Weighing patient safety against encouraging medical innovation is no easy task. The FDA has been struggling with it off and on, mostly on, since its creation in 1906 (yes, I had to look it up). It took very gross meat and a crusading Upton Sinclair to force the FDA’s very existence. Hopefully we won’t need anything so dire to effect some positive change this time around.

Over the past decade most critics have said the agency has been too understaffed to effectively regulate the F(ood)and D(rugs) of its name. When it comes to assessing its medical device activity, it’s a bit tougher to analyze. But that just might get a little bit easier. Last week the FDA unveiled two big evaluations containing recommendations that address three key objectives of the agency’s public health mission as it relates to medical devices – foster device innovation, create a more predictable regulatory environment, and enhance device safety.

The Center for Devices and Radiological Health (CDRH) assessment consists of two preliminary reports. The first focuses on ways to strengthen and clarify a premarket review process called the 510(k) program for medical devices that do not need to undergo a full premarket approval review. The second evaluates CDRH’s use of science in decision-making, with an eye toward adapting to new scientific information, while maintaining regulatory predictability necessary for innovation.

The two documents overlap in several places and cross-reference information. Both are available here.

“Having FDA 510(k) clearance is a big milestone, one which further validates” a company’s products, notes WellDoc CEO Ryan Sysko. He’s just been through the 510(k) approval process with a happy outcome (approval in July).

“We found the FDA to be very open and willing to talk, willing to offer guidance,” Sysko says. His advice to other young companies is “first thing, call the FDA, talk about your product and what it is trying to accomplish, and get a sense of the regulatory climate.”

Make sure the FDA understands your technology or product so they can better understand how doctors and patients use it, stresses Sysko. Also it important to put quality system programs in place early on and have strong employee training programs, Sysko adds. “It is absolutely critical to show the FDA your good work, too” he emphasizes. FDA on audits wants to see SOPs, document control, training records, among other items, and you’d better be ready to demonstrate it.

Back to what the FDA did last week.

CDRH established two staff committees on these issues in late 2009 as part of its 2010 strategic plan. The committees collected and reviewed input from public meetings, open dockets, data analyses, and input from CDRH staff over the course of several months to prepare the complementary evaluations.

We’ve heard from some medical device firms that scream bloody murder (off the record, of course) about how cumbersome and counter-intuitive the FDA’s 510k system has been. Even the agency admits that “concerns have been raised both inside and outside of the FDA about whether the current 510(k) program achieves its goals of making safe and effective devices available to the public while fostering innovation. Concerns about the program have centered on whether it allows devices to enter the market without sufficient safety and effectiveness evidence and whether a lack of predictability, consistency, and transparency is hindering device development.”

In other words, the FDA seems to understand that the system is broken. Is this a fix? Most say it is a good start, if nothing else. “The challenge the FDA will face is how do we take what’s being accomplished with technology while ensuring patient safety,” Sysko says, noting it’s obviously easier for Apple or Google to launch a new innovation than it is for medical device companies.

FDA makes some effort to defend itself, specifically CDRH, in its announcement. “CDRH uses science to guide its regulation of medical devices across the total product lifecycle,” notes the agency release. “At any stage of that lifecycle, new, unfamiliar or unexpected scientific information may arise that warrants a change in the FDA’s thinking, expectations, and actions.” CDRH says it is trying to find the right balance between the ability to adapt its approach as new science emerges and to provide predictable regulatory pathways.

“Taken together, these preliminary reports show a smarter FDA – an agency that recognizes both sides of our mission to protect and promote public health,” said CDRH Director Jeffrey Shuren, M.D. “The agency is ready to make necessary improvements to support device innovation while assuring patients receive safe and effective devices.

“Even with our significant outreach, it’s important to remember that these recommendations are preliminary,” said Shuren. “CDRH opened another public docket to receive additional comments on both reports. We will make a decision on which recommendations to adopt only after a thorough review of additional comments.”

While the agency has a prime directive to protect patient safety, it doesn’t want to slow or even destroy a medical device that’s ready to roll and ready to help patients. But the agency has often been accused of slowing innovation to the detriment of patient safety. It’s a balancing act, to be sure, and we should at the minimum give the FDA for addressing this and trying to come up with a good solution.

Selected recommendations and the key public health objectives they address include:

Fostering Device Innovation

• The 510(k) report recommends major improvements to the regulatory pathway for lower-risk novel devices that cannot be cleared through 510(k) but which do not warrant the more rigorous premarket approval review applied to higher-risk devices. The report calls for major reforms in the implementation of this process – called the de novo classification process. The recommendations include streamlining the process and clarification of CDRH’s expectations for submissions that undergo this type of review.

• The science report recommends that CDRH make better use of scientific experts outside of the agency by developing a web-based network of external experts using social media technology. This network would help CDRH staff leverage outside knowledge without serving in an advisory capacity.

Enhancing Regulatory Predictability

• The 510(k) report recommends that CDRH develop a guidance document defining a subset of moderate-risk (Class II) devices, called Class IIb, for which clinical or manufacturing data typically would be necessary to support a substantial equivalence determination. This guidance document would help clarify what information submitters should include in their 510(k) submissions so that they can plan accordingly. In addition, this would also help the center’s review staff obtain the type and level of evidence necessary to make well-supported decisions without as much need for time-consuming follow-up requests for information.

• The science report recommends use of a standardized “Notice to Industry” letter that would generally be issued as a “Level 1 – Immediately in Effect” guidance document to quickly communicate when CDRH has changed its premarket regulatory expectations due to scientific information that has emerged about a certain device type. CDRH currently communicates this kind of information through individual interactions during the review process, which can lead to delays. These letters would provide greater clarity to affected manufacturers, in a timelier manner, about CDRH’s expectations with respect to a particular group of devices.

Improving Patient Safety

• The 510(k) report recommends that CDRH consider revising regulations to explicitly require 510(k) submitters to provide a summary of all scientific information known or that the submitter should reasonably know regarding the safety and effectiveness of the device under review. This is not required now for 510(k) submissions and, as a result, relevant information may not be included in an initial submission. This summary would help CDRH review staff to more efficiently make decisions, and potentially avoid extensive follow-up inquiries and questions.

• The 510(k) report recommends that CDRH develop a guidance document that clarifies when a device should not be used as a predicate, such as when the device has been removed from the market because of safety concerns. The report also recommends that the center consider issuing a regulation that would clarify the circumstances under which the center would exercise its authority to rescind a 510(k) clearance to remove an unsafe device from the market and preclude its use as a predicate and also consider whether additional authority is needed.

• Both reports recommend that CDRH build upon public databases to include meaningful, up-to-date information that supports good decision making and promotes the safe use of devices. This could be accomplished by improving the current 510(k) database so that it includes summaries of FDA review decisions, current labeling and photos. In addition, the science report recommends that CDRH build upon the existing transparency website to provide more immediate information on how devices are regulated.

For more information:
CDRH Preliminary Internal Evaluations

CDRH Device Approvals and Clearances: 510(k) Clearances

Amid continuing debate about the timing and shape of the Senate’s food safety bill (the House passed a version in July 2009), comes a new issue that affects companies in the food, drug, device and cosmetic industries.

Several months ago, FDA Deputy Chief Counsel for Litigation Eric Blumberg told industry representatives at the FDLI Annual Conference that the agency is prepared to dust off the three-decade-old “Park Doctrine” to augment FDA’s continuing efforts to ratchet up its enforcement profile. The doctrine stems from the United States Supreme Court’s decision in United States v. Park, 421 U.S. 658 (1975). In principle, it allows the government to pursue misdemeanor charges against a corporate officer for alleged violations of the Federal Food, Drug, and Cosmetic Act, regardless of whether the officer is aware of the existence of a violation, as long as the officer holds a position of responsibility so that that individual could have initiated preventive or corrective action and, for whatever reason, failed to do so.

Park represents a strict liability standard, so no warning letter is required. FDA need only request that the Department of Justice file charges based on FDA’s conclusion that an officer is guilty of misconduct, which is effectively defined as failing to know what FDA believes one should have known. In sum, what an executive does not know can be more than harmful.

The scale of punishment for misdemeanors ranges from one year in prison and/or a maximum fine of $100,000 for each count, ranging to much higher where injury or death are involved. Courts can impose mandatory prison sentences, and if FDA believes a substantial risk of injury or death is involved, judges can increase the length of prison sentences.

At a time when corporate resources are stretched, the entire spectrum of regulatory compliance issues has become every bit as critical for senior management and counsel as the other bet-the-company issues that confront each company on a day-to-day basis.

Mark Mansour is a partner in the firm, Bryan Cave, LLP

FDA Extends Comment Period for Proposed Neurological Device Regulations
The FDA has announced that it is reopening until September 7, 2010, the comment period for the proposed rule and guidance published in the Federal Register of April 5, 2010 (75 FR 17093). The document proposed to amend certain neurological and physical medicine device regulations to establish special controls for these class II devices and to exempt some of these devices from premarket notification requirements. More information is available here and here.

Device Industry Calls for Closer Coordination Between FDA, CMS
Members of the device industry are calling for closer coordination between FDA and CMS related to the competitive bidding process. Stakeholders have said that the two agencies sometimes send mixed messages, due to their different approaches to devices, and particularly for sophisticated therapy products for home use, with CMS focused on pricing and the FDA focused on support services and safety issues, including labeling and training. Members of industry have indicated that they hope that new FDA guidelines on home-use devices will make certain that suppliers ensure that training and support are provided as part of their bids.

FDA Weighs New Approach to Regulation of DTC Genetic Tests
In the wake of a recent GAO report finding that direct-to-consumer genetic tests are providing inaccurate results to the public, the FDA has indicated that it is considering an approach to regulating the tests that would increase oversight without creating heavy reporting burdens on individual companies. The agency’s potential approach, as currently envisioned, would not require the developers of certain diagnostics to submit data on their individual diagnostics, if a manufacturer had previously provided information on the overall indication of the diagnostic to the FDA.

Pharmacies Calling for Removal of Reimportation Amendment from Food Safety Bill
Pharmacies are ramping up their efforts to encourage lawmakers to remove an amendment to the food safety legislation, offered by senator Byron Dorgan, that would allow for the reimportation of drugs from Canada and Mexico into the United States. Pharmacies are stating that the safety of such drugs cannot be ensured and that the use of reimportation means that individuals would not be consulting with a pharmacist at the time that they obtain the drug. Some are speculating that the amendment, which Dorgan also attempted to introduce in the health reform legislation, could prevent the passage of the overall bill, and are thus encouraging its removal.

Mark Mansour is a partner in the firm, Bryan Cave, LLP

I’ve got to admit, despite months (or years?) of hearing from those inside and close to the FDA that the agency intended someday to begin actual enforcement of 21 CFR Part 11, I was beginning to have my doubts.

No one likes to be told he’s crying wolf or acting like Chicken Little squawking about the sky falling.

Finally, however, the FDAs CDER division issued a blandly worded release that may have some serious repercussions for regulated drug companies:

The FDA “will be conducting a series of inspections in an effort to evaluate industry’s compliance and understanding of Part 11 in light of the enforcement discretion described in the August 2003 ‘Part 11, Electronic Records; Electronic Signatures — Scope and Application’ guidance (Guidance). The Agency intends to take appropriate action to enforce Part 11 requirements for issues raised during the inspections that do not fall under the enforcement discretion discussed in the Guidance.”

That’s about all they said publicly, but it’s a mouthful after waiting a long long time for any agency activity backing the Part 11 rule.

While this announcement focuses on drugs, don’t be surprised to find a similar action coming soon on the device side.

“I’d expect FDA inspectors to focus on Part 11, too, when they inspect device manufacturers,” agrees former FDA inspector Ken Miles.

When it comes to preparing for FDA inspections, Ken says he’s a big fan of the Boy Scouts motto: Be prepared.

We’ve heard in the past that many FDA inspectors weren’t comfortable yet inspecting or enforcing Part 11 provisions. The result: Very few inspections, and some inconsistent inspectors.

In the coming weeks, we’ll report back on what kind of inspections FDAers are conducting, and how you can best prepare for them.

“Check back in August,” FDA spokesman Dick Thomspon told us this week when we asked if the eMDR guidance was coming out anytime soon. “The guidance is not yet complete,” Thompson said. “At this point, I would not expect this to be issued before the end of the summer.”

The FDA has missed several unofficial deadlines for the guidance, others in and close to the agency have told us in recent months. The latest missed deadline was June, when several folks inside the agency told us and others off the record that it was going to be issued that month.

Well, that didn’t happen.

It’s unclear exactly what the cause of the delay is; we’ve heard from those inside the agency who say it’s more about workload and shifting priorities than any guidance content issue, e.g. the eMDR guidance gets shoved off someone’s desk when something else “more important” comes up. More ominously, we’ve also heard some rumblings that the eMDR process is getting a little political much like the Part 11 process did.

At any rate, the agency asked us to check back in August.

Have a nice summer.