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.

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.

Many of the stories in the mainstream media are contributing to a public outcry for greater regulation in the medical device space. This has resulted in greater enforcement from the FDA.  As an industry, there is a great desire to constantly improve and innovate to bring new therapies and devices to market. As an industry we need a platform to address the public and the regulators, to show all that we are doing as an industry to remain vigilant for the pubic health.

With that I am excited to start the open pre-launch (Beta) of my510k.com as a new way to collaborate with colleagues in the Medical Device industry. Many of us who will use this site are certainly experts in our own right, with years of experience in the field. Many of us have developed strategies over time, and we have been able to get products to market.   The site has some new features like Messages, Groups and Blog features to allow members to communicate about issues that are importat to them.  Whether you are in Engineering, Marketing, Manufacturing, Quality Assurance, or Regulatory Affairs, we all have a stake in the 510k process.

 If you want to join  my510k.com  as a Beta user, please register onsite using OpenID or Facebook.  If you need an invite code for standard registration please inquire via email. Full launch is planned for later this Spring. For now, any inquires about the site can be directed to info(at)my510k.com. Thanks to all who have helped so far!

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.”

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.

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.

Beyes’ 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.

Companies have to watch the messages they send on their website and in social media channels.  In a recent letter to Bracco Diagnostics, the FDA alleged the company made unfounded claims about its diagnostic agent Isovue, and even minimized or outright omitted its risks on their website.  The FDA’s letter contends that the claims were based on a clinical study, as opposed full-blown prospective trial for Isovue.  According to the company, those web pages were taken down, but it remains to be seen if any legal action will be filed.

Lawsuits and fines did not escape Kimberly Clark’s I-Flow division, which allegedly encouraged doctors to use its OnQ Pain Buster infusion pumps following arthroscopic surgery.  This intra-articular use of the pump was not approved by the FDA, and so far the case has cost Kimberly Clark $4.75 million. These are not isolated events.  In fact, other manufacturers face similar lawsuits and impending action by the FDA as it seeks to devote more time and money towards enforcement of regulations.

According to the latest public documents, the FDA is looking to raise its budget for the medical device division (CDRH) to $1.4 billion, an increase of over $100 million.  With the request for over 1,000 new employees, the FDA may soon have the capacity for monitoring labeling much more closely.

Most device makers are careful not to promote off-label use, but FDA may soon want them to be more of when it is occurring.  This includes monitoring social media sites for information being exchanged between users promoting off-label use.   The FDA has stated in recent communications and at its public meeting on the topic, that they are monitoring social media sites for issues like off-label use and patient harm.  That information is being fed right back into the inspection process as part of the criteria for judging a company’s regulatory compliance.

Even companies that are doing all they can to comply, need to be aware and active in online social networks.  If companies want to avoid enforcement actions and costly legal disputes, they will need to remain vigilant in the digital social world.

Last time we woke up in this situation, it was 1993.  Punxsutawney Phil had predicted 6 more weeks of winter as then-President Bill Clinton was in his first term with a large agenda.  Health care reform and changes to the FDA were at the top of his list.   Legislation was being pushed by late Sen. Edward Kennedy (D-Mass) to increase regulations under then-Chief, Dr. David Kessler (actually appointed by former-President George Bush).  Dr. Kessler made it his mission to take on medical device companies.  The fear and uncertainty of increased regulations had the industry very concerned by late 1993.    Many companies were forced to delay major product releases, while struggling to comply with FDA regulations.  It seemed that this was to be the future for medical devices in the 90’s…until the 1994 Congressional election.

Once the power of congress was reversed, the newly appointed House Speaker, Newt Gingrich (R-Ga.) moved to streamline the FDA, claiming that slower medical device approvals were “killing jobs–and people”.  The reforms were designed to create a more efficient FDA, and encourage the regulatory agency to work with manufactures of new drugs and devices.  Eventually, Kessler resigned in 1996, and a year later legislation finally passed that benefited the industry, the FDA, and patients.

So now, here we are again.  Punxsutawney Phil gave us the same weather outlook, and it would seem we have the same regulatory forecast as well.  Previous posts on the Five-Ten Blog have discussed the current industry climate at-length; suffice to say we are still looking at proposals of increased regulations and slower device approvals via the 510(k) process.

What does this mean?  It may mean that the upcoming meetings to discuss reforms will only be part of the story.  We as an industry certainly need to make our case to the FDA.  However, we have an important mid-term election coming as well, and President Obama needs Congress to approve his FDA budget.  If the pendulum swings back to a more balanced Congress, it will affect the scope of any proposed reforms.  Hopefully, we see a balance that allows safe and effective medical devices to have more timely reviews, and ultimately an industry that continues to innovate and improve the health outcomes of our patients.

Happy Groundhog Day!

The President addressed the economic climate, specifically the credit markets.  He cited that, “financing remains difficult for small business owners across the country, even those that are making a profit.”  This is especially telling if we consider that  most of the new products in the medical device industry come from small and medium sized companies.  Statistics and reports from GlobalData reveal that 56% of medical devices in the R&D pipeline are being developed by small businesses in the United States.   These small businesses need strong capital markets in order to survive and deliver cutting-edge therapies to the market.  These economic pressures combined with stronger regulatory enforcement, were cited in last week’s post as causes for a weaker VC market in the wake of  a proposed medical device tax.  Innovation needs a strong financial backing to survive.  Unfortunately, the President did not relate this to the medical device industry.  Instead, he focused more on the politically charged area of renewable energy.  Clean coal and other green energy technologies seem to be where the President is most interested in seeing new developments.  He stated, “And no area is more ripe for such innovation than energy…It means continued investment in advanced biofuels and clean coal technologies”  This leave some room to wonder where the medical device industry fits into President Obama’s overall plans to strengthen small business and innovation.  The medical device tax was not explicitly mentioned, but the President did discuss his health care reform initiative.

President Obama reiterated his vision for changing America’s health care system, and contended that, ” We are closer than ever to bringing more security to the lives of so many Americans”.  Both parties can agree that some form of restructuring is needed.  The President went so far as to state,

“By the time I’m finished speaking tonight, more Americans will have lost their health insurance. Millions will lose it this year. Our deficit will grow. Premiums will go up. Patients will be denied the care they need.”

Part of the cost for this proposed health care policy would be offset by the controversial “medical device tax”.  It would seem that this tax has a good chance of being reduced and maybe even eliminated in the final bill.  Most political analysts agree that with the recent Senate victory by Republicans in Massachusetts, the President will have to make some concessions in order to get a bill passed.  If that is the case, it certainly would ease some of the pressures in the Medical Device market.

The State of our industry is difficult, but it is starting to strengthen.  Several leading companies, like Medtronic, GE and, Boston Scientific are forecasting 10-12% sales growth and up to 15% annual earnings growth for 2010.  If real progress can be made in the area of the economy, the only concern remaining is regulatory reform.  Federal workloads should be easing as the FDA ramps up its operations.  In the past 2 years, the agency saw its budget  increase by 30%  to $3 billion and hiring grew by 20% to over 8,550 employees.  If the industry is able to influence changes in the 510(k) process to make it more efficient, then increased growth can be achieved.  However, the FDA has made it clear that they intend to tighten regulations.  It remains to be seen how this plays out, but indeed the fate of the medical device industry hangs in the balance.   If the spirit of the medical device industry and the country can be summed up, perhaps the President ended well saying, “We have finished a difficult year. We have come through a difficult decade. But a new year has come. A new decade stretches before us. We don’t quit.”