1. VOLUME 11, ISSUE 1Winter 2011 Crossroads: U.S. Medical Device Regulation vs. Innovation The U.S. medical device industry is at a regulatory and potentially economic crossroad as the FDA continues to refine its 510(k) regulatory submission requirements and guidelines. Medical device manufacturers have been urging the FDA and Congress to expedite new product review processes to spur innovation and bring new medical technolo- gies to market faster. However, supporters of stricter FDA regulations claim that a faster regulatory review process causes unsafe devices to enter the market. As a result of numerous exchanges between both sides of the issue, CDRH (FDA) recently issued multiple updates to its initiatives for the 510(k) approval process. To shed light on key changes, we obtained the support of the office of Dr. Jeffrey Shuren MD JD, Director of CDRH and Dr. John Smith MD JD, of Hogan Lovells, a prominent international law firm with a medical regulatory specialty, on their interpretations of the 510(k) regulatory guidelines and the impact these guidelines will have on medical device manufacturers.Laws & Regulations:Medical Device Safety & InnovationThe average cost to bring a 510(k) cleared device fromconcept to approval is estimated to be $31M, with $24MRecent studies have been published analyzing the FDAs 510(k) spent on regulatory-dependent activities; but, for a PMAproduct recall and approval rates which bring many facts andapproved product, the figures rise to $94M and $75Mexpert interpretation into the public spotlight regarding the 510(k)respectively.review and approval process. Sources: U.S. Food and Drug Administration; The Boston Consulting Group; The New York Times;Analysis of Product Recalls: Josh Makower MD, Consulting Professor of Medicine, Stanford UniversityIn 2010, there were a total of 47 medical device recalls, anincrease of 52% compared to the 31 device recalls that occurredCASE STUDY:in 2009. New Product Formulation TestingAccording to a January 2011 study by Boston Consulting Group,the recall rate across the European Union and the U.S. are The Company: A specialty pharmaceuticals and medication deliveryequivalent.company wants to validate and optimize the product design forOf the 113 high-priority device recalls between 2005 and maximum patient and prescriber adoption. A product prototype was made available to show and trial with physicians, nurses and2009, 80 involved products that were cleared through the 510(k) patients.regulatory process. The Challenge: The client needed to compare the utility and valueMedical Device Approval Trends:of their product with alternative treatments currently available. In addition, factors which might impact adoption by practitioners orIn 2009, CDRH approved 3,000 products under its 510(k) patients, as well as any healthcare environmental factors which mayclearance process, while only approving 15 original PMA sub- also affect adoption required in-depth exploration.missions. Both 510(k) and PMA approvals have been trending Our Solution: TMTG implemented human factor analysis with prod-downward in terms of total number of approvals over the past uct usability and adoption analysis by testing the existing design,decade.and provided critical patient Voice-of-Customer (VOC) feedback from face-to-face dyads and multiple focus group sessions with physiciansIn a survey conducted with 204 med tech companies, it took anand nurses. average of 10 months from the first 510(k) filing to clearance. The Impact: The client received the human factor analysis needed toFirms with similar experience with European agencies stated it successfully prepare the product for upcoming clinical trials.In addi-took an average of 7 months to receive CE marking from the first tion, the study enhanced the clients understanding of primary issuescommunication. that would drive clinician and patient acceptance of this product, particularly compared to existing competing alternatives.The Costs of Seeking FDA Approval: For each additional month a medical device manufacturerTo find out what The MarkeTech Group consultants can do to works through the 510(k) review process, it costs an estimated put the latest planning and technology services to work for $520,000 per month and, for a pending PMA, $740,000 peryou, visit our Web site at www.themarketechgroup.com month.USA: +1 (530) 792-8400, EU: +33 (0)2 72 01 00 80 The MarkeTech Group, LLC 2011

2. HOT TRENDof the Quarter: Regulatory Expert Weighs InINTERVIEWJohn Smith MD JD, partner at Hogan LovellsQ: In addition to internal and administrative matters, we see that the FDAs plan of action includes changes to guidance for the 510(k) clearance process. Can you please outlinewhat the most impactful changes will likely be?A: The significant changes include first, what will FDA find to be considered substantially equivalent? For example, FDA has a long-established history of allowing the use of onepredicate device for intended use, and another device for technological characteristics. CDRH now considers these split predicates to be unreasonable. The second is what thedata requirements will be for something subject to 510(k) process. The standards have been raised to such a point...that they are very rigorous and raise a higher hurdle to getcertain products to market. Q: Will there be a subdivision of Class II into a and b? If so, what will this accomplish? A: There is a potential for a system more like that in Europe, with Class IIb being products that require clinical data; and Class IIa products which would not require clinical data. Its not clear if this is going to happen. The real question is, What are the data requirements?, since FDA is always free to place a product into any classification. Its really an issue of semantics and sponsors should focus on what data is going to be required. Q: These reforms could be seen as increasing the cost and complexity of the regulatory approval process, which will in turn delay or stifle medical technology innovation, decrease investments in technology development, and ultimately undermine patient care. How can the medical technology industry minimize these concerns? A: Planning is important and there are two key elements. First, it is critical to understand the regulatory process and seek competent regulatory advice, especially for evolutionary or cutting-edge technologies. For instance, select a single appropriate predicate device, not a split predicate. Second, plan on longer time-frames and more expense. Now, 2-3 rounds of FDA review, lots of questions, and requests for additional data are common. Plan for 6-9 months for anything not straightforward; and, if any clinical data is required, plan for 9-12+ months. There are three sources of increased cost: regulatory submission cost (a small increase); cost of additional data: usability, pre-clinical, clinical (which is time plus cost); and lost revenue, which could be the biggest cost when considering burn rate, etc. Q: In addition to the expected improvement in public health (product safety of approved products), what improvements to the business environment do you see coming out of the FDA plan of action? A: One positive outcome in a related area of regulation involves the increasing role of third party payers. Traditionally, products could be approved by the FDA and marketed with minimal data; securing reimbursement was a secondary concern, and sometimes very challenging. Now, sponsors will likely have adequate data to secure reimbursement with relative efficacy data from their submission and can answer the question a priori: does a new product help patients more than an existing product? For more information about Dr. Smith, please visit: http://www.hoganlovells.com/john-smith/ Long version of this interview: http://themarketechgroup.com/minute/tmtg-min28-smith.pdfON THE HORIZON: AN EXCLUSIVE FDA SPOTLIGHT:FDA Seeks to Foster InnovationCDRH Provides Roadmap to ClarityHIGHLIGHTSThere are eight specific guidances related to the 510(k) program and theuse of science in CDRH decision-making that are part of our recent action Eligible medical devices will get CDRH assistance earlier in the pre-clinical product devel-plan announcement. These include, in Q3: Clarification of which device opment phase through a new priority review program, the Innovation Pathway.changes do or do not warrant submission of a new 510(k), Improvement Third-party certification programs for U.S. medical device test centers will help to moreof the quality and performance clinical trials, Streamlining the de novo efficiently and safely develop and test medical devices.classification process, and Providing greater clarity on the 510(k) Para- CDRH will be enhancing their current technology scanning process by developing its own digm. In Q4: Clarification of the appropriate use of consensus standards, network of experts and seeking additional public input to identify important medical device technologies. Clarification of the process for appealing CDRH decisions, Supplement-ing available guidance on pre-IDE meetings and enhancing the quality ofpre-submission interactions between industry and Center staff, and MoreAT STAKE! consistent development and assignation of unique product codes. Device manufacturers may gain an advantage in their regulatory review and approval process as the FDA seeks to better understand newer technologies before they are We have deferred a final decision on establishing a Class IIb to give the submitted for approval.Institute of Medicine an opportunity to provide feedback as part of its An increase in device approvals is likely for manufacturers who interact sooner with the review of the FDAs 510(k) Program. Regarding split predicates, the FDA in the technology development and regulatory pathway.FDA will issue guidance that will clarify the circumstances under whichit is appropriate to use multiple predicates to demonstrate substantialSO WHAT?equivalence, a practice we strongly support. Medical device manufacturers with novel technologies or devices will be able to receive earlier investment of CDRHs time and resources at the pre Investigational Device Exemp- The actions we are taking to strengthen the 510(k) review system, includ- tion (IDE) phase to aid in the regulatory review pathway at an earlier starting point bying our new Innovation Initiative, will increase the clarity and predictabil- applying for the CDRH Innovation Pathway program.ity of our requirementssomething we agree with industry is vital for a Manufacturers can potentially save significant time and money with the proposed CDRH robust, innovative and healthy medical device industry. certified test centers that assist manufacturers in identifying and correcting device short- comings more quickly.Dr. Jeffrey Shuren, MD JD is Director of Center for Device FDA will remain receptive to outside of the US (OUS) data and this can absolutely be usedand Radiological Health. to support a 510(k) notice if the sponsor can show that populations and standards of care are comparable. For an IDE, for statistical purposes, the majority of data still needsFor additional information, go to www.fda.gov/downloads/AboutFDA/Cen- to come from US. tersOffices/CDRH/CDRHReports/UCM239450.pdf Sources: U.S. Food and Drug Administration; Smith, John J., MD JD The MarkeTech Group, LLC 2011