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Pink Sheet – US FDA Looks To Proactively Update Old Generic Drug Labels Under Pilot

Pink Sheet – US FDA Looks To Proactively Update Old Generic Drug Labels Under Pilot

Executive Summary

Concept mentioned during Gottlieb’s ‘star’ turn at Davos may sound similar to now-withdrawn generic labeling rule, but actually appears based on a proposal from the Friends of Cancer Research to get current clinical guidelines reflected on labels.

The US FDA is interested in establishing a system where it can more easily drive generic labeling updates, rather than wait for sponsors to act independently.


Commissioner Scott Gottlieb said Jan. 26 during a panel at the World Economic Forum in Davos, Switzerland that the agency is looking to “initiate proactive updates on old generic drug labels.”


The concept may sound akin to the now-withdrawn generic labeling rule, but actually resembles a new idea that could offer a similar result.


Indeed, it appears FDA was not willing to give up on efforts to incorporate new data into generic labels that usually remain largely static. Among the problems with older generics, including in instances where the reference product has been withdrawn, are that labeling cannot be easily updated.


The concept described in Gottlieb’s remarks appears to resemble a “straw man” paper from the Friends of Cancer Research which outlined a system that would allow FDA to update the labels with new data, as well as correct misleading prescribing instructions.


Under the FOCR proposal, FDA would be able to identify products on the market at least 15 years whose labels are missing critical information or other problems. After working with stakeholders to review the relevant postmarketing data, the agency would invite sponsors to submit a supplemental ANDA and make the labeling change, if warranted. (Also see “Labeling Updates For Old Drugs Could Be Faster Under Streamlining Proposal” – Pink Sheet, 28 Nov, 2017.)

It appears from Gottlieb’s comment and an agency policy document that FDA may have embraced the concept, although FDA did not sign on to the paper when it was released.


The agency also seems interested in becoming the primary driver of labeling changes, unlike under the proposed generic labeling rule, where sponsors had the power to unilaterally change them. FDA wrote in its 2018 Strategic Policy Roadmap that it would “launch a new pilot initiative” to create a structure allowing it “to have its own capacity to more routinely update old generic drug labels with new safety and efficacy information.”


Jeff Allen, FOCR president and CEO, told the Pink Sheet that the pilot project will be a “good first run at trying to enhance postmarket data development and collection” and hopefully add some incentive for doing it well.


The generic labeling rule met widespread opposition from industry when it was issued in 2013. Industry argued that the agency should approve labeling changes before they are made because it has access to the most data. (Also see “Generic Labeling: FDA Ponders Global Process Uniformity” – Pink Sheet, 27 Mar, 2015.)


Generic and brand industry trade associations offered a counterproposal that would have required FDA approval of all safety-related label changes before they were implemented once the first generic had reached the market. (Also see “Label Change Proposal From GPhA, PhRMA Makes FDA Responsible For Timing” – Pink Sheet, 20 Feb, 2015.)


FDA officially withdrew the proposed rule in September 2017. (Also see “Generic Labeling Rule Dies In Latest Reg Agenda, But Electronic Labeling Is Reborn” – Pink Sheet, 14 Dec, 2017.)

Clinical Guidelines Can Be Added To Labels, Gottlieb Says

Gottlieb also suggested during the panel discussion, which was focused on precision medicine, that clinical guidelines could become part of drug labels outside the opioid context.


He said that among the challenges with the targeted treatments is ensuring the associated data reaches providers. Proactively updating labels and incorporating clinical guidelines could better ensure the data influences treatment decisions.


“We do have the ability, the legal authority, if there are clinical guidelines developed by expert groups … to incorporate that into drug labeling and then it can become part of prescribing recommendations that we give,” he said.


Gottlieb already has suggested that clinical guidelines on dosing could be incorporated into opioid labels and used to dictate packaging requirements. Ideally, the changes would better control opioid dispensing and potentially reduce abuse and misuse. (Also see “Opioid Packaging Standards Could Emerge From Dosage Guidelines in Labeling” – Pink Sheet, 11 Dec, 2017.)

Gottlieb’s ‘Star’ Turn

Gottlieb’s profile at the Davos meeting was heightened during a dinner President Trump had on Jan. 25 with European business leaders.


During the introductory remarks, Novartis AG CEO Vasant Narasimhan said, “We’re really pleased with the tax reform, but also very pleased with the great progress being made at FDA. We believe you have a great leadership team there, and they’re doing all the right things to accelerate innovation.”


Trump replied, “Scott is great, and Alex [Azar, the newly-confirmed HHS secretary] is great. You know, Alex is just starting, and he’s highly respected. So that’s fantastic. Scott Gottlieb, as you know, is a star.”


Narasimhan said, “He is a star. And I think his vision for tobacco and trying to … reduce the use of tobacco around the world is also very inspiring.”

More Combination Product Policy Expected

FDA’s talk of creating a system for updating generic labels is one of several issues that could affect the space that are mentioned in the 2018 policy roadmap.


The agency also expects to continue its work streamlining the assessment process for generic drug-device combination products in the hopes of promoting “more efficient market entry,” according to the roadmap.


That may include a change in the agency’s approach to the backbone of the generic drug market: the Hatch-Waxman Act.


In its mention of the upcoming policy on combination products, FDA added that it would “develop new guidance to address and modernize the FDA’s current interpretation and adoption of Hatch-Waxman.”


The agency added in the document that while the approach outlined in Hatch-Waxman “has worked well for many years, as part of our roadmap we will take new steps to make sure this framework continues to support the interests of patients.”


FDA did not offer additional detail on the statement, telling the Pink Sheet that “the agency will communicate publicly as we are able to share additional information about guidances and policies mentioned in the roadmap.”


Some potential changes already have been discussed, including allowing more flexibility to rely on a broader data sets for complex product assessments, in addition to bioequivalence and bioavailability data when necessary (Also see “Complex Generics May Be Part Of White House Drug Pricing Response” – Pink Sheet, 22 Jun, 2017.), as well as allowing some device variations to ease the burden on generic entry. (Also see “Generic Combination Products May Be Permitted Delivery Device Variations” – Pink Sheet, 4 Jun, 2017.)


Complex product sponsors also can conduct pre-submission meetings with FDA to gain advice on approval requirements as part of the 2017 generic drug user fee reauthorization. (Also see “Complex ANDAs To Be Allowed Pre-Submission Product Meetings” – Pink Sheet, 24 Oct, 2016.)


The focus on generics is part of Gottlieb’s priority that FDA encourage competition and potentially help lower drug prices. (Also see “Gottlieb Places Drug Pricing Out Front In First Speech To US FDA Staff” – Pink Sheet, 16 May, 2017.)


FDA’s policy roadmap also includes initiatives focused on new drugs, advanced manufacturing and biosimilars. (See sidebar above.)…