Cell-based therapies have gained prominence as effective approaches to develop biological treatments for tissue and organ damage. Among these, Human Mesenchymal Stem Cells (hMSCs) are vital and categorized as Cell-Based Therapeutic Medicinal Products (CTMPs). To ensure the safety and effectiveness of hMSCs, a stringent Microbiological Quality Control Program (QCP) is imperative.
The Importance of Microbiological Control
As the manufacturing process involves extended ex vivo expansion, the risk of microbial contamination rises, potentially compromising product safety and quality. Contaminated CTMPs can lead to severe patient reactions, underlining the need for a robust QCP. This program focuses on maintaining aseptic conditions, following Good Manufacturing Practice (GMP) rules to prevent contamination and ensure patient safety.
Comprehensive Quality Control
The QCP covers the entire production process, from selecting cell types and source materials to reagents, intermediate products, and the final CTMP. Key factors under scrutiny include bacterial, fungal, and mycoplasma contamination, as well as bacterial endotoxin levels. Each analytical procedure adheres to pharmacopoeia standards, regulatory guidelines, and International Conference on Harmonization (ICH) recommendations.
Ensuring Sterility – Sterility Test
The sterility test is crucial to validate medical products’ safety by confirming their freedom from viable microorganisms. Various methods, such as membrane filtration and direct inoculation, are employed. These involve subjecting samples to conditions conducive to microbial growth and observing for any growth. Absence of visible growth indicates sterility, while microbial growth triggers further identification and assessment.
Tackling Bacterial Endotoxins
Bacterial endotoxins, found in Gram-negative bacteria, pose risks due to their biological activity. The Limulus Amebocyte Lysate (LAL) assay, utilizing blood cells from horseshoe crabs, is commonly employed. Methods like the gel clot, turbidimetric, and chromogenic methods enable accurate bacterial endotoxin testing, ensuring products are devoid of harmful endotoxins that can induce adverse reactions.
Detecting Mycoplasma Contamination
Mycoplasmas, tiny bacteria lacking a cell wall, can contaminate cell cultures, affecting research outcomes and product quality. Polymerase Chain Reaction (PCR) stands out among mycoplasma detection methods for its sensitivity. This method amplifies mycoplasma DNA in samples, indicating contamination if amplification occurs.
The implementation of a Microbiological QCP is paramount in guaranteeing the safety and quality of cell-based therapies like hMSCs. By adhering to strict control measures, the risk of contamination is minimized, maintaining patient well-being throughout the production and administration process.
Gálvez P, Clares B, Bermejo M, Hmadcha A, Soria B. Standard requirement of a microbiological quality control program for the manufacture of human mesenchymal stem cells for clinical use. Stem Cells Dev. 2014 May 15;23(10):1074-83. doi: 10.1089/scd.2013.0625. Epub 2014 Feb 20. PMID: 24417334; PMCID: PMC4015505.