Sterility Testing for Hematopoietic Stem Cells.

Over the last two decades, rapid technological advances have led to the wide adoption of cell and gene therapy products for the treatment of a variety of disease states. In this study, we reviewed the literature between 2003 and 2021 to provide a summary of overarching trends associated with microbial contamination in hematopoietic stem cells (HSCs) derived from peripheral blood, bone marrow, and cord blood. We provide a brief background on the regulatory context for human cells, tissues, and cellular and tissue-based products (HCT/Ps) as regulated by the US Food and Drug Administration (FDA), sterility testing expectations for autologous (Section 361) and allogeneic (Section 351) HSC products, and discuss clinical risks associated with the infusion of a contaminated HSC product.

Controls to Minimize Disruption of the Pharmaceutical Supply Chain During the COVID-19 Pandemic.

This article reviews currently available scientific literature related to the epidemiology, infectivity, survival, and susceptibility to disinfectants of Coronaviruses, in the context of the controls established to meet good manufacturing practice (GMP) regulations and guidance, and the public health guidance issued specifically to combat the COVID-19 pandemic. The possible impact of the COVID-19 pandemic on the pharmaceutical supply chain is assessed and recommendations are listed for risk mitigation steps to minimize supply disruption to pharmaceutical drug products. Areas addressed include a brief history of the COVID-19 viral pandemic, a description of the virus, the regulatory response to the pandemic, the screening of employees, the persistence of the virus on inanimate surfaces, cleaning and disinfection of manufacturing facilities, the use of GMP-mandated personal protective equipment to counter the spread of the disease, the role of air changes in viral clearance, and approaches to risk assessment and mitigation.

Risk Assessment Approach to Microbiological Controls of Cell Therapies.

This technology review, written by a small group of pharmaceutical microbiologists experienced in cell therapies, discussed a risk-based approach to microbiological contamination detection and control during gene and cell therapy production. Topics discussed include a brief overview of cell therapies, a risk analysis related to donor selection, cell collection and infectious agent testing, cell transformation and expansion, packaging, storage, and administration, and cell therapy microbial contamination testing and release.

Method Verification Requirements for an Advanced Imaging System for Microbial Plate Count Enumeration.

The Growth Direct™ System that automates the incubation and reading of membrane filtration microbial counts on soybean-casein digest, Sabouraud dextrose, and R2A agar differs only from the traditional method in that micro-colonies on the membrane are counted using an advanced imaging system up to 50% earlier in the incubation. Based on the recommendations in USP <1223> , the system may be implemented in a microbiology laboratory after simple method verification and not a full method validation. The Growth Direct™ System that automates the incubation and reading of microbial counts on membranes on solid agar differs only from the traditional method in that micro-colonies on the membrane are counted using an advanced imaging system up to 50% earlier in the incubation time.

The Application of Noninvasive Headspace Analysis to Media Fill Inspection.

Unlabelled: The results of a proof-of-principle study demonstrating a new analytical technique for detecting microbial growth directly in pharmaceutical containers are described. This analytical technique, laser-based headspace analysis, uses tunable diode laser absorption spectroscopy to nondestructively determine gas concentrations in the headspace of a media-filled pharmaceutical container. For detecting microbial growth, the levels of headspace oxygen and carbon dioxide are measured.