Pharma Update July 2013: FDA, Preemption & SCOTUS

Once again, it is time to catch up on the news from the pharmaceutical industry. And so, here is the latest monthly compendium in which we attempt to highlight some of the more noteworthy and fascinating news with a focus on the Food and Drug Administration (FDA), preemption and the Supreme Court.

1. FDA to Allow Generic Drugmakers to Update Labeling

The FDA is following through on plans to issue a proposed rule to revise regulations to allow generic drugmakers to update labeling. The rule would update current regulations that prevent generic drugmakers from doing so, even if they become aware of a potential risk not mentioned in labeling. By contrast, brand-name drugamkers can update warnings and precautions on labeling before obtaining FDA approval.

The moves comes in response to a US Supreme Court ruling two years ago that generic drugmakers are not required to strengthen product labeling, even when alerted to side effects, so long as the same change has not been made to the labeling for the branded medicine. The decision sparked an outcry that product labeling would be insufficient to warn patients about the risks associated with numerous medications.

The step was disclosed on the web site of the Office of Management and Budget, and was described as an attempt to “create parity” in the responsibilities required of both brand-name and generic drugmakers. The rule change would mean that generic drugmakers could face the same sort of liability over product labeling as brand-name drugmakers.


The rule would “amend the regulations regarding new drug applications, abbreviated new drug applications and biologics license applications to revise and clarify procedures for changes to the labeling of an approved drug to reflect certain types of newly acquired information in advance of FDA’s review of such change,” according to the statement on the OMB web site.

In the 2011 Supreme Court case, which is known as Pliva v. Mensing, two women claimed in different lawsuit that generic drugmakers could have made changes to their product labeling under state law and without FDA approval for such changes. They cited an earlier 2009 Supreme Court decision – Wyeth v. Levine – that found FDA regulations do not protect drugmakers from being used under state law over labeling.

Generic drugmakers argued they would have been required to provide labeling that is different from what appears on labeling of the brand-name drug, effectively convincing the court that federal law preempts state law. The court found that it would have been impossible for generic drugmakers to comply with both state and federal regulations.

The decision sparked a flurry of unsuccessful legal maneuvering in subsequent cases in which attorneys sought to avoid the preemption argument while hoping to force generic drugmakers to be held liable for harm. Meanwhile, Public Citizen Health Research Group filed a citizen’s petition with the FDA to demand a change in regulations.



2. Supreme Court Says No to State Drug Design Lawsuits

The US Supreme Court handed the pharmaceutical industry an important victory by ruling that state lawsuits claiming that drugmakers failed to adequately design their medications cannot proceed because these are preempted by federal law.

The case was closely watched because the decision clarifies the extent to which consumers will be able to file lawsuits against generic drug makers stemming from alleged harm caused by their medicines. However, the issue had the entire pharmaceutical industry on edge because brand-name drugmakers feared the same notion might also be applied to their practices.

In fact, the Obama administration earlier this year had filed a brief in support of the pharmaceutical industry over concerns that the entire FDA regulatory review process could be undermined if medicines deemed safe and effective by the agency could later be considered “unreasonably dangerous.”

At issue was a lower court ruling that was being appealed by Mutual Pharmaceutical, which wanted to overturn a $21 million jury award to Karen Bartlett. In 2004, the New Hampshire woman had taken its generic non-steroidal anti-inflammatory called sulindac for shoulder pain.

But she developed Stevens-Johnson Syndrome and toxic epidermal necrolysis, and is nearly permanently blind and suffered burn-like lesions over most of her body due. She is unable to read, drive or work, and must use a feeding tube, according to court documents.

Barlett sued Mutual for alleged design defects under New Hampshire state law, and last May, a federal appeals court upheld the award. Mutual, however, argued that federal law preempts this type of claim because the FDA had already approved sulindac and federal law requires a generic drug to have the same design as the brand-name medication.

Mutual objected to the jury verdict by pointing to a Supreme Court ruling in June 2011 in Pliva v. Mensing, which found generic drugmakers are not required to strengthen product labeling if alerted to side effects, so long as the same change has not been made to the labeling for the branded medicine.

Bartlett, however, argued that the FDA should never have approved the drug in the first place and claimed the medicine was inherently dangerous based on the number of incident reports of the skin reaction that were filed with the FDA. On that basis, Bartlett and her attorneys had maintained that the design of the drug was “unreasonably dangerous” and defective.

But a majority of the Supreme Court disagreed. While calling the Bartlett case a “tragedy,” Justice Samuel Alito wrote in the majority opinion. that the earlier Pliva ruling “makes clear that federal law prevents generic drug manufacturers from changing their labels. Accordingly, Mutual was prohibited from taking the remedial action required to avoid liability under New Hampshire law.”

“…State law design-defect claims like New Hampshire’s that place a duty on manufacturers to render a drug safer by either altering its composition or altering its labeling are in conflict with federal laws that prohibit manufacturers from unilaterally altering drug composition or labeling,” he continued.

3. Merck Wins Preemption Ruling

Merck won an important court ruling for the entire pharmaceutical industry. A federal court decided that, under certain circumstances, drugmakers may defend themselves against product liability lawsuits by citing preemption, which was at the heart of a contentious 2009 ruling by the US Supreme Court. In that case, the court found that a Vermont woman was entitled to sue Wyeth, which is now owned by Pfizer, because the drugmaker failed to adequately include safety warnings on one of its medicines.

The court found there was no evidence to show the FDA would have rejected a stronger warning if Wyeth had sought to do so. In other words, it was not “impossible” for Wyeth to have attempted to update its label. But the court also left the door open to another scenario that invites a preemption defense. If a drugmaker can provide “clear evidence” the FDA would not have approved a unilateral labeling change to include an updated warning, a drugmaker could argue this demonstrated it was impossible to comply with both FDA requirements and a state law finding for a stronger warning.

And a federal court judge decided that Merck had, in fact, attempted to strengthen the warning about a possible link between its Fosamax treatment for osteoporosis and femur fractures, but the FDA did not approve such an addition to the precautions section of the labeling. This attempt occurred in 2008, before an elementary school teacher suffered such a fracture the following year. She argued Merck was aware Fosamax might increase fracture risks years before the drug was made available, but failed to include info in the label.

However, US District Court Judge Joel Pisano disagreed and wrote that “preemption is warranted, because there is clear evidence that the FDA would not have approved a change to the precaution section of the Fosamax label prior to Mrs. Glynn’s fracture.” In citing FDA e-mails to Merck in 2009, he noted that the FDA rejected the updated labeling during the same month in 2009 that Glynn suffered a fracture, and that the agency warned Merck its drug may have been considered misbranded if the labeling change was made before FDA consent was given.

It was only after the American Society of Bone and Mineral Research issued a report in 2010 that the FDA required Merck and other drugmakers to strengthen the wording in their product labeling to reflect the possibility of an association between bisphosphonate drugs such as Fosamax and femur fractures. The teacher, by the way, already lost her case in court. In April, a jury found in favor of Merck, but Pisano deferred a ruling on a preemption motion until after a jury had made a decision.


4. Post-Marketing Studies

For years, the FDA has regularly been criticized for not doing more to ensure drugmakers follow through on commitments to conduct post-marketing studies. Now, a new analysis suggests the FDA needs to get tougher on violators because a rising percentage of studies are delayed and a hefty percentage had not begun.

Specifically, 43 percent of post-marketing studies had not yet gotten under way as of 2011, and the number of delays doubled to approximately one in eight that year, according to a research letter published in the Journal of the American Medical Association that examined study commitments that were issued between 2007 and 2011.

The academics chose 2007 because that was when Congress passed the Food and Drug Administration Amendments Act, or FDAAA, which authorized the agency to require drugmakers to conduct post-marketing studies as part of the process for granting an approval. The FDA was also given authority to mandate adherence to deadlines.

So far, though, industry performance has been a mixed bag. On the bright side, the analysis found that the number of studies not yet begun fell from nearly 57 percent in 2007 to 43.5 percent in 2011, while the number of studies required under the FDAAA, but not yet started, rose steadily each to 15.2 percent, or 271 studies, in 2011.

Meanwhile, the trend went in the opposite direction for studies that fulfilled the requirements. These increased from 122, or 6.6 percent, in 2007 to 224, or 12.6 percent, in 2011. But there were no fulfilled FDAAA studies during this period. Also, delayed studies rose from 125, or nearly 7 percent, in 2007 to 241, or 13.5 percent in 2011. By then, 1 percent of studies required by FDAAA were delayed.

So what do the authors recommend? The FDA “must enforce the law against companies failing to comply with study requirements.” They note the agency can issue warning letters and initiate litigation for “significant failures,” and seizures and injunctions are in the regulatory toolbox.

To what extent the FDA takes such action, however, is unclear. There was one prominent example – Merck received a warning letter last year for failing to follow through on a post-marketing study for the widely used Januvia diabetes treatment. The study had been required to assess the risk of pancreatitis, a malady that has plagued the drug and others in the same class of therapies.

5. Dear Health Care Provider

Each year, drugmakers send Dear Health Care Provider letters to physicians and other health care providers, but does anyone really know if they receive the correspondence and what, if any, impact these letters have on the providers and patient behavior?

To answer these questions, the FDA three years ago issued a draft guidance to recommend drugmakers evaluate the extent to which providers received these letters and were aware of the information that was to have been conveyed. Another suggestion: assess the impact of the letters.

Now, the FDA has backed down after receiving nine comments that objected on the grounds that the recommendation was overly burdensome, beyond the agency’s statutory authority and would cause an unnecessary increase in correspondence that could minimize the effect of the initial letters.

Instead, the final guidance is being modified to suggest that manufacturers conduct an evaluation – for their own use – concerning the usefulness of these letters and their success in reaching providers, according to a notice in the Federal Register.

Just how burdensome might this requirement have been? The FDA reviewed MedWatch safety alerts for 2008 and 2009 to identify letters sent and estimate that about 30 such missives will be sent annually by about 25 different companies. Each one should take about 100 hours to prepare and send.

There is merit in both arguments. On one hand, it is conceivable that follow-up letters can dilute the impact that comes with receiving the initial letter, which raises the risk that important information is not seen immediately or even ignored.

On the other hand, the decision not to require follow-ups and evaluations means that the agency will continue to be in the dark when it comes to knowing the extent to which these letters are actually seen and the impact they have on providers and patients. But by not requiring drugmakers to collect and share this information, the public loses a potential benefit.


Warning & Disclaimer: The pages, articles and comments on do not constitute legal advice, nor do they create any attorney-client relationship. The articles published express the personal opinion and views of the author as of the time of publication and should not be attributed to the author’s employer, clients or the sponsors of Read more.

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