1. Medical Devices and Pediatrics Shannon Nees, PGY-2 December 9, 2013

2. Outline  Medical device development and approval  Medical devices in pediatrics  History of pediatric device legislation  Current and future legislation

3. What is a medical device? According to the FDA: any instrument, apparatus, implement, machine, contrivance, implant, and in vitro reagent, similar or related article that is not metabolized in the body; has no chemical action in/on the body; is not a drug, biologic, or food; and is used to diagnose, treat, prevent, or cure.

4. Medical Device Development and Approval  Medical devices are regulated by the FDA  Approval process is based on the category of device, which is determined based on the presumed risks  Class I: tongue depressors  Class II: EKGs and hearing aids  Class III: Implantable or life-sustaining devices  For FDA approval of Class III devices, need to prove both safety and efficacy prior to approval  Devices must also be approved for an Investigational Device Exemption (IDE) to be used in clinical trials  FDA can also grant approval for compassionate use of a device or emergency authorization

5. Medical Device Development in Pediatrics  Majority of devices used in pediatrics are developed for adults and then adapted for use in children  FDA has the ability to allow extrapolation of device efficacy from adults to children  Many devices are used “off-label” in children  Pediatric diseases are relatively rare compared to many adult conditions so there is less financial incentive to develop devices for them  Designing clinical trials involving children can be logistically and ethically complicated  Pediatric devices need to account for the variability in size and developmental stages of children  Need long term follow-up data to determine safety of devices used in children

6. Media Coverage  NY Times, May 2013:

7. Why can’t we just make devices smaller?  Different physiology than adults  Ex: faster respiratory and cardiac rates  Different metabolic responses to material used  Devices may require significant redesign due to size constraints  Materials used in adults may not be safe over long time periods required for use in children  Anatomy may differ making percutaneous device delivery difficult  Controls that are accessible to children must be childproofed  Ex: Ventricular assist devices

8. Examples of Medical Devices for Children Marilyn J. Field and Hugh Tilson. Safe Medical Devices for Children Executive Summary. IOM 2005.

9. Example: Pacemakers and ICDs  More intense and varied types of physical activity puts additional strain on these devices in children compared to adults  Children often require lead replacement due to fracture or malfunction  Rapid growth in children may require additional length of leads to avoid increased tension  Increased heart rate in children leads to faster battery depletion so battery needs to be easily removed and replaced  Devices designed for adults may incorrectly interpret sinus tachycardia as ventricular tachycardia, and deliver an inappropriate shock

10. Why should we care?  Most research into drugs and medical devices is focused on adults and adult diseases  Children are not just small adults: they have different medical problems as well as different reactions to medical devices  As pediatricians, we use medical devices constantly in our practice and we need to understand their indications and potential side effects in children  Developing new devices for pediatric conditions can be difficult and it is important to understand this process

11. History of Pediatric Device Approval and Regulation  Prior to 2007, approval process for pediatric devices was the same as for adult devices  Post-market surveillance of devices was also the same and was generally limited to 3 years  There was no requirement for device companies to submit information about potential pediatric uses when submitting an application  Pediatric devices could be approved under the Humanitarian Device Exemption Pathway (HDE)  Device can be used to treat or diagnose a disease that affects <4,000 patients  Have to demonstrate safety but not efficacy  HDE manufacturers can recoup research and development costs but cannot profit from sale of devices

12. History of Pediatric Device Approval and Regulation  Medical Device User Fee and Modernization Act of 2002 called for the IOM to assess the system under the FDA for the post-market surveillance of medical devices in pediatric populations  The IOM report was published in 2005 and made many recommendations including:  The FDA should develop additional guidance on the identification and evaluation of pediatric questions or concerns at all stages in the design and evaluation of medical devices used with children.  Congress should amend the Federal Food, Drug, and Cosmetic Act allowing the FDA to change the duration of Section 522 studies beyond the three-year limit for devices likely to have significant pediatric use so that studies can take into account children's growth and development.

13. History of Pediatric Device Approval and Regulation  In 2004, the FDA issued a report to Congress: Barriers to the Availability of Medical Devices Intended for the Treatment or Diagnosis of Diseases and Conditions that Affect Children.  They gathered comments from various stakeholders and developed recommendations.  The main recommendation was to further research and define unmet pediatric device needs.  Other recommendations included:  Enhanced interaction and communication between pediatric clinicians and device manufacturers.  Development of a network of children’s hospitals and healthcare facilities with expertise in pediatric diseases and conditions.  Consideration of certain pediatric device issues by the Office of Pediatric Therapeutics or the Pediatric Advisory Committee in order to improve pre-market review of pediatric devices.

14. Pediatric Medical Device Safety and Improvement Act (PMDSIA)  Passed by congress in 2007 and signed into law by President George W. Bush  Created a mechanism for the FDA to track devices designed for use in pediatrics  Removed profit restriction for devices marketed and approved as HDEs as long as they were labeled for pediatric populations  Enhanced post-market surveillance including the ability to extend studies past the three year limit for devices likely to have significant pediatric use  Included the introduction of the pediatric device consortia  Significantly increased the number of medical devices designated for pediatric patients  Needs to be renewed every 5 years

15.  July 9 th 2012, the reauthorization was passed as part of the FDA safety and innovation act  Reauthorized and preserved the pediatric profit incentive for HDEs  Reauthorized the pediatric device consortia at $5.25 million dollars per year  Included a provision requiring medical and surgical device companies to submit available pediatric information in their device applications.  Established a timeline for implementing a pediatric device tracking rule to improve surveillance of devices in pediatric population  This will require companies to submit available pediatric information in device applications  Final rule must be submitted by Dec 31, 2013 Reauthorization

16. FDA Pediatric Device Consortia (PDC) grant program  Support the development of a consortia to stimulate projects that will promote pediatric device development  Provides grants to programs who contribute to market approval of medical devices designed specifically for use in children  Intended to encompass devices used in all pediatric diseases, not just rare diseases  Grants awarded every two years  Grants awarded every two years to programs who:  Connect people with device ideas with potential manufacturers and resources for business development  Mentor projects through the development process  Helpsdevice developers navigate the FDA regulatory process  Currently funding consortia who have helped advance the development of over 135 proposed pediatric medical devices  This Program needs to be renewed every 5 years and was renewed in 2012  Budget of ~$6.0 million for FY 2013

17. 2013 Grants 1) University of Michigan Pediatric Device Consortium, led by James Geiger, M.D., $700,000/ year 2) Atlantic Pediatric Device Consortium, led by David Ku, M.D., Ph.D., $700,000/ year 3) National Capital Consortium for Pediatric Device Innovation, led by Peter Kim, M.D., Ph.D, $700,000/ year 4)New England Pediatric Device Consortium, led by Rick Greenwald, Ph.D., $700,000/ year 5) Southern California Center for Technology and Innovation in Pediatrics, led by Yaniv Bar-Cohen, M.D., $300,000 /year 6) Philadelphia Regional Pediatric Medical Device Consortium, led by Matthew Maltese, M.S., Ph.D., $300,000/year 7) Boston Pediatric Device Consortium, led by Pedro del Nido, M.D., $200,000/year

18. San Francisco Pediatric Device Consortia  Meets twice weekly to discuss potential projects  Meetings are open for anyone to bring in an idea or prototype  Corsortia helps with design and regulatory process, makes contacts with important resources, etc.  Acts as a think tank for new devices http://www.pediatricdeviceconsortium. org/

19. Pediatric Device Consortia – Michael Harrison, MD

20. Example: Artificial Kidney

21. Future Issues  Profit incentive for HDEs and the Pediatric Device Consortia will need to be re-approved in 2017  Although the consortia provides resources for device developers, still does not provide funding for these devices  Ongoing debate regarding the appropriate requirements for companies submitting pediatric data in device applications  Although legislation has allowed the FDA to approve devices aimed at pediatric populations, insurance coverage of HDE devices is inconsistent  We still have relatively little market data on what pediatric devices are most needed

22. Private Companies

23. What can you do?  Contact your representatives to let them know that you support legislation to encourage device development in pediatrics  Support future legislation to improve the assessment of pediatric needs  Have an idea for a device?! Contact one of the FDA funded consortia for resources to help you get started!

24. References  Bates, KE et. Al. Pediatric cardiovascular safety: Challenges in drug and device development and clinical application. Am Heart J. 2012 Oct;164(4):481-92.  Pediatric Drug and Device Law Compilation. The Best Pharmaceuticals for Children Act, the Pediatric Research Equity Act, and the Pediatric Medical Device Safety and Improvement Act As Amended by the Food and Drug Administration Safety and Innovation Act July 2012  Marilyn J. Field and Hugh Tilson. Safe Medical Devices for Children Executive Summary. IOM 2005.  Poslosky, J. Children are not little adults: Federal legislation would ensure medical surgical devices meet pediatric patients’ needs. AAP News 2012;33;5  Samuels-Reid J, Lawrence B, Millin C, Cope J. Pediatric devices and adverse events from A to Z: understanding the benefits and risks from a US FDA perspective. Expert Rev Med Devices. 2012 May;9(3):275-82. doi: 10.1586/erd.12.7.  U.S. Department of Health and Human Services Food and Drug Administration. Barriers to the Availability of Medical Devices Intended for the Treatment or Diagnosis of Diseases and Conditions that Affect Children. Oct 2004

25. Questions??