementary data
• Objective performance criteria and performance goals.
Sponsors can use data obtained for an EUA in a marketing application if they have not modified the device since the EUA. If modifications have been made, a risk assessment is required to determine the extent of the changes and the influence of the changes on performance. Data generated outside the U.S. can also be used in an FDA submission if the test procedure was performed according to the package insert with no deviations. This presentation also describes the EUA and the differences between EUA and pre-market study requirements.
Watch this presentation in Morning Sessions 1, starting at 1:21:44.
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Real-World Evidence (RWE): Context for Supporting Regulatory Decisions
Michael Waters, PhD
SHIELD Team Lead/CDRH RWE Tactical Team OIR Representative
Use of RWE to support device pre- and post-marketing decisions is a commitment made in the FDA Reauthorization Act and a strategic priority of the CDRH. Data generated in healthcare settings can be used in supporting regulatory decisions if they are high quality and provide valid scientific evidence. Data used in regulatory decisions must be fit for the purpose: complete, consistent, accurate, and contain all critical data elements needed to evaluate a medical device and its claims. They must also be relevant and reliable, and show that the benefits outweigh the risks.
FDA cleared two 510(k)s for sequencing assays for variant/variant combinations associated with cystic fibrosis using a public next-generation sequencing database. This approach of using a publicly-maintained database could also be used to support an IVD’s clinical validity in lieu of clinical trials in the EUA space. Partnerships between the sponsor, the database holders, and the FDA would be necessary to develop interoperability for the data and establish appropriate quality checks.
Watch this presentation in Morning Sessions 1, starting at 1:43:00.
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