The Unique Challenges of Gaining Approval for Drug-Device Combos

March 24, 2021

A combination product is composed of any combination of a drug and a device; a biological product and a device, a drug and a biological product, or a drug, device, and a biological product.

Consider the asthma inhaler. The primary mode of action (PMOA) is the drug because it’s the drug that’s providing the most important therapeutic action of the combination product. The device is simply delivering that drug for consumption. In the example of a drug eluting coronary stent, the stent provides the primary mode of action because its purpose is to dilate a stenosed vessel; the purpose of the drug is to keep the treated vessel from re-stenosing.

This is an important distinction in the FDA's eyes because the PMOA determines which center at the FDA (referred to as the lead center) has the primary jurisdiction for premarket review. The PMOA also dictates which regulatory approval pathway the product will follow, which leads us to the first challenge sponsors face when seeking approval for drug-device combinations.

Challenge: Different Regulatory Approval Pathways

Drug-device combinations involve components that would normally be overseen by different branches of the FDA. As a result, each combination product presents unique and challenging regulatory considerations.

Assignment is based on the determination of the product’s PMOA. If the PMOA is attributable to the drug product, the center responsible for premarket review of that drug product would have primary jurisdiction for the combination product. In this case, it is FDA’s Center for Drug and Evaluation Research (CDER).

Similarly, if the PMOA of a device-drug combination product is attributable to the device, the center responsible for premarket review of that device would have primary jurisdiction for the combination product. In this case, the lead center is the Center for Devices and Radiological Health (CDRH).

The appropriate center will take the lead in reviewing the application and will consult with the other centers regarding the relevant part of the drug-device combination.

The challenge is that each center handles matters differently. The evidentiary standards for drugs and devices are somewhat different. As a consequence, each center has their own philosophy on the regulation of the component under their jurisdiction, and they have their own idea as to what data is safe and effective enough to support approval. This can sometimes lead to misalignment within the review team which can create bumps in the road for the Sponsor.

Challenge: Expertise

Typically, Sponsors developing a drug-device combination product have significant expertise in one of the two constituent areas. They are either very experienced with the drug component or they are very experienced with the device component. This can pose a challenge because, regardless of the pathway to approval, the FDA requires them to provide substantial evidence in both areas. Therefore, the Sponsor must find a way to gain the necessary expertise prior to submitting their application.

Challenge: Cost and Time

The FDA requires that each constituent part of a combination product be tested independently as well as together. This means there is a lot more evidence that needs to be submitted to the Agency to obtain approval for a combination product. Therefore, the overall cost and time for development can be much greater than for a single entity.

Challenge: Risk of Interaction

The FDA expects Sponsors to look at all the risks that could be associated with interactions between the components. All of the components are in contact with each other, either physically or procedurally, meaning there may be interactions that pose a risk to the user. This means testing specifically focused on mitigating those risks must be conducted.

Challenge: Human Factors

The FDA often times requires a human factors evaluation for drug-device combination products, especially for those that are to be used by the patient or caregiver. When cross-labeling the device and drug constituent parts, it’s crucial that there are adequate warnings and instructions for the use of each component and that those warnings and instructions are consistent across each component. These requirements add extra layers of complexity, cost, and time to the regulatory process.

Overcome These Challenges with ProPharma

There is a range of challenges that come with seeking approval of a drug-device combination product. That’s why you should consider getting the help you need to navigate the regulatory complexities and overcome the related challenges.

ProPharma has internal resources that come from both worlds. Our consulting team is comprised of individuals with a depth and breadth of knowledge concerning drugs and devices and their associated regulatory pathways. This means we can help shepherd your drug device combination product through the approval process regardless of which Agency center has primary regulatory authority.

Contact our consulting team today to learn about the particular challenges in your project.


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