Viral clearance validation studies evaluate the efficacy of upstream or downstream process steps for clearing (inactivating or removing) potential viral contaminants from biologics process streams. Inactivation steps are designed to render viruses non-infectious, while removal steps achieve actual physical removal of viruses from the process stream. During validation, the efficacy of viral clearance steps is challenged through evaluation of inactivation and removal capacity, both for viruses known to be capable of infecting the manufacturing process (relevant viruses) as well as for worst-case model viruses (i.e., those believed to be most resistant to removal or inactivation). Worst-case viruses are used to challenge the process steps in order to assure that unknown or novel viruses that may be present in the process stream will be adequately cleared. Historically, the parvoviruses have been used as worst-case models for viral clearance studies due to their small size and lack of a lipid envelope. These characteristics are known to challenge removal by viral filtration and inactivation by a variety of physical and chemical means. In the present paper, we examine the literature on removal of viruses by filtration, and inactivation of viruses by heat, ultraviolet light, and gamma radiation. We conclude that for viral filtration, as well as ultraviolet and gamma irradiation, the use of a parvovirus as a worst-case model virus may not adequately assure that all types of viruses will be cleared using these steps…
Tag: <span>process validation</span>
Achieving very high levels of pharmaceutical product quality, particularly for the next generation of biologics, will require proactive use of a broad range of quality and process development tools throughout the therapeutic’s development and manufacturing lifecycle. These tools are most effective when integrated using an expanded form of FDA’s 2011 process validation guidelines. This article explains how process validation can be combined with quality by design (QbD), ICH Q8 design space (DS) and control strategies (CS), process analytical technology (PAT), and quality risk management (QRM) tools to provide a path to manufacturing very high-quality products. The approach establishes clear goals and then proactively builds appropriate control systems during process development to assure continuous control and verification of all manufacturing activities. Prospectively using the tools over the complete manufacturing lifecycle, from preclinical through commercial manufacturing, is particularly important to assure comparability from early product research and development all the way to commercialization. The continued evolution of these quality tools, as well as building new tools, will provide a path for the pharmaceutical industry to reach and maintain Six Sigma levels of product quality…
The treatment of animal serum by gamma irradiation is performed to mitigate the risk of introducing undesired microorganisms (viruses, mollicutes, or other microbes) into a cell culture. Serum manufacturers and end-users utilize irradiation contractors to perform this process. The irradiation process must be validated, which involves establishing the: (A) minimum dose that achieves the required inactivation of the microorganisms of interest; (B) maximum acceptable dose at which the serum still maintains all of its required functional specifications; and (C) process used by the contract irradiator that allows treatment of the serum product within these defined limits. In the present article, we describe the best practices for qualifying the distribution and magnitude of absorbed dose (performance qualification [PQ] dose-mapping) when serum is gamma irradiated. PQ dose-mapping includes the following: (1) documentation of dose distribution characteristics in defined product load configurations for a specified pathway through the irradiator; (2) assessment of the process capability of the defined product load configurations and irradiation pathway for respecting the dose specification for the serum; and (3) development of a method for routine dose monitoring of the irradiation process with the defined product load configurations and the specified irradiation pathway…