A view into the challenges and contributions of GMP facilities

The field of regenerative medicine is researching and developing numerous cell-based therapies to address many different medical conditions. In Europe, approved ‘Good Manufacturing Practice’ (GMP) facilities are required to produce cells used in these cell-based treatments to ensure safety and meet quality standards. Dr Mariele Viganò and her colleagues describe the challenges of establishing, maintaining and meeting compliance with EU standards for a GMP facility as well as offer insight to how public GMP facilities contribute to developing future regenerative medicines.

What background and points are discussed?

The initiative by Ospedale Maggiore Policlinico to develop a GMP facility for ATMP production was started in 2000 and received GMP certification in 2007. Dr Viganò and her colleagues note that their center was purpose-built to meet GMP requirements for controlled environments. The building’s layout aims to maximise efficiency by considering the workflow of all ‘life-stages’ of production, manufacturing and quality control. The GMP staff of the Ospedale Maggiore Policlinico have advanced degrees in biology or medicine, yet most still required additional training to ‘transform’ them into pharmaceutical production and quality control specialists. The authors state that the center focuses primarily on developing AMTP addressing unmet clinical needs, supporting phase I, II and III clinical trials and undertaking research to better understand the biology of cell-based therapies. In their discussion about creating and maintaining a GMP facility, Dr Viganò and her colleagues note that quality assurance of the biological products being manufactured raised several issues. Quality assurance staff in hospitals typically focus on ensuring good patient care rather than evaluating if biological products meet pre-defined characteristics. Thus, training hospital quality assurance staff to understand these differences was important and was greatly helped by the cooperation of cell manufacturing staff. GMP facility guidelines require that an “adequate number” of appropriately trained personnel must be employed to cover specific responsibilities and meet production demands. The authors note that finding personnel with experience and specific qualifications was difficult, particularly for cell manufacturing staff with pharmaceutical production training and hospital quality assurance staff qualified to monitor cell-therapy quality control. Production of AMTP in a GMP facility requires that living material and cells must be processed and handled in extremely clean environments, where air quality and equipment cleanliness are continuously monitored. This involves multiple staff dressing rooms with increasing air cleanliness and special ventilation pass-boxes for equipment to transfer in and out of these areas. Finding staff capable of installing, operating, maintaining, and repairing clean-room equipment to meet GMP requirements was challenging and sometimes required service contracts with external companies. The authors note that GMP standards for documentation have required considerable resources to record, monitor and control the numerous details of ATMP production. Integrating these details into hospital data systems also presented difficulties. Production and quality control of AMTP also required addressing several challenges caused by the inherent variability and instability of living cells. The authors remark that risk assessment strategies are very valuable for driving and supporting decisions regarding challenges and other issues their facility encounters.