Pay attention to these four best practices when developing a combination product.

Arundhati Parmar

Combination products are complex due to the fact that they involve the confluence of multiple elements—drug and device; device and biologic, or biologic and drug.

That is precisely why it's imperative to follow best practices when developing these products, David Amor, managing partner and principal at MEDgineering Inc, said at the MEDevice San Diego Conference and Tech Showcase. (Hear Amor's upcoming presentation on developing a robust quality management system for combination products at the MD&M West Conference on February 11, 2016.)

Here are the four that all companies developing combination products should consider:

Figure out Your Primary Mode of Action

Even while developing a combination product—no matter if it's drug or device or biologic—the product will have primary mode of action. For instance, a coronary eluting stent is primarily a device because the stent is what is delivering the drug, Amor explained.

Determining the primary mode of action also means that come time to apply to FDA, the company will know which center to submit to—if the primary mode of action is a device, then the application would go to CDRH.

The problem with not determining the primary mode of action as a company means FDA will make the decision on the company's behalf, and that's not where you want to be, Amor says.

"It's a binding recommendation," he says. 

So if FDA decides that the product's primary mode of action is a drug, then that decision is final.

"FDA typically has a conservative recommendation and that could lead to more development costs especially if you are designated as a drug," he said.

It's far easier to rely on cited literature, case studies, and science to make the case for yourself.

Prepare your Design History File Based on Risk

If a combination product is designated as a drug, then the design history file of the product—which includes the device portion, drug portion, and packgaging of the product—needs to be submitted to the Center for Drug Evaluation and Research (CDER). In turn CDER, turns over the device portion of the design history file to CDRH, which reviews the document.

So how detailed should the design history file be?

"The higher the risk of the device portion, the more comprehensive the design history file should be," Amor advised.

Also, it's important to see how much scrutiny a category of combination products has. 

"Over the last three years there has been more regulatory scrutiny of pen injectors," Amor pointed out. "That means you should enhance your [design history file]."

Review Avaliable Guidelines on Combination Products

Back in 2013, FDA took its first stance on combination devices though the 21 CFR 4, Amor said. Any company looking to develop combination products should look at that.

"There are also tons of device -specific guidelines on products like pen injectors, coronary stents," he said. "It's a lot easier to do a submission when there are guidances that are available."

Don't Forget Usability Testing

When developing combination devices, it's critical to ensure that the device doesn't compromise the efficacy of the drug. So for a company making a device that is delivering the drug, it is important to observe how users are operating the device.

"User error might lead to the therapy being compromised, so there is a risk associated with usability," Amor said.

FDA will need to know how the company has mitigated that risk associated with user interface error. 

Arundhati Parmar is senior editor at MD+DI. Reach her at [email protected] and on Twitter @aparmarbb 

CORRECTION: A previous version of the story incorrectly referred to the design history file of the combination product as only related to the device portion. DHFs relate to the entire product - device, drug and packaging. 

[Photo Credit:iStockphoto.com user Violka08]