Drug-Device Combination Products: Making a Step Towards Better Adherence

More than half of the world’s population takes at least one medication daily, but the safety and efficacy data from clinical trials isn’t always fully reflected in real world use. One of the causes of this is non-adherence, where patients don’t take their medications as prescribed, either intentionally or unintentionally. Patients not taking their medications as prescribed isn’t a recent issue. Hippocrates, who has been described as the ‘Father of Medicine’, reported it in the 5th century BCE. Reported non-adherence levels in patients who have a number of co-morbid conditions ranges between 44% and 77%. This has significant direct costs (for example wastage, hospitalisations) and indirect costs (loss of work time) that reach into billions of dollars, and results in thousands of cases of preventable disability and death. [1]

Increasing adherence and persistence could have a significant impact on drug spending. A study suggested that increasing drug utilisation by 1% may reduce the spending on healthcare by $3 billion for people enrolled in Medicare and Medicaid in the US. [2]

There are a number of reasons behind low levels of adherence. These include forgetting to take the medication, not fully understanding its importance (particularly in symptomless disorders such as hypertension), anxiety about any associated adverse effects, not believing it to be effective, not being able to afford prescription refills, misunderstanding instructions, having difficulty with packing or administration routes, or being affected by the stigma of using a particular medication. While it’s unlikely that any one intervention will solve non-adherence, one approach is to simplify drug regimens and make the medications easier to handle.

The role of drug delivery in adherence and compliance

In patients with long-term medical conditions, treatment regimens can be complex and involve dosing more than once daily. Fixed-dose combinations and once-daily dosing can simplify drug regimens. For example, dexedrine Spansule (dextroamphetamine), the first controlled-release formulation, was approved in 1952. It releases the drug slowly over 8-10 hours, which reduces dosing from up to four times a day to just once- or twice-daily. By reducing peaks and troughs, it helps to maintain drug levels in the blood at optimal therapeutic levels. [3]

As well as making medication regimens more straightforward, simplifying regimens through fixed dose and/or once daily dosing has been shown to enhance both medication adherence and persistence, and well as improving patient outcomes and saving costs for payers. [4, 5]

Drug-device combinations (DDCPs), which combine an active small molecule or biologic drug and a delivery device, provide another way to simplify medication regimens. By allowing self-administration, they also reduce the need for regular hospital or clinic appointments, increasing convenience for patients and carers, and freeing up healthcare professionals for other tasks. DDCPs range from transdermal patches, through prefilled syringes, to implanted delivery pumps that incorporate sensors and deliver drugs (for example insulin) based on the patients’ needs. Drug-device combinations can also be used to monitor adherence, for example Otsuka’s antipsychotic Abilify (aripiprazole) in oral tablet has been approved in combination with an ingestible sensor embedded in the tablet. This digitally records when a patient has taken the tablet by sending a message to a wearable sensor, which is then relayed to a Bluetooth-enabled device such as a mobile phone. Other drug-device combinations targeting adherence include smart insulin pens and smart inhalers. [6, 7]

Developing and manufacturing patient-centric combinations

To ensure uptake, developing the drug-device combination products as patient-centric dosage forms is an important step. The process begins with understanding what patients and carers want from the product and gaining their input on how it can make drug administration easier and more straightforward. Factors to be taken into account in usability studies include the packaging, instructions for use (IFU) and the device, and how these can be adapted to make the device more usable and reduce any errors in administration. [8-11]

Developing a drug-device combination product requires thorough and detailed design planning to ensure that the drug and device together don’t affect the efficacy, functionality, safety or stability of the individual drug or the device. Clinical trials must include safety, efficacy and real-world evidence as required by the regulatory authorities. [11]

Drug-device combination products cross over the boundaries between drugs, biologics and devices, and therefore come with additional challenges, and each regulatory authority will have its own guidelines to ensure safety and efficacy. In Europe, for example, the regulatory pathway depends on the product’s principal mode of action (PMOA) and whether it is classified as a drug or device. If it is primarily a medicine, for example a patch for transdermal drug delivery, it is regulated under EU pharmaceutical legislation and needs to gain marketing authorization, with CE marking or a conformity assessment for the device. If it is a device with an ancillary medicinal substance, for example a drug-eluting stent, it will fall under medical devices legislation and must be CE marked, along with scientific opinion from the EMA (European Medicines Agency) for the medicinal substance. [11, 12]

At the manufacturing stage, it is important implement to current good manufacturing practice (cGMP) and quality control measures at every step, from sourcing raw materials to packaging and labelling. [11]

Drug-device combinations in drug delivery: The market

According to a report from Research and Markets, the drug-device combinations market will be worth an estimated $243.02 billion in 2025, climbing by a compound annual growth rate (CAGR) of 9.3% to an estimated $379.17 billion. The market drivers include ongoing increases in chronic conditions such as diabetes, respiratory disease, cancer and cardiovascular disease, along with the growth in patient-centric design and an increase in the numbers of patients who are self-administering medications. Other factors include access to better technology and support from governments and payers. [11, 13]

The North American market is the biggest, with the Asia Pacific market expected to grow the most quickly. Breaking the market down into categories, injectable drug delivery systems, especially autoinjectors, have the largest market share. This area is expected to continue to grow. [13]

References

1.           Kardas, P., et al., Medication non-adherence: reflecting on two decades since WHO adherence report and setting goals for the next twenty years. Frontiers in Pharmacology, 2024. 15: p. 1444012.

2.           Baryakova, T.H., et al., Overcoming barriers to patient adherence: the case for developing innovative drug delivery systems. Nat Rev Drug Discov, 2023. 22(5): p. 387-409.

3.           DEXEDRINE® (dextroamphetamine sulfate) SPANSULE® sustained release capsules Cll Rx Only. FDA. Last accessed: October 2013. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/017078s048lbl.pdf.

4.           Elnaem, M.H., et al., Impact of Medication Regimen Simplification on Medication Adherence and Clinical Outcomes in Patients with Long-Term Medical Conditions. Patient Prefer Adherence, 2020. 14: p. 2135-2145.

5.           Paoli, C.J., et al., Effectiveness of Single-Tablet Combination Therapy in Improving Adherence and Persistence and the Relation to Clinical and Economic Outcomes. J Health Econ Outcomes Res, 2024. 11(1): p. 8-22.

6.           Vallejos, X. and C. Wu, Digital Medicine: Innovative Drug-Device Combination as New Measure of Medication Adherence. J Pharm Technol, 2017. 33(4): p. 137-139.

7.           Zijp, T.R., et al., Smart Medication Adherence Monitoring in Clinical Drug Trials: A Prerequisite for Personalised Medicine? EClinicalMedicine, 2019. 15: p. 3-4.

8.           Elvidge, S., Improving the Patient Experience: Developing Patient-centric Dosage Forms. Pharma Sources: An eye on the biopharma industry, 5 February 2025. Available from: https://www.pharmasources.com/industryinsights/improving-the-patient-experience-76944.html.

9.           Elvidge, S., The Importance of Patient-Centricity in Drug Development. Pharma Sources: An eye on the biopharma industry, 29 August 2024. Available from: https://www.pharmasources.com/industryinsights/the-importance-of-patient-centricity-in-76733.html.

10.         Welch, B., Merge Ahead: Drug-Device Combination Products from Concept to Commercialization. Contract Pharma, 1 October 2024. Available from: https://www.contractpharma.com/exclusives/merge-ahead-drug-device-combination-products-from-concept-to-commercialization/.

11.         Welch, B., Navigating the Complex Landscape of Drug-Device Combination Products: Key Considerations for Successful Commercialization. OnDrug Delivery, January 2024. Available from: https://pci.com/resources/drug-device-combination-products/.

12.         Medical devices. European Medicines Agency. Last accessed: 25 July 2025. Available from: https://www.ema.europa.eu/en/human-regulatory-overview/medical-devices#medical-devices-with-an-ancillary-medicinal-substance-13038.

13.         Drug Device Combination Products Market Analysis Report 2025-2030: Discover the Latest Advances and Opportunities. Research and Markets. Last accessed: 29 May 2025. Available from: https://www.globenewswire.com/news-release/2025/05/29/3090116/0/en/Drug-Device-Combination-Products-Market-Analysis-Report-2025-2030-Discover-the-Latest-Advances-and-Opportunities.html.

About the Author

Based in the north of England, Suzanne Elvidge is a freelance medical writer with a 30-year experience in journalism, feature writing, publishing, communications and PR. She has written features and news for a range of publications, including BioPharma Dive, Pharmaceutical Journal, Nature Biotechnology, Nature BioPharma Dealmakers, Nature InsideView and other Nature publications, to name just a few. She has also written in-depth reports and ebooks on a range of industry and disease topics for FirstWord, PharmaSources, and FierceMarkets. Suzanne became a freelancer in 2006, and she writes about pharmaceuticals, consumer healthcare and medicine, and the healthcare, pharmaceutical and biotechnology industries, for industry, science, healthcare professional and patient audiences.