Justin Schroeder at PCI Pharma Services explores why drug-device combination products can be beneficial to patients, and why partnering with PCI can help get products to market with ease.
In the swiftly advancing realm of patient-centred healthcare, the convergence of drug products and medical devices has led to the creation of a distinct category known as drug-device combination products. These innovative solutions integrate either large or small molecule drug products with medical devices, opening new avenues for therapeutic advancements.
Offering a valuable solution by providing a streamlined approach to therapy, reducing the need for multiple interventions and ensuring better patient compliance, drug-device combination (DDC) products are poised to significantly impact the healthcare sector in the coming years. Combined with the increasing prevalence of serious diseases and conditions such as cancer, heart disease, multiple sclerosis and diabetes, among others, this is propelling advancements in the drug-device combination product market. A recent report by Insightslice highlights that the global market for drug-device combination products, valued at $109.17bn in 2022, is projected to reach $236.36bn by 2033, with an estimated CAGR of 7. 2% from 2024 to 2033. Candidly, these projections likely under-consider the overall market given the unprecedented demand for currently commercialised GLP1 therapies, as well as those in near-term pipeline development. The DDC market and its supply chain needs have simply exploded.
These advanced drug delivery solutions leading to safer and more effective treatments thanks to careful and precise drug targeting, local administration and individualised therapy, hold the potential for improved therapeutic outcomes by seamlessly combining drug products with delivery devices. However, their development and commercialisation present a range of complex challenges. This article provides insight into essential considerations for achieving successful commercialisation 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, not only as a defined regulatory requirement, but as an opportunity for rich and actionable patient feedback. With a focus on patient-centric design, it is essential to understand how users interact with the product as received, including the packaging, instructions for use (IFU) and the device itself. This understanding is vital for optimising usability, minimising user errors and enhancing overall safety, efficacy and adherence, ultimately leading to improved outcomes. Critical to this approach is emulating bespoke packaging, artwork and device, and in doing so targeting specifically those individuals representative of your target patient population, assessing their ability to interpret and administer a product successfully in this ecosystem of product, device and packaging/labelling. Conducting usability studies and integrating human factors considerations early in the design process can help identify potential issues and guide necessary design modifications. Human factors and usability engineering are integral components of regulatory submissions, essential for demonstrating the product’s usability and ensuring user comprehension. Best practices for HFE would be initiating at the earliest stages of device consideration, executing exploratory and formative study leading into clinical application and IND filings, as well as progressive studies to culminate in summative studies and validation prior to commercial filing. This progression also allows for rich dialogue with the FDA or other global governing bodies to ensure a seamless pathway to commercialisation.
Design control and development challenges
The successful integration of a drug and device requires meticulous design control to address the unique challenges of combination products. Compatibility between the drug product and the device, as well as the potential impact on the product’s stability and performance, must be thoroughly assessed during the development phase. Borrowing from best practices in medical device development, drug-device combination product requirements have very specific necessities for documenting the progression of design history, design verification, design validation, risk management and control plans etc. Additionally, establishing a robust risk management plan is crucial for identifying and mitigating potential issues that may arise during product development. This includes addressing concerns related to drug product stability, device functionality and possible interactions between the two components.
Whether managed internally at the biopharmaceutical company or through a preferred partnering contract development and manufacturing organisation (CDMO), it is imperative that multidisciplinary teams collaborate across drug product development and packaging design to ensure compatibility.
Quality and manufacturing considerations
Ensuring the quality and consistency of drug-device combination products is of utmost importance. Both biopharmaceutical companies and their preferred CDMO solution providers must strictly adhere to good manufacturing practices (GMP). This adherence is crucial for ensuring the reproducibility and reliability of the products, and involves implementing rigorous quality control measures at every stage of production, starting from raw material sourcing and sterile filling of the drug product into primary containers, to the final assembly, labelling and packaging of the drug-device combination product.
Validation of robust and scalable manufacturing processes and controls is essential. It ensures that combination products maintain consistent quality and performance throughout their life cycle, spanning from clinical trial to commercial market supply.
Underpinning sophisticated manufacturing processes and inspections is a comprehensive approach to both analytical and functional testing, borrowing from ISO standards and also establishing very bespoke methods in some instances depending on the drug product.
Device strategy
Typically, during phase 2b clinical trials, biopharmaceutical companies seek to make decisions on the therapy’s drug-device strategy. Whether to continue with a pre-filled syringe, convert to a needle safety device or insert into an auto-injector to provide ultimate flexibility for various healthcare professionals, patient populations or reimbursement schemes.
Considering the target product profile (TPP)/quality target product profile (QTPP), decisions can be made if there is a unique need for device innovation for specific patient populations or if traditional, readily available platforms would be suitable. Selecting established platforms that have received regulatory approval as part of a drug-device combination product previously, may be deemed lower risk for a new programme and may provide greater speed to market, allowing you to get life changing therapies to patients and gain a first to market advantage.
For innovative platforms, as part of your device strategy, securing intellectual property (IP) rights is crucial in the competitive landscape of drug-device combination products. Companies must carefully navigate the patent landscape to protect their device innovations and establish a strong IP position. This involves considering both the drug and device components, as well as any novel aspects of their combination. It is noteworthy that biopharmaceutical companies may opt to progress several DDC forms for the same product, depending on factors such as reimbursement models, strength and user populations, in-home vs institutional administration, geographic considerations etc. As an example, companies may look to commercialise both an auto-injector as well as pre-filled syringe with needle safety device. This may also be considered as a risk mitigation strategy for commercial filing as well.
Securing supply chains
Ensuring a robust and secure supply chain is crucial for the commercial success of drug-device combination products. Companies must establish strong relationships with suppliers and partnering CDMOs, implement risk mitigation strategies and develop contingency plans to address potential disruptions. This is especially important given the interconnected nature of the drug and device components, each with distinct manufacturing and sourcing considerations.
Given the shear complexity of device assembly, DDCs can substantially expand both the development and readiness times for establishing both a clinical and commercial supply chain. Furthermore, regulatory requirements unique to drug-device combination products predicate the need for demonstration of validated activities much earlier in development than those for traditional oral products or legacy injectable forms such as vials.
Ensuring a sustainability led approach
Often under-considered in the overall device selection and commercialisation strategy, an explicit prioritisation for an environmental sustainability approach needs to be interwoven into the end-to-end programme architecture, with mindfulness towards ensuring considerations for materials selection, supply chain configuration, potential for closed-loop systems for device recovery, drug substance and drug product sourcing, and other aspects in a comprehensive approach. With prioritised and elevated goals for environmental sustainability across the breadth of the life cycle, this should be continually assessed and evaluated throughout clinical supply, commercial readiness, launch, post-approval commercial expansion and ultimately life cycle management. With collaborative and explicit prioritisation, companies can succeed both in optimising patient delivery whilst also succeeding in being good environmental stewards.
Best practices and strategies
With many integral considerations along the journey to commercialisation of drug-device combination products there are several best practices to help ensure a smooth and efficient process, including:
- Early collaboration: establishing cross-functional teams of all stakeholders involved in the development process, including CMC scientists, packaging engineers, process and testing engineers, regulatory experts, quality assurance professionals and patient focus groups. Fostering collaboration and open communication from project initiation ensures alignment of goals, troubleshooting and efficient execution pathways from the outset
- Risk management: proactively identifying and addressing potential risks, such as technical challenges or regulatory hurdles, help mitigate delays and ensure project success. At the earliest stages stakeholders should collaborate on control plans and mitigations, with the commitment to regularly re-evaluate key aspects such as FMEA, evaluation of real-time data and impacts to future plans
- Iterative development: embracing an iterative approach allows for continuous refinement and optimisation based on feedback from user testing, regulatory feedback and market insights
- Regulatory compliance: ensure compliance with regulatory requirements for both vials, pre-filled syringes and auto-injectors in the target markets. This includes adherence to relevant guidelines for drug product packaging, device design, quality control and documentation. Drug-device combination filings have very defined and elevated requirements and stakeholders need to understand these requirements from the onset of their programme
- Flexibility and adaptability: maintain flexibility and adaptability throughout the development process to accommodate any unforeseen challenges or changes in project requirements. Be prepared to adjust timelines, resources and strategies as needed to optimise your drug-device combination product.
Scalable injectable packaging solutions at PCI Pharma Services
The increasing use of biologics, which often require specialised delivery systems, has contributed to the growth of drug-device combination products and the need for technically advanced sterile manufacturing and specialised advanced drug delivery assembly, testing and packaging support. Committed to being a market leader in the packaging of injectable drug products for our global clients, our goal is to support our customers in safely and efficiently bringing their novel therapies to patients.
Driven by innovation and patient-centricity, our design and development expertise combined with our device assembly and injectable packaging capabilities offer flexible solutions for a diverse portfolio of conventional and specialty injectable drug-device combination products. We have the scalability to handle dynamic volumes whether large or small, from niche personalised medicines to large-volume treatments.
Expert advice from device strategy to packaging design
With a global network of experts with extensive experience, PCI provides guidance at critical milestones through the drug product life cycle to assist our clients in developing an optimum patient-centric drug-device combination product.
Our deep industry experience can help determine the best device strategy for your patient and drug product, from the use of established well-accepted platforms that have previously received regulatory approval as part of a drug-device combination product, to alternatively developing a more innovative device approach which may be more attractive for specific patient populations compared to that of more readily available platforms.
PCI’s pharmaceutical packaging design department provides an innovative and value-added service. Our in-house team of specialists deliver insightful packaging design and practical knowledge to deliver differentiated, sustainable and cost-effective packaging solutions.Working with our client partners as early as possible during their drug products clinical phases, our design team together with a cross-functional network of experts in sterile drug product manufacturing, engineering, operations and approved vendors develop expert design processes focused on human-factors engineering and technical functionality to deliver patient-centric designs optimised for manufacturability, scalability and automation.
Utilising state-of-the-art software, our design teams can analyse the sustainable factors of packaging down to individual components. By having a complete view of which specific elements of packaging are contributing most to a package’s carbon footprint, clients can make more informed decisions. Sometimes small changes can have a compounding impact. For example, this software revealed that when changing from a plastic tray to a moulded, paper fibre tray, the impact on global warming is reduced by 50%. Together with our client partners, PCI works to develop the most appropriate solution that aligns to goals and budget. This seamless packaging design solution ensures key considerations are addressed at the right time, leading to both cost- and time-efficiencies and ultimately ensuring speed to market.
Expansion of drug-device combination product capabilities and capacities
Complementing the continued growth and investment across our sterile manufacturing network, we continue to expand our European, North American and UK Centres of Excellence for clinical and commercial packaging. These state-of-the-art facilities are equipped with advanced drug delivery packaging technologies for the assembly and labelling of vials, cartridges, pre-filled syringes, advanced safety syringes, auto-injector and pen devices complete with integrated top-open cartoning and serialisation. Most recently we announced an investment of $150M in a new 310,000ft2 facility at our Rockford, IL, US, site to meet the growing biologic market need of specialised assembly and packaging for injectable drug-device combination products. Over 20 dedicated suites will support the final assembly and packaging of vials, pre-filled syringes, auto-injectors, on-body injectors and pen-cartridges such as those for glucagon-like peptide 1 agonists (GLP-1) for treatment of diabetes and obesity, as well as those needed for oncology treatment and autoimmune diseases.
Flexible, scalable autoinjector assembly
As a world-leading CDMO, PCI provides highly flexible, reliable injectable packaging solutions to meet the dynamic needs of our clients. Meeting the exponential growth in the development and use of auto-injectors, PCI continues to invest in innovative scalable auto-injector assembly, labelling and packing technologies.
Although many auto-injector devices have similar components, their design varies in terms of size, material and shape. With true customer focus and flexibility at the core of our injectable packaging service offering, our technologies can adapt to the unique requirements of each global market from concept to commercialisation.
For example, our small-mid scale auto-injector assembly lines provide multi-platform auto-injector solutions including Ypsomed Ypsomate, SHL Molly, Becton Dickson (BD) Physioject alongside other platform devices. They also have the capability to assemble and label needle safety device platforms such as BD Ultrasfe/Plus and Nemera Safe and Sound making them ideal for development studies, clinical trials and niche orphan drugs.
Providing integrated scalable solutions, our larger scale technologies are also able to accommodate various auto-injector types to support product launches and commercial market supply. Providing true customisation, our larger-scale lines can easily and cost-effectively be retooled for future new drug delivery formats allowing us to respond quickly and efficiently to technological changes and future innovation.
Seamless manufacturing, packaging and testing solutions
At PCI, ensuring life-changing medicines reach those who need it most is our highest priority. As a truly integrated global CDMO, we are manufacturing, packaging and supply chain experts, harnessing our experience and expertise to deliver seamless solutions with the ultimate aim of improving the lives of patients.
Providing expert sterile fill-finish and lyophilisation solutions from development to commercialisation together with integrated custom assembly and packaging solutions for sterile injectables allows for ultimate knowledge sharing and communication between teams to ensure the drug product packaging is optimised for the product, patient and production.
With in-house laboratories we provide a range of packaging and analytical services to support clients’ development, clinical and commercial supply of medicines globally. From product ID testing, method transfer, release and stability testing to auto-injector device system testing with ISO 11608 functional tests such as cap removal force, activation force, extended needle length, dose accuracy, injection time and lockout force, we ensure life-changing therapies meet global regulatory guidelines and are safe for patient use.
Conclusion
Successful commercialisation of drug-device combination products requires a multidisciplinary holistic approach, combining expertise in drug product and medical devices. From early-phase clinical trials to successful commercial launch, considerations such as drug product device compatibility, device strategy, manufacturability and packaging design must be carefully navigated.
By proactively and strategically addressing the key considerations outlined above and when needed, partnering with an expert CDMO such as PCI Pharma Services, biopharmaceutical companies can streamline their clinical to commercial journey, ensuring the successful integration of drug and device components and, ultimately, delivering life-changing therapies to patients.
About the Author
Justin Schroeder is the global vice president of technical services. Mr Schroeder is responsible for ensuring PCI’s global clients realise seamless life cycle management and successful commercialisation of their therapies. With 25 years of experience in outsourced pharmaceutical services, he has held leadership roles in various functional disciplines in global roles including package engineering and design development, project and programme management, marketing, business development and progressive roles in senior executive leadership.
Clinical to commercial success: essential insights for drug-device combination products with Justin Schroeder | As seen in Pharmaceutical Manufacturing and Packing Sourcer (PMPS) | Parental Technology Supplement 2024
We are committed to supporting clients at every stage of the manufacturing cycle, delivering best-in-class services efficiently and effectively.
Find out more about our Advanced Drug Delivery Solutions.