Human granulocyte colony-stimulating factor (GCSF) is produced by biotech laboratories and production facilities for reducing neutropenia duration and sequels in patients with myelosuppressor treatments, among other applications. However, real challenges for these laboratories started in 2015 when the PEGylated-GCSF patent expired, opening alternatives for developing biomanufacturing processes and new applications. Thus, the purpose of this study was to analyze downstream process controls designed to ensure recombinant human GCSF (rh-GCSF) quality and to provide some evidence of the downstream process validation status. Study outcomes proved that the rh-GCSF expression system was stable and chromatographic profiles were reproducible among samples.
Category: <span>Risk Analysis and Management</span>
“Closed system.” The term itself appears deceptively simple. However, the definition of a closed system, its implementation, and its impact on biomanufacturing has been anything but straightforward.
The journey toward implementing closed systems spans over 20 years. The concept of closed systems was introduced in January 2000 with the draft issue of ICH Q7. Since then, other industry guidance documents emerged, defining and supporting process/system closure as a primary means of risk mitigation to meet the baseline requirement of protecting the product, as defined in cGMP.
Presently, global regulatory agencies recognize three distinct definitions of a closed system. These definitions, found in EU Annex 1, EU Annex 2, and the PIC Annex 2A, all focus on product protection where the product is not exposed to the immediate room environment during manufacturing. This is where the journey begins.
The ability to scale a cell culture effectively and efficiently, from lab to manufacturing, is critical to maximizing productivity whilst minimizing the risk of run failures and delays that can cost millions of dollars per month. The task of scaling well, however, is still considered to be a challenge by many upstream scientists, and this can be an exercise in trial and error. Traditionally, scaling has most often been performed using arithmetic in a spreadsheet and/or simple “back of an envelope” calculations. For some, it may even come in the form of support from a team of data scientists using advanced analytical software. This dependency on what some consider to be complex mathematics or statistics has resulted in the common consideration of using just one scaling parameter at a time, one scale at a time.
However, it is difficult to determine easily or optimally, from the start, whether a process successfully transfers across scales based on only one process parameter, at one scale. In this article, we describe the benefits of using a risk-based approach to scaling, and the development of a software scaling tool known as BioPAT® Process Insights for predictive scale conversion across different bioreactor scales. BioPAT Process Insights can be used to consider multiple parameters and across multiple scales simultaneously, from the start of a scaling workflow. We briefly describe how it was used in a proof-of-concept scale-up study to allow a faster, more cost-effective process transfer from 250 mL to 2000 L. In summary, using BioPAT Process Insights, in conjunction with a bioreactor range that has comparable geometry and physical similarities across scales, has the potential to help biopharma manufacturing facilities reach 2000 L production-scale volumes with fewer process transfer steps, saving both time and money during scale-up of biologics and vaccines.
The rapid and seemingly uncontrolled spread of African swine fever (ASF) throughout China and many of its neighboring countries within the last 19 months (August 2018–March 2020) has put the rest of the world on high alert. The geographic distribution of viruses of importation concern, like ASF virus (ASFV), can change very quickly, putting at risk conventional sources of porcine serum and other porcine-derived products used as ingredients in research, the manufacture of biologics, and other biomedical applications. This article reviews the 2019 information from the World Organization for Animal Health (OIE) regarding the presence or absence of eight viruses of importation concern in the swine populations of 30 countries from animal serum-producing regions of the world. Companies importing porcine raw materials for formulation into porcine products – and their customers – should be aware of the geographic location of swine diseases of importation concern. The article also identifies ten adventitious viruses of concern cited in United States Department of Agriculture (USDA) and European Union (EU) regulations that need to be tested for or eliminated through one or more barrier treatments when porcine ingredients are used in the manufacture of biologics.