University College London (UCL) have announced, that in partnership with University College London Hospital (UCLH) and Formula One, they will be working to develop Continuous Positive Airway Pressure (CPAP) breathing devices.
Prof Tim Cook, Anaestheia and Intensive Care Medicine, Royal United Hospital Bath NHS Trust, said:
“If the patient can stay on a CPAP machine they can stay on a ward looked after by specialised nurses rather than ICU nurses. A ward can probably look after 10 of these patients with 2 nurses and one doctor. 10 patents on ICU may need 5 or 10 nurses and 3-4 doctors. The cost and manpower needed on ICU is much much greater and ICU is a lot more complex and hazardous.
“Anyone who can be kept out of ICU by using CPAP is a win-win-win for patient, healthcare system and staff!
“The work described is amazingly quick and everyone is absolutely doing their best to achieve things which are
These things usually take months or years so it is remarkable.
“It requires great skill to achieve this without cutting corners and I think the MHRA have an important role in governance oversight but with a lighter than normal touch … something that is hard to achieve!”
From the Institute of Physics and Engineering in Medicine, Dr George Dempsey, Vice President Engineering, Professor Mark Tooley, Immediate Past President and Professor Stephen O’Connor, President, said:
How do these kinds of machines get regulatory approval for use in clinical settings?
“Medical devices must be certified with the Conformité Européenne, European Conformity, Mark, commonly abbreviated to CE Mark, before they can be put into service. A manufacturer supplies the Notified Body, the CE awarding body, with their technical and clinical dossiers for examination by experts to ensure compliance with the relevant medical device regulations. The clinical dossier will consider the results of studies working to an approved protocol.
“MHRA review the technical dossier prior to approving the commencement of a clinical trial in the UK and also agree the clinical protocol with the manufacturer.
What does a device being recommended by MHRA mean?
“MHRA do not recommend devices. MHRA is an executive agency of the Department of Health and Social Care, responsible for ensuring that medicines and medical devices work and are acceptably safe. It should be noted that, at this time, MRHA are accepting applications for approval of certain devices, such as personal protective equipment, directly.
What does reverse engineering involve?
“Reverse engineering is the deconstruction of an object to reveal its design, architecture, or to extract knowledge from the object in order to duplicate, improve or use the techniques for a different project.
How do these machines keep people off ventilators? Why is that important?
“Covid-19 causes a Pneumontis, an inflammation of the lining of the lungs. The small buds in the lungs responsible for oxygen transport, alveoli, can collapse and the inflammation can slow down oxygen transport. A severe pneumonitis will lead to a lack of oxygen being transported into the blood stream from a breath drawn into the lungs. Oxygen in the blood stream keeps all of the organs in the body alive and working.
“CPAP stands for Continuous Positive Airways Pressure and can be used to help patients affected by Covid-19, provided that these patients are able to breath on their own. A stream of oxygen is applied to the patient’s airway, using either a tight fitting mask or a hood. This stream is applied with a higher pressure than is normally in the air. CPAP feels similar to breathing whilst having your head out the window of a moving car. The extra pressure helps to open up, and keep open, the collapsed alveoli and push oxygen across the inflamed lung membrane. Therefore, CPAP increases blood oxygen more than just giving oxygen using a conventional oxygen mask.
“If CPAP is used appropriately, it can obviate the need for a patient to be placed on a ventilator, whilst still delivering a safe amount of oxygen into the patient’s blood and organs. However, CPAP is not suitable for all patients. Patients who are not be able to breath sufficiently on their own, or require sedation because of their illness, will still require ventilation. In the current crisis, ventilators are a precious commodity as they are in short supply.
What is novel about this process compared to how it would happen under normal circumstances?
“The novel approach being adopted for acceptance of these devices lies mainly with the speed of assessment.
“MHRA have issued guidance for manufacturers on exemptions from the Medical Device Regulations during the coronavirus outbreak. This is a fast-track approval of medical devices, known as derogation, through which manufacturers will be required to seek approval of their devices before placing them on the market.
“The link is link www.gov.uk/guidance/exemptions-from-devices-regulations-during-the-coronavirus-covid-19-outbreak.
“The Institute of Physics and Engineering in Medicine is the professional body for, clinical engineers, biomedical engineers and medical physicists, a learned society and a charity. Expert advice is being provided to government by senior members of the Institute at this time. IPEM is disseminating advice to our members, and wider CE community, many of whom work within the NHS, on the set up, training, maintenance and safety implications in the role out of medical devices, including ventilators, which are urgently required at this time.”
Professor David Delpy CBE FREng FRS FMedSci, a Fellow of the Royal Academy of Engineering, says:
“Continuous Positive Airway Pressure (CPAP) does exactly what it says on the tin. The CPAP machine produces a steady flow of air (or air with added oxygen) into a reasonably airtight facemask, which covers the mouth and nose of a patient who is breathing of their own volition. The pressure of the airflow is controlled at a steady but low level, which means that when the patient is breathing out, the slight pressure means that the alveoli in the lungs remain open rather than collapsing. This helps with oxygenation and also reduces the effort of breathing in (opening up the collapsed alveoli takes a lot of effort, especially when there is a lot of sticky mucus and the airways are constricted).
“The engineering team in this instance looked at all the elements/components of existing CPAP systems (or one particular CPAP system) and did a rigorous engineering analysis of their function and design with the aim of simplifying both construction and manufacturing costs but maintaining all the important functionality. Having done this they built a new version which can be shown to be ‘substantially equivalent’ to the original CPAP system, which would make obtaining regulatory approval much easier.
“Reverse Engineering is a standard engineering approach (very much used when people or companies want to develop a ‘me too’ version of an existing product). What is novel here is the speed of the development and the particular focus of the process – to produce something that is fit for purpose, easy to mass manufacture, probably has a more limited design lifetime than would apply to existing devices yet has a ‘substantial equivalence’ to existing CPAP systems enabling rapid approval by the MHRA. A further unique element here is the mix of companies and organisations involved.”
John Ling, Manufacturing Excellence Project Manager, Institution of Mechanical Engineers (IMechE), said:
“After stringent clinical trials, CPAPS were approved by MHRA for use in the NHS several years ago. Unlike ventilators, which pump air and oxygen directly into the lungs, CPAPS provides a monitored supply of air and oxygen to patients who can breathe it normally.
“What this team has done is to take one of the current CPAPS devices, disassembled it and, using reverse engineering (basically copying) changed the design and materials of various components to make it more suitable for mass and rapid manufacture.
“The UK has some of the best mechanical engineers in the world, working in many diverse industries and this is a first class example of what can be achieved with excellent management.”
Dr Peter Bannister, Healthcare Chair, Institution of Engineering and Technology, said:
“Medical devices obtain regulatory approval based on a review of design evidence, including safety test reports and risk analyses, by either the MHRA or by a licensed Notified Body. For a medical device to be recommended by the MHRA, the manufacturer must be able to show that it meets stringent requirements contained in established safety standards covering aspects such as sterility and immunity to electromagnetic interference from other devices found in a hospital. Reverse engineering means that the component designs and manufacturing processes have been derived from an existing sample device to allow other manufacturers to copy it.
“CPAP breathing aids are important as they can be given to patients before their condition has significantly deteriorated without needing to admit them to intensive care. This is likely to lead to better clinical outcomes as well as reducing the burden on intensive care units which are already hugely overstretched . What is novel about the current situation is that companies from other industries known for high volume precision engineering, such as automotive, are partnering with specialist medical device manufacturers in response to the urgent healthcare need to accelerate the mass-production of these breathing aids and also that the MHRA are prioritizing their review and approvals. This is one of a number of examples of cross-sector collaboration brought about by the current pandemic, responding to published government requirements. It is likely that more new consortia will emerge to address other population needs as the situation develops.”
Prof Duncan Young, Professor of Intensive Care Medicine, University of Oxford, said:
“These machines slightly increase the pressure of the air/oxygen that a patient breaths in. To do this the patient usually has to wear a snugly-fitting face mask or a transparent helmet, though devices that fit under or over the nose also exist. They are most commonly used with room air (without added oxygen) for sleep disordered breathing conditions. In patients with COVID-19 they are used to deliver a mixture of air and oxygen to the patient at a slightly increased pressure. This helps to keep the patient’s lungs expanded and increases the amount of oxygen in the blood.
“They are used in patients who are too unwell for simple oxygen masks but not quite ill enough to need a ventilator. In the absence of CPAP machines patients failing to stabilise with oxygen masks would be put straight on to ventilators. If they are put on to CPAP machines a number might recover without needing a ventilator. The use of CPAP machines or high flow nasal oxygen machines is routine in ICUs during normal times. In the context of the COVID-19 outbreak, these devices might save lives if the number of ventilators available is less than the number of patients needing them.
“The use of CPAP machines in patients with contagious respiratory infections is somewhat controversial as any small leaks round the mask could spray droplets of secretions on to attending clinical staff.
“Normally a CPAP machine would come under the MHRA rules for general medical devices (https://www.gov.uk/guidance/medical-devices-how-to-comply-with-the-legal-requirements). In general these require the device to have been properly designed and manufactured and be safe. The regulations do not require evidence that the device alters a patients outcome or the course of their illness, unlike drugs. The MHRA does not usually recommend one particular device.
“The team disassembled an off-patent design to see how it was made, and then set out to manufacture a similar but improved device. As it was off-patent there was no infringement of the intellectual property rights of the original manufacturer.
“The speed with which the team developed the device is remarkable.”
Dr Tom Wingfield, Senior Clinical Lecturer and Honorary Consultant Physician, Liverpool School of Tropical Medicine (LSTM), said:
“CPAP machines when used appropriately can save lives in people who are critically ill with conditions including pneumonia that require high levels of oxygen delivered with some “positive pressure”. Positive pressure means that the oxygen from the CPAP machine flows into the lungs under a safe amount of pressure that is sufficient to keep the air sacs (alveoli) open to help people with breathing difficulties to breath more easily. While CPAP machines are not routinely used on standard hospital wards, they are routinely used on specialist respiratory wards or high dependency units (HDU) or intensive care units (ICUs). Some people may also be aware of CPAP machines that are used overnight at home by people who have obstructive sleep apnoea.
“The use of CPAP in people with Covid-19 related lung disease and pneumonia has been shown in other settings to help people to AVOID being intubated and put onto mechanical ventilation and could potentially save lives.
“The latest PHE Infection Prevention and Control guidelines (page 29*) state that “Non-invasive ventilation (NIV) e.g. Bi-level Positive Airway Pressure Ventilation (BiPAP) and Continuous Positive Airway Pressure Ventilation (CPAP)” are potentially infectious aerosol generating procedures.
“It is not described in the press release but there may be potential to adapt a CPAP machine that means they generate fewer aerosols or that the machines are used in particular settings with high levels of ventilation (e.g. “negative pressure rooms”) and with staff who are wearing full, appropriate PPE for aerosol generating procedures.”
An additional comment from an academic involved in the project
Professor Mervyn Singer, UCLH critical care consultant (UCL Medicine), said:
“If health care staff are wearing appropriate personal protective equipment (PPE), the chance of transmission through droplet spread appears to be very low.
“The new NHS England guidance (NHS Specialty guides for patient management. Guidance for the role and use of non-invasive respiratory support in adult patients with coronavirus (confirmed or suspected) 26 March 2020 recommends the use of CPAP for COVID-19 infections:
“This guidance was based on a consensus document drawn up by 22 UK experts in critical care and respiratory medicine, and with backing from the National Emergency Committee for Critical Care (NECCC) (comprising the Royal College of Anaesthetists, Faculty of Intensive Care Medicine, Intensive Care Society, Association of Anaesthetists; March 2020).
“CPAP is being used extensively in Italy. Prof Stefano Grasselli (ICU consultant from Milan), in a webinar for the European Society of Intensive Care, noted there were 1425 patients in Lombardy intensive care units and 2200 patients receiving CPAP on wards.”