Handling the different requirements for commercial and investigational MNC collections by apheresis.

BACKGROUND: With the success of chimeric antigen receptor T-cell (CAR-T) and similar cellular-based therapies, the demand for collection of autologous mononuclear cells by apheresis (MNC(A)) from blood by apheresis has increased. From an apheresis technical standpoint, the collection of MNC(A) is relatively straightforward, especially when compared with collection of hematopoietic progenitor cells (HPC(A)). Most of the collection for MNC(A) are performed for the commercial entities, who use the product for manufacturing cellular therapeutics. We have noticed discrepancies in the handling and apheresis processes required by different companies in obtaining essentially the same product (all companies in the study manufacture CAR-T-based products). We have analyzed the MNC collection requirements from all FDA-approved CAR-T cellular products and some investigational products collected at University of Nebraska Medical Center. We identified discrepancies in the process and suggested mitigation strategies. METHODS: Step-by-step analysis of the collection requirements. Review of the current guidelines and recommendations on this issue. RESULTS: Multiple discrepancies in the collection process have been identified, even in the products collected for the same company. Practical approach of satisfying all the requirements based on University of Nebraska Medical Center experience has been suggested. CONCLUSION: The current recommendations from multiple sources were reviewed in discussion.

Comparison of the CMNC and MNC apheresis protocol for the collection of T-cells showed comparable outcome: An observational study in a single centre.

BACKGROUND: An increasing demand for human lymphocytes require an efficient, reliable and reproducible lymphocyte process. Here, we compare the Spectra Optia® CMNC protocol with the Optia MNC platform in unmobilised donor lymphocyte collections. PURPOSE: To establish and compare the feasibility, efficiency, and practicability of the two apheresis protocols. METHODS: Data was collected prospectively from 60 non-cytokine stimulate donors who underwent a total of 64 T-cell collection procedures. Of these, 24 procedures were performed in the CMNC cohort and 40 procedures in the MNC cohort. All donors in the CMNC group were related; all donors in the MNC group were donors from a registry. Donor characteristics, procedure parameters and cellular product content were analysed and compared. RESULTS: Donor characteristics and full blood count results were comparable, except the median white blood cell count, which was higher in the CMNC cohort (6.87 vs. 5.58 ×109 /L, P < .005). This resulted in higher lymphocyte (1.95 vs. 1.57 ×109 /L, P < .009) and CD3+ cell counts (1476 vs. 1060/L, P < .02). A total blood volume processed of 2.0 resulted in i) run time (222 vs. 242 min), ii) product volume (192 vs. 183 ml), iii) platelet content (2140 vs. 1345 ×106 /ml, P < .003). CD3+ CE2 (%): 54.7 vs. 50.4. CONCLUSION: The CMNC and MNC protocols are reliable, efficient and comparable in performance parameters and cell composition of final product, respectively. One advantages of the CMNC protocol is the potential ability to tailor the cell composition of the final product accordingly to demands from cell processing laboratories.

Evaluation of the Spectra Optia apheresis system for mononuclear cell (MNC) collection in G-CSF mobilized and nonmobilized healthy donors: results of a multicenter study.

The Spectra Optia apheresis system is a newer centrifugation-based device that in comparison with the COBE Spectra includes features that enhance procedure automation and usability. In this FDA-approved three-center two-arm observational study we characterized the performance of the Spectra Optia for collection of MNCs and CD34+ cells from nonmobilized and granulocyte-colony stimulating factor (G-CSF) mobilized healthy donors, respectively. There were a total of 15 evaluable subjects in each arm. Key performance indicators included collection efficiency of MNCs/CD34+ cells, product purity and cellular viability. For nonmobilized donors, median MNC collection efficiency, platelet collection efficiency, product hematocrit and granulocyte contamination were 57%, 12%, 4%, and 1.7%, respectively. For mobilized donors, median MNC collection efficiency, CD34+ cell collection efficiency, platelet collection efficiency, product hematocrit and granulocyte contamination were 61%, 77%, 19%, 4%, and 15%, respectively. Average WBC viability in the mobilized products was 99%. There was one severe (grade 3) adverse event related to citrate toxicity. This study demonstrates that the Spectra Optia can be used for safe and efficacious collection of MNCs, and results obtained are in line with expectations on collection efficiency and product characteristics. Adverse events were limited to those that are well documented in the stem-cell mobilization and leukapheresis process. As of the time of this writing, FDA 510(k) approval for use of the Spectra Optia device for MNC collection was achieved in the US based partly on the results of this study.