June 26, 2024
Risk Evaluation and Mitigation Strategies (REMS) for Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies Modified to Minimize Burden on Healthcare Delivery System
A Risk Evaluation and Mitigation Strategy (REMS) is a safety program that the Food and Drug Administration (FDA) can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. Because of the risks of cytokine release syndrome (CRS) and neurological toxicities, the following currently approved (listed alphabetically by trade name) BCMA- or CD19-directed autologous CAR T cell immunotherapies are available only through a restricted program under a REMS:
In accordance with section 505-1(g)(4)(B) of the Federal Food, Drug, and Cosmetic Act (FDCA), FDA determined that the approved REMS for these products must be modified to minimize the burden of complying with the REMS on the healthcare delivery system. Currently, information regarding the risks for CAR T cell immunotherapies can be conveyed adequately via the current product labeling, which includes a boxed warning for the risks of CRS and neurological toxicities, and the Medication Guides which are a part of the approved labeling. Thus, the REMS have been modified to remove requirements for educational and training materials. Additionally, the requirement to report adverse events suggestive of CRS or neurological toxicities to the REMS has been removed. Adverse event reporting requirements in accordance with 21 CFR 600.80 are adequate for continued routine safety monitoring for these products.
The goal of the modified REMS is to mitigate the risks of CRS and neurological toxicities by ensuring that hospitals and their associated clinics that dispense the above products are specially certified and have on-site, immediate access to tocilizumab. The REMS for each product (implemented at the time that the original Biologics License Application for each product was approved) requires that a minimum of two doses of tocilizumab must be available on-site for each patient before infusion of the CAR T cell immunotherapy. The currently approved REMS are available at REMS@FDA.
To report suspected adverse events, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Healthcare providers, clinical investigators, patients and caregivers who have questions may contact FDA’s Center for Biologics Evaluation and Research (CBER) at ocod@fda.hhs.gov.
