1. AMERICAS | ASIA PACIFIC | EMEA Medical Devices: Concept to Commercialization How to avoid delays in getting your product cleared/approved by FDA Robert Seiple, MS, MPM, RAC-US EMERGO | Senior Consultant, QA/RA 29 October 2015

2. AMERICAS | ASIA PACIFIC | EMEA Early product development

3. AMERICAS | ASIA PACIFIC | EMEA Proof of concept and strategic planning Is there a market for the device? Have other products been cleared/approved by FDA? Is US the right market to enter first? Maybe Europe? Is reimbursement critical to your success? Do you have financial resources to complete development & handle clinical or regulatory delays?

4. AMERICAS | ASIA PACIFIC | EMEA Overview of US FDA regulatory framework

5. AMERICAS | ASIA PACIFIC | EMEA Classification scheme Classification scheme in US (like EU, Canada & others, based on risk – primarily to user Class I– low risk, relatively few requirements – tongue depressors, etc. Class II – medium risk – very large number of products, most subject to 510(k) system. Class III – Higher Risk – most require PMA

6. AMERICAS | ASIA PACIFIC | EMEA Device companies (sponsor) must submit a 510(k) or PMA application Important that you understand which process you will need to go through! Huge implications for costs and time to approval – 510k <1 year; PMA – many years. If clinical trials are required, consider where & with whom you should conduct them. Completely different regulatory requirements Companies often run out of money  The regulatory roadmap

7. AMERICAS | ASIA PACIFIC | EMEA Marketing authorization under 510k (21CFR 807, subpart E) considers a product safe and effective IF the device can be determined to be “Substantially Equivalent” to a device already on the market. Poses a problem for innovators of lower risk devices Substantial Equivalence determined (primarily) by same intended use and similar technology. Clinical studies sometimes needed to demonstrate efficacy. Substantial equivalence

8. AMERICAS | ASIA PACIFIC | EMEA What is a predicate device? US FDA system based on predicate system of classification, not rule based like Europe or Canada Device similar to yours must have been “cleared” by FDA Innovative new devices go through De Novo or PMA process

9. AMERICAS | ASIA PACIFIC | EMEA FDA has a comprehensive database for finding the classification of your device and identifying predicates

10. AMERICAS | ASIA PACIFIC | EMEA How to search for predicate devices Tip: The FDA database is picky. Start with shortest and simplest search term for your device so you find all results. Narrow your results with more descriptive terms later.

11. AMERICAS | ASIA PACIFIC | EMEA Finding predicate device(s) Search 510k database for similar or competitor products …by business name (must be close match) …by product code – but not necessarily unique. …by device name (use simplest term, then refine) Once found, record CFR and product code references and uses these as search terms.

12. AMERICAS | ASIA PACIFIC | EMEA 510(k) or PMA? Vast majority of Class II devices require a 510(k) Most Class III require Pre Market Approval (PMA) FDA does not “approve” devices that go through the 510(k) process – they clear (authorize) them to the marketed in the US. FDA clears about 3,100 devices via the 510(k) process each year. Average clearance time via FDA internal review: 6 months FDA clears less than 40 new PMA devices each year

13. AMERICAS | ASIA PACIFIC | EMEA 510(k) issues to be aware of ‘Refuse to Accept’ – preliminary review, (off-the-clock) to determine if all the required elements of the 510(k) are present. Electronic submission – very specific requirements for document formatting, file conventions, etc. If not met, submission is refused Usability – a type of validation study used to demonstrate that intended user can use device properly. Risk Management – International standard for identifying & controlling risks (ISO 14971). Performance Standards – vary by product, Ex: ISO 60601-1, 3 rd edition – Electrical Safety, ISO 10993-x, Biocompatibility, etc.

14. AMERICAS | ASIA PACIFIC | EMEA Medical device design controls

15. AMERICAS | ASIA PACIFIC | EMEA What are design controls? 21CFR 820.30 – Manufacturers of specific Class I, all Class II or Class III devices will control (and document) design efforts. Nine specific elements to Design Control: Design Plan (project planning) Design Inputs Design Outputs Design Review (how many, when?)

16. AMERICAS | ASIA PACIFIC | EMEA Design controls – continued Design Verification Design Validation Design Transfer Design Changes (control of) All documented in the Design History File Source: FDA

17. AMERICAS | ASIA PACIFIC | EMEA When to start design control 21CFR820 is Quality System Regulation – mostly concerned with marketed device However, when does Device Design begin? Frequently, YEARS before marketing

18. AMERICAS | ASIA PACIFIC | EMEA 21 CFR Key parts you should read: Part 801 - Labeling Part 807 – Pre-Market Submission Part 812 – Investigational exemptions Part 820 – Quality System Regulation Part 830 – Unique Device ID Part 860 – Classification All available online or in Emergo app Emergo app

19. AMERICAS | ASIA PACIFIC | EMEA Questions? Please contact Robert Seiple EMERGO | Senior QA/RA Consultant robert@emergogroup.com Questions? Please contact Robert Seiple EMERGO | Senior QA/RA Consultant robert@emergogroup.com Thank you for your attention Downloadable PDF of US regulatory process available online at: www.emergogroup.com/resources/united-states