Tag: Medical Therapy

Preparing for the new IVD regulations
By Sarah Follett
October 25th 2019
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Sarah Follett

Consultant Quality Specialist

Preparing for the new IVD regulations

It may seem like there is plenty of time before the new IVD (in vitro diagnostics) regulation (IVDR) [EU 2017/746] comes into effect. The deadline for transfer is 2 years later than that for medical devices [EU 2017/745], so May 2022 might seem distant. However, given the changes that are required, clued-in manufacturers should be working now to be ready.

For those with products currently certified by a notified body (NB), there is additional breathing space. The key here is to get the current certificate renewed and extended by the current NB, which can give 5 years transition, meaning product can still be put on the market until 2024 and stay in use until 2025.

However, for the vast majority, their product was self-certified against the IVD directive [98/79/EC], which means come the 26 May 2022 deadline, the CE mark required for sale in Europe will be null and void. So, what do you need to do, as a manufacturer with a self-certified IVD on the EU market?

Where to start?

Firstly, do not panic! Easier said than done, but there is a wealth of information out there, if you know where to look or who to ask.

Step one, rationally review the Intended Purpose of your product. Have you really nailed it down in terms of what type of test it is, what is measured and how it is measured, patient population, intended user, use setting, purpose of the test? This will dictate much of what happens next and determining where your gaps lie. Without a proper Intended Purpose statement, you may not classify your product accurately, and within some classifications there are groups of products that have their own specific requirement above the standard ones. For example, near-patient testing (Point of Care) and Companion Diagnostics both have specific requirements in addition to those for other devices of the same classification.

This exercise shouldn’t be conducted by your Regulatory department in isolation. There may be market and business considerations to be made; Is there really a market for the Intended Purpose that you can support? Will there be an adequate return on the additional investment that may be required?

New requirements

An obvious difference is the change from the Essential Requirements Checklist (ERC) to the larger General Safety and Performance Requirements (GSPR). This is another good place to start, because completing all the relevant references to the Technical File within the GSPR will immediately point you towards where there are disparities, or the evidence is insufficient.

The key gaps in current Performance Evaluation data are likely. Previously not required, the IVDR now calls for things like Trueness, Precision, positive and negative predictive values (PPV/NPV) and specimen handling and controls. For some, this will require new calculations to be made using existing data, while other manufacturers will find they just don’t have what they need to meet these new requirements. For older products, was the clinical trial run with a comparison against something still considered state of the art? For self-certified manufacturers, it is important to be aware that it is going to be much harder to provide justification for not carrying out clinical performance studies. There is no grandfathering for the new regulations; all products are considered new and must stand up on today’s merits.

Risk and risk management has a far bigger presence in the IVDR than it had in the IVDD. This is one area that current self-certified manufacturers, in particular, should turn their attention. Have all possible indirect harm situations been considered and included? Are all residual risks in the IFU? And all manufacturers will need to consider the latest version of ISO 14971 when it is published at the end of the year.

The Post Market surveillance requirements and activities have been significantly beefed up from the IVDD. It requires more than logging customer complaints within internal systems, instead involving active and systematic data gathering, together with a Periodic Safety Update Report (PSUR) for Class C and D devices and Post Market Performance Follow-up. Processes will need to be in place that capture new requirements to log information in EUDAMED, to review scientific literature for new off-label use scenarios (as just one example), and ensure risk is considered and updated throughout the product lifecycle.

Out of your hands

The elephants in the room, which are totally out of manufacturer’s control, are EUDAMED being ready for use, and NBs being certified against the IVDR. EUDAMED is required for use with the MDR, so expectations are it should be ready in time for the IVDR. Of greater concern are the NBs. Currently, just 2 notified bodies have received this certification (DEKRA, Germany and BSI, UK). Others are known to be in the pipeline (approximately 10 more), but until they are announced there is big uncertainty. Add to that, the scope of the certifications, which also won’t be known in advance, so some manufacturers may still need to change their NB, even if they are certified to the IVDR, because they cannot support their product range.

There is a lot to do to be able to sell your IVD after 26th May 2022. However, with the right planning and support, all the documentation can be put into place. It remains to been seen if the notified bodies will be able to keep up with demand, but at least manufacturers can be prepared when they get to the top of that queue!

Connect with CDP

For more on how to navigate the new IVDR requirements and prepare your IVD products for EU market compliance, contact Cambridge Design Partnership.

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Developing guidance for regulatory submissions
By Helen Simons
September 12th 2019
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Helen Simons

Quality Specialist

Developing guidance for regulatory submissions

RAPS (Regulatory Affairs Professionals Society) publish a set of excellent “Fundamentals” books, each covering a different regulatory context: US, EU, Canadian and International (which covers other markets). These books detail the key aspects of the regulations for pharmaceuticals, medical devices and IVDs (In vitro diagnostics) with considerations about how they should be followed and implemented.  These are essential for healthcare companies looking to make submissions outside of the jurisdictions they are familiar with.

These books need to be regularly updated as regulations evolve to ensure they are current, and I have been chosen as a subject matter expert for the US fundamentals book that looks at the requirements of the FDA (Food & Drug Administration).  I have recently updated the chapter “supply chain and traceability”, along with a second author, Jyoti Chauhan.

This chapter was initially introduced in the last edition (10th) and so was relatively new to the book. Upon reading, I was most surprised that it did not cover any elements of supply chain or traceability for medical devices, only focusing on pharmaceutical requirements, specifically the Drug Quality and Security Act. I felt the chapter was lacking in detail on medical devices because traceability is a key topic at the moment with the introduction of UDIs (Unique device identifiers) in the last few years, so this was a big gap to be missing.

My first task was to pull together all the existing guidance on the topic of UDIs which the FDA have published as well as the key aspects of the CFR (code of Federal Regulations) in relation to supply chain and traceability. It was interesting to compare them at the same time as different pieces of information are emphasised in different guidance, so I wanted to summarise these in a cohesive overview.

Adapting to the formal writing style of these publications was a practical challenge, but I hope my description and analysis will help other regulatory professionals navigate the tricky waters involved in submitting their products to the FDA for approval.

If you want to know more about these subjects or how CDP can help you with your quality and regulatory activities, then please do get in touch with us at hello@cambridge-design.com.

Mars Petcare – smart-pill illustration
August 13th 2019
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CDP create a remarkable ‘smart pill’ for Mars Petcare

A team from Cambridge Design Partnership has created a ground-breaking ‘smart pill’ to gather crucial nutritional information to help develop innovative new pet foods.

CDP scientists and engineers worked with the world-renowned Waltham Centre for Pet Nutrition on an electronic pill to collect food samples inside the canine gut during digestion.

“It was certainly an unusual request and a major challenge,” says Will Bradley, who led the project for CDP. “Mars Petcare wanted to find out more about how dog food is digested, with the aim of improving their pet food. So they asked us here at CDP for help.”

“They needed samples of partially-digested food that they could gather in complete safety for the dog.”

Part of Mars, Incorporated, Mars Petcare has a portfolio that spans pet nutrition and health through brands including ROYAL CANIN®, WHISKAS® and PEDIGREE®. For Mars, CDP created a smart pill about the size of a grape that a dog could easily swallow.

“We gave it a sensor so that it knows when it has left the acidity of the stomach and entered the first part of the intestine,” explains Will. When it is correctly located the pill opens and takes a food sample, using a miniature piston-type mechanism. “This needs to be absolutely foolproof. The pill then closes, to contain and protect the sample as the pill moves through the remainder of a dog’s digestion.”

CDP was approached by Mars Petcare to bring to life an idea for intestinal sample collection in dogs. CDP created the pills at its laboratory in Cambridge, which were trialled at the WALTHAM Centre for Pet Nutrition in Melton Mowbray, the global pet research centre for Mars. There were many studies and iterations needed to refine the design.

The samples that are collected will be used to analyse the way various nutrients are absorbed during digestion. “The scientific understanding of this whole process had basically stalled for decades,” explains Mike Cane at CDP, who has worked on the project for the past 18 months, “because no one could retrieve these samples without invasive surgery to the dog.”

Working with animals is not straightforward, Mike admits: “At all times, there were such high welfare standards. An independent observer was on hand whenever we worked with the dogs. If any dog was looking uncomfortable they would intervene to stop that day’s trial. They really do pride themselves on the way the animals are treated there.”

Once the pill passes through the dog and is excreted, it is retrieved and the data from it is collected. “The data from the trials has been analysed by the lead scientist from WALTHAM, David Wrigglesworth, who will soon be publishing his findings in peer-reviewed scientific journals,” explains Mike.

In addition to surviving the rigours of a dog’s digestion, the pill can also be tracked on its journey. “Once it was clear that the pill worked well, Mars Petcare asked us if we could also find a way of knowing accurately exactly where it was as it passes through the dog,” says Mike. “So we also devised a special interactive coat worn by the dog which picks up a radio signal from the pill.”

The smart pill is so unique that it has been patented by the team.

“Here at CDP, we’re very proud of our achievement,” says Will. “I feel sure that it will enable Mars to create innovative new pet foods for many years to come.”

For further information and media enquiries, please contact: media@cambridge-design.com or call 01223 264428

Innovation in Hemodialysis event|
By Clare Beddoes and Matt Brady
July 19th 2019
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Clare Beddoes

Clare Beddoes

Senior Medical Innovation and Research Consultant

Matt Brady

Partner

Innovations in Hemodialysis

In our recent blog post ‘What’s Next In Hemodialysis’ we looked at some of the trends that are driving the industry. This month we report from the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) congress in Budapest. With more than 110 companies exhibiting to 9,500 attendees, Matt Brady, Partner and Head of Medical Therapy, and Clare Beddoes, Senior Healthcare Innovation Consultant, highlight some of the latest innovations in renal care.

Home dialysis on the up?

This is the question we asked before the conference, and from what we saw the answer seems to be a resounding “yes.”  And within the home hemodiaysis (HHD) space, we see a definite trend toward user interface enhancement.

We visited the stand of home haemodialysis (HHD) market leader NxStage, which we noted was nicely connected to its new owner Fresenius Medical Care’s booth by a smart, ‘on-brand’ blue carpet. Here we had the chance to open, load and look at all aspects of the NxStage machine that a patient would have to learn to interact with at home. Undoubtedly the world leader in HHD, the NxStage system has now been around for nearly 20 years. Whilst its user interface is clearly effective to date, we imagine NxStage will move to modernise this under its new owner, with a view to reclaiming UI leadership from less established players.

Quanta is a good example of a company launching a modernised user interface on an existing HHD setup, this update launched at ERA-EDTA last year and was again on display this year.  The clean and stylish tablet-controlled Physidia machine impressed us, with a detachable tablet-style UI which allows patients to program and control their machine from the comfort of their armchair, as opposed to having to reach up to a screen, which can be difficult or uncomfortable during a dialysis session.

As well as those companies we know are dedicated to producing machines for patients to use at home, we heard interest in HHD from other players, perhaps currently better known for their expertise in in-center dialysis. Several told us they are considering, or are currently developing, machines dedicated to HHD. In our opinion, understanding the complexity of physician, patient and healthcare system drivers, needs and barriers for HHD will be key to successful new entries into this market.

Emerging competition from China – or Canada?

As we anticipated, we again saw many interesting companies from China, several of whom still hint at an interest in entering western markets – but there was no “big reveal” at this time.  Instead, the big surprise entrant at the congress was a new company from Canada. NephroCan is a Vancouver-based company offering a range of dialysis products including membranes, blood lines, a chair and reverse osmosis machines – with the promise of an in-center dialysis machine by the end of the year. An impressive debut with a large booth – NephroCan is certainly one to watch.

Biofeedback is gaining traction

At one level biofeedback is well established in HD – for example through routine monitoring of venous blood pressure, flow and arguably clearance (Kt/V). This year we noted an uptick in interest in novel approaches to biological monitoring to help ensure successful dialysis and safeguard the patient.

The South Korean company InBody markets various formats of a non-invasive device which works using inductive measurements through the soles of the feet and the hands. This indicates not only how much fluid to remove from a dialysis patient (by determining their “dry weight”) but can also measure various nutritional status indicators, such as segmental muscle and fat mass,  and evaluate segmental fluid imbalances to identify circulation issues.  Although InBody’s biggest market focus currently is gyms (tracking athletes’ hydration status, lean muscle mass, etc) rather than dialysis clinics, the company has recently been accepted onto the NHS Supply Chain and has UK dialysis clinics in its sights.

Meantime, market leader Fresenius Medical Care was promoting active control of sodium levels as a software upgrade to their existing 6008 dialysis machine, and we heard of other firms who are exploring the use of sensors and algorithms to more tightly control fluid balance and blood pressure during dialysis.  Here at Cambridge Design Partnership, we see this as a very positive trend, given that variations in blood pressure and volume are key drivers of congestive heart failure, one of the most significant comorbidities of End Stage Renal Disease (ESRD).

Bespoke patient care

The sheer number of companies offering dialysis products such as bloodlines and membranes was staggering. How does a company differentiate its products in such a crowded marketplace? One solution could be by promoting the use of bespoke prescriptions, according to an interesting presentation we listened to by a leading nephrologist, citing an eminent Japanese physician who holds a stock of 25 different membranes. This gives him greater flexibility to tailor prescriptions to the individual patient, taking into account comorbidities, nutritional status, stage of disease etc. and to monitor and change this over time. Many delegates that we spoke to agreed that bespoke prescribing of this nature should become more commonplace.

This is, indeed, an exciting time for the renal care industry. In such a crowded space it will be increasingly important for all players (large or small, new or established) to understand where the opportunities for innovation and improved patient care exist.  CDP’s innovation research & human factors team, biomedical engineers, industrial designers, software & electronics team, and manufacturing engineers, all share a passion to develop products to improve patient lives. We have the experience and innovation skills to create new products in this life-saving sector, and we are ideally placed to continue to play our part in driving innovation in renal care.

By Louise Place
January 18th 2019
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Louise Place

TitleHead Of Regulatory Affairs and Senior Quality Assurance Consultant

Is medical device regulation failing to ensure patient safety?

For the last decade I have been part of the medical devices industry, most recently as part of a design consultancy firm specialising in medical device innovation. In the last few years our world has been shaken with reports of the failure of medical device implants and the insinuation of industry wide misconduct.  The headline statistics are certainly shocking, in the investigation recently published by the ICIJ, their research suggests that in 2017 nearly 300,000 patients were harmed by medical devices in the US alone. Clearly something is wrong.

However, personally I have never come across anyone in the industry who wishes to cause harm to a patient, in fact it’s completely the opposite. Where I work, it is our company’s primary policy to improve lives through innovation and the stories that have hit the headlines do not to make it clear that most people in the industry are diligently working towards making sure all new devices are safe.

I spend my life around medical devices. These include items as varied as a surgeon’s scalpel, an insulin injection pen or a portable oxygen delivery system. They also include implantable meshes and spinal support systems and complex hospital equipment designed to keep extremely sick people alive.

Each device I work with is the product of many years of design and testing before it is allowed near a patient. During that time, it undergoes substantial testing to ensure that it works according to the design intent, for the conditions it is expected to experience and the intended life both on the shelf and in use. Biocompatibility testing is carried out to ensure that anyone encountering contact with materials does not suffer an adverse reaction and a robust risk management process, including medical professional opinion, underpins all this to attempt to account for foreseeable harms from the use of the product. At every stage in this development process the concern is for the patient and one of the most common questions asked is whether you would be happy for a close relative to use the final product.

If a device does reach a human being for clinical evaluation, and not all do, the use in that person is strictly controlled. The safety profile, as far as possible, needs to be determined and the risks of the use of the device, as well as the benefits, need to be established and controlled as far as possible. In the United Kingdom, this assessment is carried out by the Medicines Healthcare Regulatory Authority (MHRA) and it takes several months for agreement, during which this information is assessed. It is also usual for an independent Research Ethics Committee to confirm the well-being of trial participants and agree to the trial. Once agreement is obtained recruitment may begin and appropriate volunteers may start a trial once they have signed an informed consent form which details the potential risks and benefits of the study. All trial participants may withdraw from a trial at any time without needing to give a reason.

Prior to a device being launched on the open market in Europe and depending on risk classification (the lowest risk devices can be launched after the creation of appropriate technical document with limited oversight), the summary of all the development documentation detailed above, and more is assessed by a Notified Body. These organisations, whilst not part of governmental structure, are designated by their national competent authority (e.g. MHRA) as having passed a strict assessment which confirms that they have the relevant in-house knowledge to question and approve a device for use. Post market surveillance also takes place to ensure that as more information becomes available through use, appropriate changes are made to the design and even withdrawal of product if it is deemed necessary because of a safety risk.

Europe is currently poised to welcome an update to the Directives and Regulations governing the development and assessment of Medical Devices to the market. This is the culmination of nearly a decade of discussions from the European Commission downwards to ensure the safe development of medical devices. The new Medical Device Regulations (MDR) place stricter requirements on the in-patient testing of devices, the post market follow-up (especially with regard to implantable devices) and the re-classification of some devices into higher risk categories. All medical devices, both yet to be conceived and those on the market already, must meet these regulations as manufacturers will no longer be permitted to rely on historical approval.

I am not claiming my world is perfect and the statistics show this. But carefully implemented medical device regulation maintains and promotes high standards of safety and efficacy. I’m proud to say that here at Cambridge Design Partnership the focus is always on the welfare of the patient. I wouldn’t have it any other way.

September 24th 2018
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A breath of fresh air – How interactive technology could transform the patient experience in intensive care

24 September 2018 – A doctor’s experience of dealing with acute trauma on the battlefield is being used to help improve the lives of critically ill civilian patients in intensive care units (ICUs). Dr Charlotte Small and the critical care research team at the Queen Elizabeth Hospital Birmingham (QEHB) in the UK are working with technology and product design firm Cambridge Design Partnership (CDP) on a novel approach to the complex task of weaning recovering patients off ventilators.

Millions of people are admitted to ICUs around the world each year – with the majority recovering and eventually returning home. But discharge from the ICU is often not the end of the story – many patients experience significant and persistent physical, psychological or social problems. One key contributor to these issues can be the process of weaning patients off ventilator support after an extended period of chronic critical illness.

The weaning process involves various regimens of progressive reduction in mechanical support – analogous to athletic or resistance training. But, unlike athletic training, the ICU process is out of the control of patients – who may also be disorientated, confused and suffering short-term memory loss. As a result, they can be prone to distress or panic when breathing support is partially or temporarily withdrawn. As well as contributing to psychological trauma, this can lead to extended ICU stays and poorer long-term outcomes.

Now Dr Small and CDP are harnessing interactive technology in a bid to make the process more patient friendly. With funding from the National Institute for Health Research (NIHR), they are creating a ‘digital liberation from ventilation’ (DELVE) system to give patients easy-to-understand information on a screen about their breathing performance – both real time and historical – and so engage them in the weaning process. The dashboard will also enable clinicians to see at a glance a patient’s breathing performance and improve their understanding of an individual’s progress – mechanical ventilator devices currently provide no easy way of viewing historical patient data, so doctors usually piece together data from multiple sources such as vital signs monitors and clinician notes.

Loss of muscle mass whilst on mechanical ventilation is another significant challenge to patient recovery. Patients typically undergo physiotherapy sessions to rebuild body strength as soon as they are medically stable enough on the ICU. The dashboard could include a gamification element to make breathing exercises more interesting and enable patients to do them on their own – speeding up the process of building up their diaphragm muscles and relearning how to breathe for themselves.

“This novel approach has the potential to improve the patient experience – and patient outcomes – whilst preserving precious healthcare resources,” said Matt Brady, partner and head of medical therapy systems at CDP. “It’s a fantastic example of what can be achieved when human factors, design and user experience expertise are combined with electronic and software skills in a cost-effective way for the benefit of the patient and the healthcare system.”

Dr Small works in anaesthesia and pain medicine at the QEHB. Her previous role as an anaesthetic trainee in the Royal Air Force led her to undertake research and quality improvement work into the management of acute trauma-related pain. She is the chief investigator for a programme of work at the NIHR Surgical Reconstruction and Microbiology Research Centre investigating how interactive technology could benefit the experience and performance of patients during early rehabilitation in ICUs – which includes a feasibility study of the DELVE system.

“This exciting programme of work has huge potential for patients and their loved ones,” said Dr Small. “By improving understanding of the process of recovery from critical illness – and combining that with the knowledge gained from our research – we aim to enhance clinician decision making and prediction of recovery pathways. Working with the CDP development team – with its understanding of the technical aspects, as well as patient and clinician perspectives – has been crucial to bringing our ideas to life.”

The NIHR Surgical Reconstruction and Microbiology Research Centre funding the project is a partnership between the NIHR, the Ministry of Defence, University Hospitals Birmingham NHS Foundation Trust (which runs the QEHB) and the University of Birmingham. The initiative brings both military and civilian trauma surgeons and scientists together to share advanced clinical practice on the battlefield and innovation in medical research to benefit all trauma patients in the NHS at an early stage of injury.

Notes for editors
Cambridge Design Partnership is a technology and product design partner focused on helping clients grow their businesses. Some of the world’s largest companies trust CDP to develop their most important innovations. Located in both Cambridge (UK) and in Palo Alto, California (US), CDP specialises in the consumer products, healthcare, energy and industrial equipment markets. Its multidisciplinary staff have the expert knowledge to identify opportunities and tackle the challenges its clients face. For more information, visit: cambridgededev.wpenginepowered.com.

The National Institute for Health Research: improving the health and wealth of the nation through research. Established by the Department of Health and Social Care, the NIHR funds high-quality research to improve health; trains and supports health researchers; provides world-class research facilities; works with the life-sciences industry and charities to benefit all; involves patients and the public at every step. For more information, visit: www.nihr.ac.uk

The NIHR Surgical Reconstruction and Microbiology Research Centre is a national centre for trauma research, transferring innovation used in the treatment of injured military personnel to improve outcomes for all patients. It brings together the pioneering advances in surgery and infection control made by military and civilian scientists and medics working together. Launched in January 2011, the national trauma research centre will share its discoveries with the wider NHS to support delivery of excellence in a complex area of acute care. Based at the Queen Elizabeth Hospital Birmingham (QEHB), the centre harnesses expertise from the Ministry of Defence, the University of Birmingham and the QEHB and has been funded over five years with a total investment of £15 million investment. For more information, visit: www.srmrc.nihr.ac.uk

For further information, contact the marketing team:
+44 (0)1223 264428
marketing@cambridge-design.co.uk

By Carl Pullen
April 30th 2018
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Carl Pullen

Senior Consultant Mechanical Engineer

Defining a strategy for design history file remediation

When pharmaceutical companies launch a new product, often it is a combination of a new drug in an existing, proven delivery device. Because all new pharma products have full regulatory scrutiny, it is important to make sure the medical device design history file (DHF) is up to date and meets the latest standards. This is particularly critical when considering design history file remediation to ensure ongoing compliance.

DHFs can become surprisingly complex documents because they may have been through long-running development programmes incorporating many changes or they may have been acquired from other companies and contain significant legacy elements. Sometimes the passage of time has meant a DHF is no longer of the standard needed to pass FDA audit so it presents a business risk.

In any of these cases, factors such as new standards and regulations or changes in intended use, risk profiles or manufacturing processes make it important to defining an appropriate strategy for design history file remediation at the outset.

There are several aspects central to defining an effective strategy – such as building a detailed narrative, using a suitable quality management system (QMS) framework and effective planning. In fact, design history file remediation can be an intricate process that requires careful consideration of all these elements.

A design file history remediation story

Central to the concept of generating a robust DHF is the aspect that should frame the mindset of both development and remediation projects – to create a narrative, or history, of the development journey. The goal should ideally be not to create a clean set of ‘Revision A’ documents but to use and develop the tools of an efficient quality system to create a narrative of the complete development process. This is, most importantly, about creating visibility of all the technical decisions, learnings and changes along the way but can include broader aspects such as changes of ownership, changes to major standards or evolution of the supporting quality systems. Creating a narrative can be more challenging in remediation projects but employing the right philosophy can create opportunities to simplify a complex challenge.

Fit for purpose

The two key elements of the DHF generation are the specific technical content and the quality system framework used to collate and describe the format of the file.

It’s critical to define early on what success looks like for the revised DHF and understand the strategic decisions that need to be made to facilitate creating a robust file.

Remediation projects are usually not an ideal time to implement a comprehensive change to QMS processes in parallel, however appealing that may seem, so a best-practice approach leveraging existing processes is usually a sound strategy.

It is, of course, vital to check that the resulting DHF complies with the current guidance of key standards such as ISO13485 and FDA 21 CFR Part 820. In cases where a comprehensive QMS framework is not available, it is important to use other tools – such as a fully detailed quality or development plan – to describe approaches and adaptations to be employed to create a robust DHF. Therefore, proper planning during design history file remediation is essential to achieve regulatory requirements.

Planning

With these two key aspects in mind, the planning activities can then be focused on establishing the framework and resources required to move forward.

A fully detailed project plan will describe all the tasks to be delivered but is also vital to ensure any relevant experts and stakeholders are in place and available when required. The early planning of workshops and stage-gate reviews is very important to ensure smooth progress.

An effective and fully detailed quality plan with scope, objectives and a clear set of deliverables will greatly help to get alignment on the specific goals with all relevant stakeholders and help to assess the skills and resources needed.

Employing an effective stage-gate process is a great way to monitor progress and assess the status as the project progresses. Communication and stakeholder engagement are vital to progressing effectively so using stage-gate meetings to record open actions, assess risks and assign tasks gives visibility of issues and allows detailed planning.

A successful remediation project depends on many elements – but a robust strategy, expert resources and effective communication are vital aspects that will certainly reward additional investment. In summary, design history file remediation not only mitigates business risk but also ensures products remain compliant and fit for market.

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April 18th 2018
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Breathing new life into clinical outcomes

The rise of connected devices and the variety of information they can generate is set to drive an increase in patient adherence to therapies. Our trials have shown that remote and hidden sensing of actual user behaviour can uncover unexpected and significant opportunities to improve the patient experience.

So how can connected technology help in the development stages of a new product, especially in a clinical environment? A recent study – Non-adherence: a direct influence on clinical trial duration and cost – by Moe Alsumidaie highlights the significant costs of non-adherence during pharmaceutical development. The study reported a 40% increase in patient enrolment to allow for non-adherence – adding an estimated $12m to the cost of a Phase 3 study.

We are also starting to see many medical device approvals in the connected space. MobileHealth reported 51 approvals in 2017 alone – the focus being on app-based patient management of disease, especially in the cardiac and diabetes sectors. There were only two respiratory-based systems reported – namely the connected spirometer GoSpiro and a new inhaler monitoring device for AstraZeneca’s Symbicort aerosol inhaler, dubbed the SmartTouch.

These solutions are enabling remarkable new capabilities for patients – and also for payers as we move towards outcomes-based healthcare. But are there steps that can be taken earlier in medical device development that can disrupt the whole process for the benefit of everyone?

What if we took a little bit of time to insert technology into products in either the clinical stage of drug development or early device design phases to understand how patients interact with the device and dosing regime? Two of the main methods to understand what has happened in a clinical investigation is to get patients to fill in a diary during their study and, on return, count the number of doses taken from the inhaler or capsule pack. Not quite 21st century.

Maybe, in the near future, clinical plans will include more advanced technology to enable a more accurate understanding of the efficacy of a new drug in development – was that poor resultant FEV1 clinical endpoint really due to the drug or was it because the patient simply forgot to prime the device and inhaled nothing but fresh air? Being able to unpick the actual usage data, so that these distinctions can be accurately made, could potentially help all stakeholders to better understand what the patient actually did and hence clarify where the subsequent opportunity to improve patient outcome actually lies – be it drug, device or training/education. In essence, it’s about using technology to guide design and development so that the appropriate solution is selected.

Here at CDP we wanted to go further and challenge ourselves to capture some very specific usage data for inhalation, whilst avoiding the Hawthorne effect and without changing the external form factor, thereby minimising any influence on user behaviour. It is common knowledge that all inhalers have associated use errors, so we took a commercially available one that has documented use errors and inserted miniature sensors that would enable both real-time indication and post-usage remote assessment of those use errors – namely priming action, orientation of use and inhalation/exhalation profile. We enabled the data to be time stamped and communicated to an appropriate output, in this case on-screen graphical readouts.

Behind this is the need to understand the volume of specific use data that gets logged and learn how to translate and classify the events represented as peaks and troughs on a graph. At CDP we have a wealth of experience of doing this across several sectors including sports and packaging systems.

If you’re looking for a breath of fresh air in your next respiratory drug delivery development, get in touch via hello@cambridge-design.co.uk or visit us at the RDD 2018 event in Arizona, 22-26 April on exhibit table 6.

Key trends from the American College of Cardiology Conference
By Matt Brady
April 11th 2017
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Matt Brady

Partner

Key trends from the American College of Cardiology Conference

Reflections on two themes from the day;

– Usability: Continuity from marketing, through R&D, to regulatory
– Connected devices and systems: Realising the benefits

Usability: Continuity from marketing, through R&D, to regulatory

We were struck by the frequency at which we heard terms like “usability,” “workflow” and “seamless integration” during presentations on the latest cardiology suites – and by the consistency of that message across different vendors.  That’s in addition to the usual array of “smaller, faster, smarter” innovations which indirectly claim usability benefit.

We continue to be impressed by the variety we see in device companies’ approaches to usability as a function.  Since regulators took steps to clarify expectations around identification and mitigation of use risks from around 2007 (e.g. IEC 62366) there’s been a tendency for human factors / usability engineering to be addressed by regulatory departments.  We believe this approach places unnecessary constraints on achievable levels of both use risk mitigation (as required by the regulator) and especially user experience (not required by the regulator – but critical to market success)!

Happily, companies are increasingly realising that given their investment in bringing users and devices together for formative usability studies, an efficient opportunity exists to develop the user experience in parallel.  Hence we see the beginning of the rehabilitation of usability engineering as a function within R&D and new product development (NPD) groups –alongside other engineering disciplines.  Interesting variations include summative studies being run by the marketing team at one company we met, which stands to reason given the marketing function’s historical focus on user requirements.

However, rarely do companies achieve the continuity needed between upstream marketing, R&D and regulatory functions.

We strongly believe that both use risks and user experience should be tested from the earliest stages of concept development – enabled by means of prototyping at an appropriate level of fidelity for the stage of development.  In order to extend this continuity right back to upstream marketing it’s essential to objectively identify and prioritise user needs, to support development of a compelling set of user requirements before commencing concept creation.

Concepts can then be generated against user needs which are known to be both important and poorly met; and user-tested for how well they meet those needs. This is appropriate and seems obvious once articulated, especially considering the logical alternative: generating concepts in a vacuum and user-testing them without clear objectives.

Nevertheless in practice it remains a rarity to seeing this level of continuity, meaning that the competitive advantage available for getting it right should be compelling.

Connected devices and systems: Realising the benefits

With the global cardiac monitoring market projected to be worth $28 billion by 2021, it was no surprise to see numerous connected monitoring devices at ACC.  Whilst various innovations were on show, most fell into two groups: implantable cardiac monitors (ICMs) and mobile (wearable) cardiac telemetry devices (MCTs).

The prize for the successful development of this segment is surely great.  For example, up to 40% of ischemic strokes are caused by asymptomatic atrial fibrillation  and such cases are increasing.  Screening for (treatable) atrial fibrillation using low-cost devices and efficient systems promises to slash this figure, with clear benefits for patients and payer alike – but how to realise these in practice?

In hardware, we’re seeing a move away from dedicated “bedside” uplink devices (Medtronic’s Reveal LINQ), to Bluetooth smartphone connections (St Jude’s Confirm RX ICM), and perhaps towards on-board 3G/4G connectivity (National Cardiac’s upcoming Liba3 MCT).  The on-board option is not inevitable: whilst the Bluetooth solution has its challenges, the potential benefits are significant.  Challenges include regulatory (“app as medical device”) and cybersecurity (see James Baker’s column, Med Device Online).  However the potential benefits of Bluetooth versus on-board uplink may prove compelling, for example:

– device cost, weight and size;
– linking ECG data with patient observations (St Jude’s Merlin.net);
– enhanced patient engagement (and adherence) via app.

Done right, the adherence point may prove decisive.

The system side proved the more compelling conversation topic at ACC.  How should the system be developed in order to deliver the hoped-for benefits?  For example:

– Who will provide diagnoses based on these vast streams of data, and how will the health economics and reimbursement develop to support this activity?
– “The Cloud” will be a key enabler, as everyone seemingly agrees, but what functions will it provide?  Can algorithms make diagnosis more efficient – and, given the human challenges around accurately reviewing reams of data, less error-prone?  How will such algorithms be validated?
– Can the data from these devices be effectively made available to other parts of the healthcare system?  For example as an input to regular health checks, or to provide ECG history during treatment of adverse cardiovascular events?
– Can algorithms support clinical and treatment decision making by leveraging anonymised “cohort databases” of ECG data paired with treatment outcomes?

Much work remains in this space, and whilst improving device cost and usability will be important, the wider system view will be essential to achieve the prize!

1 Strokes atrial fibrillation patients rise despite improved treatments

April 5th 2017
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First principles of biomedical engineering – they’re closer than you think

It’s important to realise that beyond the realm of classical engineering principles lays the softer, squishier world of biology and medicine. By being intimately familiar with human anatomy, biomedical engineers are able to more rapidly question whether their concepts are truly viable prior to embarking on further development, using an often-neglected set of first principles – the fundamentals of human body design.

Using a scalpel, I slowly cut the failed tricuspid valve out of the heart of the cadaver. We had been told that our donor body had died of heart failure but nothing prepared me for the sensory impact of the hard, black necrotic tissue surrounding the three leaflet structure – it appropriately reflected what “dead” should look like physically. That was about half a decade ago and not a day goes by where I don’t reflect on my time spent wrist deep in a cadaver, and how it shaped how I approach my work as a biomedical engineer.

When you start designing medical devices, it’s tempting to seek out simplifying assumptions in order to get 80% of the solution in 20% of the time. We can model the circulatory system with pipes, we can model the lungs with foam, and we can model the bones with metal. Reasoning by analogy is often the first step to taking a first principles approach, utilising equations that govern the fundamental processes of our world. And there’s nothing inherently wrong with this approach until you discover that by simplifying the problem definition you’ve missed out on a wealth of potentially more appropriate and lucrative solutions as well.

Let’s take, for example, the case of my former cadaveric colleague’s heart – he had had an aortic valve replacement at one point in his life. Simplifying the complex procedure of heart valve replacement, we could think of the problem like fixing a broken piece of plumbing: restrict the flow of fluid, remove the defective valve, put the new valve in, and let the fluid flow resume hoping that everything worked the first time. And for valve replacement, that’s been more or less the gold standard since advancements made to cardiopulmonary bypass (artificial heart and lung) machines enabled the heart (blood flow) to be stopped during surgery. Using the plumbing mentality, it’s difficult to imagine how you could improve on this procedure which is why it’s important to question and occasionally reject the simplifying models we use for medical device design. Finding the optimal level of detail at which to examine the problem is critical to the success of the endeavour.

In reality, heart valve replacement has started heading towards the plumbing equivalent of replacing leaky valves from your neighbours couch by snaking tools through their plumbing, into the main pipes, back into your flat to the leaky valve and there, instead of taking the old valve out, you just put the new valve in on top of it. This procedure, known as Transcatheter Aortic Valve Replacement (TAVR), in which a new valve is implanted into the heart by navigating through an artery in your leg, is expected to worth $5.5B USD by 2020. If we remained focused solely on the heart valve in absence of the larger circulatory system and body-scale system as a whole, the ability to utilise a less-invasive approach would have been lost before the first ideation session even began.

Ultrasound Elastography is another example where conventional analogies fall short of an optimal solution. Frequently surgeons will probe or palpate tissue with their fingers to try and differentiate boundaries of different structures, like a tumour amongst healthy tissue. This physical sensation can aid with the detection of diseases in certain organs, particularly when the tumour doesn’t show on certain imaging modalities but relies on subjective tactile feedback and cannot be used in regions that can’t be palpated. Obviously then we need to improve the ability of existing imaging systems to “see” the tissue but there’s something significantly cleverer available.

Researchers realised that “seeing” a tumour depended on the type of information being made available. Traditional x-ray imaging relies on the absorption of ionizing radiation by anatomical structures and maps this absorption onto a display, whereas palpation creates a tactile sensation map in the physician’s head. So instead of thinking, “we need a more sensitive imaging system to detect the differences in radiation absorption in the tissue”, they realised that they could blast the target tissue with ultrasound waves, mimicking a palpation then measuring the resulting mechanical properties by observing the response to this “push”. What was created is a novel imaging system that provides a tactile map of tissue stiffness, enabling doctors to more clearly see the tissue they’re interested in without requiring physical access to it.

As efficiency and cost reductions pressure healthcare systems globally, the demand from next generation medical devices requires successful inventions to not only improve outcomes but reduce costs compared to the existing gold standard. By recognising that your medical device needs to be designed with respect to not only the classical mechanical and electrical first principles but the anatomical first principles as well, you can get that much closer to a safer and more effective device.

To speak to Jeremy further or to find out more about our medical device and drug delivery capabilities contact hello@cambridge-design.co.uk or phone +44 (0) 1223 264 428.