BioTech Startup School@KU

1. BioTech Startup School@KU Spring 2019 KUMC Module 4: Regulation of Devices

2. Overview of SS@KU

3. USA Food and Drug Administration (FDA) • Governing body over implants & medical products in USA (not the rest of the world) • FDA does not inhibit or regulate the practice of medicine • it regulates interstate commerce and how the companies can market their devices.

4. FDA Mission Statement “The Food and Drug Administration is responsible for protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices; and by ensuring the safety of our nation's food supply, cosmetics, and products that emit radiation. FDA also has responsibility for regulating the manufacturing, marketing, and distribution of tobacco products to protect the public health and to reduce tobacco use by minors. FDA is responsible for advancing the public health by helping to speed innovations that make medical products more effective, safer, and more affordable and by helping the public get the accurate, science-based information they need to use medical products and foods to maintain and improve their health. FDA also plays a significant role in the Nation's counterterrorism capability. FDA fulfills this responsibility by ensuring the security of the food supply and by fostering development of medical products to respond to deliberate and naturally emerging public health threats.” https://www.fda.gov/aboutfda/whatwedo/

5. Products FDA Regulates • Food • Drugs • Medical Devices • Biologics • Animal Feed and Drugs • Cosmetics • Radiation-Emitting Products • Combination Products

6. Step 1: Is your product a regulated medical device? “If a product is labeled, promoted or used in a manner that meets the following definition in section 201(h) of the Federal Food Drug & Cosmetic (FD&C) Act it will be regulated by the Food and Drug Administration (FDA) as a medical device and is subject to premarketing and postmarketing regulatory controls.” https://www.fda.gov/medicaldevices/deviceregulationandguidance/overview/classifyyourdevice/ucm051512.htm

7. Step 1: Is your product a regulated medical device? “A device is: "an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is: • recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them, • intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or • intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.” Section 201(h) of the Federal Food Drug & Cosmetic (FD&C) Act

8. Classifications of Medical Devices • Regulatory barriers could be your biggest road block in successfully commercializing your medical device, even if the need is great and the market is large • Classification of your device is based on • Level of risk to patient and associated hazards • Previously regulated devices • How different is your device • Intended use • Quality systems and controls required • Marketing date

9. Classifications of Medical Devices Lowest level of regulation Highest level of regulation • Class I • With exemptions • Without exemptions • Class II • With exemptions • Without exemptions • Class III Related to controls Requires a predicate device Increased cost/time Increasing severity/risk to patient De Novo

10. Predicate Device and Substantial Equivalence • The predicate is the 510(k) cleared device to which you are comparing your new device • Your new device is substantially equivalent if • it has the same intended use as the predicate device; and • has the same technological characteristics as the predicate device; or • it has different technological characteristics, that do not raise new questions of safety and effectiveness, and the sponsor demonstrates that the device is as safe and effective as the legally marketed device. • A claim of substantial equivalence does not mean the new and predicate devices must be identical

11. Example: Substantially Equivalent Device Knee Fusion Nail (for knee arthrodesis) Substantially equivalent to a Compression Hip Screw (for hip fractures) Common technological risk feature was a sliding barrel for bone compression during fracture healing

12. Classifications of Medical Devices • Is there a predicate for your medical device? If so, how was it classified? • https://www.fda.gov/medicaldevices/deviceregulationandguidance/ • General ways to predict your classification • If the predicate device was Class I, you may have a Class I device……UNLESS your device has different critical technological characteristics • If the predicate device was Class II, you may have a Class II device……UNLESS your device has different critical technological characteristics • If the “predicate device” was Class III, you likely have a Class III device • If you can’t find a predicate device, you are likely either Class III or De Novo

13. Medical Device Classification – US FDA PreMarket Approval (PMA) Submission Class III Preclinical Data Clinical Data Special Controls No De Novo Low risk Substantially equivalent to a predicate device? Bench Testing PreMarket Notification 510(k) Submission General Controls Class II Yes Device is “not exempt” Marketing Clearance/Approval Class I Device is “exempt” from 510(k) process Class III PMA approved DeNovo510(k)  granted Class II 510(k)  cleared

14. Medical Device Classification – US FDAThe higher the potential patient risk, the greater the level of investigation, testing, trials, and controls to be established to permit device access to the US market. Cost/Time to Develop Likelihood of translation Source: http://www.presentationeze.com/presentations/medical-device-validation/medical-device-validation-full-details/fda-approach-medical-device-classification/

15. FDA Impact on U.S. Medical Technology Innovation:A Survey of Over 200 Medical Technology Companies November 2010 Makower et al., “FDA Impact on U.S. Medical Technology Innovation,” 2010.

16. FDA Support of Innovation for Medical Devices • Informational Meetings • No unofficial opinions from FDA • Teach FDA reviewers about new ideas • No feedback from FDA required • Pre-Submission Meetings • Unofficial opinions from FDA • Feedback from FDA that can be used to derisk investment opportunities • Humanitarian Device Exemptions (HDE) • devices that will only be used to treat a relatively small number of patients per year that otherwise would need PMAs • Early Feasibility Study (EFS) Program • small clinical studies (often less than 20 patients) that are intended to obtain initial insights into device performance • Expedited Access Pathway (EAP) Program • medical devices intended to address unmet medical needs for life-threatening or irreversibly debilitation diseases or conditions

17. My Advice to Fellow Medical Device Innovators • Determine your likely classification early in the innovation process • Try to think about how the reviewers will look at your product concept • If your device concept has a risk of Class III designation, make sure that the market and need are both very high  customer discovery • Follow industry trends on regulatory classifications in your space • Think about how your choices in research and development of your device will influence the classification • If there is any question about the classification, ask the university to invest in a professional regulatory opinion before pushing out for licensing opportunities • If you start your own company for translation, hire a regulatory consultant and form a regulatory strategy before licensing • Consider a stepwise approach for your device development for both regulatory and reimbursement