Merger Ahead: Drug-Device Combination Products from Concept to Commercialization

In the rapidly advancing field of patient-centered healthcare, the convergence of drugs and medical devices has formed its own hybrid category: drug-device combination products (DDCPs). Such symbiotic solutions integrate large or small molecule drugs into medical devices, virtually obliterating the increasingly blurred boundaries between drugs and their delivery systems while opening new avenues for therapeutic advances.

In the near future, the already significant impact of drug-device combination products will only increase. Among other value propositions, DDCPs offer efficiency-focused therapeutic approaches by reducing the need for multiple interventions and promoting higher patient compliance. Such streamlining features are timely, and innovative DDCPs are often deployed rapidly to address the increasing prevalence of serious, often chronic, diseases and conditions such as cancer, heart disease, multiple sclerosis and diabetes. In fact, a recent report from Insightslice finds that the global drug-device combination product market, estimated at just over $109 billion in 2022, is expected to surpass $236 billion by 2033, a high estimated average annual growth rate of 7.2%.

Thanks in part to careful and precise drug targeting, local delivery, and individualized therapy, DDCPs lead to safer and more effective treatments and hold potential for improved therapeutic outcomes due to the seamless integration of drugs and their delivery devices. However, the development and commercialization of DDCPs poses a number of complex challenges. This article examines critical considerations for successful commercialization of drug-device combination products.

Human factors and user experience

Human factors engineering (HFE) is a crucial element in the development of drug-device combination products. With the focus on patient-centered design, it is important to understand how users interact with the product as delivered, including the packaging, the Instructions for Use (IFU), and of course the DDCP itself. This understanding is critical to optimizing the user experience, minimizing user errors and improving overall safety, effectiveness and adherence to the overall goal of improved patient outcomes.

Conducting usability studies and incorporating human factors early into the design process can help identify potential problems and initiate necessary design changes from there. Human factors and usability engineering are integral parts of regulatory submissions and are critical to demonstrate the product's usability and ensure it is understood by the user.

In fact, the successful integration of a drug and delivery device requires careful design controls to address the unique challenges of combination products. The compatibility between the drug product, the drug container and the device, as well as the possible impact on the stability and performance of the product, must be thoroughly evaluated during the development phase.

Additionally, creating a robust risk management plan is critical to identifying and mitigating potential issues that may arise during product development. This includes addressing concerns about drug product stability, device functionality, and potential adverse interactions between components.

Whether managed internally by pharmaceutical companies or through Contract Development and Manufacturing Organizations (CDMOs), it is essential that multidisciplinary teams work together to ensure drug product development and packaging design are aligned, compatible and optimized.

Quality and manufacturing aspects

As with any healthcare scenario, maintaining consistent, uncompromised quality and effectiveness of drug-device combination products is always of utmost importance. Both pharmaceutical companies and CDMO solution providers must strictly adhere to Good Manufacturing Practices (GMP). Such guidelines are crucial for ensuring the reproducibility and reliability of products and require the implementation of strict quality control measures at every stage of production – from raw material procurement and sterile filling of the drug into primary containers to final assembly, labeling and packaging.

Only by validating robust and scalable manufacturing processes and controls can a pharmaceutical company or CDMO demonstrate that a DDCP maintains consistent quality and performance throughout its lifecycle, from clinical trial to commercial market supply.

Considerations for near-commercialization

In Phase IIB clinical trials, pharmaceutical companies typically make final decisions about a therapy's drug-device strategy. Considerations here include, for example, whether to continue with a prefilled syringe, switch to a needle safety device or switch to an auto-injector. The idea is always to provide maximum flexibility for different healthcare professionals, patient groups and reimbursement systems.

Taking the Target Product Profile (TPP)/Quality Target Product Profile (QTPP) into account, it is ultimately necessary to determine whether the therapy requires novel device innovation for specific patient groups or, conversely, whether traditional, readily available platforms are sufficient for all potential patients. Of course, selecting an established platform that has received regulatory approval under a previous, now established DDCP may be viewed as lower risk for a new program. This route can also lead to faster time to market, allowing a life-changing therapy to reach patients in a shorter time while achieving first-to-market benefits.

When innovative platforms are required, securing intellectual property (IP) rights is part of any comprehensive device strategy. Companies must carefully navigate the patent landscape to protect their device innovations and establish a strong IP position in today's increasingly competitive environment. The drug and device components as well as any new aspects of the relevant DDCP must be taken into account.

As commercialization approaches, a robust and secure supply chain is also critical. Companies must build strong relationships with suppliers and partner CDMOs, implement risk mitigation strategies, and develop contingency plans to address potential disruptions. This is particularly important because the drug and device components are interconnected and each require different manufacturing and procurement aspects. In such situations, the supply chain and DDCP manufacturing process are truly only as strong as their weakest link.

Five key findings

With so many complicated, integral considerations on the path to commercializing drug-device combination products, some bulleted best practices may be helpful.

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  Early collaboration. From the concept, assemble cross-functional teams of all stakeholders involved in the development process, including CMC scientists, packaging engineers, regulatory experts, quality assurance experts, and patient focus groups. Encouraging collaboration and open communication from the start of a project best ensures goal alignment, informed troubleshooting, and efficient execution paths.

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  Risk management. Proactively identifying and managing potential risks, such as: B. technical challenges or regulatory hurdles, helps reduce delays and ensure project success.

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  Iterative development. The iterative approach allows for continuous refinement and optimization based on feedback from user testing, feedback from regulators and market insights.

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  Regulatory Compliance. Observe and comply with regulatory requirements for vials, prefilled syringes and autoinjectors in various target markets. This includes compliance with relevant guidelines for drug packaging, device design, quality control and documentation. Remember: The “C” in DDCP stands for “combination,” which means that if one element fails the test, none of the other elements pass the test either.

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  Flexibility and adaptability. Remain flexible throughout the development process to respond to unforeseen challenges or changes in project requirements. Be prepared to adjust schedules, resources, and strategies as necessary to optimize the drug-device combination product.

Successful commercialization of drug-device combination products requires a multidisciplinary, holistic approach that combines expertise in both drug products and medical devices. From early clinical trials to commercial launches, considerations such as drug and device compatibility, device strategy, manufacturability, and packaging design must be carefully considered.

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Bill Welch is Executive Director Market Development for PCI Pharma Services, a Leading CDMO providing integrated end-to-end drug development, manufacturing and packaging capabilities that accelerate time to market and increase the chances of commercial success. The company has 30 locations in seven countries and employs over 7,000 people working to bring life-changing therapies to patients.