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>viral inactivation</span>
An effective disinfection program is an essential component of a pharmaceutical/biopharmaceutical manufacturer’s contamination control strategy. A good disinfection program can help prevent microbial or viral contamination of the manufactured product, further ensuring product safety for patients. The term disinfection is often used interchangeably with cleaning, but the purpose of disinfection is quite different from that of cleaning. Disinfection of a surface will result in inactivation of infectious agents such as bacteria, fungi, and viruses, whereas cleaning a surface removes soil, debris, and other residues.
In this paper, we review the efficacy data for low and high pH inactivation of viruses in solutions (i.e., liquid inactivation) and discuss the mechanisms of action and the impact of temperature and treatment time, as these are the primary determinants of inactivation efficacy, besides pH, for different viruses. Only enveloped viruses were considered for low pH inactivation, as the literature concerning low pH inactivation of non-enveloped virus is not extensive and low pH is not considered to be an effective inactivation approach for most non-enveloped viruses. We conclude that for low pH treatment of enveloped viruses, and high pH treatment of both enveloped and non-enveloped viruses, an enteric flavivirus such as bovine viral diarrhea virus represents a worst-case model virus…