Manufacturing
GMP Manufacturing & Solutions
GMP, or Good Manufacturing Practices, are a set of regulations applicable to the manufacturing of health product candidates, especially medicines intended for human use, such as UCART product candidates. A company is required to comply with GMP regulations in order to be granted a license from governmental regulatory agencies to manufacture pharmaceutical product candidates. The Manufacturing department takes manufacturing processes established at the R&D level, converts them to GMP, and ensures their deployment with GMP compliant raw materials and environments. The department is responsible for the manufacturing of clinical trial material (“CTM”), making it available for clinical studies and afterwards, and also for the manufacturing of final GMP commercial cellular gene therapy products. The team interacts internally with different departments ranging from development and planning, to regulatory and legal, as well as externally with raw materials contractors or GMP manufacturing contract organizations.
Cellectis Proprietary Manufacturing Process
With more than 5 years of experience in allogeneic CAR-T manufacturing, we have utilized our validated TALEN® gene editing technology and process development capabilities for the scalable manufacture of 5 Universal CAR-T product candidates (UCART). As a result, Cellectis has a quality control system in place for the 3 wholly controlled product candidates cleared by the U.S. Food and Drug Administration (FDA).
We follow Good Manufacturing Practices (GMP), which are a set of regulations and quality standards devised by the FDA for the manufacturing of health product candidates and advanced therapy medicinal products (ATMPs) to help patients – such as our UCART product candidates to treat cancer. In order to do this, our department collaborates with other internal departments and GMP manufacturing contract organizations, to establish reproducible and processes at scale and to ensure their deployment with GMP compliant raw materials, methods, and environments.
Through our manufacturing process, therapeutic UCART product candidates are made from healthy, tested and qualified donor T-cells; unlike autologous CAR-T approaches derived from patient samples. This off-the-shelf approach leads to lower production costs, as we expect that T-cells from one healthy donor and one manufacturing batch could generate hundreds of doses of UCART product to treat hundreds of patients. In addition, our process – powered by TALEN® and our proprietary PulseAgile electroporation technologies – inactivates genes in a highly efficient manner that avoids harming T-cells during processing. As a result, we can manufacture quality UCART products with high yields --and potentially in bulk. We expect that T-cells from one healthy donor, and one manufacturing run of UCART, could be used to create hundreds of doses of product and more when scaling up the process. These efficiencies may not only reduce costs to patients but also lead to competitive gross profit margins.
CELLforCURE is producing clinical batches of UCART123, our first wholly controlled UCART product candidate, to meet the needs of the Phase 1 clinical trial, as part of the development of UCART123 in malignancies, such as acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN).
Manufacturing process
Step 1: Collect peripheral blood from pre-selected healthy donors; isolate the mononuclear cell fraction (PBMCs); freeze the leukopaks.
Step 2: Thaw the frozen cells when ready to begin process; isolate a subtype of T-cells.
Step 3: Combine T-cells with lentiviral vector to add the Chimeric Antigen Receptor (CAR) in the surface of T-cells. This step is called cell transduction.
Step 4: Use our proprietary Pulse Agile® technology to transport the TALEN® into the CAR T-cell to make a precise edit that will delete the T-cell Receptors, source of rejection from the patient immune system.
Step 5: Amplify the amount of gene-edited CAR T-cells using automated bioreactor systems; closed, controlled, and scalable cell culture.
Step 6: Purify the cells to ensure that only gene edited T-cells remain.
Step 7: Fill and label vials of our allogeneic UCART product candidate.
Step 8: Freeze and package the vials so the UCART medicament can be preserved until it is sent to hospitals for patients to receive.
Quality Control: During the manufacturing process (in-process controls) and to characterize the critical quality attributes of the UCART product candidate.