Did you forget something on your premarket approval application? Check it twice, because the rules have changed...again. The FDA is now requiring manufacturers of medical devices to include pediatric patient information with all premarket approval submissions. The Agency has even said that they may withhold approval of any applications missing such data, until the required information is provided. We can add this to the growing list of data "requests" that the FDA is now mandating on all PMAs and 510(k)s. So how can the industry benefit from this new requirement? (glad you asked!) There seems to be an undeserved but growing market in the pediatric medical device space. If federal regulators are going to require investigating this patient population, it would be advantageous for manufacturers to better understand the upside potential.

First, let's define exactly what is required. As of August 16, 2010, the FDA will officially begin to enforce the 2007 mandate that device manufacturers must provide pediatric patient information on all new HDE, PMA and PDP submissions. Under the requirements listed in the FDA Amendments Act of 2007, manufacturers must provide certain pediatric information, if readily available, with each premarket approval application or supplement, humanitarian device exemption request, or product development protocol. Manufacturers must now define and describe any pediatric patient subpopulations that may suffer from the disease or condition that the device is intended to treat, diagnose, or cure.

When designing medical devices, most device makers have a key patient population in mind. While few devices are developed specifically for use by pediatric patients, the new rules now create the opportunity to better understand this patient population. The market for pediatric devices continues to be a growing niche, which most economic sources estimate to be increasing by 10-13% annually. But, if the growth potential is there, one might wonder why everyone has not already jumped in with both feet. Lucile Packard Foundation's surgical resident Kevin Chao, MD thinks he understands why.

"There is a trio of barriers that limits the availability of pediatric medical devices," Dr. Chao said in a press release. "There are very small markets in a heterogeneous population with high regulatory hurdles and poor payer mix. This perfect storm of barriers makes it hard to create a sustainable business, or get investors excited."

This is partially why there is now an online "idea campaign" to promote innovation in the pediatric medical device market, which experts like Dr. Chao say has a great economic potential. The eight-week campaign launched by the Kansas City, Mo.-based Ewing Marion Kauffman Foundation and Lucile Packard Foundation's Pediatric Medical Device Innovation fellowship team will run until April 21.

For device makers new to this area, it is encouraging to see research funding already being allocated to the pediatric market. The University of Michigan Pediatric Device Consortium (M-PED) is working with the Regulatory Affairs Associates (RAA), a leading FDA consulting firm which deals in both pharmaceuticals and medical devices. M-PED is funded by a 2-year, $2 million dollar grant from the FDA to promote commercialization of pediatric medical devices. Other non-profits continue to support the development of pediatric devices, including the Cambridge, Mass.-based Institute for Pediatric Innovation and Cleveland-based PediaWorks. Ross Trimby, the COO of the Institute for Pediatric Innovation, is a strong proponent of the new FDA regulations.

IPI COO Ross Trimby told MassDevice he sees a great deal of upside in the new rules. "Having existing companies recognize and quantify the pediatric uses of any of their devices during the approval process is going to be a nice awakening experience for them all, in terms of what the actual implications are in terms of selecting that device for pediatric use," Trimby said. "Just having these companies that are bringing out a product that is certainly going to be used in pediatric care [anyway] actually look at that while they're going through the regulatory process will help them make the decision that this is a market opportunity they should go after."

According to the Mass Device report, IPI announced a joint program with hospitals in California and Ohio for the development of a new pediatric endotracheal tube intended for neonatal care, in an effort to reduce the number of needle sticks required to locate a vein.

These are just a few examples of what is to come in the emerging pediatric device market. Now that the cost of assessing these patients will be compulsory to filing a premarket approval application, we will likely see continued advances in the pediatric space. With all of the new attention on pediatric indications for use, medical device makers may indeed uncover an undeserved patient population. If the regulatory barriers can be overcome economically, there seems to be plenty of potential in the ongoing innovations within the industry.

If you want to know what changes may be in store for medical device approvals, look no further. Change is coming, and it looks like it will start with "substantial equivalence". Since the Premarket Notification (510k) has been established, medical device approvals have centered around the idea of substantial equivalence to a predicate device. Substantial equivalence means that the new device has the same intended use as the predicate, and is at least as safe and effective. As this paradigm has recently been called into question, a few common ideas have emerged regarding possible changes to the process. These suggested changes place more emphasis on risk analysis and test data, however they approach it by very different means.

Once such method gaining support is Comparitive Effectiveness Research (CER). According to Maria Shepherd, Founder and CEO of Data Decision Group the method is already being funded by the current political administration. Ms. Shepard provided some financial numbers during the Medical Devices Summit, in Boston, Massachusetts. According to her research, the American Recovery and Reinvestment Act of 2009 provided $1.1 billion for Comparative Effectiveness Research, splitting the funds between two agencies; The Agency for Healthcare Research and Quality (AHRQ) Received $700 Million and the National Institutes of Health (NIH) was alloted the remaining $400 Million. Medical Devices are a high priority group for CER proponents, especially for atrial fibrillation (AF) , endoscopies, prostate cancer and obesity treatments. FDA and the medical community like CER because it is outcomes based. The merits of CER were also touted in a recent paper by Alec B. O’Connor, MD, MPH published in the Journal of the American Medical Association (JAMA). Dr. O'Conner wrote that, " The current FDA standards for approval fail to assess whether newly approved drugs and devices are less efficacious or less well-tolerated than existing alternatives. This raises the possibility that patients may be harmed by receiving a newly approved treatment instead of an alternative with established efficacy and safety." He goes on to suggest that FDA should provide oversight of CER active-comparator trials, designed to prove superiority, equivalence or at the very least, noninferiority. While this makes sense from an analysis standpoint, the actual practice of designing a CER study can make it difficult to statistically prove superiority or non-inferiority. Based on the sampling, small differences in outcomes may be hard to detect or rule out. The FDA has suggested the use of a Beyes study, which was explained in an earlier post. Still, time and and cost can be a significant issue. Because of the large sample size and costs that can reach upwards of $15 Million to conduct, a fully designed active control trial for CER will not be economically feasible for Class I & II device makers. Still some migration from a predicate system to a risk-based system of device approval may be in store.

To give us an idea what the new model might look like we can review the comments of, Craig Coombs, faculty at University of California Berkeley and President of Coombs Medical Device Consulting. Mr. Coombs made his case during the FDA public meeting about ways to strengthen the 510(k) process. He suggested a shift from the current precedent justified system to "truly risk-based system" in order to regain consistency in review and increase public confidence in the Agency. This idea would align with FDA's renewed focus on test data for regulatory submissions. Using the system suggested by Mr. Coombs, device approval would be more heavily based on data to substantiate the application of the new device for its intended use. Rather than focusing on a comparative study against a predicate, the device is truly evaluated on it's own merits. As Mr. Coombs said during the meeting,

" An unless a predicate is considered gold standard my client does not test predicate devices or compare themselves to a predicate when it comes to performance testing. Rather, all devices including 510(k) devices stand on their own testing. This is a requirement of the quality design regulation and been the reality of the 510(k) process for years. "

With all of the continuing debate over possible changes in the FDA's medical device review process, there are a few emerging points of concensus. First, most believe that some form of change is needed to strengthen the current 510(k) process. Second, there is more emphasis being placed on risk and test data. Many of the ideas discussed in last month's meeting are being reivewed at the FDA, and additional time was granted for submitting comments to the official docket. Anyone with thoughts or ideas on the process should submit their comments before March 19, 2010.

It seems lately, the thing to do when one fails to achieve their desired result, is cry foul. This can be true whether you're an Olympic ice skater or a health policy leader. This conclusion comes after reading the post from MassDevice interviewing Diana Zuckerman, about the recent FDA meeting reviewing the 510(k) process for clearing medical devices. Diana Zuckerman is the president of the National Research Center for Women & Families. While she and her insititute work towards improving public health, her comments to MassDevice only served to further misrepresent the position of companies within the medical device industry.

Regarding attendance at the FDA meeting back on February 18, Zuckerman made the erroneous claim, "I think it was all industry, one patient and me, and on the discussion panel it was industry plus FDA people and me." Looking at the record of speakers, it is clear that the group ranged from physicians, to university professors, private citizens, consultants, and yes...the "industry". The other point to make clear is that this was a public meeting, with no limits on who could attend or register as a speaker. This was not a case of the odds being in favor of the medical device industry. Quite the contrary, the meeting finally gave companies a small opportunity to answer their critics in the media and public sector that want to depict the 510(k) as a "fast track" process.

As discussed in the meeting, anyone who has filed a 510(k) application knows that it is accompanied by rigorous testing to show safety and efficacy. This was brought up by industry representatives and confirmed Dr. Donna-Bea Tillman, director of the FDA's office of device evaluation who said, "It doesn't mean FDA just sort of rubber stamps the 510(k). In order to demonstrate that [substantial equivalence] we require the submission of testing... a lot of it." These companies document their testing in literally hundreds (sometimes thousands) of pages within their 510(k) applications.

Ms. Zuckerman also said she felt that public health concerns were not even addressed at the meeting. In another hyperbole stated by Ms. Zuckerman during the interview she stated, "I did not see one word expressed in terms of concern about public health, not one word," The truth from reviewing the archives and transcripts, is that statements of concern for the patient were brought up over 50 separate times by at least 10 speakers in addition to Zuckerman. The reality is that medical device makers are in business of improving the health and well-being of their patients. They invest hundreds of millions of dollars into research and development to provide the latest technology to improve patient care. This does not mean that problems do not arise, and device makers employ entire departments to work on improving design controls, production QC, and supplier quality management.

If you missed it, you can watch the meeting again for yourself, and feel free to comment on your take. While I do share her concerns for the patients on these devices, there is little if any basis for Dr. Zuckerman's allegations about the industry's attitudes. The 510(k) process will need to be addressed, but is not a catch-all or "magic pill" solution, nor was it ever intended to be this. I think that Medtronic CRO Susan Alpert put it best during the meeting in suggesting, "I think we need to be careful as we think through how we're going to change the program that we change it in ways that don't get rid of the good things about the program, but allow the program to evolve."

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.

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.

While the games are underway, bringing stories both great and tragic from the mountains of Vancouver, there is an unsung chronicle of the technology supporting these athletes in their quest for Olympic Gold. The Vancouver Olympic Committee estimates $5 million in medical equipment/supplies have been donated for the Games in 2010. In fact, many athletes would not be able to maintain top form or in some cases even compete without the great Medical Devices advancing sports medicine at the Olympics. Three examples of such products come from three very different companies.

Kris Freeman may not have won a medal in yesterday's 15k, but he is still regarded as one of the country's most elite cross-country skiers. As a member of US Ski Team he has won many international races, and all while battling Type I diabetes. Freeman is able to compete even with his condition thanks in part to Insulet's OmniPod® System, the only tubing-free insulin pump. With its durable design, Freeman can actually can use the pump to manage his diabetes during the race. Freeman hopes to continue the games injury-free and perhaps medal in his 2 remaining events.

Injuries are an unfortunate part of the Olympics. In severe cases, athletes can lose a significant amount of blood from a sustained injury. Belmont Instrument Corp's Rapid Infuser is being used at the Mobile Medical Unit (MMU), which acts as a mobile ER. In addition to hospital use, the Rapid Infuser is actually "battle-tested" at the US Army stations in both Iraq and Afghanistan. Olympic athletes in need of care can benefit from such devices and facilities. These facilities also need to connect with each other in order to be most effective.

Providing the IT infrastructure, GE is probably the most prominent at the games, with their $80 million "Healthymagination" campaign. Once an athlete in need of care is receiving medical treatment, GE's Centricity® solution is used to connect medical staff to real-time information about their patients. In its debut at the Olympic Winter Games, GE Healthcare's technology allows doctors to quickly access the latest information and images needed to treat an injured athlete. The solution has been installed at the MMU, linking it to both the main Vancouver Polyclinic, and the Whistler Polyclinic. The athletes at these stations count on the medical equipment and technology, but surprisingly so do the spectators and staff.

More than 250,000 people are attending or supporting the venues at Vancouver and Whistler for the 2010 Olympics. Judging from the Winter Games held in Salt Lake City, UT more of them will need medical attention than will the athletes. Back in 2002, 11,575 medical cases were recorded, with Olympic athletes accounting for only 1,377. These number include officials, media, contractors, volunteers and staff in addition to the spectators in need of medical attention.

As the games continue, we will no doubt look to the headlines for the medal counts and stories of Olympic glory. Still, "below the fold", there is a less-read but equally great story. This is the story of the scientists, engineers, marketers, manufacturers, and regulatory specialists who are creating the medical equipment that supports these athletes in their quest to become Olympic champions.