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FDA Looks to Update, Improve Labeling of Existing Drug Products

Posted 11 July 2013 | By Alexander Gaffney, RAC

In February 2013, the US Food and Drug Administration (FDA) announced its intent to launch a new initiative aimed at voluntarily converting the majority of currently marketed pharmaceutical and biological drugs to a consistent standard for content labeling, noting that many products have been grandfathered in to outdated standards that put consumers at risk. Now the agency is looking to get that program started, issuing a solicitation to find a partner willing to help it conduct the actual labeling harmonization process and possibly improve it as well.


Drug labeling has been standardized in the US since 1979, when measures to introduce uniformity were first passed. Since that time, FDA notes that drug labeling has become considerably lengthier and more complex to account for improvements in regulatory science and additional requirements, generally related to the safety of the product.

In 2000, FDA began an evaluation of its labeling processes and requirements with the ultimate goal of improving the labeling to make it more effective at its given purpose: informing its user about the drug's properties, including the risks and benefits associated with its use.

That process resulted in a 2006 final rule, Requirements on Content and Format of Labeling for Human Prescription Drug and Biological Products, better known as the Physician Labeling Rule (PLR).

Under the rule, labeling highlights could be no longer than a half-page including the bulleted boxed warning and indications, must contain a "Table of Contents" for easy referencing, must identify all major changes, and must include the date of initial US approval. The label was also reformatted to allow for the most pertinent information to be more prominent, and established 8-point minimum font and other typography requirements to make the type easier to read.

Notably, the new labeling also included contact information (phone number and a website address) to facilitate adverse event reporting.

"Providing healthcare professionals and patients with clear and concise information about prescriptions will help ensure safe and optimal use of drugs, which translates into better health outcomes for patients and more efficient delivery of healthcare," said Mike Leavitt, at that time the secretary of the US Department of Health and Human Services (DHHS) under President George W. Bush. "By improving the package insert to make it more useful for healthcare providers in their day-to-day clinical practice, we are making it easier for them to explain the benefits and risks of medications for their patients."

The rule applies to all products approved under a New Drug Application (NDA), Biologics Licensing Application (BLA) or efficacy supplement (ES) approved between 2001 and 30 June 2006, as well as all products thereafter. Older drugs may subject themselves to the rule on a voluntary basis.

The Rationale for a New, Voluntary Initiative

But changing labels would be a time-consuming affair, and FDA proposed at the time to prioritize labels for new drugs more highly, and then work backward until all drugs utilized a standardized format under the PLR.

The implementation process established by the PLR expired on 30 June 2013, posing a problem for regulators: as thorough as the PLR process was, it only accounted for 15% of all drug products on record. "If no further action is taken," FDA said in a Federal Register notice, "the only additional drug products with labeling in the PLR format will be new NDAs, BLAs and ED, which are required to be submitted in that format."

The remaining 75% of drug products generally fall into one of two categories: NDAs and BLAs submitted to FDA before 30 June 2001, and generic drugs.

Generic drugs, it should be noted, were not required under the PLR to convert to the new labeling format unless their reference listed drug (RLD) has done so. By law, generic drugs are required to have the exact same labeling as the RLD. Only 10% of generic drugs have been converted to the PLR, garnering concern from regulators who noted that generic drugs compose approximately 80% of all prescriptions made to consumers.

"FDA believes that it is in the best interest of the public health to facilitate conversion of generic drug labeling to the PLR format so the labeling is equally useful to prescribers as the labeling for more recently approved drug products." It said.

The Prescription Drug Labeling Improvement and Enhancement Initiative

That's where FDA's new Prescription Drug Labeling Improvement and Enhancement Initiative (PDLI-EI) is set to come into play. In a February 2013 Federal Register notice, FDA explained that in light of concerns that a lack of labeling standardization could potentially hurt consumers and cause difficulties in newer electronic systems (which are set up to take in information from newer labeling schema), it wanted to get as many pharmaceutical products under a standardized format as possible.

The goal of the PDLI-EI, FDA said, is to increase compliance with the PLR for products approved even before 2001, as well as for generic drug products, and would take place over "several years," though FDA's Federal Register notice did not indicate a specific timeframe. Given the huge number of drug products, it would likely be a multi-year process, if not longer.

The Transition Process

While the process would be strictly voluntary, FDA said it wants to prioritize drugs based on their respective public health impact. And, importantly, neither FDA nor industry would have to do much work to update the labels of pharmaceutical products. Instead, FDA has said it will work with an outside contractor to oversee the process and facilitate the switch by preparing draft PLR-compliant labeling for applicants who indicate they need assistance with converting the labeling. That supplement would then be sent by the applicant to FDA for review.

FDA's call for a contracting partner has now been published on the Federal Business Opportunities Website, with FDA saying the contract term would be for a five-year period, with an initial focus on a list of products to be developed by FDA based on their public health impact.

From the perspective of the contractor, the project will involve the development of a labeling conversion database to document and track PLR labeling conversions and conducting the actual conversion process.

Once the contractor completed the changeover, the sponsor of the product would need to formally submit a supplement with the labeling to FDA.

FDA said it expects the contractor to submit no more than 25 PLR labeling conversions per month for at least 295 prescription drugs

Other Labeling Changes Pending?

However, FDA's contract notice also notes several other opportunities the agency may wish to take advantage of.

"While the initial focus of the PDLI-EI is to increase the number of drugs with labeling that complies with the PLR content and format requirements, FDA intends to initiate other labeling and enhancement projects throughout the 5 year period of the contract," FDA wrote.

"Other examples of labeling enhancements could include developing, testing, or evaluating patient labeling, facilitating the accessibility and use of the FDA-approved electronic prescription drug labeling, evaluating and drafting revisions to prescription drug labeling in PLR format, or obtaining and summarizing feedback from the public on user preferences and usefulness of prescription drug labeling (e.g. through public meetings, workshops, or other means)," it wrote.

The total cost of the program is still to be determined, based on rates submitted by contractors who ultimately bid for the project.

Contractor Solicitation

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