Cell Production Core Facility

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

Major Activity: The mission is to provide support to the NCI Surgery Branch (SB) immunotherapy program under the required regulations that govern cellular aseptic processing facilities. Support is primarily provided by producing the final cell products for all SB clinical trials, validating and onboarding new and improving current cellular therapy manufacturing protocols, scheduling patient treatments with the clinical team. All processes are performed with oversight from SB QA and CC Office of Research Support and Compliance (ORSC). Specific Objectives: Provide support as the cell processing and final product manufacturing group for SB adoptive cellular therapy (ACT) clinical trials. Assess, validate, and onboard new ACT/manufacturing protocols and refine current therapies. Maintain and improve systems to increase the efficiency of cell manufacturing and effectiveness of the therapies in conjunction with the SB research and clinical team to meet the patient and clinical trial needs while operating within compliance with regulatory requirements. The SB Cell Prep Core (ZIC BC 010905) receives patient tumors and blood products for processing which may be used as starting materials for ZIC BC 011569 product manufacturing. These materials are used by the NCI SB researchers in the discovery of patient tumor specific neoantigens and reactive tumor infiltrating lymphocytes (TILs) and as critical materials in all aspects of the SB research program. Once patient specific neoantigens or TILs are identified, a unique patient ACT can be manufactured under cGMP regulations by the CPF core with oversight from the NCI SB QA group. Currently, all final products are generated through a 24-day manufacturing process and are fresh infusion products. The process requires 2 qualified technicians, supervisory oversight, and regular process review by QA. The manufacturing timeline for each patient and overall queue is carefully scheduled with the patient clinical status and anticipation for eligibility. The schedule is managed by Dr. Halas and the clinical team with assistance from senior members of CPF and the product quality control testing (QC) team with consideration to the other processing activities from ZIC BC 010905 occurring in the facility and performed by the CPF staff as well as all facility maintenance and operational oversight. Adjustments to the schedule during the process may be necessary as the clinical status of patients shift and checkpoints to minimize reagent and material use while maximizing potential treatment options and clinical schedules are employed. During the reporting period, 37 cellular therapy manufacturing lots (24 TIL related protocols, 13 genetically modified PBL treatment protocols) were initiated with 33 patients treated. 2 patient treatments consisted of a multi-neoantigen product which required additional resources. All products are manufactured in the cGMP T30 facility on the NIH Bethesda campus with adherence to the regulations for Phase 1 and 2 products. Products are tested for quality control (QC) by Dr. Rachel Beyer's core (NCI SB). All requests for ACT materials for research and tracking needs throughout the branch are received and distributed by CPF. In addition to manufacturing cellular therapies, the Cell Production Core Facility ensures the facility, all equipment, and materials used in manufacturing are meeting cGMP regulations. This requires constant reporting, documentation and review of each processing step, and a log of all materials (biological and raw materials). The core lab also performs routine environmental monitoring of the facility (via services from DLM, STS) and during aseptic processing events. The QA oversight requires a personnel training program that ensures competency and emphasizes the responsibilities and duties of all personnel involved in manufacturing cell therapies in the Surgery Branch. The core lab staff train all new technicians for manufacturing processes under these requirements and undergo annual re-training as well. The facilities, staff, and QMS are audited minimally on an annual basis by external groups or through internal NCI SB QA audits. The success and achievements of CPF for ZIC BC 011569 under the required regulations necessary for patient safety and GMP regulations are dependent on resources to include adequate levels of qualified staff, access to reagents and consumables for manufacturing and testing, regulatory and product oversight (via QA and quality control testing), and multiple internal and external services to ensure the facility, staff and patients are properly protected. These and other resources are needed to efficiently serve the patients eligible for SB clinical trials in a timely manner with the ability to pivot and respond to changes to the clinical schedule and onboard new treatment protocols while remaining in compliance. The key results/achievements related to clinical impact are reported and tracked by the clinical team. The scientific research findings and the outcomes to treatment protocols result in high impact publications (see H. Halas publication lists) which include several members of CPF as authors and acknowledgement of CPF/TIL lab as a critical resources and service. CPF's work and collaboration with the Clinical Center Department of Laboratory Medicine to improve and onboard an NIH wide testing systems was recognized with the NIH Clinical 2024 CEO Awards. This was presented to several members of CPF for a collaboration that spanned ZIC BC 010905 and ZIC BC 011569.