1. Speakers: Khatereh Calleja, JD Senior Vice President, Technology and Regulatory Affairs Sandra Cohen Kalter, Vice President and Chief Regulatory Counsel, Medtronic Geoffrey M. Levitt, Senior Vice President & Associate General Counsel, Regulatory & Policy, Pfizer, Inc. Moderated by Iris Gibbs, Associate Director, Advertising and Promotions, Regeneron Pharmaceuticals, Inc. 1 Patient Engagement in the FDA Industry Perspective on FDA Guidances

2. Industry Perspective on FDA Guidances and Challenges in Implementing Case of Evolving Guidance re. Social Media and Internet Promotion Khatereh Calleja, JD Senior Vice President, Technology and Regulatory Affairs October 1, 2015

3. 3 Background/Description Background/Description Initial Considerations Initial Considerations Long Road to Guidance Long Road to Guidance What We Learned What We Learned Where We Are Where We Are Other Guidance to Watch Other Guidance to Watch Way Forward Way Forward Outline

4. AdvaMed is the world’s largest association representing manufacturers of medical devices, diagnostic products, and medical information systems. AdvaMed is the world’s largest association representing manufacturers of medical devices, diagnostic products, and medical information systems. AdvaMed member companies produce the technologies that are transforming health care through earlier disease detection, less invasive procedures, and more effective treatments. AdvaMed member companies produce the technologies that are transforming health care through earlier disease detection, less invasive procedures, and more effective treatments. AdvaMed Description 4

5. Piecemeal approach to advertising and promotion issues has often been challenging amidst uncertain environment and limited guidance i.e., online/social media & scientific exchange Piecemeal approach to advertising and promotion issues has often been challenging amidst uncertain environment and limited guidance i.e., online/social media & scientific exchange Important to distinguish key differences in drug and device regulatory frameworks and how devices are developed and used Important to distinguish key differences in drug and device regulatory frameworks and how devices are developed and used Initial Considerations 5

6. FDA internet/social media hearing and collection of docket comments (11/09 - 3/10) FDA internet/social media hearing and collection of docket comments (11/09 - 3/10) FDASIA Sec. 1121-guidance on product promo using internet, including social media (7/12) FDASIA Sec. 1121-guidance on product promo using internet, including social media (7/12) Long awaited (draft) social media guidances (6/14) Long awaited (draft) social media guidances (6/14) Presentation of risk information when character space limits Correcting 3rd party misinformation One more earlier in year (not for devices) Long Road To Guidance: Ex. of Social Internet/Social Media 6

7. Regardless of media, statements must be truthful and non- misleading, balanced, and consistent with labeling Regardless of media, statements must be truthful and non- misleading, balanced, and consistent with labeling Promotion not necessarily rendered false and misleading by Promotion not necessarily rendered false and misleading by use of a link Manufacturers are responsible for their own communications and promotions Manufacturers are responsible for their own communications and promotions What We Learned (or Knew Already) 7

8. One size fits all approach can create hurdles (e.g., highlighting 1 risk in device tweet) One size fits all approach can create hurdles (e.g., highlighting 1 risk in device tweet) Recommended approaches can be clunky and even prohibitive (e.g., multiple segmented links may not serve fair balance versus centralized info) Recommended approaches can be clunky and even prohibitive (e.g., multiple segmented links may not serve fair balance versus centralized info) Scope can be limited and not have answers for all (e.g., what about other evolving platforms beyond Twitter and sponsored links?) Scope can be limited and not have answers for all (e.g., what about other evolving platforms beyond Twitter and sponsored links?) What We Learned, Challenges 8

9. Helpful rules of road (e.g., may incentivize voluntary corrections) Helpful rules of road (e.g., may incentivize voluntary corrections) Examples are always helpful Examples are always helpful Make clear conceptual boundaries (e.g., firms not responsible for monitoring entire Internet or addressing all misinformation) Make clear conceptual boundaries (e.g., firms not responsible for monitoring entire Internet or addressing all misinformation) Answer questions, but sometimes raise additional ones Answer questions, but sometimes raise additional ones What We Learned: More Food for Thought 9

10. Manufacturers focused on minimizing risk and training/implementation of SOPs Manufacturers focused on minimizing risk and training/implementation of SOPs High public health value of new emerging media for education and awareness, but barriers remain and need to ensure flexible policies that work for diversity of products High public health value of new emerging media for education and awareness, but barriers remain and need to ensure flexible policies that work for diversity of products Challenges for both FDA and industry Challenges for both FDA and industry Where We Are: Byproduct of Limited Guidance 10

11. Links to 3rd Prty Sites in Internet/Social Media Links to 3rd Prty Sites in Internet/Social Media Another key area for helpful policy, but status unclear— scientific exchange Another key area for helpful policy, but status unclear— scientific exchange Other Guidance to Watch 11

12. Clearly significant efforts invested by FDA to develop guidance Clearly significant efforts invested by FDA to develop guidance Valuable to industry; help reduce gray areas Valuable to industry; help reduce gray areas Continuing challenge of balancing targeted solutions with comprehensive policies Continuing challenge of balancing targeted solutions with comprehensive policies Cross-center collaboration will be important Cross-center collaboration will be important Encourage collaborative industry-FDA dialogue where at all possible (early and often) Encourage collaborative industry-FDA dialogue where at all possible (early and often) Way Forward 12

13. FDLI Advertising and Promotion Conference Industry Perspective on FDA Guidances October 2, 2015 Sandra Cohen Kalter, Vice President and Chief Regulatory Counsel, Medtronic

14. FDA has substantially increased the resources devoted to generating guidance documents –Notwithstanding concerns about particular elements of certain guidance documents, they de-mystify FDA’s thinking about certain activities –Since 2009, FDA has issued a number of guidance documents relating to promotional issues Presentation of risk information & direct to consumer communications Unsolicited requests/questions guidance Dissemination of reprints, clinical practice guidelines, & reference texts 2 social media guidances for device companies

15. FDA’s Recent Guidance Efforts: Social Media –FDA issued three draft guidance documents addressing various aspects of social media (one does not pertain to devices) –Overall takeaways: Some products, such as those with a high-risk of serious side- effects, are not good candidates for space-constrained advertising platforms like Twitter because of the inability to provide FDA-required risk and safety information Manufacturers may be responsible for content produced by third parties over which they have some level of control, such as paid experts and affiliated speakers All content must be truthful and not misleading, as well as presented in a balanced manner that includes risks and benefits in each promotional communication

16. FDA’s Recent Guidance Efforts: Correcting Misinformation Draft Guidance provides steps manufacturers can take if they wish to correct misinformation –Firm must correct misinformation on its own websites, websites it controls, or postings made by employees or agents on third-party sites –Firms may choose to correct other misinformation Corrective communications should be: –Relevant to the misinformation, limited and tailored, accurate and nonpromotional –Consistent FDA labeling and/or supported by evidence –Posted in conjunction with the misinformation Manufacturers may choose to correct only certain misinformation but must correct all misinformation in the “clearly defined portion” of the forum

17. FDA’s Recent Guidance Efforts: Character Space Limitations –Does not make significant accommodations from general promotional and advertising requirements for platforms with character space limitations –If a manufacturer makes a benefit claim, it must include information about the product’s most serious risks within the same communication –Manufacturer should include a way for customers to access more complete information about risks associated with a product, such as providing a hyperlink to a page describing only risk information –Hyperlink should be direct, and landing page should not be promotional in tone or content

18. FDA’s Recent Guidance Efforts: Interactions with Patient Groups –FDA distinguishes between information presented to HCPs and information presented to patients or consumers –Information disseminated to patient groups should be: Truthful and not misleading Center around patient needs, product education, and/or access Include a fair balanced presentation of product data with safety and efficacy discussions Be in accordance with FDA-approved product labeling or IFU and supported by valid scientific evidence Not involve offering or providing anything of value to induce the purchase or use of medical devices Avoid unnecessary access to protected health information Refer patients to their healthcare professionals for more information

19. FDA’s Recent Guidance Efforts: Responses to Unsolicited Questions –Addresses company responses to unsolicited questions regarding off-label uses Unsolicited requests are initiated by persons or entities that are completely independent of the manufacturer Requests that are prompted in any way by a manufacturer or its representatives are not unsolicited requests –Draft Guidance distinguishes between public and non- public requests –Non-public requests are directed privately to a company using a one-on-one communication approach –Public requests are made in a public forum, and may be directed to a company specifically or to a forum at large

20. 2014 Draft Guidance Covers Re-Prints, CPGs and Reference Texts –Publications distributed as recommended will not be used as evidence of an intent that the product be used for an unapproved new use –FDA recognizes that public health may benefit from HCPs receiving truthful and non- misleading scientific or medical publications on unapproved new uses –Discusses dissemination of third-party data where the company has a financial relationship

21. FDA’s Recent Guidance Efforts: Dissemination of Scientific and Medical Publications Hallmarks of Appropriate Articles/Texts Independently published Current Authored by subject matter experts Peer reviewed by subject matter experts Based on a systematic review of existing evidence Widely available through independent channels Disseminated independent of promotional literature Separate criteria for distributing portions of texts Include a permanently affixed, prominently displayed statement disclosing: Manufacturer Fact that off-label uses are included Financial interests of authors, if applicable Include a copy of approved labeling or IFU if one or more text chapters is dedicated to a discussion manufacturer’s product(s)

22. Pegged to IOM’s criteria for trustworthiness Based on a systemic review of the existing evidence Developed by knowledgeable, multidisciplinary panel of experts and representatives from key affected units Considers important patient subgroups and patient preferences Transparently developed and funded to minimize biases Provides a logical explanation of care options Is reconsidered and revised to reflect new information When distributing a CPG, manufacturer should: Disseminate the most current version Distribute CPG separately from promotional materials and not in promotional venues Ensure it is properly labeled with disclosures If portions of the CPG contain a primary substantive discussion of an individual product, include the approved labeling or IFU Clinical Practice Guidelines (CPGs)

23. In the form of a special supplement or publication that was funded by a manufacturer of the product at issue Marked, highlighted or summarized, by the manufacturer, in writing or orally, to emphasize an unapproved use Primarily distributed by a manufacturer; should be generally available Written, edited, or excerpted specifically for, or at the request of, a manufacturer Edited or significantly influenced by or at the request of the manufacturer Attached to specific product information (other than the approved labeling/IFU) Materials disseminated should not be:

24. Industry Perspective on FDA Guidances Geoffrey M. Levitt, Senior Vice President & Associate General Counsel, Regulatory & Policy, Pfizer, Inc. October 1, 2015

25. The Guidance Document Explains FDA’s interpretation of, or policy on, a regulatory issue Primary audience is regulated industry Also useful for staff or other stakeholders May address, among other matters, scientific issues and enforcement policies Not legally binding, but shows a way to reach a regulatory goal (safe harbor)

26. The Guidance Process Addressed in statute (FDCA sec. 701(h)) and regulation (21 CFR 10.115) - GGP May be initiated internally or externally Developed by a working group; reviewed at Center level and then (depending on issue) HHS and OMB Stakeholder input should be a significant part of the process (but not required in advance) Recommendations for guidance topics Comments on draft guidances Public meetings/workshops Guidances are “critical to support industry efforts to comply with the law” and “develop new products that may benefit the public health” Should be “relevant, timely, and easy to find”

27. Guidances Today Have eclipsed regulations as means of communicating agency expectations Increasingly enshrined in legislation Offer flexibility (relevant), relative speed (timely) Loss of transparency, process protections?

28. COMMIT THANK YOU

29. Questions? 29