The next step in innovative medicines manufacturing

June 21st 2018

This month’s Manufacturing Medicines Industry Partnership (MMIP) conference – Propelling growth: taking the next step in innovative medicines manufacturing – took place at an exciting time for the pharma industry. Advanced therapies (ATs) – such as cell therapies in which patients are treated with living cells – have been under development for the last 20 years as we apply our ever-increasing understanding of the genome. But the field has been catalysed by the recent regulatory approval of several very promising products such as Novartis’s Kymriah and GSK’s Strimvelis.

These flagship products put the pharma industry at an inflection point and present an opportunity to move medicine from palliative care to an entirely new paradigm where cures and personalised medicine are fast becoming reality. These new therapies are, however, very complex – and manufacturing needs are significantly different from existing therapies (e.g. small molecule and traditional biotherapeutics). This complexity presents both challenges and opportunities.

Themes and challenges

Roger Connor from GSK kicked off the conference with an introduction on how moving to a new medical paradigm will not be straightforward and what this future will mean for medicines development and manufacturing – and the implications for the wider supply chain and, of course, therapy delivery.

The complexity of these therapies means collaboration at all stages of the lifecycle will be vital. This is especially relevant at the research and development (R&D) stage. Manufacturing these complex therapies is a significant challenge – Andy Evans from AstraZeneca highlighted the need for very early discussion between R&D and manufacturing to build manufacturing strategies around lead therapy candidates.

Once manufacturing processes have been proposed, then robust quality control methods will also need to be established. Cell and gene therapies have a lower R&D attrition rate due to their high specificity. But the enhanced specificity puts more emphasis on manufacturing, as small process fluctuations can have a large effect on the final product and thus therapy specificity.

Currently ATs with regulatory clearance are for rare disease conditions with very small patient populations and low manufacturing volumes. Discussion at the conference highlighted that new therapies under development will move to larger patient numbers. James Miskin from Oxford BioMedica highlighted a gene therapy under development for Parkinson’s disease as an example. It was also said that a medium to long-term challenge will be the development of strategies, tools and technologies that enable manufacture of such ATs in larger volumes.

The delicate nature of the biological materials used in ATs also presents challenges to the wider supply chain – with therapy packaging and delivery now just as important as manufacturing. Challenges here relate to the implications of handling and shipping for product quality and ensuring the integrity of cryogenic conditions to prevent degradation of the delicate biological material affecting therapy quality.

Cost is also a major consideration – commercially available ATs are currently extremely expensive, with each treatment costing hundreds of thousands of pounds. Implementing solutions to the above challenges will have to occur within a cost-sensitive framework to ensure any new therapies are as affordable as possible.

In addition, the complexity of the genome is likely to result in many different therapies, each with their own different manufacturing and lifecycle challenges. It will not be a case of developing one solution for each technical challenge – platform technologies and configurable solutions will be required to provide solutions for multiple therapies.

Innovations

Despite recent success, ATs are still relatively immature. Whilst it is clear these therapies will require new tools and technologies to reduce cost and mitigate manufacturing complexity, it is not clear to the pharma industry exactly what solutions are required – and requirements will continue to evolve as the field matures. This presents opportunities for potential solutions to be adopted early and influence how the AT field matures.

Different speakers at the conference presented on future enabling technologies. These included Mike Houghton from Siemens presenting on digital technologies and Lionel Clarke from the Synthetic Biology Leadership Council discussing synthetic biology. Digital solutions are particularly attractive as development and manufacture of ATs is an inherently data-rich activity. Collection, aggregation and analysis of data at all stages of the AT lifecycle – from R&D and manufacturing to supply chain and therapy administration – offers significant value.

Supply chain challenges were also discussed – including opportunities to implement strategies from other logistic-intensive industries. Just-in-time (JIT) supply chain approaches – as used by the automotive industry – were cited by Anette Doherty from GSK. JIT approaches are particularly relevant given the limited shelf life of biology-derived therapies and could also potentially enable exciting possibilities in decentralised production closer to the point of care.

It is clear there are significant challenges to overcome in the industrialisation of ATs and there is a risk of forcing new therapies to fit into existing solutions and infrastructure. There is, however, an opportunity to develop new tools, technologies and solutions – and implement new manufacturing strategies fit for purpose, as Dave Tudor from GSK discussed.

The inherent complexity of ATs will require pharma companies to be bold and embrace innovation – looking to adjacent industries in addition to developing new first-of-a-kind technologies. These innovations will require a holistic perspective encompassing the entire AT lifecycle, and apply to manufacturing strategies and the wider supply chain, not just R&D.

Despite the challenges, ATs have huge potential – the market for cancer immunotherapies alone is predicted to be worth more than $100bn by 2021. The players – and indeed countries – that are first to understand the challenges across R&D, manufacturing and supply will win the opportunities and become the market leaders of tomorrow.

Shining a light on photomedicine

April 24th 2018

Leigh Shelford

Senior Consultant Physicist

Light has become a powerful medical tool. Continuing advances in the understanding of biological interactions with light, and newly developing light technologies, have given rise to a wide range of light-based therapies. As a physicist, I use light to study and modify the properties of materials down to the nanoscale. My strong interest in biophysics and medical technologies has now inspired me to explore the world of photomedicine. There are many varied interactions between biological processes and light, hugely dependent on wavelength and intensity. Medical treatments and choice of light sources are dictated by the desired treatment outcome.

Photothermal

A beam of light transfers energy. The more photons there are, the higher the light intensity and the more energy is transferred. The invention of the laser in 1960 introduced a light source capable of supplying high-intensity light with surgical precision. A laser can be used in place of a scalpel as a surgical instrument. The intense light tool can seal blood vessels and nerves as it makes an incision – reducing bleeding, pain and inflammation. High-intensity laser light is also used to destroy and remove cells and tissues through a process called photoablation. The absorption of laser light can raise the temperature of a cell so high and so rapidly that it is vaporised while leaving other tissue nearby unharmed. Laser ablation can be used to treat superficial and early stage cancers including some forms of skin cancer.

Large tumours which are causing blockages – e.g. in the throat – can be partially removed using an endoscope combined with a laser. Light can even be applied inside tissues and tumours in places which are hard to reach with traditional surgical techniques – for example, brain tumours. Live magnetic resonance imaging (MRI) can be used to guide a catheter containing a fibre-optic cable to a tumour. Once correctly situated, laser emission is engaged to heat the tumour, causing cell death by hyperthermia. An even greater degree of treatment localisation is becoming possible using nanoparticles, guided to cancerous cells by conjugation with specific antibodies. Designed to interact strongly with light for efficient conversion of light energy into heat, the nanoparticles allow for treatment with lower intensity light and with increased precision.

Photochemistry

Photochemical processes are those which are triggered by the absorption of light. Perhaps the most famous photochemical process is photosynthesis, by which all plants generate chemical energy from sunlight. Human skin also demonstrates some photochemical interactions on the absorption of short-wavelength ultraviolet (UV) light – some negative and some positive. Famously, UV absorption in the skin enables the generation of vitamin D which is important for maintaining the health of bone, teeth and muscles. Sunburn is caused by direct photochemical damage to DNA in skin cells by UVB (280-315 nm) light absorption. UVA (315-400 nm) absorption can also be harmful indirectly by increasing the generation reactive oxygen species. Both damage mechanisms can increase the risk of developing skin cancer. Balancing the positive and negative impacts of UV exposure can be key to designing an effective treatment. UV light is often used to treat skin conditions including psoriasis by slowing the production of skin cells and suppressing the immune system. UV exposure is also used for repigmentation of skin in conditions which cause skin cells to lose their natural colour. UV illumination may also be used to stimulate wound healing and as an antibacterial agent – the latter is particularly relevant at time when resistance to antibiotic drugs is increasing.

Cancer therapy is also a large area in photochemical photomedicine. In a treatment called photodynamic therapy (PDT), photosensitive cancer drugs can be administered which are activated only when exposed to light. Limiting light exposure to the target treatment regions reduces side effects in healthy tissue. In late 2016, a trial of a prostate cancer treatment using a drug which is only activated when exposed to laser light was reported with very encouraging improvements in cure rates compared with traditional treatments. PDT may also be used to treat blood cancers by exposing blood treated with a photosensitising agent to light outside of the body.

Photoperiodism

Controlling exposure to light, particularly blue light, can be used to treat some sleep disorders and circadian rhythm (‘body clock’) disruption. Eyes contain photoreceptors which communicate time-of-day information to the brain’s central timekeeping zone. Increased artificial blue light exposure from device screens, for example, is suspected of causing disruption, and most laptops and smartphones now feature a ‘blue light’ mode to reduce blue light intensity according to the time of day. Products to increase ‘natural’ light exposure are also available – which claim to improve sleep patterns and treat seasonal affective disorder.

Conclusion

Developments in our understanding of the interaction of the human body with light, and advances in light sources and light guiding technologies, have generated the enormous field of photomedicine. Surgical procedures and cancer therapies look set to continue to make use of laser light to improve precision and to extend treatments beyond traditional techniques. Advances in technology and continued innovation should lower the barriers to use, including the requirement of specialist training, access to equipment and cost. The market for natural light exposure management may mature as evidence of links between biological processes and artificial light exposure increases.

For light in medicine, the future is bright.

Breathing new life into clinical outcomes

April 18th 2018

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.

New phase of growth in drug delivery

November 7th 2017

Technology and product design firm Cambridge Design Partnership (CDP) has announced the appointment of drug delivery industry veteran Bastiaan de Leeuw as it embarks on a new phase of growth in the sector. As head of drug delivery business development, he will be driving CDP’s expansion into new markets around the world.

Bastiaan will be working alongside CDP partner and head of drug delivery Uri Baruch, who has overseen huge growth in the sector over the past five years. Uri’s drug delivery team has delivered a variety of projects – ranging from an award-winning needle safety device and an emergency auto-injector to pen injector packaging designs for drug delivery devices and inhalation products – including successful regulatory submissions in both the US and Europe.

“I am delighted to welcome Bastiaan to our growing world-class team,” said Uri. “He has a wealth of knowledge and experience of the industry that will be invaluable as we continue our record-breaking growth.”

In his long and diverse career, Bastiaan has held a string of senior posts in organisations such as Cambridge device design and development company Oval Medical Technologies and medical device development and manufacturing firm Bespak. He has particular expertise in combination products – but has also spent five years working in diagnostics as CEO of molecular diagnostic research and service company NovioGendix, now part of multinational healthcare company MDxHealth. He has a degree in biopharmaceutical sciences from Leiden University in the Netherlands.

“I am excited to be joining the CDP team at such an interesting time, as the drug delivery group continues its phenomenal growth,” said Bastiaan. “I am looking forward to bringing together the varied strands of my healthcare career to help clients around the world translate opportunities and challenges into real-life drug delivery devices for the benefit of patients.”

Unique dialog service to unlock patient-friendly drug delivery devices

November 6th 2017

6 November 2017 – A new approach to drug delivery device development is set to transform the experience of patients who face the challenge of regularly injecting themselves as part of their treatment for chronic diseases such as rheumatoid arthritis (RA). Technology and product design firm Cambridge Design Partnership (CDP) has applied its unique user insight service diialog™ to an auto-injector to unlock the secrets of creating a truly patient-friendly drug delivery device.

The diialog service throws a spotlight on two measures that suggest how easy or difficult a patient finds using their auto-injector. The first of these is ‘dwell time’ – how long a patient hesitates before actually injecting themselves once they’ve prepared the device. The second measure is ‘cap removal force’, which in the worst-case scenario can lead to a patient accidentally stabbing themselves with the needle during their preparations for injection.

“Our aim is to put the patient at the centre of drug delivery device development,” said Tom Lawrie-Fussey, healthcare digital strategist at CDP. “But to do that you need detailed, reliable information about how a patient uses their auto-injector in the privacy of their own home. A patient might tell their doctor they never miss a dose of their medication – but in reality they might skip some of their injections because they are too awkward to administer.

“Drug delivery device developers are required to meet regulatory human factors requirements. But accurate information about usability and the whole patient experience is also crucial if a great idea is to go beyond those requirements and translate into a successful product that is patient friendly and delivers improved health outcomes. Yet trial users of a new device often tell you what they think you want to hear. With the help of diialog, you can discover what really happens – whether the device is used correctly and the drug is stored at the correct temperature, for example, or whether an elderly patient struggles to remove the cap.”

The miniature sensing technology used by diialog is small enough to fit inside an existing clinical trial injector and can monitor a range of key factors such as orientation, preparation sequence and injection technique. Another crucial element is the sophisticated algorithms that analyse the data and translate it into an accurate picture of how a device is being used in the real world. The technology is even programmed to ignore ‘false positives’, such as movements due to patients carrying their device around in their bag.

“With diialog we can translate a stream of data into valuable information for our clients to enable them to make more informed investment decisions,” said Tom. “It complements their existing research techniques and can help minimise the risks, especially for pharma companies facing the challenge of migrating to device development. As well as auto-injectors, diialog could be used in the development of any other drug delivery devices as well as over-the-counter diagnostic products such as pregnancy tests – and it has already been successfully deployed in the cosmetics and sports industries.

“Another benefit of diialog is that it can provide a practical stepping stone for companies that are new to connected device development. Our clients are able to quickly assess the return on investment for their own specific product requirements – and hence de-risk their connected device development pathway. A diialog user trial enables them to select the sensors, on-board processing and data connectivity features that generate the most value – and avoid investing in technology options that ultimately won’t give them sufficient patient adoption.”

The CDP team will be demonstrating its diialog technology – and showcasing its novel Klarus drug delivery system – at PDA’s Universe of Pre-filled Syringes and Injection Devices event, 7-8 November, at the Austria Center Vienna, stand X92. CDP partner Jez Clements will also be presenting the diialog story and its latest results alongside Markus Bauss, managing director of SHL Connect, during the pre-conference workshop on Connected Health & Drug Delivery on 6 November. They will be exploring how the technology can enable even deeper understanding of human factors in design.

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: www.cambridge-design.co.uk

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

DELIVERING PEACE OF MIND A novel approach to drug delivery from CDP is set to transform the patient experience

October 18th 2017

18 October 2017 – Help is on the horizon for patients juggling complicated treatment regimens for chronic diseases such as rheumatoid arthritis (RA). A novel approach to drug delivery from technology and product design firm Cambridge Design Partnership (CDP) is paving the way for a new generation of treatment that is easier for patients and cost effective for healthcare providers.

Klarus is set to transform the world of auto-injectors – doing away with the need for RA patients to worry about storing their drugs in the fridge, warming them up to the correct temperature for injection, preparing their auto-injector for use and disposing of the device safely. Klarus does everything for them – they simply have to pick up the reusable auto-injector from its base station when prompted to do so, inject themselves and then return the device to its cradle.

“It’s the Nespresso of auto-injectors,” said Uri Baruch, head of drug delivery at CDP. “Klarus will store drugs at the correct temperature and warm them up when required – minimising the pain of injecting cold medication. It will then prepare the auto-injector with the correct needle and medication cartridge, and prompt the patient to take their drug.

“After injection, Klarus will collect the needle and cartridge ready for safe disposal – alerting the patient when supplies are running low, and reordering if required. The base station technology could be adapted to cope with multiple users and different medications – either in the home or at a small clinic, for example. It uses fingerprint recognition technology to identify the correct user each time and a childproof lock to prevent accidental use.”

As well as RA, Klarus could be used to treat diseases such as multiple sclerosis or to administer vaccines. It could also enable some cancer patients to be treated at home using drugs that are currently only allowed to be given in hospital. And it opens the door to the emerging world of companion diagnostics and truly personalised medication, where treatment is tailored to each individual patient using genetic information.

“All too often, patients with a chronic disease face the additional burden of struggling with a complex treatment regimen at home,” said Uri. “Learning how to use a new drug delivery device and remembering multiple treatment steps can be challenging – particularly for the elderly or those with dexterity issues. That’s one of the reasons why adherence rates are often low – many patients just give up or fail to take their medication correctly.

“Our Klarus system alleviates that burden for the patient and helps ensure they get the full benefit from their treatment. It automates many of the use steps commonly missed or not carried out by patients – such as checking the use-by date or remembering to inject when following an irregular therapy schedule. We’ve used state-of-the-art technology and applied our user experience and human factors expertise – together with our knowledge of medical device regulation and our skills in electronics, mechanical engineering, software and connectivity – to create a radically new approach to drug delivery.”

The Klarus system could be offered to patients as a subscription-based service. It is expected to cost healthcare providers less than $1,000 per system, and the cartridges would be around $2 each. So Klarus would pay for itself in the space of just one year if, for example, a patient was having weekly injections for RA at a typical cost of $10 per single-use auto-injector. As well as helping to improve patient outcomes, it would also be more environmentally friendly – saving on packaging and involving the disposal of only a small cartridge each time, rather than an entire auto-injector.

Uri will be talking about the Klarus system in track B of the drug delivery technology presentations on 19 October at the Partnerships in Drug Delivery event in Boston, US. The CDP team will also be showcasing Klarus at PDA’s Universe of Pre-filled Syringes and Injection Devices event, 7-8 November, at the Austria Center Vienna, stand X92.

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: www.cambridge-design.co.uk

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

Point of care diagnostics: navigating systems architectures

August 1st 2017

Diagnostic testing is rapidly moving out of the lab and into the hands of untrained users. But developing the system architecture for a high-performance test that is also easy to use is a complex challenge.

A great example of advancements in point-of-care (PoC) testing is the pregnancy test. In the 1970s, Wampole’s 10-step test took two hours by a trained lab technician. Today it is carried out in minutes in the privacy of your own home using an off-the-shelf disposable device.

PoC diagnostic tests should be quick and simple – and ideally not rely on the user’s skill to generate a reliable result. But, unlike pregnancy tests, molecular-based tests currently need more complex steps. For example, sample preparation may be needed to lyse cells, remove inhibitors or increase titre and this can be extremely challenging to implement at the point of care at acceptable cost and device complexity.

Wampole’s test could be categorised as a ‘chemistry set’ where the skill of the operator is critical to generate an accurate result – there might be several critical timing steps, mixing and resuspension steps performed using a manual pipette, metering and sub-sampling precise volumes followed by vortexing and ‘gentle’ heating before looking for a subtle colour change. Lots to go wrong and not at all user friendly.

The Clinical Laboratory Improvement Amendment (CLIA) from the Food and Drug Administration (FDA) regulates laboratory testing for human diagnostics in the US and has categorised the complexity of a diagnostic test as either: waived, moderate complexity or high complexity. The level of complexity is determined by adding up the scores from seven criteria. A CLIA waived test means it is ‘simple to use, and there is little chance the test will provide wrong information or cause harm if it is done incorrectly’.

The simplest test for the user is to ‘add sample and walk away’ and the device carries out the necessary assay functions. This convenience typically generates significant market share over more labour-intensive competitor devices but there are trade-offs with device complexity and development risk. For complicated assays, ‘reader’ and ‘consumable’ system architectures are frequently used. However, consumables tend to be bulky and expensive, and the readers even more so.

Below I outline some high-level considerations when developing system architectures for a PoC diagnostic device, and how to navigate between the ‘chemistry set’ and ‘fully integrated product’.

Assay robustness

It all starts with the foundation of any diagnostic test – the assay. A correctly implemented assay is fundamental to providing high-performance, reliable and repeatable results in the intended use environment.

Identifying sensitive parts of the assay that require careful controls, and functions that are more tolerant to variability, provides the first insights into the required architecture. For example, flow-rate variations may have a significant impact on test performance, which necessitates the use of an automated pump – or the detection method may require special optics. An untrained operator may not be capable of performing these steps with the appropriate control, so reader hardware may be needed.

Ideally the assay is well characterised in the lab before the system architecture is developed – but this is seldom the case. Another issue is that lab processes can be difficult or costly to implement in a ‘highly useable’, low-cost PoC test. So designing a system architecture that is capable of accommodating the necessary functions based on preliminary lab results is a tricky challenge. Capturing risks and uncertainties, and carrying out feasibility testing of the high-risk aspects during early stages of the project, will better inform the system architecture and can avoid unpleasant discoveries later on.

User burden

Although CLIA waive is highly desirable, many PoC devices are categorised as ‘moderately complex’ – it may be a good option for the user to carry out certain functions if they are tolerant to sources of variability (i.e. by understanding assay robustness and assessing operation against CLIA scoring criteria).

User involvement can significantly reduce device complexity but operators are busy people and can easily get distracted in a PoC setting. Failure alerts and fail-safe features help reduce the risk of generating an erroneous result. Mechanical guides and ‘poka yoke’ mistake-proofing features, as well as electronic timeouts and sensing (e.g. QR code read by the reader), can notify the operator that an incorrect or expired component is used. In the event of inactivity, the reader may invalidate the test altogether.

Device complexity

Every project is constrained by time and money and, if the development team has done its job properly, the device will be just complex enough to satisfy user convenience and assay needs. Of course, it’s not as simple as that – other crucial factors such as cost of goods and ‘platform’ requirements also need consideration.

Estimating device cost early on – and continuously updating the estimates – informs the viability of the architecture and ultimate success of the product. If cost estimates are high, it may be necessary to re-examine the assay and explore alternative, lower-cost technical solutions or implement more of a ‘chemistry set’ approach (but understand the impact to the user and viability of the product). Directing functionality (and cost) away from the consumable and onto the reader is generally a good option as non-disposable parts are less cost sensitive.

When designing system architectures intended to be a ‘platform’, it is important to consider the requirements of future assays and, if necessary, build in redundant capability to minimise the effort to accommodate new tests. This is easier said than done under tight timescales. But modular system architectures and components that allow modification – for example, volume expansion or increased flow rate – allow potential flexibility.

Navigating the trade-offs to develop a system architecture that addresses all the considerations is a difficult challenge – and one that is often rushed as businesses are keen to meet their next milestone.

At Cambridge Design Partnership we use a holistic development approach involving close collaboration between our in-house human factors, mechanical, electronic, software and manufacturing engineers, as well as assay scientists. In the early phases of a project we identify the technical and market uncertainties – and thoroughly explore different architectures whilst characterising the assay and understanding user involvement, regulatory issues, manufacturing processes and ultimate device cost. This manages project risk and sets the course for a high-performance system delivered quickly to market. Get in touch for help with your next diagnostic challenge.

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For more on navigating the trade-offs in point-of-care diagnostic system development, contact Cambridge Design Partnership.

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RDD 2017 – Connectivity and medication adherence

May 18th 2017

Last month I had the opportunity to spend the week in the South of France. But instead of catching up on some much needed Vitamin D, I joined other industry experts in the world of Respiratory Drug Delivery (RDD) at the 2017 conference in Nice.

One of the main themes running throughout this year’s event, and generally within the drug/device combination products industry, was connectivity. Connectivity means many things to many people, however, in the world of RDD right now the core issue is ‘adherence’. But how do we define ‘adherence’? There were several perspectives presented including the regulators, payers, pharma companies, healthcare professionals and the patients themselves.

Dr Federico Lavorini of the Careggi University Hospital, Florence, references a paper published by the WHO, which showed that adherence in long term therapies was an issue in 2004 and estimating that the ‘cost’ of non-adherence may run into billions of dollars of wasted medication and hospital admissions. But if I look at the design of devices available on the market I don’t see much change over the last decade. Whilst two generic versions of GSK’s Advair Diskus have recently received Complete Response Letters from the FDA, Dr Lavorini’s presentation highlighted that the Diskus DPI device has several significant observed use errors, including dose dumping. Although pMDIs have been around for over 50 years and are being repurposed in the administration of biologics, pMDIs also have well-documented use errors. Studies have shown that the observed natural operation of a pMDI is to inhale sharply due to the aerosol generated being ballistic – even though the instructions for use state to do so slowly. This was brilliantly depicted by Dr Lavorini in the form of ‘Le Chiffre’ from the ‘James Bond-Casino Royale’ film having really poor inhaler technique. How unusual for Hollywood to get it wrong.

So can connectivity help us? There were a number of new designs and products on show that try in one form or another. From apps that can remind us when to take our medication, to integrated device sensors that give the patient feedback on correct use. It raises some questions – will this give us adequate insight into how patients/users truly interact with their devices? Will this information be beneficial in providing evidence of the value proposition for the product? And, will the healthcare professional have to log onto yet another website? An idea that caused a small uproar at the conference.

As I see it, the status of this movement towards connectivity and adherence is one of lots of good ideas and energy, however, there is a need to collectively figure out how to bring it all together for the good of all involved. Improved patient treatment, reduced burden on healthcare providers and true value based healthcare.

At CDP we like to think that the way forward is to start with understanding stakeholder behaviour to inform design decisions, leading to quantified use interaction during the clinical investigation and appropriately selected product connectivity in the commercial space.

To read more on just one solution we are working on please click here to read about our new user insight service that helps gain a deeper understanding of consumer behaviour.

And as for the Vitamin D, I will be back in France this August with the family to catch-up on it!

Key trends from the American College of Cardiology Conference

April 11th 2017

Matt Brady

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

Meet Caroline: Drug delivery devices expert

April 6th 2017

Meet the team at Cambridge Design Partnership – a brief profile of the experts, engineers and interesting people that work here. This month we’re talking to Caroline Zakrzewski, a drug delivery devices expert.

1. Why did you join Cambridge Design Partnership?
I’ve been very lucky in my career to have worked on drug delivery devices from concept stage right up to commercialisation. Recently my roles have been focused on the later stages of manufacturing scale up and preparation for commercial launch which I’ve enjoyed, but I missed the excitement of the research and front end innovation stages. CDP have a strong front end innovation capability, unlike many other consultancies, and my knowledge and big pharma experience means I can really contribute to those projects.

2. What background do you come from and how do you apply this knowledge to your current role?
I gained my MChem degree from Durham University after which I started out in analytical chemistry in support of drug delivery devices. I quickly got distracted by the mechanical elements of the devices and how to make them perform more effectively and reliably. This lead naturally into quality and the way devices are designed and manufactured, whether it be specifying and testing devices to meet certain ISO standards or working to GMP (Good Manufacturing Practice). Along the way I gained my MSc degree in Pharmaceutical Manufacturing from the University of Manchester. It seemed a natural progression to bring this range of experience to the quality group at CDP.

3. What interesting projects are you working on at the moment?
The range of projects that I’m involved with is amazing, drawing on a wide range of my knowledge and experience. CDP take client confidentiality very seriously so I can’t say much but I am enjoying being involved in the quality initiative creating CDP’s new ISO 13485 approved small scale manufacturing capability.

4. What do you see as the hot trends in your area at the moment and what is coming up in the future?
One of the hot trends in drug delivery devices that is generating a lot of discussion is connectivity. What exactly this means is also open to interpretation; is it about a better user interface to encourage patient compliance, will it involve collecting and trending patient data, or is there a disruptive technology that we’re not aware of yet. At CDP we believe the degree of connectivity needs to have a real benefit for the patient as well as the manufacturer and that there may need to be degrees of connectivity within a product range to suit different demographics.

5. Do you have any hobbies outside work?
I love to be active outside work and when I’m not pottering around on my allotment or in my garden I can often be found running around Cambridge, occasionally getting a medal in the process. I only started running a couple of years ago, primarily to keep up with my son, and am gradually improving – as with lots of things it takes practice and patience. Running’s given me so much more than just fitness and I now volunteer as one of the Run Directors at Cambridge junior parkrun. Watching the children get so much pleasure from running and such a sense of achievement when they complete the 2km course always brings a smile to my face on a Sunday morning.

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