Ursula Nollenberger, product line director and Kevin Ehlert, segment manager, Trelleborg Healthcare & Medical discuss the necessary steps to launching a succesful drug/device combination product.
Product launch
For decades, silicone has been used for short- and long-term implantable applications due to its high level of biocompatibility. Today, a further characteristic—exceptional permeability—holds the key to the next generation of combination products, as the ability of long-term silicone-based drug-eluting implants to improve patient outcomes is beginning to be realised.
However, these combination products are notoriously challenging to design, manufacture, and shepherd through the regulatory process.
Combination product growth
Long-term implantable combination products (those spending longer than 29 days in the body), augmented with one or more active pharmaceutical ingredients (APIs), are currently being used to improve lives. For example, by eliminating the need for daily administration of contraceptives or API to prevent retro-viral infections. Since silicone-based intrauterine combination products can hold more than one API, a combination product can simultaneously deliver a precise dose of an antiviral medication and a hormone.
Cancerous-tumour reduction is another area of enormous promise for long-term drug eluting implantable combination products. Tiny combination products capable of delivering a precise amount of cytostatics used in chemotherapy over a specified period can be placed exactly where needed, significantly lowering care costs while dramatically reducing side effects.
Thus, it’s not surprising that iHealthcareAnalyst, Inc. predicts that the global implantable combination product market will grow at a 5.8% CAGR to reach 30 billion USD in 2025. One important driver is the increased incidence of chronic diseases; others are the rising popularity of both minimally invasive surgeries and wearable combination products.
Enhanced patient outcomes may ultimately be the greatest driver, with combination products concurrently increasing treatment efficacy and lowering costs ⎯ the all-important healthcare sweet spot. Furthermore, combination products enable pharmaceutical companies to use FDA-approved formulations in novel ways, expanding drug usage and potentially extending patient life.
Go-to-market challenges
The design, manufacturing, and approval processes for combination products can be extremely challenging but very rewarding when successful. Some of the greatest challenges combination product manufacturers face are related to solving technical and scalability issues connected with their manufacturability, even before clinical trials begin.
To tackle these issues, the relationships and interactions between drug, device, silicone, and manufacturing process must be understood between all involved parties in terms of technical feasibility, regulatory compliance, and of course functionality and efficacy in treatment. Each of these variables has an impact on the others. Finding the optimal balance prior to design and manufacturing process freeze is critical. Silicone extrusion, moulding, and other manufacturing methods, all use heat to cure the silicone. If the API is heat sensitive, the silicone choice and method of curing are critical factors. New, low-temperature curing silicones or alternative curing technologies offer good solutions, for example.
Significant expertise is required to create the desired release rate for a specific drug contained within the specified silicone type. Silicone has a matrixed polymer structure. During the development process, the silicone matrix is matched with the API’s molecular structure to ensure optimal elution over the desired timeframe. Expertise in how the silicone and API interact is essential to success.
Finally, scale-up is an often-overlooked element of the overall success of the product. A process that is feasible on a small scale, during the development phase, may lead to inefficient or prohibitively expensive full-scale manufacturing. A partner who understands both the lab scale development and commercial production at much higher volumes will be important to market viability.
In the typical partnership, the combination product owner focuses on drug development, clinical strategy and coordination, regulatory submissions, specifications and design control. The development and manufacturing partner concentrates on efficiently making the product and planning for scalability from bench scale to commercial production including validation in line with the regulatory path planned for a combination product.
Four key questions
When selecting manufacturing and supply chain partners for development of your combination product, here are a few questions you should ask:
- What experience do you have with the government regulatory review process for combination products? Combination product creators who are not intimately familiar with the dual regulatory path of combination products can benefit by selecting a manufacturer with this experience and the ability to help develop a project plan. Underestimating the amount of time needed for product development and testing (e.g., an elution rate study), conducting a series of clinical trials, and guiding a combination product through multiple regulatory reviews can easily and quickly derail such a project.
- Can you recommend the best process for the drug-delivery system we’re designing? First, an experienced manufacturing partner should have broad processing experience to recommend the optimum manufacturing process for the intended combination product. Second, the partner should be experienced in concurrent engineering and have a DfM (Design for Manufacture) mindset. Third, the partner should be able to contribute to early development decisions, providing essential design and processing input relating to fit, form, and function of the combination product to ensure that scalability and commercialisation are fully considered.
- What is the extent of your materials knowledge? Look for a manufacturer with strong material development and processing experience and long-term relationships with material makers on a global basis. Understanding the processing characteristics of materials and how they can be influenced and controlled is critical to the successful validation and launch of an end product. Close technical collaboration between parts and material manufacturers facilitates the process of adapting existing materials or developing new ones as needed.
- What is the full range of your capabilities? Depending on the specific needs of your project, it may help to choose a manufacturing partner capable of offering an array of services in addition to the production of the combination product. To ensure a lean supply chain, it may be beneficial to select a manufacturing partner that is able to offer a fully finished combination product, including all aspects of post-manufacturing processes, packaging, labelling, and sterilisation.
Summary
Development timelines for combination products are measured in years rather than months. Therefore, eliminating guesswork is critical to ensuring projects stay on track. Investments made in engineering support and guidance from a trusted and experienced source will ensure the combination product can be successfully manufactured, easily produced in small quantities for initial trials, and cost-effectively produced at scale. Selecting the right manufacturing partner early-on to guide the project through the development process could significantly accelerate the timeline.
The potential to provide advanced treatments via combination products is enormous, and competent manufacturing partners can help combination product creators successfully develop any type of combination product, regardless of the drug-delivery method, manufacturing approach, or material.