The U.S. Food and Drug Administration withdrew a proposal that would have permitted generic drug companies to independently revise their product labeling with new safety updates before regulators reviewed or approved such changes, like brand-name manufacturers already can do.
The November 2013 proposal had long-been expected to be pulled after the FDA delayed implementing the rule a number of times and generic and brand-name companies alike had vigorously pushed back on the idea, saying it would create confusion because of varying information at times in drug labels and would add additional financial burdens for manufacturers that make copies of innovator small-molecule medicines.
The consumer watchdog Public Citizen, though, had called for the rule to be employed — requesting it through an August 2011 citizen petition to the FDA, saying generic drugmakers should be held accountable for ensuring their safety information was up to date in their labeling.
The group said the FDA's withdrawal of the proposed rule was a "flagrant disregard for public health and common sense."
Generic companies, in particular, said the proposal would have opened them up to more liability.
Currently, generic makers are protected against liability under two U.S. Supreme Court rulings — Pliva v. Mensing and Mutual Pharmaceutical v. Bartlett.
In those rulings, the justices said generic manufacturers do not have the same obligations as brand-name drugmakers to update product labeling when new risks come to light and state law design-defect claims that turn on the adequacy of a medicine's warnings are pre-empted by federal law.
Responsibility for all, but different standards
Even though all drugmakers must inform the FDA about all adverse event reports the companies receive, currently only brand-name manufacturers are permitted to independently revise their safety information in drug labeling on their own by submitting a so-called changes being effected supplement, or CBE.
The CBE changes are a narrow exception to the general rule that labeling changes require the FDA's approval before implementation, the agency noted in a Federal Register notice posted online Dec. 13.
If regulators sign off on CBE safety updates, then generic drug companies are required to include the same revisions in their labeling.
But when a generic company becomes aware of a potential risk, it cannot update its drug's labeling without first submitting supporting information to the FDA, which then determines if the label should be revised for those medicines and the innovator drugs.
The now-withdrawn proposed rule would have enabled generic drug companies to independently update and promptly distribute revised product labeling to reflect certain types of newly acquired safety-related information, even though the revised labeling may have temporarily differed from the corresponding brand-name drug on submission of a CBE supplement to the FDA.
During a media call with reporters, FDA Commissioner Scott Gottlieb acknowledged there are often long gaps between the time a generic company advises the FDA of a potential risk and the agency acting on it. But he blamed a lack of resources to respond.
"It's resource-intensive work," he said.
While in some cases there are branded drug companies that are able to work with the FDA on updating the generic labeling, in others, the innovator has left the market, "so we have to take on the challenges ourselves and do the work," Gottlieb told reporters.
He said the FDA has been in discussions with Congress and the administration about the need for additional funding, "and I've gotten some support for those activities."
Gottlieb noted that in withdrawing the proposed rule, the FDA simultaneously embarked on a new initiative to more quickly update the labels on certain generic cancer drugs with modern safety and efficacy information.
He said the agency would play a more proactive role in identifying and facilitating the updates for older generic cancer medicines — many of which remain the backbone of modern oncology treatment.
"This effort can help us promote generic utilization by making sure that old generic labels, some of which correspond to drugs that are still very important medicines in modern chemotherapeutic regimens, not only have up-to-date safety information but also up-to-date efficacy information on how they can be combined in modern combinations," Gottlieb said.
"It's a very careful balancing that we're trying to strike," he added. "It's one reason we may look to Congress to get additional resources."
Pros and cons
The FDA acknowledged it received a number of comments that supported carrying the rule forward and finalizing it as originally proposed, while others expressed concern that temporary labeling differences between generic drugs and the corresponding branded products could complicate healthcare decision-making.
Comments in support of the rule maintained that it would enhance drug safety by making healthcare practitioners and the public aware of new safety-related information about a drug more quickly, the FDA said in its Federal Register notice withdrawing the proposal.
Others also said that the threat of a lawsuit for failure to adequately warn patients about a known hazard may be an incentive for drug manufacturers to ensure their product labeling reflected the most current safety information.
But the FDA noted that it also received a number of comments opposing the proposed rule, saying it raised policy, legal and cost considerations.
"A number of comments asserted that generic drug application holders do not generally receive or possess all the data necessary to evaluate post-market safety information and to support safety-related labeling changes," the agency stated.
Some also said that even a temporary difference in labeling could undermine confidence about the therapeutic equivalence of generics to the brand-name drugs.
Gottlieb said the proposed rule could make drug development more costly for generic makers, potentially leading to higher prices of their medicines, which could impede access for some patients to those products.
He noted there also was a concern those added development costs could lead to some companies exiting the market, resulting in shortages of generic medicines.
But most of the opposing comments revolved around the increased risk of lawsuits brought against generic drug manufacturers and others in the healthcare system, the FDA said.
The Association for Accessible Medicines, the lobbying group representing the generics industry, was one of the loudest voices on that front.
David Gaugh, senior vice president of sciences and regulatory affairs at the trade group, said the FDA "correctly recognized the need for consistency and the potential for adverse consequences."
"The FDA's action further exemplifies its focus on the best interest of the public's health and provides patients with the utmost confidence in their health care choices," he said in a Dec. 13 statement.
While the brand-name lobbying group, the Pharmaceutical Research and Manufacturers of America, told S&P Global Market Intelligence it supported the rule's withdrawal, it also pushed for the FDA to require an "expeditious prior-approval" process for all safety-related changes to labeling, regardless of whether the requests come from innovators or generic manufacturers.