INNsight article by Alan Klein and John M. Lyons, Duane Morris

Federal preemption provides a complete defense in pharmaceutical products liability litigation, but generic manufacturers have encountered difficulty persuading American courts that compliance with FDA labeling regulations alone is sufficient to preempt all suits in which a plaintiff’s claims are based on an allegedly inadequate warning.  Generic drug manufacturers need to rethink their approach to preemption and consider seeking dismissal only after full regulatory, scientific, and pharmacovigilance records for the drug have been carefully evaluated by the company and its counsel.  If a manufacturer can demonstrate that no pharmacovigilance signal or development in the science supported a stronger warning at the time the drug was prescribed to the plaintiff, this should serve as complete defense in the case.

The Generic Preemption Defense After Wyeth v. Levine

Following the U.S. Supreme Court’s decision in Wyeth v. Levine in March of 2009, federal courts have considered efforts by generic drug companies to have products liability suits dismissed on the basis that they are preempted by U.S. law and the FDA’s labeling regulations.  Generic manufacturers have sought to have these cases thrown out of court without providing a complete regulatory and pharmacovigilance history relative to the drug involved.  Most courts have rejected these attempts, finding unpersuasive the companies’ claimed inability to implement label changes and contention that generic drug manufacturers must await label changes initiated by the FDA or innovator.

Courts in these situations have considered themselves bound by the Supreme Court’s preemption standard in Levine that “absent clear evidence that the FDA would not have approved a change to [the drug’s] label, we will not conclude that it was impossible for [the manufacturer] to comply with both federal and state requirements.”  Similarly, the Supreme Court’s imposition of responsibility upon drug manufacturers to “[craft] an adequate label and . . . [ensure] that its warnings remain adequate as long as the drug is on the market” has been applied equally to innovator and generic manufacturers following Levine.  Generic manufacturers will now need to assemble their complete pharmacovigilance and regulatory records to show that no signal indicating that a strengthened warning was appropriate existed at the time the plaintiff was prescribed the drug.  They will also need to establish that the medical science did not support a strengthened warning and that communications with the FDA clearly indicate that the agency would not have approved a stronger warning.

Generic Manufacturers Can Use Their Ongoing Pharmacovigilance Obligations to Advantage

Hatch-Waxman allows manufacturers to introduce generic versions of drugs after demonstrating bioequivalence to a reference-listed drug.  This abbreviated procedure allows generic manufacturers to save the significant expenses associated with new drug development, including clinical trials required to demonstrate safety and efficacy.  FDA regulations impose the same ongoing pharmacovigilance obligations on both innovator and generic manufacturers.  Since Levine, courts considering preemption arguments from generic manufacturers have been unwilling to conclude that generic manufacturers have no responsibility of ascertaining whether pharmacovigilance signals or the developing science suggest that a stronger label warning would be appropriate.

Generic drug companies documenting adverse event reports received from the field, in peer reviewed literature, and from other sources, may themselves create an excellent foundation for a successful preemption defense.  In the absence of any signal from either a significant increase in the number of reports received or the severity of the adverse events reported, the generic manufacturer has no basis for either implementing or requesting that the FDA approve strengthened warnings.

Pharmacovigilance and the Regulatory Record—Elements of a Successful Preemption Defense

Defendants in products liability suits should consider delaying dispositive preemption motions until complete pharmacovigilance and regulatory records for the drug have been compiled and reviewed.  Generic defendants should work with the manufacturer of the reference-listed drug to obtain all communications with the FDA about the warning, as well as any other evidence available from the innovator to support a claim that the FDA would not have approved a label change.

Even without the innovator’s regulatory record, generic manufacturers may be able to successfully argue that products liability claims are preempted if their own pharmacovigilance program and the medical science did not produce any signal indicating that a strengthened warning was appropriate.  Generic manufacturers generally do not have access to clinical trial data or the adverse event reports received by the innovator.  In the absence of such information, a generic manufacturer can only rely upon its own records and the reported science in professional journals to determine whether a strengthened product warning or the issuance of a “Dear Doctor” letter to prescribing physicians is necessary or appropriate.  In the absence of substantial evidence available to the generic company indicating that a stronger warning was appropriate when the plaintiff was prescribed the drug, a generic manufacturer will be able to furnish the court with convincing evidence satisfying the strict standards of Levine.

Conclusion

Generic pharmaceutical defendants must consider a new approach when seeking the dismissal of American products liability suits based on federal preemption.  Pharmacovigilance data and a record of communications with the FDA should be utilized by the manufacturer to prove that there is “clear evidence that the FDA would not have approved a change” to the label.  If a generic manufacturer is able to show that the FDA would not have approved a strengthened warning based upon the information available to the generic at the time the plaintiff was prescribed the drug, a court applying Levine should conclude that this provides a complete defense.