As of early May 2020, over 4.7 million people have been confirmed to be infected with the SARS-CoV-2 coronavirus[1], and governments are scrambling to contain its spread. The high R0 value (a measure of contagiousness- estimated to be between 2.0 and 3.02) of SARS-CoV-2 means that those infected copiously spread the virus and develop complications suddenly. As a result, health care systems are overwhelmed, and the effective delivery of medical care to all patients has become a challenge worldwide. Insufficient attention to early warning signs, inadequate stockpiling, lack of access to testing kits and personal protective equipment (PPE), and nationwide variability in the approaches to testing, distribution of PPE, and timing and degree of social distancing measures likely all affected the spread of the disease. Inadequate PPE, overcrowding, and difficulty protecting existing patients are key challenges the medical industry is grappling with[3].
Medical device manufacturers have not escaped the pandemic’s impact. Similar to pharmaceutical companies, medical device manufacturers rely heavily on healthcare facilities for their clinical trial data collection. Most medical device products must undergo clinical trials both pre- and post-market before manufacturers can obtain certificates for market approval. As the COVID-19 pandemic continues to unfold, medical device companies are finding it difficult to make informed decisions about their products, supply chains, and regulatory obligations in the midst of uncertainty. Medical device professionals have the unenviable task of asking for a pause amid the panic. No matter how bad it is or how bad it might get, here’s the truth: heedless action will make it worse. Despite the adrenaline telling us to produce as fast as possible, this is the moment when quality matters more than anything else.
With a strategy that leverages exemptions, production procedures that innovate to fill needs and a communication plan that works across public and private entities, you can navigate the chaos and support public health. Announcements from governing bodies and conversations with key decision-makers and regulatory experts hold the key to the success of the medical device industry.
Overall, the implementation of several new regulations may be postponed allowing both companies and regulatory agencies time to react to the crisis. However, there is no evidence this will alter reporting deadlines for established legislation.
At present, this is what we know about specific regulatory impacts:
1. Impact of COVID-19 on regulatory approvals in EU
In the European Union (EU), the Medical Device Regulation (MDR) requires manufacturers to conduct Post Market Clinical Follow-Up (PMCF) studies to demonstrate the continued safety and performance of their devices, as well as capture any emerging risks these may carry. However, the COVID-19 pandemic has delayed clinical trials and disrupted processes. While certain trials such as Investigator-Initiated Studies (IIS) are necessary for the broad healthcare system to come to a consensus around the efficacy of certain therapeutic options, other clinical trials are initiated by sponsors to investigate the safety and clinical performance of devices to satisfy regulatory requirements.
Due to the COVID-19 pandemic, the European Commission recently adopted a proposal on April 3, 2020, to postpone the application date of the MDR for one year. “As the coronavirus crisis increases demands for certain vital medical devices, it is crucial to avoid any further difficulties or risks of potential shortages or delays in the availability of such devices caused by capacity limitations of authorities or conformity assessment bodies related to the implementation of the Medical Devices Regulation,” the Commission wrote in a statement. Based on this proposal, the functionality of the European Database on Medical Devices (EUDAMED) will instead be announced by March 25, 2021, with reporting requirements beginning May 26, 2021. While reporting requirements have been delayed, companies should aim to have their supply chain data compiled and ready for submission by March of next year to give themselves adequate time and ensure they can make this deadline.
Among some of the biggest changes seen under EU MDR are:
- Increased requirements for clinical evaluation
- Digital and physical labeling
- Postmarket surveillance (PMS), and
- Total life cycle traceability.
There is no word yet on the In-vitro Diagnostic Medical Devices Regulation (IVDR), or the impact of this potential delay on European Notified Body audit activities.
The European Commission recently adopted revised harmonized standards to expedite the production of medical face masks, gloves, containers for intravenous injections, sterilization devices and disinfectants, and alter particular requirements for emergency and transport ventilators. In collaboration with the European Committee for Standardization (CEN) and the European Committee for Electrotechnical Standardization (CENELEC), the European Commission has agreed to make a number of these harmonized standards freely available.
2. Impact of COVID-19 on regulatory approvals in the US
Emergency Use Authorizations
In the US, the FDA has issued Emergency Use Authorizations (EUA) for medical devices including IVD test kits to diagnose COVID-19 as well as PPE (including conservation of gloves, gowns, and masks) needed to protect healthcare providers interacting with patients. Under EUA declarations, the FDA has the authority to authorize rapid emergency use of specific devices via expedited premarket review during public health crises such as the COVID-19 pandemic. The EUA submission should include as much safety, effectiveness, and risk-related data as is available pertaining to the devices in question. Although obtaining an EUA designation provides expedited access to the US healthcare market, these authorizations last only as long as the public health emergency for which they are granted by the FDA.
Supply chain
The FDA is collaborating with manufacturers of ventilators, ventilator accessories, and other respiratory devices to better understand the current supply chain issues related to the COVID-19 outbreak and to help mitigate any widespread shortages of these devices.
Ventilator guidance
The FDA has issued final guidance on ventilator devices that facilitates EUA designations for these products to treat COVID-19 patients. Non-medical manufacturers (such as automotive and industrial manufacturers) have the opportunity to enter the medical device space during this unprecedented time but they need to be aware of the quality, safety and performance standards the FDA requires for the production and modification of ventilator hardware, software and materials.
3D-printed PPE
The FDA has also released a recent FAQ regarding 3D-printed PPE devices and components, cautioning healthcare providers that they may not provide the same level of protection as conventional products. Manufacturers should review the FDA’s final guidance on technical considerations for 3D-printing for a range of recommendations on medical device applications, including device design, software workflow, material controls, post-processing, and process validation.
3. Medical device shortage and exemptions for COVID-19 related devices
During this global pandemic, the medical device regulatory environment is quickly adapting to meet the challenge of supplying sufficient PPE to front-line healthcare providers and life-saving equipment to those people in medical need. Medical device manufacturers must also rise up to meet this challenge and embrace these opportunities to bring their device faster to the market and help us to come out safely on the other side of the COVID-19 curve. One industry that is majorly impacted by this global crisis is the ventilator industry. There’s currently thought to be a global shortage of thousands of ventilators as the world attempts to tackle the deadly pandemic. The US and the EU are still short of the ventilators they would need to treat burgeoning numbers of COVID-19 patients during the pandemic.
Both Prime Minister Boris Johnson and President Donald Trump, have called on the automotive, aerospace and other industries to help plug the shortage. Ford, GE, and Tesla are among those to have used heating, ventilation, and air conditioning factories to produce respirators in the US, while the VentilatorChallengeUK consortium has been established in Britain to produce 10,000 devices. Alongside seven UK-based Formula 1 teams, the UK consortium features manufacturers as diverse as Rolls-Royce, Airbus, Accenture, Dell Technologies, Siemens, and Unilever working to upscale production of ventilators by slightly modifying existing designs used by medical device manufacturers Smiths Group and Penlon. Dyson, the engineering innovator behind bagless vacuum cleaners and touchless hand dryers, designed a completely new ventilator design in just 10 days.
While most of these efforts involve using established ventilator designs, regulation remains a key consideration for manufacturers involved — many of which have little-to-no experience of medical devices.
If we take a little deep dive, ventilators are categorised as Class II devices in the US. This means they pose a moderate-to-high risk to patient safety and should be subject to rigorous, lengthy clinical trials and regulatory processes. FDA has 510(k) policy, which covers a range of devices including ventilators, allowing manufacturers to place an item on the market after far less extensive testing — providing they can prove it is substantially similar to a product already in use. From my personal experience of dealing with FDA, I can say in case of ventilators, there’s not necessarily need to conduct full clinical trials as ventilators are not new. So, even if there is no situation of pandemic such as COVID-19, they wouldn’t always require huge clinical trials. However, they need to exhibit some clinical evaluation with respect to the design of a new ventilator compared to previous ventilators, to know whether the clinical data utilised by the new ventilators can be assumed as the same.
In the UK regulation, ventilators are considered a Class 2b device by the EU, meaning they pose a medium-to-high risk to patients and must undergo extensive safety checks. However, because they have been around for decades, new models rarely require the one or two-year-long regulatory process associated with novel MedTech innovations.
While the FDA’s 510(k) notification is based around “substantial equivalence” — showing a new device to be sufficiently similar to a product already on the market — the EU’s version is known as a “demonstration of equivalence”, a system that’s slightly stricter but ostensibly the same as the US’.
Not only the US and the EU but the global regulatory landscape is currently in flux for all medical device companies. Regulatory frameworks are shifting around the world, and existing rules may be evolving. However, most of this depends on where a device is being sold and what type of device is being manufactured. Leveraging the right exemptions may lead to faster market entry.
4. Impact of COVID-19 on personal protective equipment (PPE)
The impact of COVID 19 on the PPE has exposed the unpreparedness of enterprises to cater to an unprecedented demand surge. In response to WHO’s sanitation guidelines and the requirement from healthcare professionals attending the infected patients, a range of PPE such as sanitizers, medical masks, gloves, ventilators are hitting the bottom of their repositories. This visible instance of supply chain disruption in the PPE market is getting worse with the rigidity of government policies pertaining to the import and exports of essential medical components. Levying of import tariffs and export restrictions are adding to the supply crisis in this market in the wake of the impact of COVID 19.
During my current involvement with a MedTech company based out of New York, USA, dealing in the PPE market, we are heavily reliant on the exported medical components from China which is one of the top exporters of PPE globally. While the government has exhibited its intent of relaxing import tariffs by announcing a 90-day deferral of certain duty payments of a range of medical products imported from China, it declined the request of rolling back Section 301 tariffs on a wider range of PPE imported from China. This will result in the procurement price hike for enterprises in the market that will induce them to cut short their imports.
To address the sudden surge in the demand for protective equipment, a majority of countries have risked a breach of the basic principle of the GATT 1947 agreement and have restricted the export of medical components and equipment. This has created major supply chain disruptions in the PPE markets across countries that are heavily reliant on the medical imports. Protective equipment and respirators are some of the protective equipment types that are currently restricted to be exported from some of the EU member states which are seen as an aftermath of the impact of COVID-19 on the civilization.
5. Impact of COVID-19 on medical device grant funding
Funding agencies across the world are working closely with the scientific research community and companies to bolster the national response to COVID-19. Organizations and individuals can now apply for grants specific to COVID-19 research.
COVID-19 grants in the EU
For example in the EU, the scope of the European Union Solidarity Fund (EUSF) has been extended to encompass major public health emergencies. This fund supports EU member states and accession countries that are hit by major natural disasters. Due to the current crisis, the European Commission proposed to extend the scope of the EUSF to allow financial assistance for those seriously affected by COVID- 19. Hence, in 2020, up to EUR 800 million are available to finance medical assistance, medical devices, laboratory analyses, PPE, special assistance to the population, health checks, sanitation of buildings and facilities, development of vaccines and medicines, and many more.
The European Commission had also created a strategic rescEU stockpile of medical equipment. The stockpile includes equipment such as ventilators and personal protective equipment to help EU countries in the context of the COVID-19 pandemic. The initial EU budget of the stockpile is EUR 50 million, of which EUR 40 million is subject to the approval of the budgetary authorities.
COVID-19 grants in the US
In the US, the National Science Foundation is funding dozens of research projects on COVID-19 to mobilize the scientific community to better understand and develop measures to respond to the virus. NSF’s Rapid Response Research (RAPID) funding mechanism enables the agency to quickly process and support research that addresses an urgent need. US congress has pumped up the national funding programs to fast-track COVID-19 research. Critics are arguing that the money the government will be spending on funding new research on medical devices and treatment options is a tiny slice of the $2 trillion stimulus package crafted by legislators to help the country deal with the unprecedented situation of COVID-19. The National Institutes of Health (NIH) has issued several funding opportunity announcements for researchers to submit competitive revisions or seek supplemental funding for existing projects, in order to redirect their research efforts to COVID-19. Other agencies that are typically less focused on health research have also sought to shift their R&D priorities on medical device development for COVID-19.
6. Impact on clinical trials and IRB reviews
The impact of COVID-19 on clinical trials has been immediate, due to challenges posed by travel bans, hospital/clinic visitation restrictions, and social distancing precautions, just to name a few. These factors have translated into multiple issues that pose challenges related to corporate milestones, budgets, and data integrity. IRB meetings and processes are not impacted by any restrictions on travel. As a standard practice, the IRB meets remotely via video conference technology. IRB has been prioritizing the review of the numerous COVID-19 protocols received as well as amendments relating to changes in research conduct because of unforeseen circumstances. Clinical trial protocols are required to be changed to eliminate apparent immediate hazards to participants such as changing in-person visits to virtual visits, elimination of study visits/procedures that do not impact the integrity of the study or participant safety, incorporation of screening questions to identify potential COVID-19 exposure.
Other challenged posed by sponsors of clinical trials include:
- Delays in study initiation activities resulting from the inability to perform site selection/initiation visits and/or clinical vendor qualification visits, and subsequent downstream delays in patient enrollment,
- Protocol adherence issues arising from an inability to comply with visit schedules, study procedures, drug administration, and monitoring procedures,
- Delays in clinical material distribution and import/export delays due to limited manufacturing and operations staff, limited or reprioritized hospitals staff, and travel bans,
- In some cases, suspension of all patient activities for trials, sites, or studies that do not have active patients being treated,
- Cancellation or postponement (indefinitely, in some cases) of major scientific and professional conferences and meetings, and KOL, investigator, and scientific advisory board meetings.
The FDA issued guidance in March 2020, Conduct of Clinical Trials of Medicinal Products During COVID-19 Pandemic4, which emphasises mitigation and precautionary strategies based on study-specific circumstances. It also provides recommendations on the management of procedural modifications, protocol amendments, and deviations (e.g., implementation, IRB approvals, FDA consultation), as well as preparedness, to describe the tactics and impact in the corresponding clinical study reports. Some of these recommendations are also highlighted in the Association of Clinical Research Organization’s (ACRO’s) Considerations to Support Clinical Trial Monitoring Oversight During COVID-195 and in the UK Medicines and Healthcare products Regulatory Agency’s Advice for Management of Clinical trials in relation to Coronavirus6.
Summary
In closing, I would like to reiterate that we’re in the midst of an unprecedented global health crisis. This crisis calls on the medical device industry to work closely with customers, patients, regulators, and public organizations for the sake of public health. The news will be fast-paced, and much of it will be disappointing, frustrating, and dispiriting.
The key, however, will be for companies to focus on how they can make the most effective contributions to control the spread of the virus and save lives.
Short term, that might mean ramping up production to new levels; long term, that might mean sticking closely to regulatory guidance to ensure that speed doesn’t destroy quality, creating even more problems in the future. No matter what, medical device professionals will have an essential role to play in the fight against COVID-19.
References
- Coronavirus Resource Center. COVID-19 map. Baltimore, MD: Johns Hopkins University; 2020. Available from: https://coronavirus.jhu.edu/map.html. Accessed 2020 May 17
- Carlos del Rio, Preeti N. Malani. COVID-19—New Insights on a Rapidly Changing Epidemic. JAMA. 2020;323(14):1339-1340.
- Jessop ZM, Dobbs TD, Ali SR, Combellack E, Clancy R, Ibrahim N, Jovic TH, Kaur AJ, Nijran A, O’Neill TB, Whitaker IS. Personal Protective Equipment (PPE) for Surgeons during COVID-19 Pandemic: A Systematic Review of Availability, Usage, and Rationing. Br J Surg. 2020 May 12.
- FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-medical-products-during-covid-19-public-health-emergency).
- Considerations to Support Clinical Trial Monitoring Oversight During COVID-19. ACRO. (https://www.acrohealth.org/wp-content/uploads/2020/03/ACRO-Statement-on-Monitoring-Oversight-FINAL-3.13.20.pdf)
- MHRA, Advice for Management of Clinical trials in relation to Coronavirus. (https://mhrainspectorate.blog.gov.uk/2020/03/12/advice-for-management-of-clinical-trials-in-relation-to-coronavirus/).
About the author
Shrinidh Joshi is a freelance medical writer at Kolabtree, the world’s largest freelance platform for scientists. Kolabtree helps medical device companies consult experts for help with medical writing, clinical trials and regulatory compliance. Shrinidh has over 10+ years of experience in pharmaceutical, clinical, regulatory and medical writing and has worked in companies like Sun Pharma, Virgilant, CannTrust and ThermoFisher Scientific.