I’m very pleased and honored to be selected to serve on the Board of Advisors for Health in Place, an initiative to develop a new approach to considering innovations which impact health:

➪across the generations, recognizing the unique needs at various stages of life,

➪for each state of well-being, recognizing that they may be independent of age, and

➪regardless of location, recognizing that health is delivered and managed beyond the clinical setting, including —at and on the way to and from — home, school, work

Health in Place is an initiative of Disruptive Women in Healthcare with support from leading companies such as Philips and United Healthcare, and includes disruptive innovative technologies from Rock Health, a newly formed venture capital organization in Silicon Valley late in 2011. 

I’m here to look at the challenges that stand in the path of achieving the vision of HIP from a technology and regulatory perspective, and look forward to a busy 2012.   More on HIP as the year unfolds.

Cheaper submissions?! Great!

But, how did that happen? I thought FDA has been fighting for increased user fees? The Medical Device User Fee and Modernization Act of 2002 amended the Federal Food Drug & Cosmetic Act (FD&C Act) to authorize FDA to collect user fees for certain medical device submissions. When the Act was renewed in 2007, Congress and FDA calculated user fee payment amounts for FY2008-FY2012 based on a number of things, including the estimated number of each type of submission per year requiring FDA review. The fees for FY2008 were established and scheduled to increase 8-9% each fiscal year, based on the assumption that submission rates would increase incrementally each year. However, to ensure that FDA would stay true to its budget and that Industry wouldn’t have to pay a large excess (remember, the fees are based on estimations and assumptions), the 2007 User Fee Amendments included an offset provision for the fee structure. Under the offset provision, if the total amount of fees collected during FY 2008 through FY 2010, including the estimated amount to be collected in FY 2011, exceeds the cumulative amounts specified by Congress to be appropriated in these four fiscal years, the excess amount is credited to FDA’s account and subtracted from the amount of fees that would otherwise be collected in FY 2012.

FDA has reported a whopping $18,003,760 received (or expected to be received by the end of FY2011) in excess fees! It estimates that $8,491,930 of this amount represents fees that have been paid for applications not yet received. This brings the offset down to around $9.5 Million, which, when spread across the various user fee categories, results in a reduction of FY2012 fees by up to 75%! The PMA fee, representing the highest medical device user fee and the “base” for which other fees are calculated, has been reduced by 15%; Panel-track Supplement by 75%; 180-Supplement by 15%; Annual Reports by 3.5%; 510(k) by 1.8%; 513(g) by 1.4%; and Establishment Registration by 15%. The Small Business fee remains a 25% reduction for all fees except 510(k), 513(g), 30-day Notice, and Establishment Registrations. For a 510(k), 30-day notice, and a 513(g), the small business fee is a 50% discount. There is no Small Business reduction for Establishment Registrations.

Below are the published fees for FY 2012. As for the future user fee amounts, FDA and Congress have until mid-2012 to determine a new fee structure. I would expect that the volume of submissions from new companies, as well as the tighter regulatory controls that are resulting in higher submission rates, might keep FDA’s revenue from user fees fairly stable, thus not creating a dramatic increase. Anson is currently working with several start-up companies and first-time filers and we expect to see even more of these companies in the future as mHealth and personalized medicine arenas continue to grow and attract new companies to the regulated medical device industry.

FY 2012 Medical Device Review User Fees (U.S. Dollars)

IOM brought up the fact that there is an absence of reliable pre and post-market data on safety and effectiveness of 510(k) cleared devices. They acknowledged that it can be reasonably believed that most of the devices on the market are fulfilling their intended function, but that not much can be said about safety and effectiveness. Maybe the committee doesn’t know about FDA’s MAUDE database, which captures safety incidents for all medical devices?!

In regards to FDA’s question to IOM on whether the 510(k) process promotes or inhibits device innovation, IOM responded that there are currently no requirements for a device to be innovative to go through the 510(k) process, nor should there be such a requirement. IOM was unable to determine the answer to FDA’s question, as information and data do not exist to accurately answer the question. Furthermore, IOM didn’t develop a plan or program recommendation as they had limited bandwidth (really?!).

IOM called out a few specific devices that raised particular concerns, including devices containing software and metal-on-metal hip replacements. The committee believes that, considering approximately 50% of medical devices contain software, that tighter controls are needed for these devices to ensure safety and effectiveness. Software will continue to evolve and be incorporated into devices in ways that we can’t even imagine today. The metal-on-metal hip replacements have been scrutinized over the years as they are Class III devices that are cleared through the 510(k) process, but have demonstrated huge safety concerns. IOM’s report recommends that “the Food and Drug Administration should promptly call for PMA applications for or reclassify Class III devices that remain eligible for 510(k) clearance”.

Bottom line is that IOM believes that the FDA review process should be more focused on whether the device is safe and effective, less focused on whether it’s like something else already on the market, and put a higher threshold on post market surveillance. IOM recognizes that this is a huge paradigm shift, but that it is needed in order to ensure safe devices in the future. They clarified that their report is merely a recommendation, which was solicited by FDA, but in no way does FDA have to follow the recommendations.

FDA certainly has their work cut out for them, whether they decide to completely wipe-out the 510(k) process and start over, or modify the current process. Either way, you can be sure that industry will voice their opinions loud and clear. What is your opinion of the IOM Report? Where do you think FDA will go from here?

1. Does the current 510(k) clearance process protect patients optimally and promote innovation in support of public health?
   
2. If not, what legislative, regulatory, or administrative changes are recommended to achieve the goals of the 510(k) clearance process optimally?

In addition to these two questions, Dr. Jeffry Shuren (FDA Director) had written IOM in January 2011 asking IOM to weigh-in on 7 proposals from CDRH’ s 510(k) and Science Report Recommendations:

1. Seeking greater authority to require postmarket surveillance studies as a condition of clearance for some devices.
   
2. Defining the scope and grounds for CDRH to exercise its authority to rescind a 510(k) clearance fully or partially.
   
3. Clarifying when a device should no longer be available for use as a predicate.
   
4. Developing guidance defining Class IIb devices for which clinical information, manufacturing information, or, potentially, additional evaluation in the postmarket setting would typically be necessary to support a determination of substantial equivalence.
   
5. Consolidating the concepts of “indications for use” and “intended use” into a single term, “intended use”.
   
6. Pursuing a statutory amendment that would provide the agency with the express authority to consider an off-label use when determining the “intended use” of a device.
   
7. Requiring each 510(k) submitter to keep at least one unit of the device that is under review available for CDRH to access on request.

In the cover letter to the report, IOM states that they had limited time and therefore couldn’t fully address these 7 points (7 months wasn’t enough time?!). IOM states that FDA has tools to address items 1-3 and recommends that FDA look at those tools and figure out why they aren’t working, aren’t useful and why they aren’t being used. In regards to points 4-7, IOM states, “The IOM committee’s report concludes that the 510(k) process generally is not intended to evaluate the safety and effectiveness of medical devices and, furthermore, cannot be transformed into a premarket evaluation of safety and effectiveness.” IOM doesn’t believe that it is worth dedicating resources to try to fix the 510(k) process, but rather start over with an entirely new process!

Now, let’s look at FDA’s report “Analysis of Premarket Review Times Under the 510(k) Program” to see how the frequency of additional information (AI) requests have increased since 2006. FDA reports that the percentage of AI requests on the first review round for 510(k)s has increased 21% since 2006. In 2006, approximately 56% of submissions resulted in an AI request, whereas 2010 had an average of 77%. FDA also reports that the number of review cycles for 510(k)s has increased from an average of 1.7 review cycles in 2006 to 2.1 review cycles in 2010. FDA looked at the typical AI requests, which include lack of performance or clinical data, failure to follow an FDA guidance document or recognized standard, and problems with the indications for use. These request for additional information correlate with the causes identified for the longer review times. Not surprisingly then, FDA is reporting longer review times, more AI requests, and more review cycles since 2006.

As reported in my previous post, Anson has also experienced longer review times and an increase in the AI requests and number of review cycles so this is not just empirical data for us either; it is real work and real time. Approximately 70% of all Anson-supported submissions between 2006 and 2010 have resulted in at least one round of AI requests. In 2006, 58% of Anson-supported submissions resulted in at least one round of AI requests. In 2010, this increased to 80%.

This begs the question we all want answered; what can we do to decrease the likelihood of an AI request, and therefore, longer review times? Here’s my advice:

1. Search for any FDA guidance documents or International Standards that apply to your device type. Read them carefully and be sure that you are addressing all of the requirements or provide a scientific rationale for not doing so.
   
2. Look at what other similar devices have included in their submissions either through a Freedom of Information (FOI) request or by looking at the published 510(k) summaries on FDA’s website. Learn from other’s mistakes and successes.
   
3. Write the 510(k) in such a way that assumes the FDA knows nothing about your device. With literally thousands of device submissions per year, chances are they are not intimately familiar with your product even if its capabilities have already been previewed in testing, pre-market demonstrations, or other means. That said it’s important to strike a balance between not providing enough information and providing too much unnecessary detail which can also lead to longer review times and confusion for reviewers. Clarity above all is key.
   
4. Make it clear in your submission that your device is substantially equivalent to – as safe and effective as – the predicate device. If you provide test summaries or “promise statements” in your submission, be prepared to submit the full report should FDA request them.
   
5. FDA has rolled out several new draft guidance documents recently, including one on mobile device applications. Read them and track the release of new ones carefully. Dr. Shuren has stated in testimony on Capitol Hill that FDA will continue to draft or update guidance documents as a means to be more transparent and clear in communicating it’s expectations to industry, and to make them more applicable to the rapid advancement in new technologies. If FDA provides more clear direction and industry attempts to provide more complete submission documentation based on that direction, we’re confident we will see a reduction in the number of AI requests, and most importantly, faster review times, which means getting products to market quicker

We encourage you to review this new draft guidance document closely.  Anson Group clients can schedule a free phone call or web meeting with an Anson consultant to look at the guidance document together, discuss our analysis and answer any questions you may have regarding this guidance document.  If you are interested, please contact Brittney Uzzell at buzzell@ansongroup.com to schedule an appointment.