Batch processing has long been the predominant bioprocessing paradigm, both up- and downstream. Bioprocessing fluids are processed incrementally, piped as a bolus or transferred via vessels from one process and piece of equipment to the next. This continues to work well, including a number of technological advances resulting in improvements that continue to make bioprocessing more efficient. Upstream and overall process yields are essentially doubling about every five years, with this largely driven by improved cell lines, expression systems and genetic engineering, culture media, and equipment. Among the technologies now gaining increasing adoption and market share for biopharmaceutical manufacture is continuous (bio) processing, with perfusion currently the leading technology, in terms of adoption. The use of incremental, one-step-at-a-time, classic batch processing in biopharmaceutical manufacture is different than most other major products manufacturing and high-tech industries, where processing is generally more continuous. In this context, the move toward more continuous processing in manufacturing is a common characteristic of industries starting to reach maturity. Continuous processing is exemplified by assembly lines, and petroleum refining with processing involving a rather continuous flow of the material being manufactured from one unit operation to the next. Continuous processing generally follows and eventually replaces incremental manufacturing…
Tag: <span>downstream bioprocessing</span>
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…