Two Worlds Converge Pharma/Device

1. Two Worlds ConvergePharma/Device Opportunities Challenges

2. The Code of Federal Regulations – The Rules –Title 21 defines FDA’s responsibilitiesOnline at www.gpoaccess.govRegulations multiply quickly… (1971 vs. 2004)

3. FDA Centers Organized by Commodity • Food & Cosmetics (CFSAN - Center for Food Safety & Nutrition) • Veterinary Drugs & Devices (CVM - Center for Veterinary Medicine • Biologics (CBER - Center for Biologics Evaluation & Research) • Drugs(CDER - Center for Drug Evaluation & Research) • Medical Devices, Diagnostics & Radiological Health Products (CDRH - Center for Devices & Radiological Health)

4. Definition of a Biologic (See 21 CFR Part 600 for formal definition) An agent intended for use in the diagnosis, cure, mitigation, treatment, or prevention of a disease or condition. -AND- Is derived from a living organism such as a therapeutic serum, toxin, antitoxin, or analogous product.

5. Definition of a Device (See 21 CFR Part 800 for formal definition) An instrument, in-vitro reagent, implant, component part or a similar article, which is intended for use in the diagnosis, cure, mitigation, treatment, or prevention of a disease or condition. -AND- Does not achieve its primary intended purpose through chemical action within the body.

6. Definition of a Drug (See 21 CFR Part 201 for formal definition) An agent intended for use in the diagnosis, cure, mitigation, treatment, or prevention of a disease or condition. -AND- Achieves its intended purpose by a biochemical/ physiological mechanism by which the agent produces a response.

7. Confused? You’re Not Alone. • FDA Office of Combination Products • Established in 2002 • Reports to the Office of the Commissioner • Assigns primary Center for review • FY2003: Handled 12 products • FY2009: Handled 377 products

8. What am I? • Stent • Drug Eluting Stent • Implant • Implant with Silver Coating • Glucose Monitor with Insulin Pump • Device • Combination Product: Device and Pharma • Combination Product: Device, Diagnostic and Pharma

9. Convergent Technologies An Abbreviated History • Injections • Drug eluting stents • Antimicrobial implants • Bandaid – Class 1

10. Combination Devices Benefits • Extend Patent Life – New Dose Forms • Personal Medicine • Improve Patient Care • Eliminate Potential Law Suits • Reduce Infections and HAIs

11. Device needs Pharma • Within 24 hours implants begin to develop colonies of bacteria or fungus - biofilms form • 70% of HAIs are linked to implants • 10% of catheters, UTI’s develop serious complications due to the development of biofilms • 50% of LVAD recipients develop infections and die

12. WHAT IS A BIOFILM Staphylococcus Biofilm

13. Definition of a Biofilm An aggregate of microbes with a distinct architecture Like a tiny city in which microbial cells form towers that other microbes attach to. These microbes derive nutrients and protection from this biofilm community and become highly resistant to treatment Bacteria growing in a biofilm are up to 1,000 times more resistant to antibiotics than the same bacteria not growing in a biofilm and often lead to life-threatening systemic infections Does anyone in attendance have a biofilm trying to develop in their body right now?

14. Reducing the Growth of Biofilm Antibiotics or antifungals can’t reach biofilm that is growing on an implant when taken by mouth or via the bloodstream Pharma: Drug-eluting or infused devices to prevent biofilms from forming FDA – Safety and Efficacy Will the slowly released anti-microbial affect the body’s natural flora? Will we build up a tolerance to anti-microbials used? Tridosan’s overuse has caused it to be banned in Europe

15. What defines a drug? Drug resistance is increasing while new antibiotics are decreasing Approved New Antibiotics 1989: 16 2009: 1 Any product claiming to reduce infection or inflammation must be classified as a drug Rediscover materials that have anti-microbial properties – Silver Silver has natural anti-microbial properties Devices that contain silver must be approved as a drug; silver is a drug?

16. FDA • Clinical trials are required for any device that claims to be capable of causing infection reduction, biofilm reduction or adhesion prevention • Trials require clinical trial candidates • Is the medical device industry future ready • stringent FDA requirements including clinical trials • lengthened time to market • additional financing required

17. Right now • Drug firms: Facing patent expirations, shrinking pipelines. • Wall Street wants GROWTH. • Device firms: Small, entrepreneurial. • Device path to market changing quickly.

18. Device Paths to Market Premarket Approval (PMA) • Used for new, life-supporting, or other high-risk devices • Staged clinical trials for evidence of safety & efficacy • Formal FDA review and approval Premarket Notification [PMN or 510(k)] • For relatively low-risk devices as defined in CFR • Submit evidence to FDA that the device is “substantially equivalent” (SE) to a device already on the market • Product can be marketed if FDA doesn’t disagree it’s SE • Results in marketing clearance, not approval

19. Compare to Drug Paths to Market New Drug Application (NDA) • Well-established path to market • Modeling, literature, animal studies submitted to FDA • Staged clinical trials for evidence of safety & efficacy • Formal FDA review and approval Abbreviated New Drug Application (ANDA) • Generic products allowed once patent, exclusivity expired • Submit evidence to FDA that generic is bioequivalent • FDA reviews to ensure equivalence to the safe, effective innovator drug

20. A Closer Look at Device Regulation • Device regulation began when Amendments to the Food Drug & Cosmetic Act took effect on May 28, 1976; unregulated prior to 1976 • Most devices allowed onto the market under 510(k) have no safety and effectiveness testing • From May 28, 1976 through 2009: • 127,239 510(k)s were cleared • 1,125 PMAs were approved • “Equivalence creep” = “Predicate creep” • 1977 device B equivalent to 1975 device A • 1982 device C equivalent to device B • 1990 device D equivalent to device C • 2001 device E equivalent to device D • Is the 2001 device E equivalent to the 1975 device A?

21. Problems Evident • Device recalls, literature, press attention, anecdotal reports, malfunctions hit critical mass • e.g., Archives of Internal Medicine reports that the most commonly recalled device since 2005 is the automated external defibrillator (AED) • AEDs were cleared under 510(k) • GAO report results: Congress orders FDA to study 510(k) process • FDA forms a Task Force & a Working Group

22. Changes to 510(k)s Begin • Recommendations of Task Force and Working Group evaluated by FDA • Early 2011: FDA targets 55 recommendations • Recommendations draw heavily from pharmaceutical experience • FDA makes up ambitious 2011 calendar • Schedules new guidances beginning in March

23. Some Expected Changes • Identify standards from various agencies & professional organizations FDA can adopt (mostly engineering) • Define a new class of 510(k) requiring clinical trials (IIb designation) • Require additional information in adverse event reports (AERs) as seen in drug AERs • Establish a postmarketing safety database • Identify safety signals (as in pharmacovigilance) • Enhance device reviews with medical officers (clinical practitioners) to evaluate effects on patients

24. More Changes • Establish database of device modifications (similar to supplemental NDAs) • Develop a system of universal product identifiers similar to National Drug Codes (NDCs) • Establish a consistent vocabulary to describe devices and their therapeutic categories • Work with other Centers to establish a Science Council to advise industry & FDA staff • Look at submission and formatting of electronic labels (as in the Structured Product Labeling requirements for drugs)

25. Bottom Line? • Drug firms: Patent cliff, limited pipeline • Device firms: Small, edible • Combination products a logical extension • Regulations now converging • Information needs expand

26. Information Needs Business Start-Up; Venture Capital; IPO Established Life Science Firm; SEC; Shareholders Engineering Chemistry, Biology Small Firm Challenges Large Firm Challenges Device Manufacture & Regulation Drug Manufacture & Regulation

27. Speculation FDA’s current organization by commodity is blurring; emphasis is moving to therapeutics by system. As information professionals, will we support a pharmaceutical or device firm or a health science company developing all manner of therapies for specific conditions or particular body systems? This shift will require we understand, mine and integrate more cross-disciplinary information to support complex emerging health care products.

28. Truth or Fiction? Pacemaker the size of a tic tac Inserted via a small plastic tube into a vein or artery and placed next to the heart No lead wires required Uses renewable energy Contains an oscillator for storing and dispensing an electrical charge when needed Includes memory and a telemetry system for transferring data

29. Truth or Fiction? Diabetic Contact Lenses Nano particles in lenses react with glucose molecules in patients’ tears causing a chemical reaction that changes the lens color and alerts the wearer to adjust their glucose

30. Truth or Fiction? Synthetic compounds that stimulate a body’s own immune response Delivers broad spectrum activity against bacteria, fungi and certain viruses Kills pathogens on contact by attacking the outer shell of the microbe, destroying it’s outer membrane. Microbes are highly unlikely to evolve new outer membranes and therefore, cannot adapt to this synthetic microbial agent

31. Truth or Fiction? • Artificial Pancreas • Artificial Heart • Implantable Artificial Kidney • Artificial Liver • Artificial Blood Vessels from Salmon Skin • Artificial Bones using Citric Acid • Artificial Skin that is able to bleed, heal, tan, sweat and fight off infection

32. Future Ready • Device firms have the engineers to design these products • Drugs firms have the resources and the experience needed to conduct trials, develop, and bring these products to the market • Is it logical to conclude that device and pharma will remain separate? • Conclusion is identical even when derived from an entirely unique path. • Where will our focus be in the next few years, on devices, pharmaceuticals, or both? Are you Future Ready?

33. Free Information Sources • CDRH Medical Device Innovation Initiative at http://www.fda.gov/deviceinnovation • http://wwwmddionline.com/categories/convergent-technologies • http://www.ivdtechnology.com • http://medtechinsider.com

34. QUESTIONS? Marlene Bobka, FOI Services Sandra Baker, UBM Canon MBobka@foiservices.comSandra.Baker@ubm.com 301-975-9400 215-944-9836 Thank You!