For decades, silicone has been used for short- and long-term implantable applications given 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 realized.

However, these combination products are notoriously challenging to design, manufacture, and shepherd through the regulatory process. In this article, we’ll examine potential pitfalls and outline a strategy to ensure a successful product launch.

Combination Products 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, some such products could eliminate the need for daily administration of contraceptives or API to prevent retroviral infections. Because 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-tumor 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 processes must be understood among 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, molding, 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.  

4 Key Questions

When selecting manufacturing and supply chain partners for development of your combination product, here are a few questions you should ask:

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.