Managing particulates in cell therapy: Guidance for best practice

Technical Considerations in the Freezing, Low-Temperature Storage and Thawing of Stem Cells for Cellular Therapies

“…In addition to sterility assurance, for products intended for human therapy, there will be additional regulatory requirements including absence of bioactive leachables and other particulates as well as closure integrity during storage [24]. …”

Cell Therapy for Chronic Limb-Threatening Ischemia: Current Evidence and Future Directions

“…Fifteen percentage of all clinical trials worldwide involving cell therapy are industry‐sponsored and the vast majority of the remainder by leading academic centers. Additionally facilities and logistics involved in the development of cell therapy products are becoming more available and less expensive due to increased administration as standard of care or as investigational novel treatment in other diseases . However, development of evidence‐based accepted approaches remains challenging, due to high developmental costs, regulatory hurdles, and batch‐per‐batch product variation.…”

Investigation of particle movement in irregularly shaped channels in inertial fluidics for scale up applications in bioprocessing

“…The manufacturing process of these cell therapies must comply with regulations to ensure efficacy and patient safety. With the growing number of clinical trials, particulate contamination in the final formulation of CT products is raising greater concerns with regards to patient safety [166,172]. Since the manufactured cells are mostly administered intravenously, adverse events such as blood flow occlusion and inflammatory responses introduce serious risks to the recipients [165,216].…”

“…Although microfiltration is a routine step in manufacturing of biologics, it cannot be implemented for cell therapies as cells are much larger with diameters that are above submicron. This distinguishes the manufacturing process for CT manufacturing from that of other biological products [166,175]. therapy products comply with USP<788> Particulate matter in injection [221] which dictates that for large parenteral drug container (>100 mL) the number of 10 µm and 25 µm particles cannot exceed 12 and 2 particles/mL respectively.…”

“…Single-use systems offer attributes such as eliminating the need for washing and sterilization of lot, and boosting the speed for product development in patient-specific or off-the-shelf cell therapy.However, particulates, extractable and leachable materials are inevitably introduced into the final products when single-use systems are deployed[161,167,175,184].While the development of advanced materials that produce less extractables and leachables is underway, establishing particulate-free cell therapy products seems unachievable with current technologies[175]. In particular, in addition to inherent and intrinsic particulates which originate from cell products such as cell debris[217], formulation and packaging, there are unavoidable and extrinsic sources of particulates such as personnel activities and hair[166].Membrane-based filtration is an attractive means of downstream processing due to its ease of implementation. However, there are restrictions on pore size due to the size and sensitivity of cells to shear stress.…”