Implementation of a configurable laboratory information management system for use in cellular process development and manufacturing.

BACKGROUND AIMS: Regulatory requirements for the manufacturing of cell products for clinical investigation require a significant level of record-keeping, starting early in process development and continuing through to the execution and requisite follow-up of patients on clinical trials. Central to record-keeping is the management of documentation related to patients, raw materials, processes, assays and facilities. METHODS: To support these requirements, we evaluated several laboratory information management systems (LIMS), including their cost, flexibility, regulatory compliance, ongoing programming requirements and ability to integrate with laboratory equipment. After selecting a system, we performed a pilot study to develop a user-configurable LIMS for our laboratory in support of our pre-clinical and clinical cell-production activities. We report here on the design and utilization of this system to manage accrual with a healthy blood-donor protocol, as well as manufacturing operations for the production of a master cell bank and several patient-specific stem cell products. RESULTS: The system was used successfully to manage blood donor eligibility, recruiting, appointments, billing and serology, and to provide annual accrual reports. Quality management reporting features of the system were used to capture, report and investigate process and equipment deviations that occurred during the production of a master cell bank and patient products. CONCLUSIONS: Overall the system has served to support the compliance requirements of process development and phase I/II clinical trial activities for our laboratory and can be easily modified to meet the needs of similar laboratories.

Manufacturing of large numbers of patient-specific T cells for adoptive immunotherapy: an approach to improving product safety, composition, and production capacity.

We have developed an innovative system for ex vivo processing of patient-specific cell products to produce large numbers of T-lymphocytes in support of phase 2 adoptive immunotherapy trials for hematologic malignancies. Extensive efforts were undertaken to close the cell processing system to improve the safety profile of the process and comply with new federal regulations regarding cell and tissue processing. Our results demonstrate that apheresis products can be processed in a closed system (Cytomate) with similar yields (approximately 4 x 10(9) mononuclear cells/apheresis) and recoveries (approximately 60% of starting mononuclear cells) to manual cell processing. Cells processed with this system could be cryopreserved for up to 5 months without significant loss of recovery or viability. Additionally, we have evaluated the use of gas permeable bags and developed perfusion bioreactor protocols in which T cells can be rapidly produced in excess of 10(10) viable cells per liter of culture. Using similar methods for upfront processing, we have also developed methods for positive selection and ex vivo culture of CD4+ T cells that result in 200 to 800-fold expansion of fresh or cryopreserved samples. T cells produced in these systems were shown to retain activation-induced cytolytic capability and TH1/TH2 cytokine production as a measure of biologic potency. These new methods allow for more efficient production multiple patient-specific products by satisfying the basic tenants of safety and efficacy required for early phase clinical trials of cell products.