Brad Ryba, Publisher, www.my510k.com
Much has changed in the FDA over the past year, and it appears more change is to come. Issues surrounding device approvals under the 510(k) process were front-and-center in a public meeting this past Thursday. The meeting was titled by the FDA, “Strengthening the Center for Devices and Radiological Health’s 510(k) Review Process” and the agenda included a full day of discussion. FDA invited 30 speakers including industry executives, physicians, and policy advocates. Preceding the speakers, FDA did make some presentations citing its challenges under the current system. This was followed by a round-table discussion, along with some open Q&A sessions. From this meeting, it seemed two clearly differing agendas will shape policy changes over the coming months.
The FDA was clearly laying out the case for why it wants to make changes, while trying to broaden its powers beyond the current 510(k) process. When Dr. Donna-Bea Tillman, Director for CDRH Office of Device Evaluation made her presentation, she seemed to be open minded, stating that, “Trying to find the right balance between a regulatory process that enables us to foster innovation and at the same time ensures reasonable assurance of safety and effectiveness is the challenge we are here to talk about today.” Christy Foreman, CDRH Deputy Director for Engineering and Science Review was a bit more wary of industry, particularly in areas where FDA does not have as much authority. She contended, “Submission for [510(k) ] modifications are based on firm’s determination regarding the effect on safety and effectiveness. ” Ms. Foreman seemed to be hinting that this was an area she and FDA wanted to see addressed. Their concern is that documentation for incremental device changes is currently only kept in a firm’s internal files rather than defaulting to an FDA evaluation. Many other suggestions by FDA speakers indicated that The Agency wants increased oversight into clinical trials and labeling regulation. Further, the Director of 510(k) staff, Heather Rosecrans suggested that FDA needs broader powers to more easily rescind a 510(k) clearance if necessary. Many more comments and side issues emerged during the presentations, and these comments did not go unanswered by the industry representatives in attendance.
Most of the participants from the medical device industry advocated for the continuation of the 510(k) process, with a focus on consistency and transparency. Medtronic’s Chief Regulatory Officer, Susan Alpert highlighted the result of a cumbersome 510(k) process citing, “Our products go more quickly into other markets under other schemes than under this scheme”. She and her counterparts at the round-table discussion offered several suggestions to help the program evolve, while stressing that the current process works well for the majority of devices. Putting it another way, Craig Coombs, Head of Coombs Medical Device Consulting argued, “It’s not the 510(k) process. It’s what our interpretations are… predictability is really what needs to be there in order for us to comply.” These messages were echoed by many of the other industry speakers, and it is clear that this topic will continue to receive much further discussion.
FDA will continue to hear comments on the 510(k) process, and a Working Group is scheduled to submit its report to CDRH Director, Jeff Shuren, by the end of May 2010. The docket for comments on 510(k) process will remain open until Mar. 19, 2010. Comments are also being compiled by the community at my510k.com and on Twitter. While suggestions are being taken by FDA, their position seems clear that “Strengthening the 510(k) Review Process” means getting tougher on industry.
Brad Ryba, Publisher, www.my510k.com
Before all this talk of “Snowmaggedon”, a beaming headline posted late last week stating that, “FDA Issues Guidance to Help Streamline Medical Device Clinical Trials”. If you were hoping to learn how it works, you were in for a statistics lesson on Bayesian methods for designing studies and analyzing clinical data. (Wait, don’t leave!) Good news is you don’t need a statistics lesson, to simplify the main point. FDA is now advocating the use of prior clinical data and even post-market data from a prior device to justify shorter clinical studies and/or smaller sample sizes. This is a huge change from the same Agency that has demanded more data and more time to review device approval applications. How can this be? Why does Bayesian probability allow us to do this? The answer is not rocket science.
Bayes’ Law basically views probability as just “degree of belief” that an event will occur today, given knowledge of prior events. Think of it this way…Have you ever “tried” to flip heads on a coin, or roll an 8 with dice? How is this possible, if the probability of coins and dice are already known? Since we know the physical act of flipping the coin can affect its outcome, it may not be a simple 50-50 probability. The Bayesian idea of prior beliefs, allow us to set constraints and make conclusions beyond the actual data. Humans are quite good at intuitively making predictions on very little information. Bayes just put this into mathematical notation. (not to diminish the significance of Bayes’ Law in any way.)
Now, before this starts to sound like a “free pass” to shorter clinicals, be sure to finish reading the FDA guidance. Once again for the sake of time, we can summarize… It makes sense that statistical theory cannot replace sound clinical science. The FDA is quick to caution that patient data from prior studies rarely are 1-to-1 exchangeable with the patients in the current study. Instead, a test can be applied to find their “borrow strength” from the previous studies. Also, FDA will require that you still submit to their reviewers, your rationale for considering such prior clinical data. All of the same requirements apply when filing for an Investigational Device Exemption (IDE), and all methods and assumptions will need to be reviewed before the study can begin.
That said, the fact that good prior information on clinical device use exists, and that a Bayesian approach may enable smaller-sized or shorter-duration trials is welcome news to the industry. In the official press release, FDA Commissioner, Dr. Margaret Hamburg says, “This is a terrific example of regulatory science in practice at FDA.” We at my510k.com hope to see these kinds of developments continue, balancing regulation enforcement with sound scientific practices.
Join the community at Brad Ryba’s website: http://www.my510k.com
Numbers don’t lie. Reviewing the year-end numbers for FDA’s CDRH electronic submissions (AS2 Electronic Submissions Gateway) provides some eye popping stats. This is an early indicator that electronic medical device reporting submissions have significantly increased over 2008, and certainly suggests they’ll rise even faster this year after the final rule is published.
Comment period on the draft guidance ended November 2009. The final ruling is expected within weeks. According to some FDA insiders, many were relieved the agency wasn’t overwhelmed with comments (slightly over two dozen comments were filed), and the ones received were definitely “workable”.
So, what did 2009 numbers look like?
Source: FDA
As the chart shows, early 2009 got off to a slow start, but picked up significantly in the fourth quarter of the year.
Source: FDA
But when comparing 2008 vs. 2009, total submission numbers jumped from 4,619 to 21,296. It’s apparent that the device industry has picked up the pace when it comes to electronic submissions to FDA. And if this isn’t a wake up call for device companies to move away from paper 3500A submissions to eMDR, we don’t know what is.
We’ll be keeping a close eye on this through 2010.
Michael Causey, Editor & Publisher, eDataIntegrityReport.com
As weird weather slaps both U.S. Coasts [flooding in Southern California, hail storms in the South], the forecast at the FDA looks like medical device firms could be in for some heavy stuff of their own in 2010. This isn’t Chicken Little saying the sky is falling here. Let’s review a few FDA actions in the past several weeks and probe a bit for their possible significance to medical device firms.
For starters, a relatively casual-sounding entry on the FDA’s transparency blog could signal the beginning of much more robust scrutiny and inspections for medical device companies.
Here’s a little of what it says, “FDA seeks input on whether inspection reports should be re-designed to separate out a summary or key findings page that could be made available to the public quickly. Disclosure of full inspectional observation reports would still require the same review for non-public information as it does now.”
Depending on how this in interpreted and ultimately implemented, it could mean that medical device companies are going to see a lot more inspectors doing a lot more inspections.
So far, most comments favor the FDA doing this, though one anonymous commenter raises a good point from the medical device manufacturer side: “Since FDA-483s are evidence gathered for potential legal action, it may be a violation of a company’s legal rights to have a FDA-483 released without a legal review and opportunity for a response. Also, some FDA-483s contain annotations about findings corrected during an inspection, etc. What would be the purpose in releasing such information?
Occasionally, there have been errors in findings by FDA investigators that have to be corrected after the original FDA-483 is issued. What would be the opportunity to publicize the mistakes made by FDA in correcting these errors?
The due process accorded in the current process was placed there for a purpose. Has anyone explored why the current process is in place?
Certainly, the improvements to ‘protect the public health’ are admirable, but what is the real purpose of this move?”
That’s a fair question. We encourage your comments. I think it could spell trouble for medical device firms.
“This is big and could mean more inspections [and legal exposure] for medical device companies,” agrees my blogging colleague and Bryan Cave law firm Partner Mark Mansour.
He also cites the appointment of Joshua M. Sharfstein to be the principal deputy commissioner of the FDA after serving as acting commissioner for Food and Drugs from March 29 to May 25, 2009.
“Sharfstein is incredibly enforcement minded,” says Mansour. [Look for a more in-depth legal analysis of this from Mark’s blog later this week]. “He’s giving the push” for more enforcement of medical device companies.
At the same time, CDRH has issued its Fiscal Year 2010 Strategic Priorities report – and it hints an awful lot about hiking enforcement activity to better protect the public’s health.
But wait, there’s more.
The FDA recently scheduled a public meeting on Feb. 18 to discuss key challenges related to the premarket notification, or 510(k) process, used to review and clear certain medical devices marketed in the United States. The FDA receives more than 3,000 510(k) submissions each year.
Last September, the agency announced it had asked the Institute of Medicine (IOM) to conduct a comprehensive study of the process. The IOM study is not expected to conclude until March 2011.
In the meantime, the FDA has convened its own internal working group to evaluate and improve the quality and consistency of the agency’s decision-making in the 510(k) process as well as its administration of the program. The February meeting will support the efforts of the agency’s internal working group.
The Feb. 18 meeting will run from 8 a.m. to 5:30 p.m. at the Hilton Washington, D.C./North Gaithersburg, in Gaithersburg, Md. If you want to attend or otherwise participate you have to register by 5 p.m. on Feb. 12, 2010. The agency is accepting written or electronic comments by March 5, 2010.
The meeting will be Webcast live here.
We’re not even through the first month of 2010 yet, and it already feels like a lot has happened – and there’s almost certainly more to come.
Michael Causey, Editor & Publisher, eDataIntegrityReport.com
Well, we told you 2010 was going to be a big year for the FDA.
While most of us were enjoying holiday treats or making new year’s resolutions, a leading FDA official said the agency was developing new guidelines designed to establish stricter standards for the data received from tests with human subjects used by medical device makers when they seek approval for a new or altered device.
Dr. Jeffrey Shuren, the acting director of the Center for Devices and Radiological Health, told The New York Times recently that the FDA most likely will soon urge device makers to take steps like using more sharply defined targets to measure the success of clinical trials. The agency may also urge producers to more closely follow patients enrolled in such trials to determine whether the targets are met, Shuren told The Times.
That sound you hear is the new drumbeat saying that the FDA hasn’t been tough enough on medical devices in the past, at least according to JAMA and an article published in the American Journal of Therapeutics which suggest the agency has to get stricter to better protect the public.
AdvaMed, the big medical device trade group, is taking a “wait and see” approach, at least publicly.
Or as Janet Trunzo, AdvaMed’s executive vice president, technology and regulatory affairs, told us recently, “FDA has not released any formal proposals or guidance regarding changes to the premarket approval (PMA) process. When the agency does so, we look forward to reviewing and commenting on them. In general, we support efforts to better clarify FDA submission requirements and to ensure patients have timely access to life-saving and life-enhancing medical technology.
Trunzo went on: “It is important to note that the FDA’s approval process for Class III devices is the agency’s most stringent. On average, the agency spends roughly 1,200 hours reviewing each application, and has the authority to demand additional data and to refer the application to an expert panel for review. To obtain FDA approval through the PMA process, a manufacturer must submit a detailed application that contains full reports of all investigations of the safety and effectiveness of the device; a full statement of the components, ingredients, properties, and principles of operation of the device; a full description of the methods used in the manufacture and processing of the device; information about performance standards of the device; samples of the device; specimens of the proposed labeling for the device; and any other relevant information.
“Clinical trial data is but one piece of the overall approval process for medical devices, as the FDA requires data to determine biocompatibility, mechanical strength testing, among others, which are not available through clinical trials. American patients have access to life-saving, life-enhancing technology because the FDA carefully balances the risks and benefits of each new device or advancement in a given technology.”
But Dan Walsh, a senior member of PA Consulting Group’s Life Sciences & Healthcare practice, says there will definitely be tougher standards, and some level of more stringent human clinical trial results. However, he believes there is room for straightforward 510(k) cleared products that make no substantial claims beyond equivalence to currently marketed products. Dan specializes in technology strategy and acquisition, medical device product development and improving the effectiveness of commercial launch of new medical technologies.
According to Walsh, another repercussion is that the 510(k) will be more narrowly applied, and there likely will be an extended use of ‘510(k) with clinicals’ submissions because these trials have not required the same statistical power or clinical depth (high in placebo or alternative therapy arms, etc.)
“If all products were required to obtain PMA approval with robust clinical trials, it would likely impede innovation and use of new technologies,” Walsh told us.
“Since the FDA has mandates for both protection of the public health and the oversight of launch of new therapies for unmet or underserved needs, an all or nothing approach is not feasible or practical,” he adds. “If all submissions required clinicals, one could add at least six months and many millions of dollars to the development time and cost for a medical device, all other things being equal.”
Kim Egan a partner with DLA Piper in Washington, D.C. and an expert in this arena who sits on the advisory board of Life Sciences Law & Industry Report, a publication for lawyers, business executives, directors of research and regulatory specialists practicing in health care-related life sciences fields, gave us some interesting observations, too:
- This development is not overly surprising given the open letter to President Obama that FDA scientists sent last year alleging corruption in the medical device approval process. The division head stepped down year as well. FDA is under strong Congressional pressure to reform.
- This report is based on a review of cardiovascular devices only — we can expect similar reviews of additional therapeutic areas over the coming months.
- Industry will want to take an active role in the comment period that will follow FDA’s issuance of draft guidance on new requirements.
- The impact on industry may be limited to products that require full PMA approval. Devices that rely on 510(k) approval need not submit clinical data, so providing the predicate device is unaffected by FDA’s review, the bulk of new devices on the market should not be affected by the new guidelines.
- The NY Times article contains an error regarding personal injury lawsuits. The reason personal injury lawsuits are limited is not because of the Riegel decision — that decision simply upheld existing law that provides federal preemption to medical device manufacturers, particularly on failure to warn claims. Because Congress has expressly preempted failure to warn claims for medical device manufacturers, such claims cannot proceed on state law theories. This is unlike the pharmaceutical area, where there is no Congressional preemption of state law.
It’s a fine line between regulations with teeth that protect the public without slowing valuable new medical devices. Just ask John Hanley, an attorney at Steptoe & Johnson in LA. He represents two medical device companies that have been significantly impacted by the highly conservative approach now being taken by the FDA.
“They have both decided to pursue clinical approval outside of the U.S. before continuing to attempt to navigate the very difficult road to approval here in the U.S.,” Hanley said of the two companies who wished to remain anonymous.
“In fact, it is disappointing to note that even where these companies have had multiple years of clinical data from activities outside the U.S., the FDA has not approved their pursuing expedited routes through the FDA approval process,” Hanley adds. “Unfortunately, the FDA’s recently adopted strict stances have resulted in the American public being denied the benefit of new medical technologies. Moreover, it is expected that the FDA’s conservatism will eventually lead to less investment in medical device companies domestically and thus, less medical device innovation in the U.S.”
Yes, 2010 is already shaping up to be an interesting year at the FDA.
Don’t touch that dial, we’ll keep you posted as this story moves ahead.
Mark Mansour, Partner, Bryan Cave, LLP
Some Concerned that New FDA Chief Counsel Lacks Food, Drug Law Experience
Although many stakeholders praised the selection of Maryland’s insurance chief to serve as the FDA’s top lawyer, some have expressed concern that he lacks experience with food and drug law. Still, many see his litigation background as beneficial and complementary to the FDA’s increased emphasis on enforcement.
FDA May Revise Guidance on Medical Device Approvals
The FDA has indicated that it may review its current guidelines on medical device approval and may issue a revised guidance that would require medical device manufacturers to notify the agency of any alterations to approved products. The change would occur as part of a larger agency review under Commissioner Margaret Hamburg and her chief deputy, Joshua Sharfstein.
CDRH Officials to Make 501(k) Process More Predictable
Officials at CDRH have stated that they want to break from what they acknowledge are questionable prior decisions and make the 501(k) process more predictable but are warning that this may mean that companies will need to be wary of relying primarily on past 501(k) clearance requirements or determinations.
FDA Announces Meeting to Identify Strategies for CDRH
The FDA is announcing a public meeting entitled: “Incorporation of New Science Into Regulatory Decisionmaking Within the Center for Devices and Radiological Health.” The purpose of the public meeting is to identify strategies and means for incorporating new science into the regulatory decisionmaking process within the agency’s Center for Devices and Radiological Health (CDRH). The meeting will be held on February 9, 2010, from 8 a.m. to 5 p.m. in Gaithersburg, Maryland. More information is available here.
Mark Mansour is a partner in the firm, Bryan Cave, LLP
Michael Causey, Editor & Publisher, eDataIntegrityReport.com
Well, the eMDR comment period has come and gone – and I’ve got to say I’m a little surprised at the relatively low number of comments. But let’s look on the bright side: What we didn’t get in quantity we might have gotten in quality. This is generally as well-articulated and intelligent a group of comments I’ve read in years.
The overall tone of the letters can be summed up like this: Some want more time to implement the rule, while most generally support the eMDR initiative and call for some changes, mostly of a relatively minor, if probably justified, nature.
A few days before the comment period ended, I spoke with Axis Technology President Mike Logan about why there were so few comments. A handful came in after we spoke on Nov. 11, but he and I are still both a bit surprised there weren’t ultimately more comments.
His view: “Right now I believe people are taking a ‘wait and see’ approach until more firm details are unveiled. As nice of an idea the eMDR is, there are a lot of risks involved and questions that need to be answered, such as how this impacts standards compliance and potential liabilities.” Axis is a provider of IT consulting and data security offerings for healthcare industry organizations.
Some of the comments seek the kind of clarification Logan believes some in industry need before they are fully confident in using eMDR.
From a medical device standpoint, AdvaMed’s comment is one of the most important since it speaks for so many others (its member companies produce nearly 90 percent of the health care technology purchased each year in the U.S.). It’s also worth noting that the trade association can “get away” with saying things to the FDA that an individual company might not want to risk.
At the outset, AdvaMed says it supports the initiative. But, and there’s always a but in cases like this, they want to see the time stamp issue clarified, a concern echoed by Abbott. AdvaMed also wants the agency to adopt the date and time in the first acknowledgement sent to the submitter by the FDA that the report was received. It also wants the agency to develop a grace period for companies when they have a system outage, among a few other requests.
AdvaMed also wants the final rule to take effect at least two years after publication of the final rule.
On balance, most of the changes requested by the comment letters strike me as reasonable. Industry won’t get everything it asks for here, but I suspect the FDA will work pretty hard to accommodate the most reasonable requests.
Remember, the agency is still smarting from how it mishandled 21 CFR Part 11 in 1997. Back then, it made the rule way too literal and hands-on. Its stated goal to was to advance the use of technology; instead the FDA set it back for several years.
In many ways, I think the agency is to be commended for learning from its mistakes with Part 11 and applying them to its rollout of eMDR. The eMDR guidance is not perfect for everyone, but it’s pretty good for almost all, and that kind of effective compromise strikes me as democracy at its best. Here’s hoping the FDA takes some of the best comments to heart and improves a guidance that’s pretty close to the mark.
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