Experts: FDA’s Product Jurisdiction Officers are key resources in developing combo products

Correction: An earlier version of this story misstated the title of the product jurisdiction officer and misattributed the sponsor of the case study drug. Regulatory Focus regrets the errors (7 December 2023).
Correction: An earlier version of this story misattributed several quotes. Regulatory Focus regrets the error (6 December 2023).

Fort Worth, TX – The Product Jurisdiction Officer (PJO) is a manufacturer’s prime go-to when working through the complex processes of getting a combination product over the finish line, according to a panel of experts who spoke at the 2023 Combination Products Summit held by the AFDO/RAPS Healthcare Products Collaborative.

“The PJO is your best contact if you know — or think you know — your product’s center, or if you already have an Investigational New Device application in house and want to add to it,” said Sarah Mollo, a combination product policy advisor for the US Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH).

The PJO stands at the intersection of all three of the FDA centers that may be involved in regulatory decisions for a combination product: CDER, overseeing drugs; the Center for Biologics Evaluation and Research (CBER), overseeing biologics; and the Center for Devices and Radiological Health (CDRH), overseeing the device itself.

Using the PJO as a one-stop information lead eliminates the need for sending multiple inquiries to these different offices which, Mollo said, can actually lead to confusion rather than increase the chance of getting the necessary information.

“We want to highlight that there’s really no need to send inquiries on multiple occasions. When that happens, sometimes it can cause confusion or duplication of effort,” she said. “We’re one place for your inquiries and we’ll make sure that you get the right answer.”
The PJO is also in constant contact with the Office of Combination Products (OCP), which facilitates efficient communication, Mollo said. “If we are unsure about the classification or there are new policy considerations, we will loop in OCP.”

Classification jurisdiction
The PJO doesn’t just help in the initial product development steps. Before or during a Request for Designation under the lead of OCP, the PJO conducts an initial review which includes background material and expert input. Mollo pointed out that a pre-RFD or RFD is not a requirement, but is useful in cases where there is uncertainty or disagreement about the product classification (RELATED: FDA finalizes guidance on premarket review of combination products, Regulatory Focus 31 January 2022).

“PJOs are also resources for both internal and external stakeholders on a wide variety of issues related to classification jurisdiction and combination product-related questions,” she said.

They can answer questions about regulatory pathways, consult with other centers, help with meeting requests, field questions about adverse event reporting, and even provide advice on post-marketing safety reports, Current Good Manufacturing Practice (CGMP) regulations, and patents and exclusivity issues.

In addition to classifying medical products and facilitating communications between sponsors and regulatory offices, PJOs will assign combination and non-combination products to the appropriate centers. “We can help you navigate concurrent submissions, which is actually really tricky,” Mollo said.

For example, a combination product cannot be approved if either the drug or the device it contains is being used in an off-label indication. “A really straightforward example of this would be an intrathecal delivery device using a drug that’s only been approved for intravenous use. There would be an inconsistency here, which might mean that you’d have to work with another manufacturer to get the labeling of that product updated,” she said.

PJOs are ‘often underutilized’

A PJO was critical in plotting the regulatory course for a groundbreaking bladder cancer drug, said Chelsea O’Connell, director of global and regulatory, and research and development policy at Amgen.

As a case study, O'Connell discussed Jelmyto (mitomycin for pyelocalyceal solution), a multi-step delivery system that infuses mitomycin into the bladder, a product from UroGen Pharma. The drug is a powder reconstituted to a liquid, which when instilled into the body, turns into a gel. The New Drug Application submission described the drug product and 12 devices: eight to prepare it in a sterile closed-system drug transfer device, and an additional four to instill the gel through a catheter with a syringe lever.

The challenge UroGen Pharma faced with this product was whether, despite its physical complexity, it qualified as a combination device, O'Connell noted. UroGen Pharma contacted PJOs at CDRH for an inter-center consult.

“During the review, PJOs provided feedback, reviewed this product and ultimately concluded that it’s not a combination product because the components are being provided by the facility. They are not co-packaged and they don’t form a single integral product,” O’Connell said. “And further, not all of the device labeling referenced the drug, so it was not a cross-labeled product.”

The PJO told UroGen Pharma that while the use of the devices needed to prepare and administer the drug was within the intended use, the 510(k) approvals for the devices were for liquids, not gels.

The company needed to conduct additional testing looking at drug-device compatibility, in-use stability, and human factors testing. Eventually, the drug by itself received a breakthrough therapy designation and came on the market in 2020 as the first treatment for low-grade upper tract urothelial cancer.

“Working with PJOs has greatly improved the coordination and collaboration for combination product reviews,” O’Connell said. “Of course, if drug sponsors have questions regarding classification or pathway, there are a number of ways to seek out feedback. But there’s also this ability to consult directly with PJOs in the appropriate center. I think this is often underutilized. Sponsors can request that their PJOs are included in the product meetings, and they are a critical resource for policy development or policy-related questions, and providing feedback into guidance.”

2023 Combination Products Summit

Experts: FDA’s Product Jurisdiction Officers are key resources in developing combo products

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