How the Medical Industry Can Help Combat the Current Coronavirus Crisis
Global outbreak of the recent novel coronavirus needs an all-hands-on-deck approach. Here is how QA/RA professionals in the medical industry can help.
A novel coronavirus, now called SARS-CoV-19, was first detected in the Hubei province of China in early December 2019. It rapidly caused a widespread epidemic in China and has spread to over 50 countries outside of China with more than 90,000 confirmed cases and 3000 deaths at the time of this blog article. New cases are also being reported in the United States and several deaths have been confirmed.
Seattle and its neighboring areas have seen a rapid increase in the number of confirmed cases and deaths. The situation is still very dynamic, and a large number of suspected cases are expected to be confirmed as testing increases. Travel is being restricted, large scale public events are likely to be cancelled, and schools and businesses may be closed to contain the spread of the virus.
Secretary of the Department of Health and Human Services (HHS) has declared a public health emergency. The World Health Organization (WHO) has stopped short of classifying the outbreak as a pandemic, but consistently encouraged affected countries to activate their national emergency response plans.
This is where FDA’s Emergency Use Authorization (EUA) comes into play and offers an opportunity for the medical industry to rally and help. In this blog, we are discussing the EUA pathway and offering suggestions on how we in the QA/RA profession can do our part in getting our organizations ready for such public health emergencies. Having a plan in place can help not only during the current crisis, but also in future public health emergencies.
“Section 564, as amended by PAHPRA, permits the Commissioner to authorize the emergency use of an unapproved medical product or an unapproved use of an approved medical product for certain emergency circumstances after the HHS Secretary has made a declaration of emergency.”
-FDA Guidance on EUA, Jan 2017
*Notes: Section 564 as in the Food, Drug and Cosmetic (FD&C Act); PAHPRA refers to the Pandemic and All-Hazards Preparedness Reauthorization Act of 2015
One area of current concern is the lack of diagnostic testing capability in the US to rapidly detect and confirm new cases. Detection is critical to containing the spread of infection by isolating the confirmed case and contact-tracing other potential infections. The virus is now spreading through community contact, meaning it is now infecting through community transmission among people who did not travel to China or other infected countries. Unless we can deploy reliable diagnostic capability across the country, we are practically flying blind!
There is now an FDA policy released on 29 Feb. 2020 titled “Diagnostics Testing in Laboratories Certified to Perform High Complexity Testing under CLIA prior to Emergency Use Authorization for Coronavirus Disease -2019 during the Public Health Emergency”. This guidance went into effect to allow some of the CLIA certified labs for high-complexity testing to begin using their newly developed tests for detecting the SARS-CoV-19 virus in suspect cases. As long as validation data is generated based on the FDA recommendations in this policy, these labs can begin testing while FDA reviews their submission for approval through the Emergency Use Authorization. As a result of this policy, many other CLIA certified labs are now developing their own tests to help increase testing capacity. IVD manufacturers are also working to get their tests approved through the EUA process.
While diagnostic capacity is a concern, we also need to think about potential shortage of protective equipment such as face masks, gloves and gowns. Healthcare workers in hospitals, outpatient clinics and emergency response teams are at high risk. Similarly, caregivers at home or adult care centers also need to be protected. A 2005 report HHS Pandemic Influenza Plan last updated in 2017, estimates that 25 – 35% of the population could be infected during a pandemic and recommends stockpiling adequate supplies for at least 6-8 weeks. This will require a large supply.
To be clear, the current outbreak has not yet been declared a pandemic and there is no reason to believe that it will end up affecting a very large portion of our population. The discussion is about planning and getting ready for an outbreak at such a large scale.
In an extreme situation, it is also possible we may not have enough capacity to treat patients with highly developed respiratory symptoms. We may not have enough hospital beds, ventilators or patient monitoring equipment. Antiviral treatments and vaccines may not be readily available. The HHS report anticipates that a viral outbreak of a pandemic scale will severely overwhelm the US Healthcare system and cause widespread disruption in public life.
As technology has evolved in the last decade, we now have the ability to monitor and treat patients at home or in other private settings. Remote monitoring and intervention through Telehealth is very real and already being widely used. In an extreme public health emergency, however, we may not be able to deploy these capabilities at the required scale. It is not only a matter of production capacity, but also regulatory approval and market authorization.
Whether it is diagnostics, respiratory protection devices, breathing support devices, telehealth and remote monitoring devices or vaccines and/or drugs, the EUA can be an excellent pathway to deploy these devices for emergency use.
Key Elements of the EUA Guidance
While the full guidance is available for download using the link provided in the References section below, here are a few key high-level points to consider:
There are 4 criteria for issuing an EUA – serious or life-threatening disease or condition, evidence of effectiveness, risk-benefit analysis and no adequate, approved and available alternatives
FDA recommends early engagement through “pre-EUA” activities
Submission of an IND (Investigational New Drug) or an IDE (Investigational Device Exemption) is not required, although many potential product candidates may already be under evaluation through these mechanisms and available data may be used to evaluate effectiveness.
Prioritization of EUA requests is based on seriousness and urgency of the public health emergency and availability of alternatives
EUA authorization is conditional and valid only until a termination notice has been issued
Time is typically not on our side in these situations, therefore, advanced preparation in anticipation of potential public health emergencies can be helpful. Here are a few ideas for QA/RA professionals to help position their organizations to make a significant impact on both public health and future commercial success.
Identify Potential Product Candidates for an EUA
Quality and Regulatory professionals play a key role during design and development. They are also involved in development and approval of new claims for products currently in the market. Generally, the focus is on growing or sustaining our market position through incremental innovation. We don’t usually think about having to respond to a large-scale public health emergency. But think about it – if you are involved in sophisticated diagnostics, protective equipment/supplies, or life-sustaining devices, these products offer a significant potential in a large-scale emergency.
We live in a world with evolving threats, both natural and man-made. As part of your business planning, it may be worthwhile to consider specific threats that could have a serious impact. Nuclear meltdowns, natural disasters, bioterrorism and cyberattacks on healthcare facilities are a few examples other than an infectious disease pandemic.
Why not consider such potential in the early phases of design and development? It may be not be the primary focus at the time, but a simple recognition in the business case can help you quickly respond should a need arise. Products not yet approved in the US, but approved in other global jurisdictions, may be eligible for import during an emergency through the EUA. Consider a list of potential products or claims that could be approved through the EUA as part of your current product portfolio.
An EUA issued before an emergency could permit use of an MCM during an emergency without the need for further authorization by FDA. This could offer a significant competitive advantage to your organization.
As we are learning now, it is vitally important to build risk models which take into consideration a broad perspective. Variables to consider include third party and supply chain risks, information security risks, process and organizational maturity and barriers to scalability.
Prepare a Template for Pre-EUA Activities with the FDA
According to the FDA guidance on the EUA, “early engagement between an industry or government sponsor and FDA about potential EUA products will facilitate more complete EUA requests and enhance FDA’s ability to review and ultimately grant EUA approval”. FDA refers to these interactions as “pre-EUA activities”.
Whether you have a product in development, or an already marketed product which could be used for an unapproved intended purpose during a public health emergency, having an internal template to facilitate quick compilation of relevant data for a pre-EUA meeting with the FDA can help accelerate your efforts. In most situations, you can leverage the resources you have developed for a pre-IND, IND or device pre-submissions processes.
Considering design history files, impact and risk assessments and other activities are taking place as part of the product development cycle, it makes sense to apply a risk frame through the lens of the global outbreak of the COVID-19 disease caused by this novel coronavirus. In a sense, we are being given a gift of an after-action review in real time. Using templates and other tools which guide the documentation of relevant data makes good business sense and can facilitate nimble responses when crisis hits.
Develop a Process and Capability for Quick Execution
A good understanding of the EUA process and knowledge of current and past EUAs is a good starting point for building an internal capability for quick execution just before or during early phases of a public emergency. This knowledge can help you facilitate a collaborative effort across different functions to plan and gather information for a EUA should a need arise. Validation, clinical/non-clinical data collection, risk-benefit analysis and developing an information package for the FDA are all examples of activities that will need to be carried out.
Keep in mind that the rest of business and priorities still need to continue even when there is an impending emergency looming on the horizon. It may not be feasible to take your best people away from existing projects to now start working on an EUA. One useful way is to have a generic plan for strategic projects which could outline the process, roles, responsibilities and authorities. This is no different than responding to a crisis specific to your business, say a recall. If there is a process for these situations, it is possible to respond quickly and achieve the desired goals.
Risk mitigation tools are just one part of crisis planning and communication. Just as many of us know, having these plans in place does facilitate recalls capable of surgical precision. Those of us in QA acknowledge the need to consider risk assessments as living documents. So often, risk assessments are some of the last documents to be updated during normal business cycles. Building in monitoring elements based on germane pre-defined measures, once triggered, can prompt a review of the risk assessment. This is one way to keep the documents updated based on inputs to your quality system.
In Conclusion, the Emergency Use Authorization (EUA) is an excellent regulatory mechanism to quickly deploy medical products in case of a large-scale public health emergency. Awareness and knowledge of this pathway is important to plan as we respond to this specific crisis and anticipate future emergencies. Quality and Regulatory professionals in the medical industry can take a leadership role and help their organizations in these situations. Those involved in the Diagnostic devices, protective devices, telehealth, patient monitoring and life-sustaining breathing support devices are in an especially advantageous position. It is quite likely that you have approved products that may be used for other unapproved uses, or you have products in development that can be deployed in an emergency. Having a plan and process in place within your organization can help you quickly leverage the EUA process.
Acknowledgments – this blog article was written in collaboration with Kelly Kammeraad, Principal Consultant at Baaj Quality System Consulting. We thank Kelly for her valuable contribution. Learn more about Kelly’s expertise at her LinkedIn profile.