Have US and UK medical device regulators done all they can to ease ventilator shortages caused by Covid-19?

Experts on ventilator regulation in the US and UK weigh in on what relevant bodies have done to ease shortages of these life-saving devices during the Covid-19 crisis

Patients with severe Covid-19 symptoms often need to placed on a medical ventilator (Credit: US Navy photo)

There’s currently thought to be a global shortage of 880,000 ventilators as the world attempts to tackle the deadly Covid-19 pandemic. With manufacturers from a range of industries outside the medical device sphere lending their services to plug this gap, regulators have been forced to ease restrictions on how these life-saving machines are manufactured. Jamie Bell examines the current landscape of ventilator regulation in the US and UK. 

 

From design concepts and sourcing components to testing prototypes and manufacturing, every stage of getting a new medical device on the market is subject to stringent regulations.

The average time taken for a new respiratory device to get onto the production line is between 4.4 and 6.7 years, according to GlobalData— while manufacturers making even the simplest updates to established machinery like a mechanical ventilator can face a two-year wait for updates to reach hospitals.

Put simply, any attempt to increase the supply of ventilators would be hugely challenging under usual circumstances.

But these aren’t normal times and years need to be replaced by not months, but weeks and days.

With the world embroiled in a healthcare crisis during the Covid-19 pandemic, regulators have moved quickly to ease shortages of these breathing aids – which could be the difference between life and death for patients falling severely ill from the respiratory disease.

With Covid-19 leaving the world embroiled in a global healthcare crisis, regulators have moved swiftly to ease shortages of these breathing aids, which could be the difference between life and death thousands of patients.

Tina Deng, a medical device analyst at GlobalData, says: “The ventilator business was subject to a large amount of government regulation prior to the outbreak.

“In Europe, manufacturers of respiratory ventilators and resuscitators strictly follow the current regulations and guidelines concerning performance, accuracy and safety.

“In the US, ventilators require special controls for labelling, guidance, tracking, design, performance standards and post-market monitoring — which are necessary to ensure safety and effectiveness.

“However, governments and regulatory authorities around the world have taken actions to help increase supply of ventilators, and it can be expected more countries will follow.”

 

Why ventilator regulation is being loosened during Covid-19 pandemic

Breathing aids are a crucial part of the care process for patients severely ill after being infected with Covid-19.

The most basic types, known as non-invasive ventilation, involve a mask fitted over a patient’s mouth and nose to assist breathing.

Mechanical ventilators feature a tube inserted into the airway, which is connected to a machine moving air in and out of the lungs when they have been taken over by the virus.

These complex machines – which feature digital controls for air pressure, and a humidifier to match air to body temperature and add moisture – offer the best chance of survival for the sickest patients.

An Imperial College London study in March estimated 30% of hospitalised Covid-19 patients could require mechanical ventilation.

Research by GlobalData found there was a worldwide shortage of 880,000 ventilators on 23 March. At that stage in the pandemic, there were already more than 350,000 confirmed Covid-19 cases and over 15,000 deaths globally. 

The US was estimated to be 75,000 short of the 250,000 ventilators it would need to treat Covid-19 patients during the pandemic.

The UK government initially reported it had access to 5,900 devices before revising the figure at 8,175 — but still short of the 60,000 that officials admitted could be required.

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.

It planned to bring the CoVent device into production by early April, pledging to build 10,000 units for the UK government and donating another 5,000 to the international relief effort. Construction giant JCB will build metal casings for the devices.

While many compared these combined efforts to the Second World War, when automakers on both sides of the Atlantic repurposed production lines to build tanks, military planes and weapons, dissenting voices suggested this is not a practical solution.

Craig Thompson, head of products at Penlon, told the BBC: “The idea that an engineering company can quickly manufacture medical devices, and comply with the rules, is unrealistic because of the heavy burden of standards and regulations that need to be complied with.”

He added: “The focus should be on existing medical device companies increasing supply of ventilators”.

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.

Kim Trautman, executive vice-president of medical device international services at NSF International’s health sciences division, says: “Even in this time of emergency use where there has been a lot of loosening of regulatory requirements… in the UK and abroad, as well as the US, testing ventilators is not simple

“One of the things the FDA has said is — regardless of emergency use requests — for any company that’s designing, manufacturing or producing products, there are certain requirements they have to follow because people need them to still be safe and effective.”

 

Who regulates medical ventilators?

One of the key reasons the landscape in the US looks quite different to the one across the EU and the UK is because of how their regulatory structures differ.

In the US, the Food and Drug Administration (FDA) is a singular, central entity that oversees all of the country’s medical device products — alongside work in the pharmaceutical and food safety sectors.

As a federal agency of the Department of Health and Human Services, the FDA is responsible for ensuring public health, and is backed by US legislation.

All new devices must receive approval from the FDA before they can legally be sold to healthcare providers on the commercial market.

Across the European Union, the closest thing to the FDA is the EU itself, with its own legislation to which all the individual member states are bound.

Within each individual country is a designated “competent authority” responsible for ensuring medical device companies follow EU law.

In the UK — which remains bound to EU policies during the Brexit transition period — the designated body is the MHRA (Medicines and Healthcare products Regulatory Agency).

Another rung down from the MHRA are three “notified bodies” — BSI Healthcare, SGS UK and UL International (UK) — which are all independent organisations with the authority to approve devices.

Manufacturers in all 28 member states are bound to a piece of EU legislation called the Medical Device Directive (MDD).

For a manufacturer to legally place a product on the European market, they must meet the MDD’s requirements, and receive a CE mark to prove the device is safe and appropriate for its intended use.

While the FDA is responsible for issuing all device approvals in the US, notified bodies such as BSI Healthcare — which also operates in other European countries — can issue products with a CE mark in line with EU law.

 

Ventilator regulation during ‘peacetime’

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.

However, this is where something referred to as the 510(k) notification comes into play.

This FDA policy, which covers a range of devices including ventilators, allows 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.

Trautman, who worked in the FDA for 24 years, says: “In this case, there’s not necessarily going to have to be full clinical trials for devices – ventilators really aren’t new so, even in a normal world, they wouldn’t always require huge clinical trials.

“But there does have to be some clinical evaluation with respect to the design of a new ventilator compared to previous ventilators, in order to know whether the clinical data utilised by other ventilators can be assumed as the same.”

It’s a similar story with regard to 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’.

Andrew Thompson, director of therapy research and analysis for medical devices at GlobalData, notes: “Ventilators have been around for a long time and what’s happening now is just refining the design — no one’s doing anything radically different.”

Because it is a fairly well-established device, new products will often only feature small modifications to an accepted model — such as using alternative materials to make the manufacturing process cheaper.

This means little more than routine safety testing — and data sampling to ensure the same functionality can be assumed between the old and new devices — is required.

Until the Covid-19 outbreak, the EU was set to implement what Thompson describes as a stricter, “more US-like, FDA-style device approvals process” involving more extensive testing.

After being passed into law in 2017, the updated guidelines, titled the Medical Devices Regulations (MDR), were set to come into force in May 2020 — and would most likely have been used to regulate devices in post-Brexit Britain.

However, on 26 March, implementation of the new guidelines was postponed by one year as the European Commission announced its intention to prioritise the fight against Covid-19.

When it is eventually implemented, the MDR will repeal and replace the EU MDD, and the EU AIMDD (Active Implantable Medical Devices Directive).

 

Emergency use authorisation in the US

A number of policies have been introduced by the US and UK governments over the past month in an effort to tackle ventilator shortages, and speed up production.

On 26 March, the FDA issued emergency use authorisation (EUA) for ventilators during the Covid-19 crisis.

As well as allowing the emergency use of ventilators, this authorised other modified devices, such as anaesthesia gas machines and CPAP (continuous positive airway pressure) breathing devices, to be used as ventilators.

According to Trautman, the EUA allows for the quickening of testing processes and other regulatory procedures around ventilators, and means the FDA provides less direct intervention prior to the market.

“The FDA emergency use authorisation process has really cut everything to the barest of bones,” she adds.

“Manufacturers are still going to have to follow the quality management systems, but the FDA is not going out and doing any inspections, or anything else.”

Under the EUA order, there is still a validation process that manufacturers must go through — the FDA has provided a basic criteria for safety, performance and labelling that emergency use ventilators should still meet.

Quality management system procedures, similar to the ones applied under the 510(k) notification, must also be adhered to.

Trautman adds: “The FDA is just making sure that manufacturers know they still have to ensure safety and effectiveness.

“In the US, under the EUA process, there is an application process and there’s a full guidance document specifically on ventilators.

“That lays out exactly what you have to submit, and in what format, so the FDA can look at it as quickly as possible and give it the go-ahead as quickly as they can.

“It’s more about them saying to manufacturers: Here are the assurances you need to be able to have to put out safe and effective products that are going to work in these very, very critical times.”

Alongside allowing manufacturers to modify ventilators to suit the needs of the Covid-19 crisis without requiring a pre-market notification, the EUA also details how the FDA is attempting to offer non-medical manufacturers — such as car companies — a more streamlined path to the market.

 

How have UK standards been relaxed?

On 25 March, the European Commission announced a recommendation for its member states to “exempt” certain medical devices from the normal CE certification requirements to bring important products to market quickly.

This included ventilators — as well as surgical masks, exploration gloves, gowns and PPE (personal protective equipment).

However, the details were left to each state’s competent authority — and the UK was one of the first member states to take action.

Derek Hill, a professor of medical imaging science at University College London who is also part of an independent advisory group to the MHRA during the Covid-19 crisis, says regulators in the UK have since “stripped away” much of the normal regulatory path.

“There is a process in medical device regulation, and the process — if there’s a public health need — is basically derogating some of the checks to dramatically speed up the process of getting products out there,” Hill adds.

“You don’t have to ignore the regulations, but you can use the regulations to help you move quicker.

“It’s also about asking, in this time of great urgency, how do we re-engineer the process? Because actually there’s a different balance of risk here — the risk of doing nothing is absolutely huge.

In the process of derogation Hill describes — which all member states can do as per EU legislation — the government effectively takes on some of the operational risks, whereas it’s ordinarily the manufacturer of a medical device that is legally responsible if anything goes wrong or a patient is harmed.

Under this exemption, manufacturers still have to produce a ventilator that conforms to certain “minimally acceptable” performance and clinical requirements for use in UK hospitals during the crisis.

After receiving Department of Health and Social Care (DHSC) approval, the manufacturer can then apply to the MHRA for the ventilator to be exempt from normal regulations.

In its exemption guidance, the MHRA also noted that to give manufacturers more flexibility, and to increase medical device availability, derogation requests such as this will not be required for devices that already have a CE mark and will only require a limited change in their intended use — for example using a ventilator in intensive care rather than a hospital ward.

In the UK, the process of derogation was established in December 2014 in a piece of legal guidance entitled “Exceptional Use of Non-CE Marked Medical Devices”.

It offers a general framework under which manufacturers can supply a “non-compliant medical device” that does not comply with the law on “humanitarian grounds” — to protect patient health if there is no legitimate alternative available.

GlobalData’s Thompson says: “What it means is these devices are going to be produced and they’re not going to be classified as medical devices — some might eventually get a CE certification, but I very much doubt it.

“So, once the Covid-19 crisis is over, they won’t be used anymore because they effectively won’t be legal devices. The relaxation will expire with the disease.

“And then no country on the planet will want unregulated devices. They will just be scrapped and the cost will be written off.”

 

Remaining hurdles for manufacturers

Having followed the government’s direction on rapidly manufactured ventilator systems (RMVS), Dyson and VentilatorChallengeUK both anticipate their designs will gain regulatory approval in April, after which mass production looks set to begin.

However, even in the derogated regulatory procedures, there may still be a number of hoops for other manufacturers to jump through — especially smaller companies, or those with less experience of medical device regulation.

Under the DHSC’s minimally acceptable standards for a ventilator, there are still several rules around how the machine provides ventilation, its gas and electricity supply, sterilisation, patient monitoring and alarm systems.

Infection control and cleanliness may be the most significant regulatory barrier that remains — especially for smaller, non-medical manufacturers that don’t have on-site cleanrooms.

“The biggest risk right now for non-medical manufacturers is building machines that are safe for patients,” says Thompson.

“You don’t want to build a machine that’s full of fungi and spores that are going to be pumped into the patient’s lungs as soon as it’s turned on. That’s why you need the cleanrooms.”

Mark Schirmer, a spokesperson for US car dealership operator Cox Automotive, echoed this when he admitted regulations are likely to be “the biggest issue” for car companies.

“Even these advanced auto production facilities are not sterile enough to produce medical equipment or would not pass the regulation as is,” he added.

Despite regulations being relaxed, there are currently no less than 19 medical device standards listed on the British Standards Institute (BSI) website for manufacturers to consider — although the DHSC has indicated they should be considered “helpful advisory standards” rather than regulatory requirements during the crisis.

The MHRA has also declared that manufacturers must supply them with the following information before gaining approval for new ventilator designs:

• Details of the product(s) (including model name, description and intended purpose of use)
• Reasons why the product does not have a valid CE mark
• Clinical justification for requesting an exemption from the regulations for the product
• Explanation of any alternative products on the market and reasons why using these products would not be appropriate
• Numbers of product likely to be supplied under the exemption, plus an indication of how widely used the product is
• Expected time to gain/re-gain CE certification

Manufacturers are also expected to have evidence the device performs “as intended” — which may involve performance or study data.

The decentralised nature of medical device regulation in the EU also presents its own challenges.

As Trautman notes, the lack of a single coordinating point means “you’ve got 28 authorities all potentially handling things slightly differently in situations such as this”.

However, while the omnipotence of the FDA may make the regulatory response to emergencies such as the Covid-19 crisis easier, US manufacturers are currently facing their own potential barriers — despite the EUA process being implemented in March.

As Trautman suggests, there are still dozens of different testing protocols for a variety of specific types of ventilator devices — including the “two page-long” list of standards just for ventilators that appear in the EUA guidance document.

Quality management systems mean that initial design specifications regulation, as well as engineering and clinical testing, still have to take place before a ventilator can reach the market and ultimately be used to treat patients.

Because of this, “how long it takes really depends on where you start from”, she adds.

“The companies that are going to have the best chance of moving things forward are, for example, Tesla or General Motors in the US, or Rolls-Royce in the UK — if they’re cooperating with a medical device manufacturer that already has historical data, then it’s a lot easier to do verification testing just to prove the devices they’re now mass-producing are comparable.

“Many of the bigger companies like Medtronic, GE and Ventec have engineers in-house that have done this for years, and therefore many of them have in-house testing capabilities too.

“This is why these partnerships between medical device manufacturers and industries like automotive have really been the most beneficial in this crisis — from the perspective of transferring technology and knowledge, raising manufacturing capacity and being able to leverage each other’s resources.”

Because they contain several components and are used to treat patients directly, ventilators themselves also present a unique challenge for the regulators in the US.

“The EUA was used several times in my career at the FDA — but mostly for testing in these pandemic situations,” says Trautman.

“It’s not as usual in these situations to have hardware [like ventilators] so involved — this is a very complex device that includes a lot of very different engineering and software aspects. So, this one’s going to be a little bit trickier.”

Trautman believes that even after the FDA relaxed its regulations on medical devices, new ventilators may still take between three and six months to go from the design phase to becoming usable.

 

Can regulators do any more to help plug ventilator shortage?

“Not that I can see” is Trautman’s response when asked if there is anything else medical device regulators can do to ease ventilator shortages.

“It’s not the regulators at this point that are standing in the way,” she adds.

“The regulators are out there saying ‘you know the public health issue, you know the basic quality system requirements’ — and automotive, aerospace and other industries have similar requirements in their systems too, so this isn’t foreign to some of those companies.

“If we’re talking just about market entry requirements — that would be with the US FDA, or the MHRA — I honestly don’t think there’s anything wrong with the regulations.

“And again, the FDA has, for quite some time, had some EUA procedures in place to handle things like this.”

The EUA process is already well established in US device regulation — Trautman cites a number of occasions in her two-and-a-half decades at the FDA where it was used, including during the original SARS (severe acute respiratory syndrome) viral outbreak in 2002, as well as in response to the swine flu pandemic in 2009.

“I really don’t think it’s the regulations that need adjusting or prohibit anything — as long as there’s good emergency use authorisation procedures and planning in place,” she adds.

Ultimately, the consensus seems to be that regulation has already been relaxed as much as possible without creating a threat to patient safety in both the US and UK.

“When we talk about the regulations being relaxed ‘recently’, they were actually relaxed in 2014, when the MHRA brought in this emergency-type legislation to allow for exactly this kind of thing,” says GlobalData’s Thompson.

And with this legislation — the UK’s “Exceptional Use of Non-CE Marked Medical Devices” guidance — now being utilised by the government, he adds that it’s “fair to say UK regulation has been somewhat thrown out of the window” already.

“I don’t think there’s anything more the government can do to increase the supply, or speed up the supply. I don’t think the government is sitting on a pile of ventilators.

“The only remaining regulation I can see is a request from the government for companies to try and conform, as best they can, to British standards for ventilators.”

Thompson also claims the main remaining challenge for manufacturers is sourcing components for their ventilators — not regulatory hurdles.

While the timescales for producing ventilators have been slashed from years to weeks could suggest the MHRA has done all it can to “streamline” the regulatory process in the UK, there may be other areas that device manufacturers can explore to increase supply even further.

 

Other solutions to the ventilator crisis

Alongside the relaxation of regulations through March and April, a variety of measures have been suggested to increase the supply of ventilators and ease shortages in hospitals.

On 14 March, US-based doctor Charlene Babcock posted a video online in which she indicated that — under especially dire circumstances — a respirator could be modified to treat multiple patients at the same time.

The spread of Covid-19 and the resulting shortages are likely to be considered dire enough to warrant this — and GlobalData’s Thompson claims “it’s perfectly possible”.

“It’s not ideal medical practice, but it can be done,” he adds.

However, this innovation raises its own issues regarding regulation.

“One of the areas that’s becoming a bit of a challenge right now is there’s a lot of great ingenuity and innovation going on in trying to make a single ventilator usable by multiple patients,” says Trautman.

“And it’s not just a simple mechanism of splitting breathing tubes — you don’t want to cross-contaminate, which is very important.

“You also need particular valves, and the air pressures that patients require according to their health needs may be different, so the support settings may vary.

“There’s a lot of people trying really hard to be innovative but, again, there still has to be a fair amount of design and development control procedures in place to document all the necessary verification testing and clinical evaluation.”

Another possibility being explored in the US — which may present fewer regulatory hurdles than trying to attach multiple patients to the same device — may involve moving ventilators from place to place “on a rotational basis”.

Trautman says this would merely be a temporary measure to ease the three-to-six-month wait hospitals may have to endure until new ventilators can be manufactured and approved.

“Of course, the traditional medical device manufacturers like Medtronic, GE and Ventec have already increased their existing capacity,” she adds. “So they’re kind of going full blast.

“But in order to bridge the gap before they can deliver some additional manufacturing, there are some plans I’ve heard about that involve rotating ventilators between regions — depending on the outbreak of the virus and the severity in different places.

“That’s another way they’re looking to leverage what they have currently.”

Because regulation around modifying other medical devices to act as, or instead of, ventilators have been stripped down in the UK and the US alike, respiratory machines like CPAP (continuous positive airway pressure) devices and types of anaesthesia machines may also be used to treat Covid-19 patients.

Thompson says CPAP devices are already used to supply oxygen to patients — more than one million of these machines are sold every year in the UK, and they are both cheaper and easier to mass-produce than ventilators.

F1 team Mercedes-AMG is working alongside University College London to “reverse engineer” existing systems — which have been used effectively in both China and Italy — to help build thousands for Britain’s hospitals.

For CPAP machines to work, they need to be fitted with a high-efficiency particulate air (HEPA) filter — the logistics of which are currently being looked into — to stop expired air from the patient’s lungs going straight back into the hospital’s atmosphere.

However, if this is done effectively, CPAP devices could be used to reduce the number of patients who need to go on to a ventilator, Thompson adds.

Anaesthesia gas machines — which are used to supply anaesthetic and oxygen during surgical procedures — can be effectively converted into ventilators.

According to Thompson, because they supply air and regulate breathing in the same way as a ventilator, this is as simple as turning off the flow of anaesthetic supplied by the machine.

Also, because the Covid-19 outbreak has led to a number of hospitals temporarily placing the majority of minor surgeries on hold, many of them have anaesthesia machines that are not being used for their primary function.

“And I don’t think there’s an issue there — they’re perfectly safe and already covered by regulation,” he adds.

As well as both CPAP and anaesthesia machines holding potential in easing shortages in the UK, modifications to these devices are also covered by the FDA’s EUA order in the US.

There are seemingly a number of viable solutions that could, over time, mean the total deficit of 135,000 ventilators across both the UK and the US is felt less severely.

But Trautman believes, ultimately, it is the healthcare systems themselves that may have to rethink their own structures in order to prevent a similar medical device crisis in the future.

“There’s all kinds of articles out there about how we may have become too efficient from a manufacturing and government perspective,” she adds.

“Because we haven’t stockpiled, we’ve lost a lot of the mentality from the First and Second World Wars.

“And therefore we’ve gone too lean and efficient — which is great from a business perspective, but not when something like this happens.

“This is where stockpiling, and those warehouses full of emergency products, really come into play.

“I don’t think it’s the regulations that are going to have to change — I do believe the healthcare and hospital systems are going to have to rethink their supply chains.

“There are some things that medical device manufacturers will have to look at too, like supply chain issues, during shortages, when they need onsets of large quantities of equipment fast.

“But, again, that’s not a regulatory issue, that’s really more business efficiency – I don’t think it’s going to change the regulations on either side of the pond to be quite frank.”