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…
Tag: <span>process validation</span>
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…