Can Failure-to-Warn Claims Against Generic Drug Manufacturers Be Preempted?

Let us now look at the current legal landscape to see how courts have decided cases raising these issues.

Courts Finding the Federal Preemption Doctrine
Applicable to Generics

In Gaeta v. Perrigo Pharmaceuticals Co., 562 F. Supp. 2d 1091 (N.D. Cal., Nov. 9, 2007), the Northern District of California found that plaintiffs' claims were preempted by the federal Food, Drug, and Cosmetic Act (FDCA) insofar as the generic drug manufacturer's abbreviated new drug application (ANDA) would be jeopardized if additional warnings were required by state law, since the generic drug's labeling would no longer be the “same as” the listed drug's labeling. See 21 C.F.R. ' 314.150(b)(10). In Gaeta, plaintiffs alleged that the generic over-the-counter version of ibuprofen caused liver failure, and such a warning should have been included in the generic ibuprofen's labeling. The FDA, however, had considered a warning for the risk of liver injury and concluded that the risk was not scientifically supported by available data.

The U.S. District Court for the District of Minnesota also rejected a plaintiff's failure-to-warn claims on the basis of the federal preemption doctrine. In Mensing v. Wyeth, Inc., 562 F. Supp. 2d 1056 (D. Minn. 2008), the district court found that a generic drug manufacturer may not unilaterally change its drug's labeling absent FDA approval. Although the plaintiff claimed that the CBE supplement process could be utilized by a generic drug manufacturer, the court held that the CBE regulation does not permit a generic manufacturer to change its products' labeling unilaterally to be inconsistent with the branded drug. The district court found that an irreconcilable conflict would arise if a generic drug manufacturer had to change its federally-approved labeling due to state law requirements.

In Masterson v. Apotex Corp., 2008 U.S. Dist. LEXIS 60238 (S.D. Fla., Aug. 7, 2008), the plaintiffs alleged that their ingestion of paroxetine, the generic version of Paxil, caused their child's birth defects. The plaintiffs asserted that generic drug manufacturers could seek labeling changes from the FDA as an exception to the federal requirement that the generic drug labeling be the “same as” the listed drug's labeling. The Southern District of Florida disagreed, finding that the presumption against preemption does not apply in the context of implied conflict preemption and adopted the analysis and conclusions of the Mensing court. The Masterson case was consolidated with two other matters venued in the Southern District of Florida: Bolin v. SmithKline Beecham, 2008 U.S. Dist. LEXIS 60241 (S.D. Fla., Aug. 7, 2008) and Valerio v. SmithKline Beecham, 2008 U.S. Dist. LEXIS 60242 (S.D. Fla., Aug. 7, 2008).

Another federal case holding that a generic drug manufacturer cannot unilaterally change its product's labeling by utilizing the CBE supplement process is Morris v. Wyeth, Inc., 2008 U.S. Dist. LEXIS 87734 (W.D. Ky., Oct. 24, 2008). The plaintiff alleged that generic drug manufacturers failed to provide adequate warnings regarding the long-term effects of ingesting metoclopramide, the generic version of Reglan. Specifically, the plaintiffs alleged that the manufacturers failed to propose label changes to include the alleged risks of tardive dyskinesia associated with metoclopramide. The generic manufacturers argued that the imposition of heightened warnings under state law was in direct conflict with FDA requirements, and that plaintiffs' failure-to-warn claims should be preempted. The district court, in discussing the claims against the generic manufacturers, held that the FDA, as opposed to state court juries, has the sole responsibility of determining whether a generic drug manufacturer failed to notify the FDA or the medical community about any significant drug safety risk. The Masterson decision was extended by the court to apply to two other cases venued in the Southern District of Florida raising similar issues: Smith v. Wyeth, Inc., 2008 U.S. Dist. LEXIS 87684 (W.D. Ky., Oct. 24, 2008) and Wilson v. Wyeth, Inc., 2008 U.S. Dist. LEXIS 87726 (W.D. Ky., Oct. 24, 2008).

In each of these cases, the District Court concluded that a plaintiff's failure-to-warn claims were preempted by federal law insofar as generic drug manufacturers could not unilaterally strengthen or otherwise modify their drug labels absent FDA approval.

Courts Finding the Federal Preemption Doctrine
Inapplicable to Generics

In contrast to the cases discussed above, several federal and state courts have held that the federal preemption doctrine does not preclude plaintiffs from asserting failure-to-warn claims against generic drug manufacturers. Most recently, and following the U.S. Supreme Court's decision in Wyeth, the Northern District of Illinois refused to grant a generic drug manufacturer's motion to dismiss based on an argument that the FDCA preempted the plaintiff's state law-based failure-to-warn claims. The District Court in Stacel v. Teva Pharmaceuticals, USA, et al., 2009 WL 703274 (N.D. Ill., Mar. 16, 2009), rejected the generic manufacturer's federal preemption defense as a matter of law. Although Judge Joan B. Gottschall recognized that the Supreme Court's decision in Wyeth was not directly controlling in the context of claims against generic drug manufacturers, she did find that key portions of the majority's analysis were applicable. Specifically, Judge Gottschall held that “[i]f generic manufacturers can utilize the CBE, then the logic of Levine is directly applicable.” Even though the CBE regulations are located in Subpart B of Part 314, which is generally applicable to innovator, brand-name drug applications and not the abbreviated applications filed with the FDA by generics, the court concluded that section 314.97 located within Subpart C requires a generic drug manufacturer submitting an abbreviated application to comply with CBE regulations. Furthermore, in refusing to give deference to the FDA's statements in its 2008 proposed rule amending the CBE regulations disclaiming that the regulations were applicable to generics, Judge Gottschall found that the FDA's statements did not contradict Congress' understanding that state law failure-to-warn actions “lend force to the FDCA's premise that manufacturers, not the FDA, bear primary responsibility for their drug labeling at all times.” The court, however, afforded the generic drug defendant another opportunity to assert the preemption defense at a later stage in the case following the completion of discovery.

Other courts prior to Wyeth found that generics are not entitled to the protection of the Supremacy Clause barring failure-to-warn claims. Although dicta, the U.S. Court of Appeals for the Fourth Circuit posited that a generic drug manufacturer may change its product's labeling utilizing the CBE supplement process. Foster v. American Home Products Corp., 29 F.3d 165 (4th Cir. 1994). The Fourth Circuit's decision in Foster has served as the basis for other federal and state courts to find against preemption. In Goldych v. Eli Lilly and Co., 2006 U.S. Dist. LEXIS 49616 (N.D. N.Y., Jul. 19, 2006), for example, the Northern District of New York adopted the holdings and rationale in Foster, albeit in dicta, since the generic drug manufacturer of the pharmaceutical at issue was not a party to the case. In Foster, the plaintiff claimed that fluoxetine, the generic version of Prozac ingested by the decedent, led to the decedent's suicide.

Similarly, the presumption against preemption was found to trump preemption by the Southern District of Alabama in Barnhill v. Teva Pharmaceuticals USA, Inc., 2007 U.S. Dist. LEXIS 44718 (S.D. Ala., Apr. 24, 2007). In Barnhill, the plaintiff alleged that consumption of cephalexin resulted in the plaintiff's developing Stevens-Johnson syndrome. The generic manufacturer argued that the plaintiff's claims should be dismissed on the basis of conflict preemption insofar as a generic drug label cannot be modified absent FDA approval. The court held that generic drug manufacturers can comply with both FDA regulations and state law requirements necessitating strengthened warning labels.

The Western District of Washington also found the Foster court's reasoning to be persuasive. In Laisure-Radke v. Par Pharmaceutical, Inc., 2006 U.S. Dist. LEXIS 57158 (W.D. Wash., Mar. 29, 2006), the court held that a generic drug manufacturer may alter its labeling in a CBE supplement. The Laisure-Radke court concluded that the FDA requirement that a generic drug manufacturer have labeling the “same as” the brand drug does not prevent the generic drug manufacturer from changing its label after its ANDA has been approved. Other courts have made similar rulings: Kelly v. Wyeth, Inc., 22 Mass. L. Rep. 384 (Sup. Ct. 2007); Barhoum v. Barr Pharmaceuticals, Inc., (N.J. Super., L. Div., Aug. 1, 2008); and McKenney v. Purepac Pharmaceutical Co., 167 Cal. App. 4th 72 (Cal. App. 2008).

The Eastern District of Louisiana also refused to dismiss a plaintiff's failure-to-warn claims on the basis of the federal preemption doctrine. In Demahy v. Wyeth, Inc., 2008 U.S. Dist. LEXIS 87014 (E.D. La., Oct. 28, 2008), the plaintiff alleged that a generic drug manufacturer failed to warn of the risk of neurological disorders from the long-term usage of metoclopramide. The generic manufacturer contended that the plaintiff's claims should be dismissed based on federal conflict and obstacle preemption. The court held, however, that only the plaintiff's claim of fraud on the FDA could be federally preempted under the U.S. Supreme Court's Buckman (531 U.S. 341(2001)) decision.

In Kellogg v. Wyeth, Inc., 2008 U.S. Dist. LEXIS 104073 (D. Vt., Dec. 17, 2008), the District Court of Vermont rejected a generic drug manufacturers' argument that the plaintiff's state law claims should be dismissed on the basis of federal preemption. The plaintiff alleged that the manufacturers failed to warn properly of the risk of tardive dyskinesia and extrapyramidal symptoms in the labeling of the metoclopramide. The generic manufacturers maintained that the CBE regulations do not apply to them. The Kellogg court, however, disagreed and found that the generics may add additional warnings through the CBE process if they receive or develop new information about health risks from the use of their drugs.

Conclusion

Court decisions on this important issue cannot be reconciled. Without clarification from the U.S. Supreme Court or a further amendment to the FDA's CBE regulations, courts are likely to continue to grapple with whether preemption bars failure-to-warn claims against generic pharmaceutical manufacturers. As the foregoing analysis suggests, the tension between the salutary purposes of the Hatch-Waxman Act (low-cost drugs widely and quickly available to patients) and the necessity to change label warnings when science or adverse event reports show a newly appreciated risk, presents a Hobson's choice to generic drug companies, complicated by the FDA's own interpretation of its CBE regulations as inapplicable to them. It is hoped that with additional consideration of these issues in the appellate courts, at the FDA and in Congress as well, the coming year may result in important developments providing greater guidance to litigants, the courts and the generic pharmaceutical industry.

Sharon Caffrey is a partner in the Philadelphia office of Duane Morris LLP and is the co-head of the Products Liability and Toxic Torts division of the firm's Trial Practice Group. Ms. Caffrey concentrates her practice in the areas of mass tort, products liability and toxic tort litigation. Alan Klein is a partner in the Trial Practice Group at Duane Morris. His primary focus in recent years has been in the area of pharmaceutical products liability litigation. Paul M. da Costa is an associate in the Trial Practice Group at Duane Morris LLP in Newark, NJ.

This year, the U.S. Supreme Court in Wyeth v. Levine , 555 U.S. ___ (March 4, 2009), considered for the first time the preemption of state law-based claims in pharmaceutical product liability cases and held that the Food and Drug Administration's (FDA) approval of a drug label does not preempt state law failure-to-warn claims. Although the case involved a brand drug, the Court's decision was vital in determining the availability and scope of the preemption defense for both brand and generic drug manufacturers. Prior to the Court's decision, several federal and state courts addressed preemption in the context of claims against generic drug manufacturers. An analysis of these decisions indicates that the courts' various interpretations of the FDA's Changes Being Effected (CBE) labeling supplement regulations, 21 C.F.R. ' 314.70(c), are crucial to their ultimate holdings. In Wyeth v. Levine, the Supreme Court of Vermont's holding of no preemption relied heavily on its interpretation of the CBE regulation.

'Newly Acquired Information'

The FDA's stated policy is that a CBE supplement should be used only to strengthen or modify the labeling of an approved drug “to reflect newly acquired information” and when there is “reasonable evidence of a causal association.” Furthermore, the FDA has concluded that with regard to its most current labeling regulations, the CBE supplement process does not apply to generic drug manufacturers. Although some courts have adopted the FDA's position, other courts have not, finding against preemption largely based on their belief that state law (in the form of state court jury verdicts) upholding the necessity of additional and/or heightened warnings can be achieved by both brand and generic manufacturers via the CBE supplement process.

Let us now look at the current legal landscape to see how courts have decided cases raising these issues.

Courts Finding the Federal Preemption Doctrine
Applicable to Generics

In Gaeta v. Perrigo Pharmaceuticals Co. , 562 F. Supp. 2d 1091 (N.D. Cal., Nov. 9, 2007), the Northern District of California found that plaintiffs' claims were preempted by the federal Food, Drug, and Cosmetic Act (FDCA) insofar as the generic drug manufacturer's abbreviated new drug application (ANDA) would be jeopardized if additional warnings were required by state law, since the generic drug's labeling would no longer be the “same as” the listed drug's labeling. See 21 C.F.R. ' 314.150(b)(10). In Gaeta, plaintiffs alleged that the generic over-the-counter version of ibuprofen caused liver failure, and such a warning should have been included in the generic ibuprofen's labeling. The FDA, however, had considered a warning for the risk of liver injury and concluded that the risk was not scientifically supported by available data.

The U.S. District Court for the District of Minnesota also rejected a plaintiff's failure-to-warn claims on the basis of the federal preemption doctrine. In Mensing v. Wyeth, Inc. , 562 F. Supp. 2d 1056 (D. Minn. 2008), the district court found that a generic drug manufacturer may not unilaterally change its drug's labeling absent FDA approval. Although the plaintiff claimed that the CBE supplement process could be utilized by a generic drug manufacturer, the court held that the CBE regulation does not permit a generic manufacturer to change its products' labeling unilaterally to be inconsistent with the branded drug. The district court found that an irreconcilable conflict would arise if a generic drug manufacturer had to change its federally-approved labeling due to state law requirements.

In Masterson v. Apotex Corp., 2008 U.S. Dist. LEXIS 60238 (S.D. Fla., Aug. 7, 2008), the plaintiffs alleged that their ingestion of paroxetine, the generic version of Paxil, caused their child's birth defects. The plaintiffs asserted that generic drug manufacturers could seek labeling changes from the FDA as an exception to the federal requirement that the generic drug labeling be the “same as” the listed drug's labeling. The Southern District of Florida disagreed, finding that the presumption against preemption does not apply in the context of implied conflict preemption and adopted the analysis and conclusions of the Mensing court. The Masterson case was consolidated with two other matters venued in the Southern District of Florida: Bolin v. SmithKline Beecham, 2008 U.S. Dist. LEXIS 60241 (S.D. Fla., Aug. 7, 2008) and Valerio v. SmithKline Beecham, 2008 U.S. Dist. LEXIS 60242 (S.D. Fla., Aug. 7, 2008).

Another federal case holding that a generic drug manufacturer cannot unilaterally change its product's labeling by utilizing the CBE supplement process is Morris v. Wyeth, Inc., 2008 U.S. Dist. LEXIS 87734 (W.D. Ky., Oct. 24, 2008). The plaintiff alleged that generic drug manufacturers failed to provide adequate warnings regarding the long-term effects of ingesting metoclopramide, the generic version of Reglan. Specifically, the plaintiffs alleged that the manufacturers failed to propose label changes to include the alleged risks of tardive dyskinesia associated with metoclopramide. The generic manufacturers argued that the imposition of heightened warnings under state law was in direct conflict with FDA requirements, and that plaintiffs' failure-to-warn claims should be preempted. The district court, in discussing the claims against the generic manufacturers, held that the FDA, as opposed to state court juries, has the sole responsibility of determining whether a generic drug manufacturer failed to notify the FDA or the medical community about any significant drug safety risk. The Masterson decision was extended by the court to apply to two other cases venued in the Southern District of Florida raising similar issues: Smith v. Wyeth, Inc., 2008 U.S. Dist. LEXIS 87684 (W.D. Ky., Oct. 24, 2008) and Wilson v. Wyeth, Inc., 2008 U.S. Dist. LEXIS 87726 (W.D. Ky., Oct. 24, 2008).

In each of these cases, the District Court concluded that a plaintiff's failure-to-warn claims were preempted by federal law insofar as generic drug manufacturers could not unilaterally strengthen or otherwise modify their drug labels absent FDA approval.

Courts Finding the Federal Preemption Doctrine
Inapplicable to Generics

In contrast to the cases discussed above, several federal and state courts have held that the federal preemption doctrine does not preclude plaintiffs from asserting failure-to-warn claims against generic drug manufacturers. Most recently, and following the U.S. Supreme Court's decision in Wyeth, the Northern District of Illinois refused to grant a generic drug manufacturer's motion to dismiss based on an argument that the FDCA preempted the plaintiff's state law-based failure-to-warn claims. The District Court in Stacel v. Teva Pharmaceuticals, USA, et al., 2009 WL 703274 (N.D. Ill., Mar. 16, 2009), rejected the generic manufacturer's federal preemption defense as a matter of law. Although Judge Joan B. Gottschall recognized that the Supreme Court's decision in Wyeth was not directly controlling in the context of claims against generic drug manufacturers, she did find that key portions of the majority's analysis were applicable. Specifically, Judge Gottschall held that “[i]f generic manufacturers can utilize the CBE, then the logic of Levine is directly applicable.” Even though the CBE regulations are located in Subpart B of Part 314, which is generally applicable to innovator, brand-name drug applications and not the abbreviated applications filed with the FDA by generics, the court concluded that section 314.97 located within Subpart C requires a generic drug manufacturer submitting an abbreviated application to comply with CBE regulations. Furthermore, in refusing to give deference to the FDA's statements in its 2008 proposed rule amending the CBE regulations disclaiming that the regulations were applicable to generics, Judge Gottschall found that the FDA's statements did not contradict Congress' understanding that state law failure-to-warn actions “lend force to the FDCA's premise that manufacturers, not the FDA, bear primary responsibility for their drug labeling at all times.” The court, however, afforded the generic drug defendant another opportunity to assert the preemption defense at a later stage in the case following the completion of discovery.

Other courts prior to Wyeth found that generics are not entitled to the protection of the Supremacy Clause barring failure-to-warn claims. Although dicta, the U.S. Court of Appeals for the Fourth Circuit posited that a generic drug manufacturer may change its product's labeling utilizing the CBE supplement process. Foster v. American Home Products Corp. , 29 F.3d 165 (4th Cir. 1994). The Fourth Circuit's decision in Foster has served as the basis for other federal and state courts to find against preemption. In Goldych v. Eli Lilly and Co., 2006 U.S. Dist. LEXIS 49616 (N.D. N.Y., Jul. 19, 2006), for example, the Northern District of New York adopted the holdings and rationale in Foster, albeit in dicta, since the generic drug manufacturer of the pharmaceutical at issue was not a party to the case. In Foster, the plaintiff claimed that fluoxetine, the generic version of Prozac ingested by the decedent, led to the decedent's suicide.

Similarly, the presumption against preemption was found to trump preemption by the Southern District of Alabama in Barnhill v. Teva Pharmaceuticals USA, Inc., 2007 U.S. Dist. LEXIS 44718 (S.D. Ala., Apr. 24, 2007). In Barnhill, the plaintiff alleged that consumption of cephalexin resulted in the plaintiff's developing Stevens-Johnson syndrome. The generic manufacturer argued that the plaintiff's claims should be dismissed on the basis of conflict preemption insofar as a generic drug label cannot be modified absent FDA approval. The court held that generic drug manufacturers can comply with both FDA regulations and state law requirements necessitating strengthened warning labels.

The Western District of Washington also found the Foster court's reasoning to be persuasive. In Laisure-Radke v. Par Pharmaceutical, Inc., 2006 U.S. Dist. LEXIS 57158 (W.D. Wash., Mar. 29, 2006), the court held that a generic drug manufacturer may alter its labeling in a CBE supplement. The Laisure-Radke court concluded that the FDA requirement that a generic drug manufacturer have labeling the “same as” the brand drug does not prevent the generic drug manufacturer from changing its label after its ANDA has been approved. Other courts have made similar rulings: Kelly v. Wyeth, Inc. , 22 Mass. L. Rep. 384 (Sup. Ct. 2007); Barhoum v. Barr Pharmaceuticals, Inc., (N.J. Super., L. Div., Aug. 1, 2008); and McKenney v. Purepac Pharmaceutical Co. , 167 Cal. App. 4th 72 (Cal. App. 2008).

The Eastern District of Louisiana also refused to dismiss a plaintiff's failure-to-warn claims on the basis of the federal preemption doctrine. In Demahy v. Wyeth, Inc., 2008 U.S. Dist. LEXIS 87014 (E.D. La., Oct. 28, 2008), the plaintiff alleged that a generic drug manufacturer failed to warn of the risk of neurological disorders from the long-term usage of metoclopramide. The generic manufacturer contended that the plaintiff's claims should be dismissed based on federal conflict and obstacle preemption. The court held, however, that only the plaintiff's claim of fraud on the FDA could be federally preempted under the U.S. Supreme Court's Buckman (531 U.S. 341(2001)) decision.

In Kellogg v. Wyeth, Inc., 2008 U.S. Dist. LEXIS 104073 (D. Vt., Dec. 17, 2008), the District Court of Vermont rejected a generic drug manufacturers' argument that the plaintiff's state law claims should be dismissed on the basis of federal preemption. The plaintiff alleged that the manufacturers failed to warn properly of the risk of tardive dyskinesia and extrapyramidal symptoms in the labeling of the metoclopramide. The generic manufacturers maintained that the CBE regulations do not apply to them. The Kellogg court, however, disagreed and found that the generics may add additional warnings through the CBE process if they receive or develop new information about health risks from the use of their drugs.

Conclusion

Court decisions on this important issue cannot be reconciled. Without clarification from the U.S. Supreme Court or a further amendment to the FDA's CBE regulations, courts are likely to continue to grapple with whether preemption bars failure-to-warn claims against generic pharmaceutical manufacturers. As the foregoing analysis suggests, the tension between the salutary purposes of the Hatch-Waxman Act (low-cost drugs widely and quickly available to patients) and the necessity to change label warnings when science or adverse event reports show a newly appreciated risk, presents a Hobson's choice to generic drug companies, complicated by the FDA's own interpretation of its CBE regulations as inapplicable to them. It is hoped that with additional consideration of these issues in the appellate courts, at the FDA and in Congress as well, the coming year may result in important developments providing greater guidance to litigants, the courts and the generic pharmaceutical industry.

Sharon Caffrey is a partner in the Philadelphia office of Duane Morris LLP and is the co-head of the Products Liability and Toxic Torts division of the firm's Trial Practice Group. Ms. Caffrey concentrates her practice in the areas of mass tort, products liability and toxic tort litigation. Alan Klein is a partner in the Trial Practice Group at Duane Morris. His primary focus in recent years has been in the area of pharmaceutical products liability litigation. Paul M. da Costa is an associate in the Trial Practice Group at Duane Morris LLP in Newark, NJ.