The FDA product label is the primary source of information for the safe and effective use of cancer drugs. Product labels can become outdated over time as new information is learned but not added to the product label by the New Drug or Biologics License Application holder, for a variety of reasons. Project Renewal aims to create a collaborative, scientifically rigorous process to review and update several commonly used cancer drug labels.
Project renewal is intended to help inform the provider community responsible for caring for cancer patients. This includes oncologists (MDs), advanced practice providers (APPs), registered nurses (RNs), and pharmacists at community and specialty pharmacies who use FDA product labeling to include the most current information about the drug to inform patient care.
OCE conducted structured interviews with healthcare providers in the oncology community to gain a better understanding of the awareness regarding FDAapproved oncology labeling. Providers were asked what other sources of product information they use and how access to these sources may differ depending on their practice settings. This work informs OCE’s role in contributing to broader FDA efforts to improve the content, access and use of FDA product labeling.
Some older cancer drugs have product labels that are not an optimal format, the Physician Labeling Rule (PLR). In addition to updating content with current scientific evidence, Project Renewal will ensure labels are in PLR and PLLR format; the PLR format was created to allow healthcare providers a consistent location for information that providers need to access, including dosage and administration, adverse reactions, drug interactions, and specific population information.
- Scientific Expert Teams: Research teams are made up of external scientific experts who will review each Project Renewal product label and evaluate available published data to generate a product report containing considerations to revise product labeling with the most up-to-date information.
- Fellows: Oncology Fellows from academic training programs will learn about FDA requirements for drug approval and regulatory science through participation in evaluation of published research and the process of labeling updates. This provides an enhanced ongoing educational experience created by Project Renewal. Fellows will conduct critical evaluation and assessment of published literature on off-label uses and assist in the development of the product report.
- FDA: Product labeling updates require a multidisciplinary team of FDA scientists including oncologists, pharmacologists, statisticians, pharmacists and toxicologists, among others. The FDA team provides guidance and feedback to the external research teams throughout the process. Upon receipt of the final product report, the FDA team will conduct a full independent review of the labeling update recommendations and engage the commercial sponsor to submit a supplemental to an approved New Drug or Biologics License Application to update the product label for format and scientifically supported information on current drug use.
- Reference Listed Drug (RLD) Holders: RLD Holders will submit a supplemental application to FDA and negotiate the final PLR formatted labeling with the appropriate clinical review Divisions at the FDA.
The OCE held five workshops in 2018 to identify and prioritize approximately 40 commonly used oncology products where updated information to reflect current use may be appropriate; these drugs were selected for Project Renewal. Two product labels are currently under evaluation in Project Renewal in 2019. As the process is refined, efficiencies may be created, allowing research teams to evaluate publicly available data for multiple products at one time. The program will be reevaluated after a 3-year pilot phase.
Project Renewal will evaluate product labeling for drugs approved several decades ago, that are not in PLR format or where there is significant off-label use in the U.S. oncology community. Most drugs are important components of standard multi-agent cytotoxic chemotherapy regimens, some of which have curative potential. Project Renewal incorporates a rarely used approach for use published literature to support potential new indications and dosage regimens. The use of published data is acceptable in this context where use is accepted by the community and the conduct of clinical trials may not be feasible (lack of clinical equipoise). The Project Renewal process is not expected to be used for contemporary product approval given the less robust post-marketing safety experience of recently approved drugs and availability of digital records for patient-level datasets collected under prospective clinical protocols and prespecified analysis plans.