FDA’s current policy for determining when a modified device needs a new 510(k) works well without major changes, device industry representatives say. But they say it could be improved with more emphasis on the importance of design controls and risk management procedures to guide a company’s decision-making process.

FDA held a public meeting June 13 at its Silver Spring, Md., headquarters to gather stakeholder input on its 510(k) device modification policy. (See Also see "News In Brief" - Medtech Insight, 17 June, 2013..)

The agency was required by the FDA Safety and Innovation Act to collect input in preparation for sending a report to Congress on the topic by January. FDASIA, enacted last year, restricts FDA from issuing any draft guidance or proposed regulation that addresses when to submit a new 510(k) for changes before submitting the report to Congress, and restricts FDA from issuing any final guidance or regulation on the topic for one year after Congress receives the report. (See Also see "FDA Subject To More Oversight Following User Fee Bill Passage" - Medtech Insight, 2 July, 2012..)

The FDASIA provisions were enacted in response to a controversial 510(k) modification draft guidance issued in 2011, which the agency withdrew in 2012 in the face of widespread opposition from device-makers claiming the guidance could lead to a 300 percent increase in 510(k) submissions. (See Also see "A “Disastrous” Draft? Device Firms Take Issue With 510(k) Modifications Guidance" - Medtech Insight, 5 December, 2011..) Since the withdrawal, FDA has relied on its previous 1997 guidance on 510(k) modifications.

Prior to the meeting, AdvaMed submitted a white paper saying FDA’s 1997 guidance, along with the current medical device and quality system regulations, were sufficient with just a few proposed changes.

“We have established standard operating procedures that reflect every question in the 1997 guidance document. We answer every question, we document our responses, and that didn’t come out at the [FDA] workshop” – Tamima Itani, Boston Scientific

The trade group suggested modifications to the 1997 guidance to clarify three points: First, every company must evaluate a change in specification, method or procedure against established procedures to determine if a new 510(k) is required and retain all records of the evaluation. Secondly, companies should establish a procedure in their quality system protocols to ensure that changes made to the device design – both pre-production and post-production – are reviewed, validated (or verified) and approved. Lastly, company responses to questions in the guidance’s decision trees should be based on the results of validation or verification testing.

Design Controls, Risk Management Supported By Industry

The FDASIA provisions stipulate specific information that FDA needs to include in the report to Congress. The agency must outline its interpretation of the phrases that are supposed to guide a company’s decision as to whether a change requires a new 510(k), specifically: “could significantly affect the safety or effectiveness of the device;” “a significant change or modification in design, material chemical composition, energy source or manufacturing process;” and a “major change or modification in the intended use of the device.” FDA also has to discuss possible processes for industry to use to determine whether a new 510(k) is required. Further, the agency has to analyze how to leverage existing quality system requirements to reduce pre-market burden, facilitate device improvements and ensure safety and effectiveness of modified devices.

At the meeting, FDA asked stakeholders to comment on some specific changes it is considering making to its 1997 510(k) modifications guidance. In particular, the agency floated revised methods for determining whether a new 510(k) is needed relying on risk management procedures, design controls, critical specifications, risk-based stratification of 510(k) devices and periodic reporting to FDA.

Industry agreed with FDA’s proposal to emphasize the reliance of design controls and risk management procedures when making determinations of whether to submit a new 510(k) for device change.

In fact, a lot companies already rely on several of these methods to make such decisions, says Tamima Itani, Boston Scientific’s VP, regulatory affairs and regulatory compliance, who spoke on behalf of AdvaMed and the Medical Device Manufacturers Association at the meeting.

“If you look at the questions about quality system, design controls, risk management and critical specs – all of that today, by regulation, has to be considered when making modifications. If I were to make a modification today and not include design controls, which includes risk management, which includes our company’s definition of critical specs, I would be out of compliance,” she said in an interview.

“So today those requirements exist and we leverage those requirements to make a decision. And I think that’s maybe where we need to work with FDA to better explain that,” she added.

Itani said she doesn’t think FDA has a good understanding of all the steps companies currently take when assessing whether to submit a new 510(k).

“We have established standard operating procedures that reflect every question in the 1997 guidance document. We answer every question, we document our responses, and that didn’t come out at the workshop,” she noted.

“There’s a pretty general consensus that the agency shouldn’t mandate that a single process should be used to assess all changes. Rather, let’s lay out a toolbox” – Ralph Hall, professor, University of Minnesota Law School

“I think part of the work that we need to do with FDA is to show them the complete assessment we do, walk them through all documentation and all the background information that we use in making that assessment.”

Ralph Hall, professor of practice at the University of Minnesota Law School, who has represented the device industry on Capitol Hill, said FDA should encourage the use of several methods or “tools” to assess whether a change requires a new 510(k).

“I think there’s a general view that stakeholders need to have multiple tools to use to assess whether the regulatory standard has been triggered, depending upon the type of changes being made, the type of product, the existing systems at the company, etc.,” he said in an interview.

“For example, in a number of situations, design controls may be a very important, valuable tool, but if I’m making a labeling change, are the design controls the best tool for that? Or maybe a better tool there is a risk assessment process.

“There’s a pretty general consensus that the agency shouldn’t mandate that a single process should be used to assess all changes. Rather, let’s lay out a toolbox.”

What Does “Could Significantly Affect” Mean?

Industry also sought clarity at the meeting on the meaning of “could significantly affect the safety or effectiveness of the device,” which is the current regulatory standard for determining whether a change to a device requires a new 510(k) submission.

“We need more clarity on what that standard is,” Hall told “The Gray Sheet.” “I’m using the word ‘clarity’ deliberately rather than ‘definition,’ because some people have a connotation with definition that I don’t mean. Clarity so that all stakeholders – agency, advocacy groups, industry, Congress – have a more common understanding of what that regulatory standard is.”

“Once you know the target, or the meaning of that concept, then you look at your processes – whether it’s design control, risk management or whatever – to assess whether or not that standard has been triggered,” he said at the meeting. “But without having a common understanding of what the standard is, I think we’re shooting in the dark … because we don’t know the target that we’re aiming at.”

Boston Scientific’s Itani agrees there shouldn’t be a word-for-word definition of “could significantly effect,” rather, FDA should lay out a process companies can use to determine if a change meets the standard.

“You look at [the 1997 guidance], the reason it has worked so well is it’s actually a process. It walks you through all the things you need to consider in making a decision. … Now, can it be augmented? I would be one of the first to say absolutely.”

Itani says one of the key updates FDA should make to the1997 guidance is to put greater emphasis on companies having standard operating procedures that reflect the guidance requirements. This makes it much easier for FDA to audit against these procedures, she explained.

Also, she said the guidance can be augmented to ensure it relies on the quality system and design controls at every stage of the process “as a reminder that you’re not making this decision in a vacuum, you’re making it based on 21 CFR-820 and the design controls and risk management requirements of that section of the regulation.”

“I think if you’re looking for a robust process, and for a robust reliance on a quality system, then you really need to proceduralize your effort.”

Resistance To Annual Reporting

Industry generally opposed FDA’s proposals to set precise critical specifications, create a risk-based stratification of 510(k) devices and require periodic reporting from companies.

The idea of mandating periodic reporting for 510(k) devices in particular attracted a heated response from industry. FDA suggested at the meeting that industry could send annual reports to the agency for each of their 510(k)-cleared devices, which would include changes made to the device over the past year. Although the agency readily admitted that this would place significant fiscal and personnel constraints on industry and FDA.

“There are a number of policy and practical challenges with the annual report obligation, including resource issues,” Hall said. “Let’s assume a company sends in an annual report, what’s FDA going to do with it? There’s the time and effort to create it; and the time and effort to review it.”

Itani alluded to the vast number of 510(k)s on the market today, versus the fewer number of PMAs, for which companies are currently required to submit annual reports to FDA.

“There are hundreds of thousands of 510(k) devices on the market and even if [a 510(k)] were to change only once a year, or once every other year, the scope is really, really big. The manufacturer has the big picture of what’s happening with the device. You have a several people working on a modification, versus one reviewer looking at one modification out of context possibly,” she said.

Hall asked, “Is the answer to send an annual report to the agency so the agency can check all your decisions, or is it through the more traditional enforcement mechanisms that already exist, and the other traditional reporting methodologies and requirements that already exist?”

Under the 1997 guidance, if industry makes a change to a device that requires a new 510(k), the company has to tell the agency of all the changes it has made to the device made since it last submitted a 510(k).

“So the agency gets the information already in that context. So when the agency is reviewing that new 510(k), they can say, ‘Wait a minute, I have a question about a change you made two years ago,’” Hall said.

“I think that there’s a consensus that not everything should be submitted. There are changes that are so trivial, so unimportant, that they should not be submitted. If you submit everything, then time gets taken away from those things that are actually important,” he added.

FDA is accepting public comments through the docket for the meeting until July 13. The agency said it plans to incorporate the comments into its report to Congress.

Industry Says Update To 510(k) Modification Policy Should Emphasize Design Controls, Risk Management

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