1. FDA’s Role in Encouraging Innovation in Combination Products Danelle R. Miller, Esq. Regulatory Counsel, Roche Diagnostics For The Combination Products Coalition FDA/DIA Cross-Labeling Workshop May 10, 2005 Diagnostics

2. Creativity is thinking up new things. Innovation is doing new things. Theodore Levitt

3. FDA’s Role in Encouraging Innovation in Combination Products  Barriers to Innovation  The Scope of FDA’s Authority  Tools for Encouraging Innovation  Policy options

4. Barriers to Innovation As a rule, men worry more about what they can’t see than about what they can. Julius Caesar

5. Barriers to Innovation: Why Companies Don’t Want to Collaborate  Potential impact on their product’s safety-effectiveness profile  Intellectual property and confidentiality concerns  Conflicting business strategies  Resource priorities  Costs  Product liability issues  Interest in competing products (drugs or delivery systems, for example)  Existing partnerships

6. Barriers to Innovation: Why Companies Don’t Want to Collaborate  Control  Risk of having someone else’s “issues” control your resources  Potential limits on flexibility  Changes have greater impact  Manufacturing and quality concerns  Desire to develop and retain internal expertise  Familiarity or lack of familiarity with a potential “partner” or product  Differing perceptions on market size and what constitutes “success”  Ex: A sizeable market to a small device company may not appear as large to a major pharmaceutical company  Additional regulatory exposure

7. The Scope of FDA’s Authority Great minds have purposes, others have wishes. Washington Irving

8. FDA’s Authority  FDA derives its authority from the Food, Drug and Cosmetic Act (“Act”).  The Act gives FDA broad authority. For example, FDA can:  Promulgate regulations for enforcement of the Act Some limitations  Approve drugs and devices, license biological products  Regulate use of drugs, biologics and devices, including those used for investigational purposes  Require manufacturers to include “adequate directions for use” in labeling

9. FDA’s Authority  AND  Take enforcement action against “misbranded” devices or drugs, including: Devices that are “dangerous to health when used in the dosage or manner, or with the frequency or duration prescribed, recommended, or suggested in the labeling thereof” Devices for which labeling is “misleading.” In determining whether labeling is misleading, FDA should look to whether “labeling fails to reveal [material] facts... Under such conditions of use as are customary or usual.”

10. FDA’s Authority  FDA’s authority is not all-encompassing. For instance, FDA does not have the authority to:  Require that companies work together  Mandate that a manufacturer seek approval for new uses of its product Association of American Physicians and Surgeons, Inc. v. FDA  Force manufacturers to “mutually conform” their labeling to include new uses As a practical matter, 3.2(e)(3) does not work  Open or reference proprietary information in a drug sponsor’s file for another sponsor seeking approval of a combination product Except: 505(b)(2)

11. FDA’s Authority In fact, industry would object to the agency playing such an active “matchmaker” role

12. Tools for Encouraging Innovation Teams work better when they work together. Alice Vernon

13. Tools for Encouraging Innovation  FDA cannot require companies to work together, but FDA can encourage companies to collaborate in a way that leads to innovation.  Existing tools include:  User fee waivers  Expedited review and approval times  Power of persuasion – “just ask”

14. Tools for Encouraging Innovation  FDA can seek additional tools from Congress, including:  Additional period of (drug) market exclusivity for voluntary collaboration in developing innovative combination products  Tax incentives for voluntary collaboration

15. Policy Options Action is eloquence. William Shakespeare

16. Policy Options  When companies refuse to collaborate, FDA has options for proactively supporting innovation while protecting the public health:  Section 505(b)(2) of the Act  Require labeling changes related to safety issues

17. Policy Options  Facilitate independent operation of a combination product sponsor.  Require sponsor to assure that: The combination product is effective under the circumstances described in combination product labeling. The combination product will continue to be effective under the circumstances described in the labeling.  Apply post-approval requirements to combination products Controls (ex: change controls). For example, allow for a post-approval testing sequence that would catch changes and ensure continued safety and effectiveness. Studies Registries  Consider a mechanism for notifying combination product sponsor of changes to component not under the sponsor’s control