Re-Thinking Plastics and Viruses
Improvements in culture and cell productivity have paved the way for smaller processes employing single-use equipment. This has pushed demand upward for prepared, ready-to-use liquid media vs. media powders, says Bruce Lehr, director of development at SAFC. “This requires us to support customers logistically, or maintain manufacturing sites that are better aligned with where products are used.”
As discrete components are added to the media or through feeding, bioprocessors must be conscious of not just their concentrations and accurate delivery, but increasingly, their interaction with plastic films from which single-use equipment is fabricated.
As a member of PDA’s single-use taskforce, Stephen Brown of Aptalis has observed an increasing tendency for media suppliers to provide fully constituted, ready-made media in disposable bags. “Too often the data package arriving with that type of media product is not sufficiently thorough, particularly with respect to the interaction between media and bag materials.”
The media itself may be well-characterized, but not the container or its potential chemical contribution. For example, leachables and extractables can interfere with critical cell functions, while the bags themselves may sequester essential lipophilic media components. Thus, due diligence is at least twice as complex with bagged liquid media than for powdered media.
The packaging of liquid media in plastic bags has also changed how bioprocessors view virus safety, particularly with respect to early upstream operations. With a greater emphasis on elimination of upstream contaminants, producers and suppliers are looking further upstream than ever before, to unit ingredient sources. Part of this strategy involves the use of ADC-free components when appropriate, and sourcing only from highly trusted countries and suppliers. Future ingredient suppliers will therefore need to be completely transparent with regard to the sources of their raw materials, and the manner in which they prepare them.
Users are employing (or asking suppliers to apply) such techniques as virus filtration for media, as well as gamma irradiation and high-temperature-short-time, in addition to virus filtration of finished or near-finished product. The point is the elimination of viruses as early in the process—and as far from the patient—as possible.
Life Technologies’ Gautam Choudhary notes a greater emphasis on process safety as biomanufacturers explore ways to reduce risk. In addition to the conventional approaches such as media filtration and pasteurization, “suppliers are scrutinizing raw materials closely, and investing in completely ADC-free manufacturing,” he explained.
Manufacturers also are employing rapid qPCR methods to detect contaminants like mycoplasma and viruses.
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