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NABP Legal Briefs: Hey Mabel, Another Generic Label
Originally published in the September 2011 NABP Newsletter
By Dale J. Atkinson, JD
At times, federal law and state law conflict, creating a situation that may lead to difficulty, if not impossibility, for compliance. Relative to the research and development, manufacture, marketing, and dispensing of prescription drugs, numerous state and federal laws apply, creating the potential for conflict. In general, state tort laws impose upon manufacturers of products a duty to provide adequate instructions for the safe use of a product. Other state tort laws require that where a manufacturer of a product has actual or constructive knowledge of danger to users, such manufacturer has a duty to give warnings of those dangers. These state tort laws apply to drug manufacturers and their products.
Federal law imposes far more complex labeling requirements on drug products. Amendments to the Federal Food, Drug, and Cosmetic Act (FD&C) enacted in 1962 mandate that drug manufacturers seeking federal approval to market a new drug must prove that it is safe and effective and that the proposed label is accurate and adequate. The new drug approval process is time consuming and expensive as it involves costly and lengthy clinical testing.
In 1984, the Hatch-Waxman Amendments to the FD&C allowed for generic drugs to gain Food and Drug Administration (FDA) approval simply by showing equivalence to a reference listed drug that has already been approved by FDA. Generic drug manufacturers are not required to duplicate the expensive clinical trials already performed during the brand-name drug development and approval process. A generic drug application must also show safety and efficacy of its labeling equivalent to the brand-name labeling. Thus, brand-name manufacturers seeking new drug approval are responsible for accuracy and adequacy of the label, while manufacturers of the generic equivalent are responsible for ensuring that such warning labels are the same as the brand-name labels.
A recent United States Supreme Court case involving a civil dispute addressed the conflict between state tort law and FD&C labeling requirements. The dispute examined by the court involved whether, and to what extent, generic manufacturers may change their labels after initial FDA approval. Consider the following.
Two patients (one in Minnesota and one in Louisiana) were prescribed Reglan® (metoclopramide) and received the generic substitution. Both patients took the drug for several years and developed tardive dyskinesia, a severe neurological disorder. Both patients initiated litigation in federal court (arguing under state law) claiming the generic manufacturers were liable under state tort law for failing to provide adequate warning labels. They alleged that “despite mounting evidence that long term metoclopramide use carries a risk of tardive dyskinesia far greater than that listed on the label,” the manufacturers did not change their labels to adequately warn of that danger. The patients specifically allege that the law requires the manufacturers to change their labels as additional evidence became known regarding the long-term use of the drug.
In both suits, the manufacturers argued that federal law preempted the state tort claims in that federal law requires generic manufacturers to use the same safety and efficacy labeling as the brand-name counterparts. In essence, the manufacturers argued that it was impossible for them to comply with both federal labeling laws as well as state tort duty laws that may require them to use a different label. In both federal court cases, the Fifth and Eighth Circuit Court of Appeals held that federal law does not preempt state law claims. The matter was appealed to the US Supreme Court.
The US Supreme Court first noted that it must compare both the state and federal laws. It cited the Minnesota and Louisiana state tort laws and the duty imposed upon drug manufacturers to provide adequate labels on the metoclopramide. The court also analyzed the federal law labeling requirements for brand name and generic manufacturers and noted the labeling requirement placed upon generic drug manufacturers – that being the duplication of the brand-name label. The court, however, identified the issue to be the extent to which generic manufacturers may change their labels after initial FDA approval. The patients contend that federal law provides “several avenues through which the Manufacturers could have altered their metoclopramide labels in time to prevent the injuries here.” The FDA informed the court that the generic drug labels must be the same as the brand name because the brand name (also known as the listed drug) provides the basis for the generic drug approval. The Supreme Court noted that FDA’s “views are controlling unless plainly erroneous or inconsistent with the regulations” or “there is any other reason to doubt that [such interpretations] reflect the FDA’s fair and considered judgment.”
First, the patients argued that the FDA’s CBE process, or changes being effected process, allows for generic manufacturers to change their labels when necessary. The Supreme Court disagreed, finding that the FDA reasonably interpreted the regulations to only allow changes to generic labels in order to match an updated name brand label or to follow an FDA instruction. Deferring to the FDA interpretation, the Supreme Court concluded that the CBE process was not available to generic manufacturers for the changes argued were required by state tort law.
The patients next alleged that the manufacturers could have used “Dear Doctor” letters to provide prescribing physicians with additional warnings. FDA informed the court that Dear Doctor letters qualify as labeling and, therefore, such labels must be consistent with and not contrary to the brand-name label. Indeed, FDA noted that a Dear Doctor letter from a generic manufacturer, which was not also sent by the brand-name manufacturer would inaccurately “imply a therapeutic difference between the brand and generic drug and thus could be impermissibly ‘misleading’.” Again deferring to the FDA interpretation, the Supreme Court concluded that in this case, federal law did not permit the issuance by the generic manufacturers of Dear Doctor letters.
In its briefs to the Supreme Court, FDA did note a mechanism for those generic manufacturers that believe additional warning labels are necessary to propose to FDA the need for such stronger labels. Under this process, FDA would work with the name-brand manufacturer to determine the need for modifications to the labeling information. FDA cited the preamble to its 1992 regulations implementing the Hatch-Waxman Amendments as a basis for this duty imposed upon generic manufacturers. The defendant manufacturers in the case at issue disagreed with the premise that the 1992 preamble created a duty upon the generic manufacturers and argued that there was no evidence of any generic drug manufacturer from ever acting pursuant to such a duty. The Supreme Court found that federal preemption existed regardless of this potential duty and thus did not resolve this particular question.
Turning its attention to the preemption issue, the Supreme Court cited the Supremacy Clause of the US Constitution and the fact that federal law “shall be the supreme Law of the Land.” In short, where state and federal law conflict, state law must give way. Finding it impossible for the manufacturers to comply with both federal and state laws, the Supreme Court held that federal law preempts the state tort law duties.
The court also rejected the patients’ claims that the manufacturers could have sought FDA intervention and potentially brought about change in the labels. The court observed the novelty of the question that before preemption can be found, the analysis requires that the manufacturers in this case must prove that FDA would not have allowed compliance with state law. That is, the patients suppose that if the manufacturers had sought FDA modification of the labeling requirements, such may have allowed compliance with both federal and state laws, eliminating a preemption analysis. The patients argued that the manufacturers did not even attempt to propose such a change to the labeling. In rejecting this claim, the Supreme Court held that the question of impossibility of compliance with both federal and state law is whether the private entity (generic manufacturers) could independently do what is required under both laws. Conjecture of FDA action does not provide a basis for finding that state and federal law can coexist. In fact, the court noted that such a conclusion would render the Supremacy Clause all but meaningless.
Finally, the patients argued that a previous US Supreme Court opinion supported their argument that the ability to seek a change in the labeling requirements defeated a preemption argument and provided a basis for compliance with both state and federal law. In Wyeth v Levine, 555 U.S. 555, 129 S. Ct. 1187 (2009), the Supreme Court held that a lawsuit against a brand-name drug manufacturer alleged to have breached a state tort law duty was not preempted by federal law because the manufacturer was permitted to “unilaterally strengthen its warnings without prior FDA approval” under the CBE regulations. This authority to change labels without FDA intervention distinguishes Wyeth from the current case. In so concluding, the court sympathized with the patients in the current matter in stating that had such patients taken Reglan (the brand name prescribed by their physicians), Wyeth would control and preemption would not be found. “But because pharmacists, acting in full accord with state law, substituted generic metoclopramide instead, federal law preempts these lawsuits.”
Acknowledging the unfortunate circumstances of the patients, the court held that “it is not this Court’s task to decide whether the statutory scheme established by Congress is unusual or even bizarre.” It cited the differing statutes and regulations, which apply to brand-name and generic drug manufacturers respectively. In short, the court held that it will not distort the Supremacy Clause in order to “create similar preemption across a dissimilar statutory scheme.” Accordingly, the Supreme Court held that federal law preempts state tort law in these two cases and reversed the Fifth and Eighth Circuit Court opinions.
Pliva, Inc. Et Al. v Gladys Mensing, 2011 Lexis 4793 (U.S. Supreme Ct. 2011).
