1. Winds of Healthcare Regulatory Change in the US Wyeth v. Levine & Related Matters BIICL – Product Liability Forum April 28, 2009 Tripp Haston

2. Wyeth v. Levine – Pre-Argument Hype   Hyped by the U.S. Chamber of Commerce as “the most important business case of the Century.”   Over thirty amicus briefs from interests as diverse as the U.S. Government, Attorneys General from forty-seven States, former F.D.A. Commissioners, and professors at leading U.S. Universities.   Subject of editorials in both the New England Journal of Medicine and the Journal of the American Medical Association.

3. Wyeth v. Levine – Pre-Argument Hype New England Journal of Medicine – July 3, 2008  Preemption will  Strip[ ] patients of their right to seek redress...  Result in the reduced safety of drugs and medical devices for the American people.  Undermine the confidence that doctors and patients have in the safety of drugs and devices.  If injured patients are unable to seek legal redress from manufacturers of defective products, they may instead turn elsewhere.

4. Wyeth v. Levine – Post-Argument Interpretation Wall Street Journal – March 5, 2009  [The] ruling will expose drug companies to a kind of double innovation jeopardy.  Now they will have to contemplate paying up front -- and paying later, even if the tragic mistake in applying the drug is someone else's.  Wyeth is a dream come true for the plaintiffs bar. New York Times – March 5, 2009  [A] major setback for business groups that had hoped to build a barrier against injury lawsuits seeking billions of dollars…

5. Wyeth v. Levine – Preemption Primer Dual Federal-State Governmental System  U.S. Constitution – Supremacy Clause  In conflicts of state & federal – federal law preempts state law Forms of Preemption  Express - Congress has Expressly Endowed  Implied – Conflict Exists Between State & Federal Law  “Impossibility”  “Objects & Purposes”

6. Wyeth v. Levine – Background - Facts  Wyeth’s anti-nausea medicine, Phenergan administered via “IV push” administration. Label details preferential administration methods (IM, IV Drip) with lower risks  Intra-arterial blood exposure during administration results in gangrene & amputation  The warning label included, inter alia, in uppercase letters:  INADVERTENT INTRA-ARTERIAL INJECTION CAN RESULT IN GANGRENE OF THE AFFECTED EXTREMITY.

7. Wyeth v. Levine – Background - Legal Legal Positions  Levine: Wyeth should have contraindicated “IV push” based on awareness of SAEs.  Wyeth: Claims preempted due to FDA’s approval of label which expressly referenced the relevant risk and its awareness of SAEs. VT Supreme Court  Claims are not preempted; compliance not impossible. Wyeth could have submitted stronger label.  FDA’s approved label entitled to no deference.

8. Wyeth v. Levine Wyeth v. Levine - Ruling J. Stevens, Kennedy, Souter, Ginsberg, Breyer & Thomas (ccing in result) HOLDING: FDA’s Approval of Phenergan label did not preempt Levine’s state law failure to warn claim BASIS:   Compliance with federal labeling requirements and Vermont failure to warn law not “impossible”   Compliance with VT law did not interfere with FDA’s role to such an extent as to create a basis for “purposes & objectives” conflict preemption

9. Wyeth v. Levine Wyeth v. Levine - Rationale J. Stevens, Kennedy, Souter, Ginsberg, Breyer & Thomas (ccing in result) Compliance with both federal labeling requirements and Vermont failure to warn law not “impossible”   Changes Being Effected (“CBE”) label regulation allows sponsors to make unilateral label changes without FDA approval   Wyeth could have unilaterally added a stronger warning via CBE and no evidence FDA would have rejected such a label change   Wyeth (and all sponsors), not the FDA, bears ultimate responsibility for adequacy of its label

10. Wyeth v. Levine Wyeth v. Levine - Rationale J. Stevens, Kennedy, Souter, Ginsberg, Breyer & Thomas (ccing in result) No “objects and purposes” conflict with FDA’s role and Vermont failure to warn law   No Congressional intent to allow FDA’s label decisions to preempt state law   FDA’s Jan 2006 Preamble “inherently suspect” and rejected as a basis for preemption   FDA failed to allow public comment after initially indicating no preemptive effect on state law   Inconsistent with longstanding FDA position that state law complimented FDA’s role   At odds with available information on Congressional intent

11. False Assumptions of Wyeth Opinion   ILLNESS? Creates True “Objects/Purposes” Conflict   Failure to appreciate post-marketing pharmaco-vigilance   Failure to understand true scope of CBE changes   Failure to appreciate FDA’s expertise in labeling   CURE? Legislation or New/More Specific FDA Regulation   Better public awareness of drug development, approval & post-marketing safety surveillance processes   Better industry-agency-medical community collaboration   Finding the proper balance between uniformity and proper incentives for individual medicine’s monitoring

12. Future of FDA Preemption ?   Available but Narrowed – a return to 2005   Must show “impossible” to comply with federal law (FDA approved label) and state law (Plaintiff proposed label)   Will likely lead to more labeling proposals   Colaccio v. Apotex & GSK (USCA - 3 rd Cir)   First “impossibility” test case post-Levine   Good record of FDA’s consideration & rejection of plaintiff’s proposed label

13. Medical Devices - Riegel v. Medtronic & 2009 MDSA   2008 – US Supreme Court found preemption for PMA- approved devices based on express preemption provision in Medical Device Amendments Act (Riegel v. Medtronic)   2009 Medical Device Safety Act – Proposed legislation that would remove the express preemption provision of the MDAA   Broad support of Democrats in House & Senate   Broad support of key interest groups – AARP, ABA   Hearings not yet scheduled

14. Today’s FDA   Signs of More Aggressive Regulatory Action   14 Warning Letters regarding Internet Advertisements   Prohibition of Marketing of Class of Pain Medications   Stated intent to review classification of 25 medical devices   Unlikely to be Preemption Sympathetic   Likely to be More Demanding on “Safety”