Given these unique logistics and toxicity profiles, the need for novel supportive care and medications, and rapid progression of these technologies toward FDA licensing, academic cellular therapists and transplant programs expressed a desire to apply existing FACT standards and/or create directed guidelines to ensure similar safety measures in this new cellular therapy field. This impetus was seconded by many commercial cell manufacturers, regulatory agencies, and academic entities. With the help of a task force representing FACT, ISCT, American Society for Gene and Cellular Therapy (ASGCT), and Society for Immunotherapy of Cancer (SITC) leadership as well as academicians and cellular therapists from 10 cancer centers, FACT has formulated Standards and an Accreditation Program for IECs, defined as “cells used to modulate, elicit, or mitigate an immune response for therapeutic intent”, including dendritic, natural killer, T or B cells.
FACT Standards address processes, documentation and oversight, not the scientific validity, vector design or actual manufacturing steps for any given cell product. The FACT IEC task force, comprised of FACT medical staff and academic experts in the field, set out to review the primary guidelines present in the Common Standards, verify they were still appropriate, and then add requirements specific to IECs. In addition to standard recommendations for donor workup, apheresis collection, labeling, storage, documentation, and product administration, specific attention and guidance were given to 4 areas (Fig. 1): 1) Location of cell manufacturing: the level of involvement in manufacturing by a clinical site for a given IEC product may vary. Under FACT, programs are responsible only for the steps in which they are involved, e.g., donor workup, collection, and administration but potentially not the manufacturing of the cellular product if it occurs at a 3rd party or commercial laboratory. Despite site of manufacture, however, agreement on how to ensure and verify chain of custody through multiple handoffs from collection until infusion needs to be reached. Programs should ask for documentation of a quality audit or report to ensure that manufacturing by an unrelated party is taking place under appropriate regulatory oversight and following acceptable standards in the field of cellular therapy, bearing in mind that regulatory requirements are minimum requirements at best. 2) Identification and management of Cytokine release syndrome: specific medications and algorithms to manage this are still evolving. Therefore, the Standards do not suggest a specific management strategy but instead suggest that physicians, nurses and other providers at a clinical program have training to detect these complications and demonstrate competency in responding to them, that pharmacy formularies are adequate to treat anticipated toxicities, and that an institution have local guidance for management considerations for all the healthcare team members to access. 3) Coordination and education: given the multiple teams involved with a patient’s product and care, an institution should demonstrate appropriate communication pathways between the many providers involved and an avenue for rapid escalation of care when needed. 4) Data management and oversight: staff should be designated to collect data on product safety, efficacy and clinical outcomes, and these should be reviewed by the IEC program director at least yearly. Data points of interest are still being identified, but use of the CIBMTR Cellular Therapy forms is highly encouraged to allow pooling of data accessible to the entire field.