Tag: Diagnostics

Six steps to build successful biodefence strategies

January 30th 2019

Pari Datta 

Biosimilars are taking on the multi-billion-dollar blockbuster drugs of today, with some sources suggesting that the market will be worth greater than $20 billion per annum within the next couple of years. The growth is being driven by factors such as healthcare systems looking to reduce costs and the growing prevalence of chronic diseases like diabetes and cancer.

Oncology and auto-immune disease therapeutic areas, where there are many significant molecules are a focus for biosimilars – with many of the hero drugs going off-patent. Last year, erlotinib (Erbitux) went off-patent. It is being followed by trastuzumab (Herceptin) and bevacizumab (Avastin ) this year. And by 2025, ipilimumab (Yervoy) and densoumab (Xgeva) will join them. Defence strategies against biosimilars have included formulation changes which enable a change in mode of administration, from infusion to subcutaneous injection. Others have included improved molecules in the same drug class or even exploiting a completely new drug class!

Herceptin is a good example as Roche reformulated it for subcutaneous use in 2014. The result was extended patent protection and a commercially-successful defence against the chasing pack of biosimilars. Other strategic moves by Roche have included the launch of Kadcyla, an antibody-drug conjugate which delivers a chemotherapy using the HER2-receptor targeting mechanism of Herceptin.

These successful strategies all share one thing: they are based on innovations that answer user needs through technology. At Cambridge Design Partnership, we work on the ethos that innovation arises by answering user needs through the right technology – no matter which market, application or industry. This is particularly effective in those difficult situations where a market is stagnant or declining, when a deeper understanding of user needs becomes essential.

As an example, in the smartphone market sales are declining. Users need a smartphone which is large when being used, but small when being stored and transported, so foldable smartphones may arrest this decline. Novel screen technology is being developed to answer this “unmet need” in the market: the iPhone that becomes an iPad when you are using it for watching movies. In a similar way, the switch from intravenous infusions to subcutaneous injections really answered user needs, from both the patient and healthcare perspectives, by removing the time required for a patient in a hospital to receive an intravenous infusion.

At CDP we use our in-house user and technology mapping techniques to discover and build the connections that lead to such novel and inventive solutions. There are six basic steps to making these connections:

1. Plot the overall care pathway around the drug.  For Herceptin, there may be opportunities to innovate at other parts of the care pathway than the administering drug, such as the initial companion diagnostic tests or even managing potential complications after treatment.

2. Map the user steps within interesting parts of the pathway. The initial problem of how to innovate around Herceptin is broad and overwhelming! By breaking it into its parts, we can identify simpler problems to solve and target those in which we have a greater chance of success. One approach is to break down the process of administering Herceptin into each single step executed by every person from its manufacture to delivery. This can be achieved through interviewing users, following national guidelines, reading blogs watching videos – with the information being analysed and interpreted in a systematic manner by a skilled interviewer/ analyst. Those steps in which improvements in time, costs, performance and experience can be made should be highlighted, eg. the injection of the drug slowly over 2 to 5 minutes.

3. Identifying the issues and their causes. For each of these steps, there are a number of issues which need to be solved in order to make these improvements. If we can identify the causes of these issues, we can work out how to solve them. For instance, a key issue in injecting Herceptin over 2 to 5 minutes is that it is difficult to keep the injection stable over 5 minutes as caused by the user’s hands beginning to shake. Another issue is that the injection device has to be held in place for up to 5 minutes, caused by the subcutaneous space under the skin only having a finite volume to receive the drug.

4. Formulate simple strategies to counteract these causes. Now that we know the issues and their causes, we can devise simple strategies to overcome them. So the user’s hands are shaking during delivery – can we remove the need to use hands during delivery? The subcellular space is too small – our strategy is to make it bigger.

5. Discover the solutions through the strategies. By expressing the strategy in simple language, the problem can be accessed by people from different background and assumptions are broken. Can we really remove hands from the process of administration? Can we really expand the sub-cellular space? Experts from many domains will come up with solutions through the strategies which align with their knowledge. Solutions which will enable improvements in injection range from large volume on-body injectors to enzymes which can break down the barriers in the sub-cellular space to increase its actual size!

6. Complete the map using multidisciplinary experts and other sources. It is important now to complete the map. Every improvable user step must be mapped, identifying the underlying issues and causes to formulate simple strategies to counteract them. This will give confidence that all potential areas have been explored, and the best possible solutions are being taken forward. Often repeated issues, causes and strategies occurring across the map can lead to the highest-impact innovations being identified.

These structured mapping techniques enable creative solutions; they are comprehensive in their approach to identifying the right defence strategies. They are competitive by helping to find technology spaces in the market and getting there before the competition. And most of all, they are user-centred, more likely to lead to market success by deeply interpreting stakeholder needs. They lead to innovative markets, technologies, propositions and partnerships from which powerful all-encompassing biosimilar defence strategies can be built.

You can hear me speak more on this topic at Pharmapack, taking place on 6 & 7 February in Paris. I’ll be talking in session 4: New in Biologicals and Biosimilar Drug Delivery Devices, 7 February at 11am. Cambridge Design Partnership will also be exhibiting on stand C78 where you can meet our drug delivery and innovation experts.

Personalised medicine brings a healthcare revolution - CDP||

Drugs that work – personalised medicine brings a healthcare revolution

October 23rd 2017
Dan Haworth

Dan Haworth 

Head of Diagnostics

It took 13 years and £2 billion to sequence the human genome back in 2003. Fast forward 15 years to today and next-generation sequencing (NGS) can do it for less than $1,000 in a matter of days. High-throughput sequencing technologies, computational power and data-mining techniques have opened up a whole new era in medical treatment – and our approach to product development.

Genetic differences in DNA allow scientists to determine how a patient will respond to certain drugs, enabling doctors to target their treatment. For example, the Sanger Institute recently discovered that the aggressive blood cancer acute myeloid leukaemia could be classified as 11 distinct disease groups, based on specific constellations of genetic mutations. This explains why some patients will be cured and others will not if they receive exactly the same treatment.

This ‘personalised’ approach promises to improve patient outcomes as the right treatment can be given from the start – time is not wasted by finding what works by trial and error – and unpleasant side effects can be minimised. Treatment is more efficient – and less money is wasted on ineffective drugs.

Diagram-01

New targeted approaches based on genetic information are gaining particular attention from pharma companies, as they can dramatically reduce drug development costs and timescales. Whereas traditional drug discovery often leads to high failure rates in phase 2 or 3 trials, targeted treatment allows smaller trials and shorter regulatory review times because the drugs are safer and more effective.

Although the market size is smaller, lower side effects mean an increased price can be charged for the drug. An example of this is the Food and Drug Administration’s (FDA’s) approval in 2012 of a new cystic fibrosis (CF) therapy for patients with a rare genetic mutation (G551D mutation). This particular gene is responsible for only 4% of CF cases in the US – around 1,200 people.

The UK government has also recognised the value of the personalised treatment approach. The NHS is undertaking the ‘100,000 Genomes Project’ – 100,000 whole human genomes from 70,000 patients are being sequenced to identify potentially new diagnostics and drive the development of new drugs.

But the race is on. Genomics and biotechnology company 23andMe – which originally provided ancestry information from a saliva sample sent through the post (direct-to-consumer genetic testing) for £125 – has recently been approved by the FDA to provide risk information for 10 genetic diseases, such as Parkinson’s disease and late-onset Alzheimer’s disease. It is estimated that the company has accumulated valuable genetic information about more than two million people.

From this vast library of genomic information becoming available, new products will emerge that target the underlying cause specific to an individual patient. This will likely involve at least two medical products – a diagnostic test and the therapeutic product itself, working together as a so-called companion diagnostic (a diagnostic that is essential for the safe and effective use of a corresponding drug).

Pharma and device companies will need to collaborate more closely to ‘co-develop’ these products to ensure the drug is safe and effective, and the performance of the diagnostic is acceptable. And, since the barriers to drug development are significantly reduced with targeted treatment, smaller innovative companies will get involved. With its access to hugely valuable genomic data, 23andMe is one such company – which is presumably why it has just raised $250 million from private investors.

I predict that NGS and data analytics will be the powerful research tools that provide the understanding. But although NGS is starting to move out of the research lab and into the clinical environment, the data it provides is unnecessarily detailed for routine testing. It will be the lower-cost, more accessible diagnostic devices that will be used to test specific genetic sequences – leading to a proliferation of companion diagnostics.

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We are just scratching the surface of personalised medicine, which is why Cambridge Design Partnership is working with both drug delivery and diagnostics clients to help them navigate this rapidly developing market. If you’d like to know more, get in touch.

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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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New connected wearable device helps medics save lives in disasters and on the battlefield

August 6th 2015

Innovative technology and design consultancy Cambridge Design Partnership today announces that it has developed the world’s first wearable device designed to measure and monitor the vital signs of multiple trauma patients for emergency response in disasters and battlefield situations.

The First Response Monitor is designed to help medics monitor both heart rate and respiratory rate. Respiratory rate is often neglected by automated monitoring systems and has been described as the ‘forgotten bio-sign’, as many existing wearable monitors focus on heart rate alone and those that do measure respiratory rate have low accuracy or are difficult to use in an emergency situation. However, the benefits of accurately monitoring respiratory rate are clear, and when combined with other parameters – such as heart rate and body temperature – can indicate life-threatening conditions such as sepsis.

When designing the new compact device, Cambridge Design Partnership interviewed a range of army medics about their needs and challenges in multiple casualty emergency situations. An unmet need was identified for a low-cost device to bridge the gap between manual methods of vital signs measurement – which can be laborious and challenging amidst the noise and stress of a disaster or on the front line – and more expensive patient monitoring systems.

The lightweight, robust and low-cost wearable biometric device not only monitors patients but collects and transmits data in real-time, enabling the medic to care for a greater number of casualties, providing more effective casualty triage to deliver improved patient outcomes.

The small device clips onto a patient’s nose and monitors breathing rate and heart rate, giving ‘at a glance’ indication of both parameters, and this data is added to a trends graph showing how these measurements have changed over time. This enables the medic to focus their efforts on providing care rather than taking measurements but also enables the care giver to understand how the patient’s condition has changed over time. The data can then transmitted using Bluetooth low energy to a smartphone app or tablet, enabling other data analyses such as multiple patient triage or situational awareness across the group.

Although the device has been primarily designed with first response medics in mass casualty incidents in mind, it has applications in many other fields – such as civilian medicine where additional monitoring of conditions has demonstrable benefit in patient outcomes, wellness monitoring and within sports for training and performance monitoring. The technology can also be developed to provide a low-cost solution for low resource healthcare settings.

Speaking about the new development James Baker, Partner, Cambridge Design Partnership said: “At Cambridge Design Partnership we’re always looking for ways to find a solution to a clear, unmet need. With the First Response Monitor we’ve combined our expertise in wearable connected devices with our extensive medical experience to develop a technology for effectively measuring breathing and heart rate. The monitor can help save lives in a variety of environments and we’re really keen to speak to partners about developing the potential applications further.”