The convergence of medical devices and pharmaceuticals presents advantages and growing pains for medical product manufacturers. 

Alex Butler

Combination products, or those that merge two or more different types of regulated drugs, medical devices or biologics, combat patient illnesses and ailments using a multifaceted approach, and they've been a hot topic at many of the industry trade shows and conferences I've attended in the past year. While traditional industry and regulatory lines have largely kept devices and pharmaceuticals separate, companies on both sides of the equation are beginning to see great potential in joining forces both from a treatment and a business perspective. As they do, the lines between drug and device are becoming blurred, presenting medical product makers with as many opportunities as challenges.

Here's a look at the key advantages and growing pains of the cross-pollination between devices and drugs in 2017 and beyond.

Opportunities

Sharing domain expertise means increased innovation. Device, pharma, and high-tech companies are all highly specialized to operate in their respective markets. But as the effectiveness and potential applications of combination therapies continue to emerge, each industry must look beyond its traditional borders to either acquire new manufacturing, scientific, and regulatory knowledge or partner with those who already have it. The latter option affords opportunities for companies across the healthcare ecosystem to collaborate and share knowledge, fostering innovation and pushing the boundaries of medical treatment. Last year, GlaxoSmithKline partnered with Google's Verily to create Galvani Bioelectronics, a joint venture combining GSK's drug development expertise with Verily's engineering know-how to pioneer a new implantable device that could improve millions of lives. This is just one of many such examples.

Continued move toward personalized medicine. In contrast to a one-size-fits-all approach, personalized medicine allows clinicians to diagnose and treat patients based on a unique subset of individual characteristics, typically with the help of two or more medical products or therapies. FDA calls it a new era of medical product development and has already begun discussing its role and responsibilities in this area. Extraordinary advances in the fields of genomics, computational biology, medical imaging, and generative medicine continue to pave the way for personalized medicine, a movement that promises to be a key driver of the combination product market.

Leveraging Existing Devices and Drug Substances. In many cases, companies can repurpose an existing device or drug to create a new combination product. The advantage here is that the bulk of the work is already done; the product has already been tested, documented and cleared by FDA, thus minimizing cost, time to product registration, and likelihood of failure. Creating one treatment by combining two previously approved products that must be taken concurrently can also improve safety and efficacy. In this way, a company's previous product investments allow it to springboard into a new and relatively untapped market. 

Challenges

Lack of predicate devices. Given the unique nature and sheer novelty of drug-device combination products, device makers don't have the luxury of leaning on predicate devices to demonstrate safety and efficacy. This means that product registrations must be compiled from the ground up--including conducting clinical trials if necessary, which can be time-consuming and daunting for medical device companies that often don't have the required in-house skills and resources. For these companies, there are a lot of unknowns and not a lot of information to work from: What do we test? Do we need to run full clinicals? Can we pull all the data and analysis from the existing clinical on the pharma side and run a "mini clinical" for the combination product? Fortunately, in a drug-device market expected to reach $115 billion by 2019, pharma companies are typically eager to partner with device makers and lend their expertise to help bring a new drug-device product to market.

Choosing a registration strategy. The rule of thumb for whether to register a combination product as a device or a pharmaceutical is to identify the primary mode of action (PMOA), or the component that has the most effect on a patient. If the PMOA of a drug-device is attributable to the drug product, the Center for Drug Evaluation and Research (CDER) would have primary jurisdiction for the combination product; if the device product has the greatest effect, then CDRH would dictate. But FDA leaves this determination much to the discretion of the registrant, which in turn opens plenty of room for error. An inexperienced device company that registers a combination product for the first time might find itself down the wrong regulatory pathway, due in large part to a lack of historical data. To determine how a product will be classified and regulated by FDA, companies should submit a Request for Designation (RFD) as soon as they have sufficient information for FDA to make a decision regarding assignment of a product. Alternatively, they can complete a Pre-Request for Designation (Pre-RFD), a less formal inquiry that can be submitted at any point during a product's development.

Human factors and usability. Bioelectronics, interoperables, and interconnected devices show great potential in augmenting drug-device combos, but even the most robust tech-assisted health tools will not benefit users if they are not adopted or used properly. Take, for example, a pillbox intended for seniors that aids in administering medications with the help of a smartphone app. It failed because the target audience was simply unable to use it. In designing combination products, particularly those that are patient-administered or -operated, engineers must consider the skill level and dexterity of the users early in the design process to promote user engagement and human factors must frequently be evaluated throughout the design and development process to improve the user experience and increase the likelihood of adoption and compliance.

The Future of Combination Products

There is no question that the medical device industry is becoming more dependent on pharma, and vice versa. Rather than an unanticipated development, combination products represent the natural evolution of the device and pharma industries to accommodate a deeper understanding of the complex nature of human and disease biology and how they respond to combination therapies, along with innovative developments in therapeutic technologies, digital health, and personalized medicine. As more drug-device partnerships emerge in 2017, expect to see novel approaches and continued collaboration as companies overcome the challenges and reap the rewards of this growing market. Further, FDA's Office of Combination Products and the Combination Product Council will continue their efforts to simplify the combination product regulatory process.

As the medical device product manager at MasterControl, Alex Butler is focused on developing solutions that help medical device companies increase efficiencies, ensure compliance, and speed time to market. Before joining MasterControl in 2014, Butler worked as a product development manager for Opal Orthodontics, a division of Ultradent Products Inc., where he helped launch several Class II medical devices, including the Opal Espirit Class II Corrector. With more than five years of direct medical device experience, as well as a deep understanding of the FDA's submission process and audit procedures, Butler is a vital part of the MasterControl product management team.