Utility of routine evaluation of sterility of cellular therapy products with or without extensive manipulation: Best practices and clinical significance

Cytotherapy. 2018 Feb;20(2):262-270. doi: 10.1016/j.jcyt.2017.11.009. Epub 2017 Dec 12.

Abstract

Background: We analyzed the results of routine sterility testing performed in our center over the last 10 years, in the context both hematopoietic stem cell transplantation (HSCT) and Advanced Therapeutic Medicinal Products (ATMPs).

Methods: For sterility tests 14-day cultures were performed in culture media detecting aerobic and anaerobic microorganisms.

Results: In this study, 22/1643 (1.3%) of apheretic products for autologous or allogeneic HSCT were contaminated, whereas 14/73 bone marrow (BM) harvests (17.8%) were positive. In 22 cases, the contaminated HSCs were infused to patients, but there was no evidence of any adverse impact of contamination on the hematologic engraftment or on infections. Indeed none of the five positive hemocultures detected in patients following infusion could be linked to the contaminated stem cell product. Our Cell Factory also generated 286 ATMPs in good manufacturing practice (GMP) conditions since 2007 and all final products were sterile. In three cases of mesenchymal stromal cell expansions, the starting BM harvests were contaminated, but the cell products at the end of expansion were sterile, presumably thanks to the presence of an antibiotic in the culture medium.

Discussion: The decreased rate of contamination of cell harvests observed with time suggests that routine sterility testing and communication of the results to the collecting centers may improve clinical practices. Furthermore, we recommend the use of antibiotics in the medium for ATMP expansion, to decrease the likelihood of expanding microorganisms within clean rooms. Finally we discuss the costs of sterility testing of ATMPs by GMP-approved external laboratories.

Keywords: advanced therapeutic medicinal products; cost analysis; hematopoietic stem cell transplantation; microbial contamination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Component Removal
  • Cell- and Tissue-Based Therapy / methods*
  • Culture Media
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Sterilization / economics
  • Sterilization / methods*
  • Time Factors

Substances

  • Culture Media