ANNUALAPPROVALREPORT

2015

“Minnesota based medtech companies have a rich history of designing, developing and marketing medical devices, hence being known as Medical Alley. This foundation is built on products to treat heart disease which represents one of the most complex and challenging clinical complications to solve. As a result the knowledge and experience of the work force has evolved into a center of excellence in Minnesota with respect to the invention, testing, and FDA approval of novel products. At its core, all participants in this product lifecycle process understand that this is a data driven process and based on sound scientific evidence. Employees and companies embrace this reality and are more successful at bringing medical devices to market faster than other regions in the world.”

Mac McKeen, MBA, RACRegulatory Affairs, Interventional Cardiology

Boston Scientific Corporation

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Key FindingsKey Findings US 510(k) clearances decline 26% in 2015, the lowest in 5 years, while OUS clearances surge 51%

China continues trend of steady growth in 510(k) clearances while European and Asian countries see dramatic 2015 spike

Cardiology top sector for original PMAs while orthopedics dominant sector for 510(k) clearances

Minnesota remains fastest medical technology hub for 510(k) clearances across all experience levels

Minnesota companies secured 11 original PMAs, 8 in cardiology, which is 4-times more than second place California

Globally, Minnesota companies top the list of recipients of approvals and clearances in 2015

2015 at a Glance

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2015: Rise of OUS 510(k) Clearances Parallels Decline in US

33% of all clearances in 2015 are OUS up from 21% in 2014, a 51% increase

US clearances decline by 26% from 2014, the lowest in 5 years

Total clearances remain stable from 2011-2015

510(k) Clearances:

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Asia and Europe Drive Spike in OUS Clearances

2015 clearances from Europe up 50% from 2014 and 92% from 2012

2015 Asian clearances up 52% from 2014 and 81% from 2012

510(k) Clearances:

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2015: Dramatic Increase in OUS Clearances from 2014

South Korea (241%), Sweden (194%), Japan (154%), and France (103%) more than double clearances between 2014 and 2015

China bucks trend with consistent growth 2012-2015 – up 126% 2015 up 19% from 2014 2014 up 29% from 2013 2013 up 47% from 2012

510(k) Clearances:

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Orthopedics Top Sector for 510(k) Clearances

US dominates cardiology (78%), orthopedics (78%), and dental (72%)

Diagnostic imaging less concentrated geographically

Other large sectors were General & Plastic Surgery (230), In Vitro Diagnostics (209) and General Hospital & Healthcare Supply (144)

510(k) Clearances:

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2015: Minnesota Remains Fastest Med Tech Hub for 510(k) Clearances Across All Experience Levels

Nationally, experience matters in 510k clearance times Highly Experienced (10+) companies 52% faster than low (1)

and 18% faster than medium (2-9)

In MN, companies with low experience receive 510k clearance 5 weeks faster on average than in CA

MN received 125 510(k) clearances, CA 469, MA 165 and all others received 2,301.

510(k) Clearances:

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Spotlight on Industry TrendsFDA’s Focus on Early Feasibility Studiesby Kristy Katzenmeyer-Pleuss, Phd and Angela Mallery

The recent FDA strategic priority to increase the number of early feasibility studies (EFS) conducted in the U.S. resulted in dramatic increases in EFS investigational device exemption (IDE) approvals. However, opportunities remain to improve the process and submission quality.

One of the big trends facing the FDA in 2016 is the continuing increase of EFS IDE submissions in the U.S. and how approval rates can improve. EFS is a type of clinical study that involves a small number of patients to investigate a device that may be early in the development process and for which the device design may not yet be finalized. EFS may be used to establish a “proof of concept” for a novel technology or a new clinical use for an existing device. In addition, EFS may provide initial insights into a device’s clinical use and safety.

Due to often burdensome IDE requirements imposed by FDA for these type of studies, early studies were commonly conducted outside of the U.S. In recognition of this shortfall, FDA focused efforts on developing an EFS program as part of their 2014-2015 Strategic Priority to “Strengthen the Clinical Trials Enterprise”. Based on published reports, the Center for Devices and Radiological Health (CDRH) saw an overall 50% increase in EFS IDEs submitted during the first 9 months of FY 2015 compared to FY 2013, and a 100% increase in EFS IDE approvals. FDA also reported 6 out of the 7 review divisions in CDRH’s Office of Device Evaluation (ODE) saw an increase in the number of EFS submissions received in FY 2015 compared to FY 2013.

In 2013, FDA published a final guidance on IDEs for EFS. One key aspect of the guidance is focused on FDA’s flexibility in allowing less nonclinical data to support approval for EFS IDEs compared to traditional feasibility and pivotal studies. Another significant feature of the guidance is communication of new FDA policy to enable more timely device and protocol iterations during patient enrollment in the EFS.

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It is reasonable for medical device manufacturers to expect FDA to continue improving the EFS submission process, which may continue to increase the number of studies conducted in the U.S. As the number of EFS submissions increase, FDA review divisions continue to gain additional experience with the EFS program. Specifically, each division has EFS representative members in place to aid the review teams in agreeing on the type and amount of supporting data needed to support the EFS IDE. The EFS guidance, as well as the Early Access Program (EAP), is expected to be revised to capture lessons learned, and to provide additional guidance to the industry on the process.

Another aspect of FDA’s focus may be on submission quality. In the report referenced above, it is not stated how many EFS IDEs are converted to Pre-Submissions during the review, which may be one route for FDA to address significant quality issues. Webinars presented by FDA’s Clinical Trials Program staff have highlighted how many IDE submissions fail to provide basic information needed for FDA’s review. Although it is not anticipated for FDA to institute a formal Refuse-to-Accept policy for IDEs due to their short review time, it is anticipated FDA will focus on other ways to try to improve the quality of IDE submissions.

It is reasonable for medical device manufacturers to expect FDA to continue improving the EFS submission process, which may continue to increase the number of studies conducted in the U.S. As the number of EFS submissions increase, FDA review divisions continue to gain additional experience with the EFS program. Specifically, each division has EFS representative members in place to aid the review teams in agreeing on the type and amount of supporting data needed to support the EFS IDE. The EFS guidance, as well as the Early Access Program (EAP), is expected to be revised to capture lessons learned, and to provide additional guidance to the industry on the process.

Another aspect of FDA’s focus may be on submission quality. In the report referenced above, it is not stated how many EFS IDEs are converted to Pre-Submissions during the review, which may be one route for FDA to address significant quality issues. Webinars presented by FDA’s Clinical Trials Program staff have highlighted how many IDE submissions fail to provide basic information needed for FDA’s review. Although it is not anticipated for FDA to institute a formal Refuse-to-Accept policy for IDEs due to their short review time, it is anticipated FDA will focus on other ways to try to improve the quality of IDE submissions.

As the FDA continues to improve the EFS submission process, it is important to ensure that industry experience is shared with the FDA’s EFS Program staff. In the coming months NAMSA will be conducting a survey to gain insight from medical device manufacturers. Results are intended to be shared with the agency and published.

Spotlight on Industry TrendsFDA’s Focus on Early Feasibility Studies Continued

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Highest Number of Original PMAs in Over a Decade

55% Increase in PMAs from 2014

US dominates PMAs claiming 98% in 2015

Original PMAs:

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On March 13, 2015, Boston Scientific Corporation secured FDA PMA approval for the WATCHMAN™ LAAC Device, the first device-based treatment for the prevention of stroke and embolism in patients with non-vulvular atrial fibrillation (AF).

More than 5 million Americans suffer from an irregular heartbeat called AF that can lead to blood clots, stroke, heart failure, and other heart-related complications. In AF, the most common treatment for stroke risk reduction is blood-thinning warfarin therapy. Despite its proven efficacy, up to 40% of patients don’t take chronic warfarin therapy due to bleeding complications and quality of life tradeoffs such as dietary restriction and regular blood monitoring. The recently approved WATCHMAN™ LAAC Device now offers an alternative treatment option to reduce AF-related strokes.

The WATCHMAN™ LAAC Device is a catheter-delivered heart implant designed to close the left atrial appendage (LAA). The LAA is a thin, sack-like appendix arising from the heart and is believed to be the source of greater than 90% of stroke-causing clots that come from the left atrium in people with AF.

New Tech Feature WATCHMAN™ Left Atrial Appendage Closure (LAAC) DeviceBoston Scientific Corporation

Although only recently available in the US, the device has been commercially available internationally since 2009, is registered in 75 countries and has been used in more than 10,000 patients.

On February 8, the Centers for Medicare and Medicaid Services announced they will cover percutaneous LAAC therapy under specific criteria, as outlined in the agency’s final National Coverage Determination. This decision, effective immediately, provides consistent and uniform access to the WATCHMAN™ LAAC Device as a non-pharmacological treatment option for stroke risk reduction for appropriate Medicare beneficiaries.

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Minnesota Secures 11 Original PMAs in 2015

Original PMAs are highly geographically concentrated

MN and CA make up 69% of all awarded

Original PMAs:

2015: Minnesota Leads Cardiology and Neurology Original PMAs

57% (8) of cardiology original PMAs awarded to MN companies, 4-times as many as second place CA

Boston Scientific and Medtronic both secure 3 original PMAs

Nuvectra and Enteromedics secured PMA approval for neuromodulation devices

Original PMAs:

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The vBloc Neurometabolic Therapy received US FDA approval on January 14, 2015 for the treatment of adult patients with obesity. It was the first new device for the treatment of obesity approved by the FDA in almost a decade and is the first weight loss treatment device that targets the nerve pathway between the brain and stomach. vBloc is indicated for patients aged 18 through 65 years who are obese, with a Body Mass Index (BMI) of 40 to 45 kg/m2, or a BMI of 35 to 39.9 kg/m2 with a related health condition such as high blood pressure or high cholesterol levels.

New Tech Feature Maestro Rechargeable SystemEnteromedics

A pacemaker-like device is implanted laproscopically, usually in an outpatient procedure, to control both hunger and fullness. By intermittingly blocking the vagus nerve, the primary nerve that regulates the digestive system and connects the brain and the stomach, it is possible to influence satiety which can help people with obesity reduce the number of calories consumed and promote safe, healthy and durable weight loss.

Obesity is a global epidemic with significant cost and health consequences. Despite many treatment options, ranging from diet and exercise to bypass surgery, the need for safe and effective treatments remains. vBloc Therapy offers an entirely new approach to the treatment of obesity that does not physically restrict or alter the anatomy, allowing the patient to eat a normal range of foods, and it is reversible.

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Supplemental PMAs Down in 2015

Supplemental PMAs down 15% from 2014

OUS supplemental PMAs down 30% from 2014 but up 78% from 2011

Supplemental PMAs:

Minnesota Leads with 757 Supplemental PMAs in 2015

Cardiology is the largest subsector with 53% of all approvals

76% of MN supplemental PMAs are in cardiology. Neurology is the second largest sector with 9%

Supplemental PMAs:

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Minnesota 33 Days Faster at Gaining Supplemental PMAs than California

Supplemental PMAs:

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The top three companies (Medtronic, Boston Scientific and St. Jude Medical) accounted for 22% of all clearances and approvals in 2015

The top ten companies made up over a third of all clearances and approvals

Minnesota Companies Top Recipients of Approvals and Clearances.

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Minnesota Continues Leadership in Urology, Cardiology, Neurology, and Drug Delivery

Minnesota’s leadership in urology was fueled by 1 original PMA, 62 supplemental PMAs and 2 510(k)s

Within cardiology MN received 8 original PMAs, 575 supplemental PMAs and 50 510(k) clearances.

Minnesota

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Medical Alley Association’s intelligence and research work is generously supported by our Foundational and Sustaining Members.

FOUNDATIONAL MEMBERS

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SUSTAINING MEMBERS

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Sources: EvaluateMedTech, January 2016, Evaluate Ltd., www.evaluate.com

FDA, January 2016, www.fda.gov

Contact UsCheryl Matter, PhDVP, Intelligence & Research

Medical Alley Association4150 Olson Memorial Hwy, Suite 430Golden Valley, MN 55422

Email: cmatter@MedicalAlley.org

Phone: 952.746.3817

MedicalAlley.org