In the rapidly evolving landscape of patient-centred healthcare, the intersection of drug product and medical devices has given rise to a unique drug delivery category of products known as drug-device combination products. The emergence of drug-device combination products, where a large or small molecule drug product is integrated with a medical device has paved the way for novel therapeutic solutions.
Author: Bill Welch, Executive Director of Services, PCI Pharma Services
This article was first published in OnDrug Delivery magazine in January 2024
Driven by the growing prevalence of chronic disease such as diabetes, respiratory disease and cancer, advancements in the drug-device combination product market are expected to have a significant impact on the healthcare sector over the coming years. According to a recent report by Insightslice, the global drug-device combination products market which was valued at $109.17 billion in 2022 is estimated to be $236.36 billion by 2033 with an estimated CAGR of 7.2% between 2024 and 2033.1
These innovative drug delivery solutions offer the promise of enhanced therapeutic outcomes by seamlessly integrating drug products and delivery devices, but their development and commercialization come with a set of intricate challenges. This article delves into the key considerations that stakeholders must address to ensure the successful commercialization of drug-device combination products.
Navigating the regulatory landscape is arguably the most critical aspect of developing and commercializing drug-device combination products. Regulatory agencies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have established specific guidelines to ensure the safety and efficacy of these complex products.
First, companies must determine the regulatory pathway applicable to their product. Understanding the regulatory classification of a drug-device combination product is essential and depends on its principal mode of action. This will dictate whether the product will be regulated as a medical device, a drug, or a combination product. This determination influences the type of regulatory submission required and the specific requirements for demonstrating safety and efficacy.
Human Factors and User Experience
Human factors engineering (HFE) is a critical aspect of drug-device combination product development. With a patient-centric focus, interaction between users and the product as-received is paramount. Understanding how patients and healthcare professionals interact with the packaging, IFU, and device itself is vital for optimizing usability, minimizing user errors, and enhancing overall safety, efficacy, and adherence to gain improved outcomes.
Conducting usability studies and incorporating human factors considerations early in the design process can help identify potential issues and inform design modifications. Human factors and usability engineering is an integral component of regulatory submissions and is essential for demonstrating the product’s usability and user comprehension.
Design Control and Development Challenges
The successful integration of a drug and a device requires meticulous design control to address the unique challenges posed by combination products. The compatibility of 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.
Additionally, establishing a robust risk management plan is crucial to identify and mitigate potential issues that may arise during product development. This includes addressing concerns related to drug stability, device functionality, and any possible interactions between the two components.
Whether internally at the biopharmaceutical company or the company’s preferred partnering Contract Development and Manufacturing Organization (CDMO), it is imperative that multi-disciplinary teams work together 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 paramount. Manufacturers whether that be the biopharmaceutical company or their partnering CDMO must adhere to good manufacturing practices (GMP) to guarantee the reproducibility and reliability of the product. This involves implementing rigorous quality control measures at every stage of production, from raw material sourcing, sterile filling of the drug product into the primary container to final drug-device combination product assembly, labeling and packaging.
Validating robust scalable manufacturing processes and controls is essential to produce combination products with consistent quality and performance throughout the drug-device combination product lifecycle from clinical trials to commercial market supply.
The generation of robust clinical evidence is paramount for the successful commercialization of drug-device combination products. Companies must design and conduct clinical trials that not only demonstrate the product’s safety and efficacy but also provide meaningful real-world data on the interaction between the drug and the device.
The design of clinical studies should align with regulatory requirements and consider the unique challenges posed by drug-device combination products. Well-designed clinical trials should consider patient populations and clinical endpoints. Collecting data on both the drug and device components individually, as well as their combined effects, is essential for building a comprehensive body of evidence to support regulatory submissions.
Device Strategy – Intellectual Property Protection:
Forming part of your device strategy, securing intellectual property (IP) rights is a critical consideration in the competitive landscape of drug-device combination products. Companies must carefully navigate patent landscapes to protect their device innovations and establish a strong IP position. This includes considering both the drug and device components, as well as any novel aspects of their combination.
Supply Chain Management:
Ensuring a robust and secure supply chain is vital for the commercial success of drug-device combination products. Companies should establish strong relationships with suppliers, partnering CDMOs, implement risk mitigation strategies, and have contingency plans in place to address potential disruptions. This is particularly important given the interconnected nature of the drug and device components, each with its own set of manufacturing and sourcing considerations.
Advanced Drug Delivery Solutions at PCI Pharma Services
The increasing use of biologics which often require specialized delivery systems, has contributed to the growth of drug-device combination products and the need for technically advanced sterile manufacturing and specialized advanced drug delivery assembly, testing, and packaging support. Committed to being a market leader in the packaging of biologic 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 advanced drug delivery 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 personalized medicines to large-volume treatments.
Expert advice from device strategy to packaging design
With a global network of experts with extensive experience in advanced drug delivery, PCI provides guidance at critical milestones 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, which may be deemed lower risk, 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 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 optimized for manufacturability, scalability and automation. This seamless 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 Centers 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 labeling of vials, cartridges, standard pre-filled syringes, advanced safety syringes, auto-injector and pen devices complete with integrated top-load cartoning and serialization.
Most recently we announced an investment of $150M in a new 200,000 sq ft facility at our Rockford, IL, site to meet the growing biologic market need of specialized assembly and packaging for injectable drug-device combination products. With over 20 dedicated suites, the new facility will support the 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 auto-injector assembly
As a leading global CDMO, PCI provides highly flexible, reliable advanced drug delivery packaging solutions to meet the dynamic needs of our client’s. Meeting the exponential growth in the development and use of auto-injectors, PCI continues to invest in innovative scalable auto-injector assembly, labeling 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 commercialization.
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 & 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 customization, our larger scale lines can easily and cost-effectively be retooled for future new auto-injector types 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 lyophilization solutions from development to commercialization 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 optimized for the product, patient and production.
With in-house laboratories we provide a range of packaging and analytical services to support client’s development, clinical and commercial supply of medicines globally. From product ID testing, method transfer, release and stability testing to auto-injector 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 your life-changing therapy meets regulatory guidelines and is safe for patient use.
Successful commercialization of drug-device combination products requires a multidisciplinary holistic approach, combining expertise in drug product and medical devices. By addressing the key considerations outlined above and when needed, partnering with an expert CDMO such as PCI Pharma Services, manufacturers can navigate the challenges along the journey to commercialization, ensuring the successful integration of drug and device components and, ultimately, delivering life-changing therapies to patients.