Gamma Irradiation of Animal Serum: An Introduction
by Rosemary J. Versteegen, PhD, Mark Plavsic, PhD, DVM, Raymond Nims, PhD, Robert Klostermann, and Karl Hemmerich
Volume 15, Issue 2 (Summer 2016)
This article serves as an introduction to a series of papers that are being authored under the sponsorship of the International Serum Industry Association with the purpose of establishing best practices for processes employed in the gamma irradiation of animal serum. It is comprised of a discussion about the role of serum in cell culture and the management of the associated risks. Additional articles in the series will address a number of topics of interest to the cell culture community, including, but not limited to: (1) performance of absorbed dose mapping for irradiators; (2) validation of the ef ficacy of pathogen reduction during gamma irradiation of animal serum; (3) comparability evaluation of irradiated serum; (4) product management throughout the irradiation process; and (5) ensuring a quality outcome when using gamma irradiation. The intent of the series is to increase awareness of the scientific community regarding the conduct of gamma irradiation and the strengths and limitations of this serum treatment approach for achieving the goals of adventitious agent risk mitigation...
Citation:
Versteegen R, Plavsic M, Nims R, Klostermann R, Hemmerich K. Gamma irradiation of animal serum: an introduction. BioProcess J, 2016; 15(2): 5–11. http://dx.doi.org/10.12665/J152.Versteegen.
Posted online July 30, 2016.
Gamma Irradiation of Animal Serum: Validation of Efficacy for Pathogen Reduction and Assessment of Impacts on Serum Performance
by Mark Plavsic, PhD, DVM, Raymond Nims, PhD, Marc Wintgens, and Rosemary J. Versteegen, PhD
Volume 15, Issue 2 (Summer 2016)
The treatment of animal serum by gamma irradiation, for the purpose of mitigating the risk of introducing a pathogen (virus, mollicute, or other microbe) into a cell culture, is a process that has been executed (and perhaps understood) primarily by irradiation contractors utilized by serum manufacturers. The selection of appropriate exposure conditions and irradiation doses is driven by a number of critical factors including: (1) the validation and control of the irradiation process itself; (2) the efficacy of the applied irradiation dose range for inactivating pathogens of interest; (3) determination and control of critical process attributes; (4) the potential impacts of these irradiation dose levels on the serum being irradiated; and finally, (5) the potential impact of irradiated serum on the medicinal product and the associated manufacturing process where serum is ultimately used. In order to increase awareness of these topics throughout the cell culture community, we have addressed these critical factors in the current review...
Citation:
Plavsic M, Nims R, Wintgens M, Versteegen R. Gamma irradiation of animal serum: validation of efficacy for pathogen reduction and assessment of impacts on serum performance. BioProcess J, 2016; 15(2): 12–21. http://dx.doi.org/10.12665/J152.Plavsic.
Posted online July 30, 2016.
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Using a Patient-Centered Risk-Benefit Structure and Appropriate Manufacturing Practices (AMPs) for Successfully Developing and Manufacturing Effective Cell Therapy Products
by Mark F. Witcher, PhD
Volume 15, Issue 2 (Summer 2016)
The development and manufacturing of advanced breakthrough cell therapies presents a wide variety of complex challenges that include:
• delivering the medical science, from research all the way through product development and clinical testing, to the patient population;
• understanding and defining the product’s modes of activity and the cell’s attributes necessary to attain therapeutic benefit and safety;
• overcoming significant manufacturing, logistical, and cost of goods issues associated with using attachment-dependent bioreactor systems; and
• defining product release challenges associated with rapidly delivering an effective product to the patients.
Successfully meeting these challenges requires new lifecycle development and manufacturing approaches based on understanding a complete set of patient goals that go beyond safety to include both efficacy and the patient’s ability to access the therapy. For many of these complex therapies, safety is perhaps the easiest of the three goals. Establishing both product and process comparability from the very beginning is required to assure the product successfully makes it through the product development sequence. The new approaches must also be based on appropriate manufacturing practices (AMPs) over the product’s lifecycle, from the earliest research phases, process development, clinical manufacturing, and finally to commercial manufacturing, to keep the development effort focused and efficient. This paper describes approaches built on product and process lifecycle paradigms that emphasize both product and process validation to assure product comparability over the entire manufacturing lifecycle, from research through commercial production. Methods previously used for chemical entity pharmaceuticals, and even protein biopharmaceuticals, are not adequate for cellular therapeutics being developed from recent advances in medical science’s understanding of complex therapeutic pathways. The safety and efficacy of cell-based therapies may be impacted by subtle and difficult-to-measure changes in the performance or behavior of the manufacturing process. In addition, the patient’s access to cell therapies is heavily impacted by the complexity and cost of developing adherent bioreactor technologies required to expand and/or modify therapeutic cells...
Citation:
Witcher MF. Using a patient-centered risk-benefit structure and appropriate manufacturing practices (AMPs) for successfully developing and manufacturing effective cell therapy products. BioProcess J, 2016; 15(2): 22–9. http://dx.doi.org/10.12665/J152.Witcher.
Posted online July 30, 2016.
Preformulation Studies and Physicochemical Properties of Intranasal Low Sialic Acid Erythropoietin
by A. Muñoz-Cernada, PhD, J. Cardentey-Fernández, L. Paradina-Fernández, L. Rojas-del Calvo, T. Figueredo-Gonzáles, D. Rodríguez-Abreu, M. Fernández-Cervera, PhD, I. Sosa-Testé, PhD, and D. Amaro-González, PhD
Volume 15, Issue 2 (Summer 2016)
Intranasal low sialic acid erythropoietin (Neuro-EPO) is a non-hematopoietic molecule that shows neuro-protective activity in some rodent models of brain ischemia. The protein formulations are susceptible to a loss of stability due to formulation, processing, and storage. The aim of this study was to perform formulation analyses of Neuro-EPO to achieve acceptable stability. Experiments were done to assess the compatibility of Neuro-EPO with selected excipients: benzalkonium chloride (BAC) preservative, sodium chloride (NaCl), and hydroxypropyl methylcellulose (HPM) K4M polymer. Instabilities were induced by creating thermal stress conditions (25 ± 2°C). Protein degradation was measured using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)/Western blot, reversed-phase high-pressure liquid chromatography (RP-HPLC), and size-exclusion HPLC (SE-HPLC). Neuro-EPO excipient compatibility tests showed instabilities with BAC, which seemed to be related to protein aggregation. Non-preserved formulations maintained a biological activity similar to that observed with the formulation preserved...
Citation:
Muñoz-Cernada A, Cardentey-Fernández J, Paradina-Fernández L, Rojas-del Calvo L, Figueredo-Gonzáles T, Rodríguez-Abreu D, Fernández-Cervera M, Sosa-Testé I, Amaro-González D. Preformulation studies and physicochemical properties of intranasal low sialic acid erythropoietin. BioProcess J, 2016; 15(2): 45–51. http://dx.doi.org/10.12665/J152.Amaro.
Posted online July 30, 2016.
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