The manufacturing and delivery of cell therapies share similar attributes of processing which distinguishes them from pharmaceutical or biopharmaceutical products. They require end-to-end visibility that ensures chain of custody, identity, and condition.

This impacts various aspects of the process including the quality management, LIMS and MES solutions leveraged in these organizations. In this blog we discuss the unique requirements.

Quality Management System

With Cell Therapy manufacturing, quality management processes and procedures, supported by systems, should be established early to ensure a secure, documented lifecycle management for SOPs, work instructions and manufacturing documentation.

Processes for manufacturing incidents, non-conformance and deviations, corrective action, audits and preventative action, change control, risk and mitigation, and training and personnel qualification management all fall under the Quality Management System.

Quality Control LIMS

The typical cell therapy manufacturing process includes tens of ‘in process’ sampling points per batch as well as final product testing, and batch specific and general environmental monitoring and sampling.

QC testing of incoming materials also needs to be performed and documented. Initially sample and test result management may be handled manually on paper, however, it will rapidly require electronic systems support as the number of patients (and batches) grows. Many mature manufacturing QC LIMS and Environmental Monitoring (EM) commercial solutions exist that can address the needs in this area. However, it should be noted that EM operations and workflows are unique and usually require specific solutions complementary to standard LIMS solutions.

Manufacturing Execution System

Manufacturing shop floor needs have typically been accommodated via paper and manual processes through early clinical. Going forward, systems will be needed to offer more accurate modeling of the manufacturing process for different product lines along with resource (people, equipment, shop floor) requirements and execution times so that finite capacity planning can be performed. The resultant models are used to provide electronic detailed production schedules across product orders.

Warehouse management capabilities will be needed to support site specific receipt, storage, and subsequent kitting and batch record capture of issued materials (if not handled within the ERP solution).

Implementation of electronic batch records (EBR) may also be considered but should be assessed relative to the maturity of the manufacturing process. Some of the key benefits to EBR implementation include the ability to review by exception and the availability of electronic data for process development use. Modern EBR systems are certainly easier to adjust but the manufacturing process must be stable enough to warrant the time and effort that will be expended in development and particularly validation.

There are many commercial MES solutions in the marketplace. Most cover the range of capabilities described above. Many have a specific focus on pharmaceutical manufacturing with consulting resources who are familiar with the pharma domain. However, as noted earlier, cell therapy processes are somewhat unique, smaller scale, multiple batches, and employ limited process automation so some of the solution capabilities may not be directly applicable. The MES space has lacked in investment for a period, but there appears to be renewed interest in revamping the technologies. Flexibility to deal with changes and user interface usability should be high on the list of evaluation considerations.

Summary

Cell Therapy manufacturing requires unique system requirements relative to a QMS, LIMS, and MES. Processes for manufacturing incidents, non-conformance and deviations, corrective action, audits and preventative action, change control, risk and mitigation, and training and personnel qualification management all need to be considered.

Given the nature of Cell Therapy manufacturing, it requires tens of ‘in process’ sampling points per batch as well as final product testing, and batch specific and general environmental monitoring and sampling. Additionally, QC testing needs to be performed on incoming materials and documented.

There are also unique manufacturing execution system needs for Cell Therapy manufacturing as well as warehouse management needs and the potential utilization of electronic batch records.

Why It Matters to You

Given the personalized nature of cell therapies, the quality management aspect also entails a certain degree of special considerations. In this blog we discussed:

• The specific processes and unique requirements for a Quality Management System.
• What is needed relative to a Quality Control LIMS solution.
• The unique needs of a Manufacturing Execution System in this environment.