Medical Device Daily National Editor

MINNEAPOLIS — Ashley Boam came to Minneapolis to share some thoughts about why and how the FDA makes decisions on medical-device companies' applications for product approvals.

She did that, but also had her own "take-aways" from her appearance during last week's IBF Med-Tech Investing Conference at the Radisson Plaza Minneapolis Hotel.

The 7th edition of the annual conference was co-presented by International Business Forum (IBF; Massapequa, New York) and LifeScience Alley (St. Louis Park, Minnesota).

Boam, acting deputy director for science and review policy in the Office of Device Evaluation of FDA's Center for Devices and Radiological Health, participated in a session dubbed "FDA Fireside Chat."

She was quizzed by Mark DuVal, president of DuVal & Associates (Minneapolis), a law firm serving life sciences companies, on a range of subjects ostensibly involving the concerns that venture-backed device firms have in dealings with the regulatory agency.

After three-quarters of an hour spent responding to DuVal's questions, Boam was asked if she had learned anything from being exposed to that morning's sessions of the highly focused meeting, whose aim is to address the issues facing entrepreneurs and those who would invest in their ideas.

"At least two things," she replied. "One, that we as an agency need to do more to explain our thinking when we send out a letter" to a company, relating to its application for product approval. When FDA has further questions of a company, "we need to better explain what we're after."

Secondly, referring to a preceding panel on "Doing Well By Doing Good," which included an emphasis on how patients are positively affected by new and improved medical technologies, Boam said, "I enjoyed the idea of maintaining that connection with patients."

She added that she finds it particularly rewarding when her work puts her in direct contact with patients. "FDA can do a better job of making contact with patients," Boam said. "They're why we do what we do."

Here's a not-quite-verbatim look at some of the questions posed by DuVal during the conference session and Boam's responses.

DuVal: Venture-backed companies want FDA to know to what extent agency policies impact those companies.

Boam: We are cognizant of that, and it's something that comes up quite a bit. We're very attuned to the fact that these small start-ups are where much of medical technology starts. So certainly the impact of our actions on small companies is very much on our minds.

DuVal: What are some of the mistakes companies make to contribute to delays in getting their 510(k) applications approved?

Boam: In that first application, some companies kind of just cross their fingers and hope they've covered what they need to. Then a letter comes from FDA, asking questions, and a quick answer comes back to us. You [companies] should understand what we're asking. Pick up the phone and call your reviewer to ask what we're looking for. And if you get a second letter that seems to ask pretty much the same questions as the first letter, call the appropriate branch chief and ask what the stumbling blocks are.

DuVal: Are branch chiefs open to being called early in the process?

Boam: I would want you to have had a conversation with the reviewer, or with the reviewer and branch chief together. If the reviewer isn't responsive or something just isn't working, the branch chief is the next step. If there's an honest difference of opinion over scientific or regulatory issues, then talk with the division director. But choose your battles. The big issues that may make a difference between approval or not — that's when to talk with a director. Internally, the question we ask when we're going over these matters with reviewers is, "Is there a way forward?"

DuVal: How about different iterations of products that come along while the product is under review?

Boam: It depends on how big the differences are in those iterations. Sometimes changes are based on physicians' feedback and don't require much to make that change at the FDA level. Come talk with us. Say "here's how we see the changes in this product — how do you see that?"

DuVal: How well are modular PMAs doing?

Boam: I think there have been both positives and negatives. For more complicated products, such as combination products, it's a way to get some of the issues out of the way as you're going along.

DuVal: To what degree do you allow companies to be politely contentious with FDA?

Boam: It's okay to be politely contentious with us. We rely a great deal on having mentors within the agency, and we also look to companies to help us understand the issues. So it's okay for you to say, "FDA, I politely disagree with you, and this is why." The politely is important. Try something along the line of, "Hey, we'd like you to take another look at this." We will sometimes change our view. We're open to hearing about this, because we're not always right. We hope that by having multiple layers of supervision, we get the things right.

DuVal: In your response times, do you ever take into consideration the financial difficulties a company may be facing?

Boam: The question of a company's financial situation does come up, but when it's a question that is critical to outcomes, we can't take that into account. However, a "heads up" call to a branch chief about your financial situation as we're considering your application can help.

DuVal: So a company can push back — politely?

Boam: Yes, you can.

DuVal: To what extent do you emphasize with your reviewers the law as well as the science?

Boam: 510(k)s are so much harder for us than PMAs. With PMAs, the approval process relative to clinical trial results is clear, while with 510(k)s, proving "substantial equivalency" can be pretty challenging.

DuVal: Companies often are asked to respond to a variety of questions by the agency. How do their answers apply to the process?

Boam: Sometimes I'll ask a reviewer or branch chief, "What are you going to do with the answer to this question?" The line between "need to know" and "like to know" can be fine. We may have a good reason for asking that predicate-device question, but we need to make sure we make clear to you why we're asking this question.

DuVal: Is the de novo process — an intermediate category that's part of the 510(k) process — working?

Boam: I think it can work. It's worthwhile legislation. — de novo provides an important process, although it's not an easy process. You essentially are establishing the "control" for this type of device in the future. When you're thinking about taking the de novo approach to your product approval, that's when you need to get on the horn with FDA. It's important to have regular communications with us then.

DuVal: Do you at the agency take the "least burdensome" principals, which were rooted in the PDUFMWA legislation — seriously, or do you just roll your eyes?

Boam: Yes and yes. It really is a mantra that is reinforced at the agency. But you as a company need to know that there may be reasons why you choosing to do a single-arm trial rather than a controlled, randomized trial may cause us problems at the end. Ask us why we think a broader trial really is "least burdensome."