Inside the FDA labeling fight that could upend the generics market
GPhA's CEO says the agency's proposed rule cuts to the very heart of the Hatch-Waxman Act
In the downtown Washington, D.C. offices of Ralph Neas (pictured above), President and CEO of the Generic Pharmaceutical Association, there is ample evidence of his commitment to social justice and civil rights, with a particular focus on affordable health care.
The office is adorned with numerous photos of Neas with civil rights icons, awards of recognition, signed plaques, and personal mementos that reflect a lifetime of work focused on those issues. And there is also evidence of a work-a-day world in which pragmatism, collaboration, and tenacity are the driving forces behind every "win."
Right now, there’s something big on the agenda. In fact, as Neas prepares to depart from his current position as GPhA's chief later this year, he is engaged in one of the biggest battles of his career—a battle which, as he puts it, ultimately comes down to defending the integrity of the seminal Hatch-Waxman Act of 1984.
Why Hatch-Waxman matters
Hatch-Waxman was designed to expedite and streamline generic drug approval by creating an approval standard based on the principle of sameness and bioequivalence. Prior to this law, generic drug companies had to conduct the same time-intensive and costly clinical trials as companies seeking approval for new drugs. Hatch-Waxman also clarifies market and patent exclusivity issues. And most importantly, under the current system, generic drugs are more affordable than brand name drugs, yet equally safe and effective.
As Neas notes, "Based on Hatch-Waxman, generic drugs have to demonstrate sameness in terms of having the same active ingredient, route of administration, dosage form, strength, intended use—and according to the original law, the same labeling.
"Hatch-Waxman is one of the most effective laws enacted in the nation’s history, as well as one of the most exquisitely balanced laws," he adds. "Protecting the integrity of this law is an issue that is neither Democratic nor Republican, or liberal or conservative. It has everything to do with getting safe, effective and affordable medicine to everybody."
In November 2013, the FDA issued a proposed rule in which generic drug manufacturers (ANDA holders) would be required to submit a "changes being effected (CBE)" supplement for safety-related labeling changes to the FDA. After submitting the CBE, the generic manufacturer would be able to distribute the revised labeling prior to the FDA’s approval. Under the proposed rule, the ANDA holder would contact the brand manufacturer (NDA holder) about the labeling change, and if the FDA approved the change, other generic manufacturers would follow suit.
This proposal, known as the "Supplemental Application Proposing Labeling Changes for Approved Drugs and Biological Products," represents a major, paradigm-shifting change as, currently, generic manufacturers must have the same label as brand manufacturers and cannot unilaterally change labeling.
The proposed rule, which is backed by Public Citizen, the American Association for Justice (a trial lawyer organization), the National Physicians Alliance, and other groups, caused a ripple effect of shocked dismay and pushback not only from the GPhA, but other concerned groups and organizations.
In March 2014, a total of 19 organizations, including disability groups, minority groups, patient advocacy organizations, and veterans organizations spoke to the FDA in a collective voice, making the case that they count on having access to affordable, generic medications—and that the proposed rule could jeopardize patient access and safety.
Moreover, when GPhA and the National Coalition on Healthcare randomly surveyed 300 healthcare providers and 150 pharmacists regarding the proposed rule, the overall assessment was negative. Of those surveyed, 81% believed that all label changes should go through the FDA. In addition, 76% were concerned that using different labels for the same drug would be confusing to patients, while 77% believed that the proposed rule could impact their legal liabilities.
From the FDA’s perspective, the proposed rule seeks to "create parity between NDA holders and ANDA holders." But GPhA and its allies contends that the new rule would not only be confusing for patients and providers, but that it would increase liability costs by billions of dollars, while decreasing the number of generic drugs coming to market and ultimately making it harder for patients to access affordable medications.
This is no small matter considering the fact that 86% of all prescription medications dispensed are generics, leading to a total annual cost-savings of $239 billion, according to 2013 data from GPhA.
A number of surprising partnerships and coalitions have sprung up on both sides of this issue. Notably, GPhA and the Pharmaceutical Researchers and Manufacturers Association (PhRMA) have jointly proposed an alternate proposal, known as the Expedited Agency Review (EAR), which is now supported by numerous advocacy groups besides PhRMA, such as the National Dental Association, the National Medical Association, the National Organization of Black Elected Legislative Women, and many others.
The EAR would speed up the process of a label update by relying on the FDA to review the new safety information and requiring that the FDA take action to change the label within a pre-specified period of time. The FDA would then notify all involved manufacturers, including the NDA and the ANDA holders, of the labeling change, with expected implementation of the revised label within 30 days.”
What you need to know about the EAR
There are a several key points that proponents of the EAR emphasize. First, the FDA is the central repository of all of the clinical trial data from both brand and generic manufacturers. If a generic manufacturer were to unilaterally change its label, it would do so without the full benefit of the entire evidence base. Plus, there could be many different and potentially conflicting labels for the same drug.
In addition, there is currently an active surveillance system in place in which all NDA and ANDA holders submit adverse event data to the FDA in 15-day, quarterly, and annual reports. Based on this reporting system, the FDA is already in a position to respond to safety issues.
Finally, the EAR initiative proposes that the FDA adopt e-labeling in order to ensure that different labels will not exist in the marketplace at the same time.
The FDA public meeting
The labeling issue is coming to a head, as evidenced by the many passionate voices both for and against the proposed rule that made their cases at the Public Meeting at the FDA campus in Silver Spring, MD on March 27. When David Gaugh, Senior Vice President for Sciences and Regulatory Affairs at GPhA, rose to speak, there was clearly a sense of urgency in the room.
According to Gaugh, when a safety issue is uncovered by either an NDA or ADNA holder, it can take up to nine to 12 months before the label is changed. This is a long and drawn out process. By contrast, according to Gaugh, "The EAR would institute defined time parameters for the FDA to take action and make a label change on all multi-source products." (Note: Multi-source products are the brand and generic versions of the same molecular or biologic entity).
Gaugh also made the point that e-labeling is a "key tenet" of the entire process, which would be easy to implement for several reasons. First, the infrastructure is already in place in the form of the Sentinel reporting system. Also, an electronic system would ensure accurate and real-time labeling changes, compared with the current approach, which Neas refers to as a "20th century approach."
The other side of the safety perspective
Proponents of the EAR have repeatedly emphasized that patient safety is their foremost concern. In fact, safety is the foundation of the argument in favor of the rule.
Speaking at the FDA Public Meeting, Dr. Michael Carome, Director of Public Citizen's Health Research Group, said, "The problem is the generic drug makers cannot make labeling changes, nor can they be held liable to patients for inadequate labeling. Therefore, they have little to no incentive to engage in fully robust safety surveillance. As a result, real risk may not be brought to the FDA’s attention in a timely manner, and patients and physicians will not be warned until the problem becomes so acute that it comes to the FDA’s attention."
The road ahead
Clearly, both proponents and opponents of the proposed rule are concerned about safety. But the labeling issue is much bigger than safety alone.
Currently, the FDA docket is open for public comments, but will close at the end of this month. At that point, we will know more about the direction in which this controversial battle will proceed. And there is a very good chance that Ralph Neas will know the ultimate outcome of this debate before he leaves GPhA.
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