Phillips-Medisize highlights the challenges and opportunities in drug delivery connectivity from incorporating modern technologies with patient requirements.
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As drug delivery devices such as inhalers have become smaller and more portable over past decades, they have simultaneously become more complex and smarter in their functions most recently, featuring the ability to provide and communicate information through appropriate modern connectivity methods.
According to Bill Welch, chief technical officer, Phillips-Medisize Corporation, drug delivery device producers need to respond to this trend by a ‘systems engineering’ approach. This aims at reducing financial and other risks in efficient device development meeting more advanced technical requirements, as well as ensuring required devices reach the market within agreed schedules. These risks go right through the value chain, from the biopharmaceutical customer, to the developer and producer of drug delivery devices through to users, patients and health system payers.
The systems engineering approach, as applied by Phillips-Medisize, requires the company to pay attention to each individual component contained within drug delivery systems, as well as to the components, sub-systems and overall system. Welch says this approach is more robust than a conventional linear product development route in that it requires some engineers dedicated to systems and others to sub-systems development, as ‘this is what makes the whole system work together’.
System engineering needs to be performed on components, sub-systems and overall systems at an early ‘proof-of-concept’ stage. This involves on one hand, higher up-front early development stage costs than with linear product development, on the other hand it saves other expenses later on (eg., if a need arises to trace back the cause for a device not properly functioning at a later stage in development or marketing).
Up-front development costs mentioned by Welch can be minimised by integrating design for manufacture (DFM) and design for assembly (DFA), as ‘80% of product cost and quality is often determined during the first 20% of the product development timeline’.
Morten Nielsen, president of the company’s Medicom Innovation Partner subsidiary, said: “If DFM and DFA are abruptly introduced at the end of the design phase, manufacturing strategy is not aligned with the device strategy, likely introducing late-stage changes that threaten stakeholder requirements or programme feasibility.”
Smart connectivity solutions
While drug delivery device development has tended to be more involved with mechanical functions, incorporating today’s compact electronic technologies into devices requires additional attention. Not only is it important to note how electronic data can be collected by the device, but also how the collected data can best be used to benefit patients, carers, nurses, doctors, payers, insurance companies and so on.
So, there is development emphasis on how sensors can be embedded in drug delivery devices, to communicate by wireless or Bluetooth technology to a smartphone or tablet app, rather than having to plug the device into some other equipment or storage device.
Once data has been captured it can be presented to all those with a justification in receiving and analysing data to optimise treatment solutions. This can include treatment correction communicated back to the patient via a smart device app, potentially reducing exacerbations or the need for hospital treatment. It is the patient who does the monitoring and applies treatment correction.
This an important factor with pulmonary diseases such as asthma, where patients can self-administer today with established dry powder inhalers (DPIs) and metered dose inhalers (MHIs), as well as more recent soft mist inhalers (SMIs).
It also means more attention has to be paid to patients’ data security and privacy rights as there will be an increasing amount of it to be handled and protected. For example, a vast increase in the production of large-molecule biologics drugs is expected to increase the market value for self-administration of such drugs, which will overtake the value of the self-administered insulin market — the largest and fastest growing self-administration area so far.
However, before drug delivery device producers start looking at connectivity requirements to provide effective outcome-based healthcare in this new market, they need to have solved how drug delivery devices can be designed to provide primarily self-administered injection of the viscous solutions involved. This is quite a different challenge compared with that of powder inhalation devices.
Patients need to have devices they can easily use for self-administration, as otherwise the ‘Big data’ connectivity reports a poor outcome for the patient due to lower dosing adherence. Additionally, less understanding of the disease is acquired by health system stakeholders.
The problem of poor adherence has been brought to light by the University of Texas Medical Branch (UTMB) in results of a study revealed in December 2014. UTMB found that only 16% of patients surveyed used an epinephrine auto-injector properly. It pointed out: “More than half missed three or more steps, the most common error being not holding the unit in place for at least 10 seconds after triggering epinephrine release.” Other common errors included failure to place the device’s needle on the thigh and not depressing the device forcefully enough to activate injection.
It was further established by UTMB that ‘only 7% of users demonstrated perfect technique and 63% missed three or more steps’. The most common ‘misstep’ here was not completely exhaling before inhaler use, while failure to shake the inhaler before the second medication ‘puff’ was also a common error.
These are the types of problems that can be addressed by incorporating real time error detection, notification and correction in smart drug delivery devices, with audio, visual and tactile feedback. It has also been suggested that problems of device clogging and patients forgetting device advisory information, received from healthcare professionals (HCPs), and/or instructions accompanying the device should be addressed in this way. Furthermore, it is suggested that patient error may also be prevented through the use of electromechanical inhalation devices with breath sensing and other advanced technology.
Smart devices and connectivity were addressed in a joint workshop in April 2017 by Welch and his colleague Kevin Deane, executive VP, Front End Innovation at Medicom Innovation Partner at the RDD Europe Respiratory Drug Delivery conference in Antibes, France.
The workshop participants gravitated around patient-centric benefits as the primary source of value drivers and opportunities for connected health. Themes around improved treatment, better patient education, patient empowerment and social support were discussed by a majority of the groups.
In the interactive workshop presentation, titled ‘Realising benefits of connected health in respiratory drug delivery’, the authors referred to healthcare costs taking increasingly high shares of gross domestic product, while ‘dosage forms evolve and connected devices proliferate’. They maintained that increasingly complex, targeted and personalised drugs mean devices are becoming ever more critical to patient acceptance and drug performance.
Connectivity was seen as an enabler for reducing waste, saving costs, personalising treatments, improving clinical trials and even evolving device designs. Furthermore, the challenges to implementing connected health seemed to align around technical issues, poor business cases, concerns around data ownership/security/privacy, regulatory risks and general reservations about ‘change’ .
That there are already more connected devices than people, with the average person soon to have as many as six devices online, should be seen in the context of the uptake rate of digital infrastructure occurring five times faster than the adoption rate of electricity and telephones, the authors stressed.
They advocated that a ‘connected health approach’ should cover the entire ‘patient care journey’, saying that the new ‘patient-centric’ approach means the delivery method becomes the key connection point between the drug, its producer and the patient for many therapies entering the market today.
Welch and Deane said that secure cloud storage is a key central element in a fully connected respiratory health service set up, in which two-way interaction takes place via the cloud between the delivery device and the patient, as well as between the patient’s app and a ‘dashboard’ for nurses and other HCPs.
While data in the cloud can be a source of information for trend analysis by health system payers and pharmaceutical companies, pharmacies can input data into the cloud. Data arising from the new Industry 4.0 ‘Internet of the Things (IoT)’, as the fourth (digital) industrial revolution, can also find its way into the same cloud storage facility. The amount and type of data available means there can be effective contracting and risk-sharing between payers and the pharmaceutical industry on a ‘no cure, no pay’ basis, Welch and Deane suggested.
Within individualised treatment scenarios in a fully connected health system, they said automated patient adherence monitoring and symptom/event logging benefit above all respiratory drug delivery. Patients can benefit here from individual disease-related information and alerts, such as data on local pollen and pollution levels, and HCPs can remotely monitor their patients.
Pharmaceutical companies also have benefits such as automated supply chain logistics for medicine re-ordering. However, Welch and Deane questioned whether longer term costs of running and maintaining a well-functioning connected health setup are known. Whether there is clarity on the return of investment (ROI) achievable from up-front investments, or on reimbursement to HCPs for provision of added value services.
The authors emphasised that a successful delivery device design must be, useful in meeting a specific need, user-friendly, desirable through its appeal to the user and capable of efficient and reliable manufacture in commercial volumes. The device strategy to address an outcome-based solution should be combined with a manufacturing strategy to get to market at target quality, cost, time and risk, Welch and Deane maintained.