Over the course of 25 years, the potential therapeutic value of biopharmaceuticals has been realized. One component of the overall safety paradigm for these therapeutic agents is the evolution and execution of viral testing, and it has been an exciting time for those of us involved in it. Participating in several of the viral contamination events that have occurred during this quarter century has proven to be particularly enlightening. Most involved hamster (especially Chinese hamster) cell substrates. This has been somewhat surprising given that biopharmaceuticals are produced in cells derived from a number of different animal species. More recently, however, viral contaminations involving human and monkey cell substrates have also been reported. While considering risk to biopharmaceutical manufacturing processes, it is not unusual to hold the belief that a mammalian production cell is riskier, although this is not appropriate. Even processes involving bacterial fermentation are at risk of viral contamination by the bacteriophage. These agents are not believed to represent a patient safety risk but they can certainly wreak havoc with manufacturing processes utilizing bacterial production cell substrates. Any discussion of viral risk to biopharmaceutical manufacturing should therefore include both cell culture and bacterial fermentation processes, and their associated viral contaminants…
Tag: <span>risk mitigation</span>
The treatment of animal serum by gamma irradiation, for the purpose of mitigating the risk of introducing a pathogen (virus, mollicute, or other microbe) into a cell culture, is a process that has been executed (and perhaps understood) primarily by irradiation contractors utilized by serum manufacturers. The selection of appropriate exposure conditions and irradiation doses is driven by a number of critical factors including: (1) the validation and control of the irradiation process itself; (2) the efficacy of the applied irradiation dose range for inactivating pathogens of interest; (3) determination and control of critical process attributes; (4) the potential impacts of these irradiation dose levels on the serum being irradiated; and finally, (5) the potential impact of irradiated serum on the medicinal product and the associated manufacturing process where serum is ultimately used. In order to increase awareness of these topics throughout the cell culture community, we have addressed these critical factors in the current review…
Biologics Biologics Production Bioreactor Scale-Up Cell & Gene Therapy Cell Lines Fed-Batch Bioreactor Process HEK293 Mammalian Cell Culture Manufacturing Regulatory Viral Reference Materials Viral Vectors
abattoir albumin animal serum animal-derived materials antibody biomedical research blood-derived products calf serum calicivirus cell culture cell medium challenge virus design of efficacy dose mapping fbs fetal bovine serum gamma irradiation heat inactivation isia kgy kilogray microbes mollicute nbcs pathogen reduction product management risk mitigation serum product serum risks spiked serum therapeutic proteins traceability viral reduction whole blood
This article serves as an introduction to a series of papers that are being authored under the sponsorship of the International Serum Industry Association with the purpose of establishing best practices for processes employed in the gamma irradiation of animal serum. It is comprised of a discussion about the role of serum in cell culture and the management of the associated risks. Additional articles in the series will address a number of topics of interest to the cell culture community, including, but not limited to: (1) performance of absorbed dose mapping for irradiators; (2) validation of the efficacy of pathogen reduction during gamma irradiation of animal serum; (3) comparability evaluation of irradiated serum; (4) product management throughout the irradiation process; and (5) ensuring a quality outcome when using gamma irradiation. The intent of the series is to increase awareness of the scientific community regarding the conduct of gamma irradiation and the strengths and limitations of this serum treatment approach for achieving the goals of adventitious agent risk mitigation.
Biologics Biologics Production Bioreactor Scale-Up Cell & Gene Therapy Cell Lines Fed-Batch Bioreactor Process HEK293 Mammalian Cell Culture Manufacturing Regulatory Viral Reference Materials Viral Vectors
abattoir albumin animal serum animal-derived materials biomedical research blood-derived products calf serum cell culture cell medium dose mapping fbs fetal bovine serum gamma irradiation heat inactivation isia nbcs pathogen reduction product management risk mitigation serum risks therapeutic proteins traceability whole blood
Accepting any identified and evaluated risk is “taking a smart risk.” The acceptance decision, before or after mitigation, is a complex and sometimes difficult choice that is based on the information generated during the ICH Q9 quality risk management (QRM) exercise along with many subjective viewpoints impacted by previous experience, knowledge, risk appetite, and bias. This paper provides an approach for understanding and making acceptance decisions centered around the risk-rating methods that define the severity (harm) and uncertainty (likelihood) of the risk’s consequence occurring. It also builds on concepts developed in the first two parts of this QRM series to provide an overall framework for identifying, evaluating, managing, and accepting a wide variety of biopharmaceutical development and manufacturing risks…