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Regulatory Focus™ > News Articles > 2020 > 6 > FDA gives Project Renewal update at AACR

FDA gives Project Renewal update at AACR

Posted 24 June 2020 | By Kari Oakes 

FDA gives Project Renewal update at AACR

Generic cytotoxic cancer drugs are a cornerstone of cancer therapy, but their labels may not reflect current best evidence regarding safety and effectiveness. Progress on a pilot FDA effort to modernize labels for these drug was shared by Patricia Keegan, MD, acting associate director for medical policy at the FDA’s Oncology Center of Excellence, at the virtual annual meeting of the American Association for Cancer Research. 
Project Renewal, begun at the end of 2018, had a goal of updating generic chemotherapy labels still in clinical use but without brand name reference products. At the time Project Renewal was kicked off, officials planned and later held six workshops to define the scope of the project and to develop procedures.
Currently, the pilot project to update labeling for cancer drugs approved prior to 2006 is evaluating fluorouracil, cisplatin, capecitabine and daunorubicin. The goal is to update labeling information “by evaluating relevant scientific evidence from the published literature,” said Keegan. To aid in this effort, FDA has tapped participants in Project Socrates, which engages medical oncology, hematology, radiation oncology and pediatric oncology fellows for 1-2 month stints at FDA, where they learn about FDA’s role in drug approval.
In giving some background to the project, Keegan reviewed recent history of FDA labeling regulations. FDA, she said, had always had an expectation that labeling content would be updated over time by manufacturers, as required by FDA’s Physician Labeling Rule (PLR). “Unfortunately," she said, "the expectation that labeling would be updated by drug manufacturers with current information was frequently not met.”
Earlier efforts to maintain updated labels had not been completely effective. Building on yet earlier initiatives, a 2013 voluntary initiative to ensure drugs not subject to PLR labeling requirements would be brought into conformity was terminated because of challenges in implementation, including a lack of subject matter expertise on the part of the contractor charged with the label conversion, with consequent high demand on FDA resources to ensure labels were updated, said Keegan.
Project Renewal also makes use of contractors, but also uses a “broad selection of scientific expertise,” including subject matter experts and fellows to bring the latest scientific evidence to bear on labeling to ensure safe use, said Keegan.  An educational program and tools for use by the evaluation team ensures regulatory standards are adhered to and allows accurate assessment of the quality of the literature used in the effort. The project has also built in interval meetings with contractors and FDA for ongoing feedback and the ability to ask and answer questions in real-time, part of a process of continual re-assessment, she said.
Still, some challenges were identified early. The scope of the mission has evolved to include updates across the entire drug label, said Keegan. Also, assessment for new indications is a complex process, not least because of the complexity of assessing a variety of trial designs for evidence of effectiveness, along with the challenges of integrating information across a variety of publications to achieve a “totality of the evidence” assessment, she said, adding that “Even the current literature leaves holes in our knowledge base of approved drugs.”  
Donald Harvey, PharmD, participated in Project Renewal as a subject matter expert. In discussion with Keegan, he noted, “As a pharmacist, many people in my profession look at labels differently than other professions,” said Harvey, a professor in the departments of hematology and medical oncology, and pharmacology and chemical biology at Emory University, Atlanta, and head of the Winship Cancer Institute’s phase 1 clinical trials unit at Emory. “People don’t think about the fact that drug development does continue past a drug’s approval,” said Harvey, speaking to the importance of ongoing review of literature in updating labels post-approval.
It’s important to update and modernize labeling for these older cancer drugs, noted Harvey: “There’s a reason these drugs are still used. They are still very effective in many, many cancers; cytotoxic therapy is still a backbone in many, many cancer treatments.” He encouraged FDA to ask for cooperation from organizations across the spectrum of cancer research, therapy, and pharmacology. The agency, he said, should address them: “We want you to think carefully and seriously about requests for proposals that will lead to data and science about older drugs – we’ll really be able to use these” in continuing to ensure that these older, yet effective drugs have updated, accurate labeling and indications.

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