Experience of contamination during autologous cell manufacturing in cell processing facility under the Japanese Medical Practitioners Act and the Medical Care Act

Abstract

Cell therapy and regenerative medicine technologies require strict cell manufacturing procedures to be defined and addressed. Maintenance of the aseptic environment is critical to preclude extrinsic contamination risks, similar to conventional pharmaceutical manufacturing. However, intrinsic contamination risks exist in all cell manufacturing processes owing to the use of cells as the raw materials that cannot be sterilized, thus giving rise to the primary and secondary risks of cell contamination and cross-contamination, respectively. Analysis of contamination risks was conducted on experienced batches (29,858 batches) for the production of immune cells derived from autologous blood mononuclear cells under the Medical Practitioners Act and the Medical Care Act in Japan. From these batches, 0.06% (18 cases) of contamination occurred, representing low probability of contamination incidence during cell processing. Almost all the causes of these contaminations were regarded to be from the collected blood (intrinsic contamination), and subsequent cross-contaminations were prevented, considering that the secondary contamination risk can be reduced by adequate managements of operational procedures for changeover in aseptic environment.

Keywords: Autologous immune cells; Cell manufacturing; Cell processing facility; Incidence of contamination; Intrinsic contamination.

Fig. 1

Three cell processing rooms in the facility included the operating areas (cleanliness ISO class 7), coupled with anterior/posterior buffer rooms, isolated from the outside by a clean corridor with a changing room (cleanliness ISO class 8). There were a total of 18 aseptic areas (cleanliness ISO class 5).

Fig. 2

Six BSCs, were used as the aseptic areas for operation in each cell processing room. A centrifuge, four CO₂ incubators, and a BSC were used by one operator as an individual operating area. The flow line for each individual operating area was isolated from the common flow line.

Fig. 3

Each flow line in the operating area was designed not to cross each other, and the other operators could not approach the area of the operator that had processed the cells at the BSC. The changeover process of each operating area was carried out after disinfection.