A possible correlation

MPN EDITOR LAURA HUGHES REACHED OUT TO JASON SMITH, MANAGING DIRECTOR AT BEDFONT SCIENTIFIC, TO FIND OUT ABOUT THE COMPANY’S RESEARCH REVIEWING A POSSIBLE LINK BETWEEN FRACTIONAL EXHALED NITRIC OXIDE (FENO) AND COVID-19.

Bedfont Scientifi c has developed the breath analysis medical device, NObreath, which measures FeNO. Smith explained how the device was fi rst developed in 2008 as a non-invasive aid in the management and diagnosis of asthma. He said: “The device works by analysing a breath sample and providing a FeNO reading in Parts Per Billion (PPB) which refl ects a patient’s level of airway infl ammation. The higher the level of FeNO, the higher the level of airway infl ammation, indicating either undiagnosed or uncontrolled asthma.”

Ten years later, the second generation NObreath device was launched. This device diff ered to the original, with both new aesthetic and functional features designed to meet the market needs and demands. These included verifi cation of successful breath tests, onscreen motivational exhalations guides, and a new aesthetically pleasing look with easily-serviceable parts.

Smith explained how, “one of the aesthetic updates was the move away from rubber casing to a polycarbonate/ABS blend, which enabled the NObreath to have a more stylish but clinical look.” The device also has a purple bezel to keep a splash of colour and to remain in line with the company branding. Additionally, the plastic casing of the NObreath now also incorporates SteriTouch antimicrobial technology for optimum infection control as a medical device.

In terms of the lifespan, “NObreath has an unlimited testing lifespan and only requires one yearly service,” Smith highlighted. The polycarbonate/ABS blend casing around the serviceable parts also means that the annual service is quick and easy to perform.

Prior to the pandemic, the device was being used in both primary and secondary care to assist with the diagnosis and management of asthma. Regular FeNO measurements indicate levels of airway infl ammation, which can help healthcare professionals with a more tailored asthma diagnosis by preventing over-/under-/mis-diagnosis, as well as improving asthma management. FeNO measurements can be also be used to evaluate the eff ectiveness of inhaler technique, and also an individual’s ICS dosing.

However, during the pandemic, Smith discussed how a colleague suggested the potential role of FeNO levels in Covid-19: “One of our medical advisory the potential role of FeNO levels in Covid-19: “One of our medical advisory board members, Prof. de Paula Vieira, explained to us board members, Prof. de Paula Vieira, explained to us that high levels of FeNO have been associated with that high levels of FeNO have been associated with bronchial infl ammation, remodelling (fi brosis) and hyperbronchial infl ammation, remodelling (fi brosis) and hyperresponsiveness in asthmatic patients, and especially responsiveness in asthmatic patients, and especially asthma severity and prognosis. Thus, due to the nature asthma severity and prognosis. Thus, due to the nature of the infl ammatory and rapid fi brotic process found in of the infl ammatory and rapid fi brotic process found in Covid-19 patients, he hypothesised that Covid-19 patients Covid-19 patients, he hypothesised that Covid-19 patients could present high levels of FeNO at the beginning could present high levels of FeNO at the beginning of the disease. In addition, some mild and moderate of the disease. In addition, some mild and moderate symptomatic patients presenting Covid-19 symptoms have symptomatic patients presenting Covid-19 symptoms have come to the hospital and some of them develop a more come to the hospital and some of them develop a more severe form of Covid-19.” severe form of Covid-19.”

At the time, Bedfont had received lots of At the time, Bedfont had received lots of correspondence asking for medical and technical correspondence asking for medical and technical innovations that could help the current pandemic innovations that could help the current pandemic and so when Prof. de Paula Vieira approached the and so when Prof. de Paula Vieira approached the company with his theory, Smith said, “we thought company with his theory, Smith said, “we thought it essential to explore whether FeNO had a direct it essential to explore whether FeNO had a direct

correlation to Covid-19 and donated the monitors and consumables necessary for the study.”

Currently, research is still in the early stages. A number of hospitals are participating, and FeNO testing is being conducted alongside other parameters. Prof. de Paula Vieira hopes to run this study for roughly another four months to ensure the data is robust.

In terms of study completion, Smith commented: “We hope to have some preliminary results by August, as one of the hospitals used for Covid-19 referrals is looking to test 400-500 non-hospitalised patients, and around 100 hospitalised patients. We aim to have collected enough data to fi nish the study in about four months’ time, and the fi nal results should be analysed and released shortly after this.”

According to Smith, the organisation does not believe anyone else is actively reviewing a possible link between FeNO and Covid-19.

We aim to have collected enough data to fi nish the study in about four months’ time.

ANKIT KEDIA, FOUNDER OF CAREMONT, A BANGALORE BASED MEDTECH START-UP, DISCUSSES THE PRESENCE OF CONNECTED HEALTH WITHIN THE MEDTECH SECTOR IN INDIA. the new normal

Connected health is a term which has become increasingly important, especially during this Covid-19 pandemic. Perhaps connected health is one of the most likely forms of technology to change the way people look at healthcare. Providing care remotely using devices, smart sensors, Artifi cial Intelligence (AI), imaging techniques, and integration with smartphones, is how I would best defi ne connected health.

CONNECTED HEALTH IN THE MEDTECH SECTOR IN INDIA

In the medtech sector, connected health has received worldwide attention, especially in densely populated countries like India, where the ratio of doctors to patients is highly skewed. While there are several notable telemedicine applications and consulting platforms available, connected healthcare devices are yet to take off due to a lack of awareness, education, and the overall mindset of the patient to trust technology over the psychomotor skills of a doctor.

EXAMPLES OF CONNECTED HEALTH

Currently connected healthcare apps like Mfi ne and Apollo 247 are some of the telemedicine apps that are making physicians available remotely, as patients are reluctant to take trips to clinics and hospitals due to fear of contracting Covid-19. In fact, many private practitioners who have regular patients with chronic issues, have also employed simple practices like phone calls or video calls to provide consultations. The use of AI and Internet of Things (IoT) will help bridge the gap between caregivers and care receivers in a country like India, which has a fast emerging rural economy.

Several examples of connected health solutions include: • TriCog, which provides ECG devices to doctors and a mobile app for patients to fi nd these doctors in case of emergency. • An AI-based early-stage breast cancer screening device is currently being developed by Niramai- Bangalore. • Caremont have partnered with a company that makes spirometers connected with smart phones to provide asthma patients with data on their lung function values, as well as a rehab device for Covid-19 patients to improve lung health.

THE BENEFITS

Connected health could help India meet the needs of increasingly educated patients. It will be very benefi cial to doctors and hospitals by cutting costs through real-time access to patient data, and improving workfl ow. It also helps insurance companies to reduce claim payments and provide assistance to deserving critical patients. In some cases, it will help pharma companies by allowing patients to begin medication sooner due to early detection of illness and diagnosis, and could also help to ensure compliance with treatments. In my view, one of the best uses of connected health technologies will be in rural areas of our country to provide remote health monitoring and enable patients to consult with their doctors in urban speciality hospitals from the comfort of their homes.

CHALLENGES

One of the challenges with the use of connected health is two-way awareness between the doctor and the patient. Inherently, our population is used to receiving care with a face-to-face interaction with doctors, and changing this mindset will take time. Companies off ering connected health technologies have to work towards integrating technology through continued persuasion and building a trust-based relationship with the patients. Other challenges, of course, lie in the regulatory framework of the country which will defi nitely get a facelift once the pandemic dust settles down. The biggest challenge with connected healthcare is the cost of developing these solutions and subsequently deploying them in the most cost-eff ective manner to be available to the masses. One also has to keep in mind that the government needs to fully advocate and endorse this connected health technology for it to coexist with some of their existing healthcare infrastructure and plans.

THE FUTURE

India will witness a complete spectrum of the healthcare ecosystem, wherein small clinics will coexist with home healthcare, as well as large sophisticated hospitals. The focus is clearly shifting towards a preventative approach from a curative approach, with several connected healthcare solutions like ingestible pill monitors and nutrition sensors. AI doctors will become more common and personal IoT-based monitoring devices will change the way we track the health of individuals. AI will never replace the emotions of a physician entirely, but it will surely take over their work including certain decision making powers. Going forward, AI will evolve from doctors versus machines to doctors and machines!

WHY SIZE MATTERS IN WEARABLE TECHNOLOGY

SIMON WARD, TECHNICAL MANAGER AT FASTENING AND FIXING SUPPLIER, TFC, EXPLORES THE POTENTIAL FOR WAVE SPRINGS IN THE GROWING WEARABLES MARKET.

In 1998, engineer Steven Mann built the world’s fi rst Linux-based smart wristwatch - earning him his reputation as the father of wearable computers. Since then, companies have developed smartwatches and other wearable electronics for a variety of industries, including fi tness, healthcare and manufacturing.

The Linux watch was designed to communicate wirelessly with PCs, mobile phones, and other wireless-enabled devices, allowing users to access emails and receive direct messages. As this technology became more popular in the consumer market, industry began to explore the potential of wearable devices, particularly in the medical sector. Patients can now wear highly accurate devices, such as blood glucose monitors, that give doctors more long-term data to help understand chronic diseases in more depth.

As diff erent industries and consumers discover how wearables can help them, manufacturers are exploring new ways to design and improve these devices.

SMALL SCALE

Size is one of the biggest challenges in wearable electronic device manufacturing. As these devices become more sophisticated, integrating all the required components becomes diffi cult. For example, the latest iteration of the Apple Watch contains technology capable of taking the user’s pulse and has ECG functions to provide critical health data - all in a 40mm wide case.

As the demand for these devices has increased, design engineers have had to fi nd ways to improve the performance of these devices while reducing their size. For example, engineers have replaced coin cells with lithium ion batteries because of their improved energy density and smaller size. As end-users require more capabilities from a smaller device, manufacturers must carefully consider what components to use.

WAVE SPRINGS

A wearable device such as a smart watch, is fi tted with function buttons that will likely contain some form of return spring. It may also require springs to take up tolerances and maintain electrical contact. Due to space constraints,

Size is one of the biggest challenges in wearable electronic device manufacturing.

We have designed Crestto-Crest springs for insulin pens that help control and measure the dosage that is injected into the patient.

Another example is surgical and dental tools that use precision bearings to operate at high speed.

manufacturers fi nd it impossible to fi t a traditional coil spring into these small spaces so need to consider alternative solutions.

Wave springs may off er this solution as they require less than 50% of the space needed for more traditional springs. They can also be manufactured in diff erent forms depending on the spring characteristics that are required in the application. By customising parameters such as the number of turns, number of waves, material type, and thickness, TFC engineers can design these wave springs to help manufacturers meet their product goals.

As manufacturers want to ensure that all the components feel right, it may take several iterations of a wave spring to fi nd the optimal fi t. As part of the process, TFC engineers will continually work with the OEM from initial concepts right through to SOP to ensure the optimal production solution.

Back in the early 2000s, Steven Mann predicted that wearable computers, such as his smart wristwatch, would become a common part of life in the future. Today, wearable electronics have evolved to off er a variety of applications, ranging from fashion accessories to life-saving devices. No matter the application, wave springs can play a small, yet crucial role in developing the right feel for a compact, functional, and long-lasting device.

CLAUDE BERNARD, PRODUCT MARKETING DIRECTOR, SEPRO GROUP, HIGHLIGHTS WHAT TO LOOK FOR IN A ROBOT FOR CLEANROOM MOULDING.

r se of the robots

Robots are being used with increasing frequency in cleanrooms, for most of the same reasons they are becoming more common across all industries. For instance, robots can improve efficiency, stabilise the process, and enhance workflow. Within the cleanroom market, robots can be used across the entire production process - from moulding to assembly to inspection, traceability and packaging.

Naturally, for use in a cleanroom, like any other piece of equipment, a robot must be designed, installed and operated so as to prevent contamination of the clean space. In Cartesian or beam robots, which are the most commonly used in injection, areas where grease or other lubrication is used must be enclosed so that none can escape into the moulding area. All cables are protected in conduits and pneumatic air is filtered to 0.3 micron. All surfaces are smooth and free of logos, stickers, or other decoration to eliminate places where dust can accumulate and to

Claude Bernard

An ISO 8 cleanroom at MGS Manufacturing in Germantown, Wisconsin (USA)

make cleaning easier. Stainless steel is used in many components - like endof-arm tooling - that come into contact with the moulded parts.

Sepro 6-axis articulated-arm robots, developed in partnership with Stäubli, have a sealed housing, and the standard robots are suitable for ISO 5 (class 100) cleanrooms without modification. Therefore, injection moulding robots can meet all but the most stringent requirements. In fact, they can exceed the level of cleanliness possible with injection moulding processes.

INSTALLATION ALTERNATIVES

The conventional way to install a Cartesian robot on an injection moulding machine is to mount it on the fixed platen (injection end of the machine) so that the main beam (X axis) extends from the area immediately above the mould and parts are unloaded to the side of the moulding machine. Here they can be placed on a conveyor or immediately packaged. The parts may also undergo secondary operations such as gauging or assembly, using human operators or additional robotic automation.

Robots can also be mounted axially, where the X-axis beam extends from the space above the moulding area along the centre line of the moulding machine so that moulded parts are discharged at the clamp end of the machine. In cleanrooms, this arrangement offers several advantages.

Firstly, when parts don’t need to be discharged to the side, it allows the machines to be placed closer together. In cleanrooms where floor space is often at premium, this can be a considerable benefit. Another potential advantage of axial mounting comes into play in applications that require the highest levels of environmental control. The IMM and the robot (installed in axial configuration) can be installed outside of the actual cleanroom, with the clamp end of the machine near a wall with an opening leading into a second room where higher cleanliness standards may be maintained. Parts can be quickly shuttled into the cleaner environment for final processing or assembly.

In any case, the moulding machine and the robot will need to be guarded to protect human operators from injury due to coming into contact with the moving robot. The metal profiles into which guarding panels are mounted should be closed on any side that doesn’t need to receive a panel. Instead of the wire mesh commonly used in general industrial applications, the guarding panels themselves should be made of PET polyester or other clear plastics that can be easily wiped clean. Cables should be routed in closed wiring ducts, and all ducts, drawers, and other components should be stainless steel, electro-polished for easy cleaning. The number of supporting legs on the floor should be kept to a minimum. Similar design rules apply to conveyors.

Robots and automation systems will continue to play a crucial role in medical injection moulding. Automation technology can be expected to continue to advance as market forces demand it to do more, and as robot technology evolves.

Changing gear

JUHA MATTILA, DIRECTOR, STERILISATION TECHNOLOGIES, STERIS LIFE SCIENCES, EXPLAINS HOW TO MITIGATE RISKS IN CLEANROOM MANUFACTURING FOR THE STERILISATION OF GOODS, AND HIGHLIGHTS THE GROWING TREND OF UTILISING AUTOMATED AND VALIDATED VAPORISED HYDROGEN PEROXIDE (VHP) MATERIAL TRANSFER DECONTAMINATION.

Manufacturing sterilised goods is more than just the terminal sterilisation step at the end of the drug delivery device or other medical device manufacturing line. Quality of the end-product depends on the preceding process steps such as raw materials, cleaning, packaging, component sterilisation and material transfer to cleanroom.

Automation of pharmaceutical manufacturing processes, related operations, and material handling are driven by the constantly growing need to mitigate any risks associated in the production of drug delivery devices and other medical devices. Any manual processing activity presents a greater risk for the end-product quality, regardless if a process takes place inside cleanroom or isolator space, or if it takes place before entering the cleanroom manufacturing area. One such process is material transfer and its related decontamination process for minimising bioburden in material transfer into cleanrooms.

Material transfer of pre-sterilised components (e.g. stoppers, vials, syringe components) is carried out using sterilisation bags covered with one or more, typically LDPE, plastic bag layers. These enable protection of goods entering from lower classifi cation areas to higher, such as going from D to C areas, or from C to B areas. Once entering an airlock, the bag surface is wiped with alcohol or another suitable disinfectant for minimising bioburden in transfer. When transferred to the other side, the bag outer surface is then removed, and the wiping of the possible next bag layer is repeated until the destination is reached (class A = isolator space).

The above described manual method is very time consuming, labour intensive and diffi cult or impossible to validate, as each process is always manual. Such a process is a true bottleneck for many pharmaceutical or medical device manufacturing facilities striving to continuously improve productivity and quality.

In response, automated material transfer using atmospheric VHP or generally VHP chambers has increasingly replaced manual methods. This technology provides greatly improved effi ciency in decontaminating transferred bags, instruments and tools outer surfaces in both existing manufacturing operations and greenfi eld facilities that have been directly designed for using automated processes as much as possible. VHP material transfer decontamination chamber cycles are manually loaded and un-loaded to carts or hooks on carts, and then pushed into the chamber. In continuous high capacity throughput systems, however, automated loading and unloading systems can be integrated to the chamber. A VHP material transfer decontamination process consists of three main phases: Preconditioning (de-humidifi cation and possible conditioning), decontamination exposure (validated 10-6 log reduction result when using Geobacillus Stearothermophilus spore biological indicators), and post-conditioning (aerating the load by removing VHP residual by catalyser and turbulent airfl ow).

Typical cycle times vary between 45 and 100 minutes depending on the materials being decontaminated. Longer cycle times (over 60-70 minutes) are most often required for cellulose tags or partial covers of bags in the load, which may need prolonged aeration to reduce peroxide residuals down to allowed unloading PEL/OSHA levels of one to three ppm. Chamber sizes vary between small box-size dimensions to small cleanroom-size applications.