The emergence of combination products is changing the medical-device landscape. Defined as two or more regulated components — drugs, medical devices, or biologics — combined through physical or chemical means, combination products inherently require two separate skill sets for development. Where medical-device companies once possessed 100% of the expertise to develop a product, they must now share ownership with a biotech or pharmaceutical partner. The shared model intensifies every aspect of product development from IP and regulatory issues to packaging and marketing strategy. For these and many other reasons, it is critical that products are well targeted.

That takes several steps. The first one: accurately assess market demand. Medical-device companies may benefit from using an external design-engineering firm to research the market. Objectivity is a central ingredient in research. With no financial stake in the technology or device, an external group fits the profile.

More than just identifying market needs, combination-product makers must consider the accessibility of the product to its target audience. For example, if a product is targeted for Type 2 diabetes, then product developers should consider the elderly population a primary market, and make a top priority out of obtaining national coverage and reimbursement from the Centers for Medicare and Medicaid Services (CMS).

Because CMS requires evidence that the combination product will provide a clinically more effective therapy than is currently offered, combination-product makers should identify clear differentiators at product concept. Similarly, CMS wants companies to demonstrate the product will provide a significant health benefit. Product developers should, therefore, have some way of measuring the health benefits of their products. Although CMS is not supposed to consider cost when making a national coverage decision, there are recommendations for it to begin doing so. Combination-product developers would be wise to design with cost in mind not only to preempt any decisions CMS may make in the future, but also to minimize threats from competing products.

Because CMS coverage will greatly influence physician adoption of the combination product, companies are advised to begin the reimbursement process as early as possible. This will help to decrease the lag time between FDA approval and CMS coverage, allowing the combination product to reach its target populations sooner.

While IP sharing is an inherent part of combination-product development, working with a neutral engineering partner can minimize IP issues between medical device and pharmaceutical companies, while ensuring confidentially and protection of the intellectual property of the products it develops. Engineering partners should advise and encourage pharmaceutical and medical-device customers to apply for patents both separately and together for the drug, the device, and the combination of the two to ensure protection for each company's proprietary technology.

Combination products also present unique manufacturing challenges. Beyond the physical design challenges of combining the two entities, sterilization, validation and drug-device interaction issues further complicate development. In addition, drug products can become contaminated if chemicals, known as extractables and leachables migrate from plastic medical-device components.

Another consideration for a combination product is its Primary Mode of Action (PMOA), or the product's single mode of action that provides the most important therapeutic result. Each combination product has a PMOA, but defining it can be complicated. To minimize regulatory confusion, it is best to establish an intended PMOA at the outset of the project. Believe it or not, device and pharmaceutical companies may not always agree on PMOA given the differences in scale, timeliness, and other matters. It is therefore beneficial to consult with experts, including regulatory counsel.

Regardless of whether the product is a combination device, traditional medical product, or an innovation in an altogether different market, planning for manufacturing should begin soon after developing a product concept. Doing so avoids developing a product that is extremely difficult to manufacture. It also lets the company determine whether standard tooling will work, and if not, begin scouting new or modified equipment. For example, discovering that a product cannot be manufactured on standard equipment after finalizing the prototype makes changes to either the product or production machinery costly and time-consuming.

Packaging combination products is as challenging as their design effort. Most require special barrier properties to protect pharmaceutical or biologic components from moisture and oxygen. For example, some drugs require refrigerated storage to preserve their shelf life.

Because combination products can be used anywhere in a hospital or healthcare environment, packaging requirements vary greatly depending on the device's intended use. For example, devices used in operating rooms call for a double sterile barrier, whereas devices used in patient rooms need only a single package.

In addition, traditional sterilization procedures, such as ethylene oxide gas, can render drugs ineffective, so new strategies may be needed to ensure product sterility, especially for biological drugs. Manufacturers must identify other suitable sterilization methods such as gamma irradiation, electron beam, or UV sterilization.