Proposed new FDA rule might allow altered labeling of generic meds

A new rule under FDA consideration could have a significant impact on the pharmacy industry and generic drug dispensing, yet most in the industry are not aware that change could be on the horizon.

FDA has proposed a new rule that would allow individual generic-drug application holders to update product labeling information to temporarily reflect changes in safety information prior to FDA review.

In a recent statement presented to a U.S. House of Representatives Subcommittee on Health, Janet Woodcock, MD, director of FDA’s Center for Drug Evaluation and Research, said that the proposed rule would add parity among application holders and "would speed the dissemination of new safety information about generic drugs to health professionals and patients."

Edith RosatoHowever, pharmacy associations have raised concerns about whether the rule as it is written would increase confusion in the industry, undermine the public's trust in generic medication, increase liability to pharmacists, and potentially create generic drug shortages.

"From a pharmacy - a professional pharmacy - perspective, this is a huge issue for us, and we want to make sure we can turn the tide on this with the FDA," said Edith A. Rosato, RPh, IOM, chief executive officer of the Academy of Managed Care Pharmacy.

Despite the debate the proposed rule has sparked among leaders in pharmacy, a new survey released by the Generic Pharmacy Association (GPhA) found that 79% of the physicians, pharmacists, and physician assistants surveyed knew nothing about the proposed rule.

"This proposed ruling right now has not gotten out to the marketplace - or at least not in a way that they are paying attention to," Rich Higginson, director of corporate research for Fairleigh Dickinson's PublicMind, said during a recent webinar to announce the results. PublicMind conducted the random nationwide telephone survey of 450 physicians, physician’s assistants, and pharmacists.

The proposed rule

In November 2013, FDA proposed a new rule, known as the “Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products,” that would allow generic drug manufacturers to change their labeling to reflect newly acquired safety information before the change is reviewed by FDA, through what FDA refers to as a "changes being effected" (CBE-0) supplement.

Under this rule, the label on a generic drug could differ temporarily from the label on the reference listed drug or other generics.

"The proposed rule recognizes the obligation of all drug application holders to monitor safety information about the drugs they market and ensure that product labeling is accurate and up to date, and proposes a pathway to ensure that all drug application holders can fulfill that obligation and communicate important new safety information to prescribers and consumers," Woodcock said in her statement to the subcommittee.

As it stands currently, generic manufacturers can't update product safety information until the brand-name product receives approval for that purpose from FDA. However, makers of brand-name drugs are able to independently update and distribute such products’ safety information before they receive FDA approval.

Under the proposed new rule, manufacturers of generic drugs would be given this same power. They would need to provide a copy of the information supporting the change to the manufacturer of the branded drug as well as to FDA.

"In the current marketplace, in which approximately 80% of drugs dispensed are generic and brand-drug manufacturers may discontinue marketing after generic-drug entry, FDA believes it is time to provide generic-drug application holders with the means to update product labeling to reflect data obtained through post-marketing surveillance, even though this will result in temporary labeling differences among products," Woodcock said in her statement to the subcommittee.

While FDA is reviewing the change, it will communicate any proposed safety-related changes to generic-drug labeling through a dedicated web page.

If FDA decides a change is justified, it will offer approval of the change to the generic-drug labeling and the corresponding brand-drug labeling at the same time, so that ultimately the two will once again have the same prescribing information.

Industry concerns

Mary Jo CardenWhile FDA believes the rule would build parity between generic and brand drug manufacturers, pharmacy associations have voiced concerns that the temporary discrepancy in labeling could cause confusion in the industry.

"If it's the same generic product, one manufacturer might have a different label than another manufacturer would have, and as you can imagine, this would create much confusion over “does this pertain over the entire product line, the generic, or the brand name, etc.,” because right now essentially what FDA does is it looks to see if this is something that is a legitimate issue that needs to go into the labeling, and typically it applies it to all of the products," said Mary Jo Carden, senior director of regulatory affairs for AMCP.  

Woodcock contends, however, that the rule would be a benefit to public health.

"This proposed rule reflects the Agency's judgment that concerns related to temporary differences in labeling between generic drugs and their corresponding brand drugs are outweighed by the benefit to the public health, which would result from all application holders having the ability to independently update drug product labeling to reflect newly acquired information regarding important drug safety issues," she said in her statement to the subcommittee.

Christopher TopoleskiBut, representatives of the American Society of Health-System Pharmacists (ASHP) say that there are already communication issues within FDA. They believe the proposed rule would only add further confusion.

"We are not in favor of the proposed rule as it's written," said Christopher J. Topoleski, director of federal regulatory affairs for ASHP. "We believe that there are too many fundamental issues at the FDA right now, in terms of communication and information-sharing and information-housing, and that allowing this would create even more disparity across specific molecules."

For instance, according to Topoleski, there are already existing generic labels that should be changed to reflect changes made to the reference product, but those changes still have not been made, leading to out-of-date labeling.

"Allowing individual labels to change brings into question which one becomes the benchmark for other generic labels for that product. It also raises the questions of when those labels will change and how you create consistency across those labels," he said. "We believe that there will continue to be increased confusion, given that FDA already has a number of places from which one must gather information about a specific drug. It's not all in one central location."

Gerald McEvoyGerald McEvoy, PharmD, assistant vice president of drug information for ASHP, believes that before FDA can allow generic manufacturers to make temporary label changes, it needs to streamline its communication process by providing all drug information in one central location.

"What they failed to do is to make it easy, or easier, for healthcare providers and patients themselves to go to a single location and find all applicable information that FDA has issued concerning the safety of a given drug product," he said.

According to the recent study performed for GPhA, physicians, physician assistants, and pharmacists are also worried about the confusion that may arise if the proposed rule is approved as it is written. The study findings revealed that 76% of those surveyed believe their patients would be at least somewhat confused, while 53% said that they themselves would also be very confused by multiple safety labels.

Impact on the generic industry

Increased confusion isn't the only concern for the pharmacy industry. Pharmacy associations have also voiced the concern that if one generic medication has a different safety label, it could shake consumer confidence in that one product or in generics in general.

"I think a lot of progress has been made with regard to generics, the use of generic medications, and their safety and efficacy. This does suddenly give a perception that some generics are less safe," said Stacie Maass, senior vice president of pharmacy practice and government affairs for the American Pharmacist's Association (APhA).

If the proposed rule is put into place, generic manufacturers will also be open to greater liability and litigation, which pharmacy association executives say could lead to higher generic drug costs.

"If you are now allowing drug manufacturers - generic drug manufacturers - to be eligible to litigation, that opens up a whole other can of worms, because clearly that's the whole premise of the generic drug industry: You know they don't have to do the research and development studies that the innovator product does, and that's how they are able to keep their costs down and pass that off to the consumers," Rosato said.

She added that it's possible that the proposed rule could lead to drug shortages, because different generic medications could have different safety indications, making some more desirable than others.

"If they are using a particular generic manufacturer over another or others because their safety profile is excellent, then all the sudden there's going to be huge surge in demand on that generic manufacturer's product, and they may not have the authority to manufacture the quantity that they would have to," she said.

Impact on pharmacists

Generic drug manufacturers aren't the only stakeholders who could be affected by the proposed rule. Jillanne Schulte, director of regulatory affairs for APhA, hopes that the FDA will provide more clarity about what the role of pharmacists would be, as well as whether pharmacists would be responsible for checking the website designated by FDA for each drug they dispense, to make sure there are no changes to the label.

"They are dispensing high volumes of generics. If they had to go and check a website for every single patient, that's a lot of interference with work flow. It can really impede practice, and it could make it more difficult. Patients may have to wait a little bit longer to get medication," she said. "We don't know how it will read when it's final, but there are concerns."

The path ahead

While pharmacy associations say they are supportive of the FDA attempt to get safety information out to patients, providers, and pharmacists as early as possible, they say that as currently written, the proposed rule leaves questions and concerns about what it could mean for the industry.

Many of the pharmacy associations and other stakeholders voiced their concerns to FDA in March through letters and statements made during a period of public comment. One such letter was signed by 21 different organizations, including pharmacy associations such as AMCP, ASHP, and APhA, as well as McKesson Corp., the Cardiovascular Research Foundation, the National Coalition on Healthcare, and AmerisourceBergen, and outlined what they believed could be the negative consequences of the proposed rule.

Pharmacy association representatives say they hope FDA provides additional clarity and addresses their concerns before a final rule is put in place.

"According to FDA, only one entity, the trial lawyers, met with FDA before the proposed rule was published. In the past, FDA has always talked to pharmacists, always talked to physicians, nurses, generic manufacturers, brand manufacturers, before doing this kind of proposed rule," said Ralph G. Neas, president and chief executive officer of GPhA, in a recent webinar. "I think everybody wants to be at the table, have a seat at the table and share their perspective, their experience."

It will be up to FDA to decide what happens next, said Topoleski. It is not under any specific deadline for decision about how to proceed.

"This was a rule that they proposed, and this could sit out there in draft form for years. If they choose to, they could rescind it, they could finalize it, or they could finalize it, obviously, with changes," he said.

Jill Sederstrom is a freelance writer in Kansas City.