Regulatory Focus™ > News Articles > Pharmaceutical Trade Groups Propose Overhaul of Drug Safety Update System

Pharmaceutical Trade Groups Propose Overhaul of Drug Safety Update System

Posted 30 March 2015 | By Alexander Gaffney, RAC

Pharmaceutical Trade Groups Propose Overhaul of Drug Safety Update System

In a rare show of unity, two trade groups respectively representing the branded and generic pharmaceutical industries have proposed an alternate policy meant to replace the US Food and Drug Administration's (FDA) controversial proposal to change the way in which generic drug labels are updated to reflect new safety risks.


In November 2013, FDA proposed a rule to allow generic drug manufacturers to temporarily update their labels if they were made aware of new safety issues that might pose a risk for consumers.

At present, generic drug manufacturers may not unilaterally update the labels on their drug products, even if they become aware of new (if rare) side effects. Instead, they must either wait until FDA requires an update to the drug's labeling or wait until the drug's original (i.e. non-generic) manufacturer decides to update its label, at which point the generic drug must bear the same label as the reference drug.

In practice, the process of updating a generic drug's label is complex and controversial. Thanks to several recent court decisions—Mutual v. Bartlett (2013), Pliva v. Mensing (2011) and Wyeth v. Levine (2008)—generic drug companies are almost entirely shielded from lawsuits regarding the labeling on their drugs. In addition, branded drug companies may occasionally refuse to update the reference listed drug's (RLD) label in some cases, such as if they believe the safety issue is unique to the generic drug. Further, some generic drugs may outlast the original drugs they reference, making it all but impossible to update the drug label without FDA help.

Read our extensive regulatory explainer on generic drug labeling here.

FDA's rule, which it began working on in the wake of the Supreme Court's Bartlett decision, was intended to remedy this problem by proposing a new system by which generic drug companies could temporarily update their drug labels.

FDA's proposal would allow generic drug companies to immediately make changes to their drug's label while awaiting feedback from FDA and the RLD holder (if the company still exists) about whether the update is necessary. Differences between drug labels would only exist on a "temporary basis," FDA said.

Industry Pushback

While FDA's proposed rule has been popular with some legislators and consumer groups, it has been received negatively by much of the pharmaceutical industry, including both generic and branded pharmaceutical groups.

For generic drug companies, some of the lack of appeal is obvious. Under the status quo, these companies are shielded from many liability suits explicitly because of their inability to control their drug labels. Under FDA's system, these companies would be able to update drug labels, and would therefore be subject to an increase in litigation (e.g. "failure to warn" claims about drug harms). The generic drug industry has suggested it might be subject to an additional $4 billion in legal costs each year, though this figure has been disputed by other analysis.

Generic pharmaceutical companies have also suggested FDA lacks the authority to implement its regulation, and that the rule might result in potential confusion if there are several temporary labels.

But in a case of politics making strange bedfellows, the branded pharmaceutical industry has also expressed its displeasure at the rule. The fear is that unfounded reports of drug safety issues could undermine public trust in the safety of drug products (both the generic and original products), and would also serve to burden branded pharmaceutical companies, which would need to review and assess labeling update requests from generic drug manufacturers.

Alternative Options

But the industry hasn't just been critical of FDA's proposed rule—it's also proposed its own alternative.

For months, the generic pharmaceutical association's main trade group, the Generic Pharmaceutical Association (GPhA), has proposed that FDA should take charge of the labeling process. "Since the FDA is the only entity with access to all the information and the expertise to evaluate and address this information, it is the only body in a position to decide whether a labeling change is warranted," wrote GPhA CEO Ralph Neas in a March 2014 op-ed.

Now GPhA has teamed up with the innovative pharmaceutical industry's main trade group, PhRMA, to offer a concrete proposal meant to serve as an alternative to FDA's proposed rule.

The plan, named the Expedited Agency Review (EAR), would require FDA regulators—not companies—to determine whether or not a safety change is necessary.

Companies already collect and submit this information to FDA on a regular basis and at pre-determined intervals. For example, if a patient taking a drug experiences an unexpected side effect, the company is required to investigate the event and, if necessary, notify FDA. Companies are also supposed to send in reports to FDA on a regular (once per quarter or per year) basis so that regulators can determine if side effects are occurring more frequently than initially anticipated.

Under the proposal, a generic or branded pharmaceutical company would request FDA expedite the review of a potential safety issue. FDA would then begin that review, and request safety data from all relevant drug manufacturers, including generic drug manufacturers. It would also probe data from its massive "Sentinel" drug safety database, which tracks data from tens of millions of anonymized patients.

Then, "If FDA determines through a review of all available safety data that a labeling change is required, FDA informs the [New Drug Application] NDA and [Abbreviated New Drug Application] ANDA holders of the content of the final labeling language immediately (within 15 days) and instructs the NDA and ANDA holders to update their labeling within 30 days via e‐labeling," the proposal states. The labels of all drugs would then be required to be updated within 30 days.

A Huge Change in the System

While the EAR proposal is floated as an alternative to FDA's generic drug labeling proposal, it would in practice dramatically change much more than just generic drug labeling. If implemented, the proposal would throw out much of the current system used to update drug labels—the "changes being effected" (CBE) process—in favor of the new FDA-centric review process.

More on the CBE process in the "How are Drug Labels Updated?" section of this piece.

In plain terms, that means FDA would be in charge of every single safety labeling update—a tall order for regulators, which would have to oversee massive amounts of safety data for thousands of drug products. It's not immediately clear if FDA has the resources, including an adequate number of staff, to feasibly implement the proposal.

In addition, the EAR proposal would likely create new legal protections for branded pharmaceutical companies, as FDA—not the company—would be the only entity which would approve a new warning. This might reduce the number so-called "failure to warn" lawsuits under the same legal theory applied to Bartlett and Mensing.

Both GPhA and PhRMA say they hope to discuss their EAR proposal with FDA "at the earliest opportunity."


Expedited Agency Review Proposal (PDF)


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