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Pink Sheet – US FDA's Label Updating Effort Needs Legislation To Impact Generics

Pink Sheet – US FDA's Label Updating Effort Needs Legislation To Impact Generics

Executive Summary

Generic labels can’t easily be changed if reference product is withdrawn, meaning legislative fix is needed to add current recommendations to outdated labels.


The US FDA believes it needs legislation empowering its desire to push manufacturers to update old and outdated drug labels.


Amid discussion of the problems associated with labels that become stagnant and a potential solution where the agency could perform most of the legwork, Center for Drug Evaluation and Research Director Janet Woodcock said the agency “might be able to change some things around the edges,” but does not have the legal authority to make a major change to a label if the reference product has been withdrawn from the market and only generics remain.


Woodcock said FDA also does not expect generic companies to volunteer labeling updates in that situation.


“The generics could choose to submit more information and become basically innovators,” she said March 20 during a Friends of Cancer Research congressional briefing on enhancing information about prescription drugs. “The generic industry, that’s not really their thing, so we don’t see that happening very often.”


Legislation creating an incentive for generic companies to apply to make FDA-suggested labeling changes could allow some currently off-label uses to become approved indications.


Should FDA find data to support a labeling change, Josephine Torrente, director at Hyman, Phelps and McNamara, said during the briefing that a bill shielding generic companies from failure to warn suits should they make that submission also may be helpful.


During the briefing, FOCR reviewed a paper it recently published proposing the agency review available evidence with stakeholders, publish a summary in the Federal Register, and invite sponsors to update an old drug label.  (Also see “Labeling Updates For Old Drugs Could Be Faster Under Streamlining Proposal” – Pink Sheet, 28 Nov, 2017.)


The agency’s hands are tied in many cases because it cannot unilaterally make label changes. Manufacturers must submit applications requesting the change.


Generic drug labels are further hand-cuffed because they cannot diverge from the reference product label. If the reference has been withdrawn from the market, the label essentially can never be changed.


FDA views outdated labels as a substantial problem. Woodcock said during the event that she worries some labels have outdated recommendations that if followed may kill patients.


Commissioner Scott Gottlieb also has said the agency is working on methods to initiate proactive labeling updates.  (Also see “US FDA Looks To Proactively Update Old Generic Drug Labels Under Pilot” – Pink Sheet, 28 Jan, 2018.)

Legislative Fix Seems Difficult This Year

Finding a vehicle for any bill may be difficult this year. The legislative calendar is growing short, especially with many lawmakers soon returning to their districts to campaign for re-election. And since Congress passed two major FDA packages in consecutive years, (the 2017 FDA Reauthorization Act and 2016 21st Century Cures Act) there may not be much appetite to push another bill for the agency.


FDARA reauthorized FDA’s user fee programs and made other changes (Also see “Implementing User Fees Should Be Lighter Lift For FDA This Time Around; Bill Heads To White House” – Pink Sheet, 3 Aug, 2017.), while the 21st Century Cures Act was intent on speeding drugs to market.  (Also see “Woodcock, Califf Give Thumbs Up To Certain 21st Century Cures Provisions” – Pink Sheet, 14 Dec, 2016.)


It is possible legislation could be attached to a mandatory spending bill, or the animal drug and animal generic drug user fee reauthorization bill, which must be renewed this year, but it may not be allowed because it could create opportunities for protracted fights on other health care-related topics.


Indeed, updating generic drug labels became a controversial subject after the agency issued a proposed rule that would have allowed generic companies to unilaterally make safety changes. Industry protested and it eventually died.  (Also see “Generic Labeling Rule Dies In Latest Reg Agenda, But Electronic Labeling Is Reborn” – Pink Sheet, 14 Dec, 2017.)

OCE Considers Encouraging Reference Product Updates

The agency may have some leeway to push for label updates if the reference product remains on the market. Woodcock said Oncology Center of Excellence experts are working to potentially find the evidence necessary to ask manufacturers to voluntarily update labels. Given many combination regimens in oncology rely on older chemotherapies as a base to build treatment, significant changes may be made for clinicians, but Woodcock also warned that effort would be limited.


Jeff Allen, FOCR president and CEO, also said that the agency cannot be expected to act as the labeling steward for all approved drugs. He said there may be a way to prioritize, such as not immediately updating labels for drugs that are no longer used or have been replaced by better alternatives.


Even if the agency completes most of the work, the sponsor still would have to bear the cost of creating and submitting the application package, which remains a difficult burden to overcome. User fees for application supplements were eliminated in FDARA to help lower that hurdle, although it may not be enough of an incentive.  (Also see “Will PDUFA VI Fee Structure Changes Slow Revenue Growth?” – Pink Sheet, 25 Jul, 2016.)


Simpler labeling update efforts also have proven difficult. The agency hired a contractor several years ago to help encourage the conversion of old labels to the new physician labeling rule format (Also see “FDA Wants All Drug Manufacturers To Adopt Highlights Labeling Format” – Pink Sheet, 5 Feb, 2013.), but it did not work as hoped and the contract was cancelled.…