Viral clearance by flow‐through mode ion exchange columns and membrane adsorbers

Miesegaes, George; Lute, Scott; Read, Erik K.; Brorson, Kurt

doi:10.1002/btpr.1832

Cited by 37 publications

(18 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Viral clearance in continuous chromatography in theory should not be affected by the configuration of the lines, the continuous flow scheme, the number of control units, variations in line, and switching valve configurations, etc. As seen previously in protein A (Lute and Brorson, ; Lute et al, ; Miesegaes et al, ; Zhang et al, ) and ion‐exchange (Miesegaes et al, ; Norling et al, ) chromatography systems, resin age generally does not impact viral clearance. In fact, the cyclical nature of load and elution in continuous chromatography systems is also a property of columns run in batch mode over a long product campaign.…”

Section: Viral Clearancesupporting

confidence: 61%

Adapting viral safety assurance strategies to continuous processing of biological products

Johnson

Brown

Lute

et al. 2016

Biotech & Bioengineering

View full text Add to dashboard Cite

There has been a recent drive in commercial large-scale production of biotechnology products to convert current batch mode processing to continuous processing manufacturing. There have been reports of model systems capable of adapting and linking upstream and downstream technologies into a continuous manufacturing pipeline. However, in many of these proposed continuous processing model systems, viral safety has not been comprehensively addressed. Viral safety and detection is a highly important and often expensive regulatory requirement for any new biological product. To ensure success in the adaption of continuous processing to large-scale production, there is a need to consider the development of approaches that allow for seamless incorporation of viral testing and clearance/inactivation methods. In this review, we outline potential strategies to apply current viral testing and clearance/inactivation technologies to continuous processing, as well as modifications of existing unit operations to ensure the successful integration of viral clearance into the continuous processing of biological products. Biotechnol. Bioeng. 2017;114: 21-32. © 2016 Wiley Periodicals, Inc.

show abstract

Section: Viral Clearancesupporting

confidence: 61%

Adapting viral safety assurance strategies to continuous processing of biological products

Johnson

Brown

Lute

et al. 2016

Biotech & Bioengineering

View full text Add to dashboard Cite

show abstract

“…Virus particles have been commonly removed via AEX chromatography in flow‐through mode . Because the ability of CEX chromatography to remove virus particles in overloaded mode was demonstrated in the present study, all major impurities in mAb preparation, including HMWS, HCP, and virus particles, may be removed via a single session of CEX chromatography in overloaded mode.…”

Section: Discussionmentioning

confidence: 83%

Cation exchange chromatography performed in overloaded mode is effective in removing viruses during the manufacturing of monoclonal antibodies

Masuda

Tsuda

Hashikawa-Muto

et al. 2019

Biotechnology Progress

View full text Add to dashboard Cite

Viral safety is a critical concern with regard to monoclonal antibody (mAb) products produced in mammalian cells such as Chinese hamster ovary cells. Manufacturers are required to ensure the safety of such products by validating the clearance of viruses in downstream purification steps. Cation exchange (CEX) chromatography is widely used in bind/elute mode as a polishing step in mAb purification. However, bind/elute modes require a large volume of expensive resin. To reduce the production cost, the use of CEX chromatography in overloaded mode has recently been investigated. The viral clearance ability in overloaded mode was evaluated using murine leukemia virus (MLV). Even under high‐load conditions such as 2,000 g mAb/L resin, MLV was removed from mAb solutions. This viral clearance ability was not significantly affected by resin type or mAb type. The overloaded mode can also remove other types of viruses such as pseudorabies virus and reovirus Type 3 from mAb solutions. Based on these results, this cost‐effective overloaded mode is comparable to the bind‐elute mode in terms of viral removal.

show abstract

“…Through a Design of Experiments study, Miesegaes et al performed a head‐to‐head comparison of viral clearance efficiency of AEX membranes and columns with multiple membranes and resins. They found that clearance of the three tested model viruses is largely comparable and effective …”

Section: Scientific and Technology Considerationsmentioning

confidence: 98%

“…AEX separation can be achieved utilizing traditional resin‐based packed‐bed columns or with chromatographic membranes. AEX membranes have become widely utilized in the industry due to their high load capacities, greater flow rates, reduced processing time, disposability, and lower buffer consumption . Several authors have demonstrated robust membrane‐based clearance at neutral pH and low salt buffer conditions .…”

Section: Scientific and Technology Considerationsmentioning

confidence: 99%

Suitability of a generic virus safety evaluation for monoclonal antibody investigational new drug applications

Sipple

Nguyen

Patel

et al. 2019

Biotechnology Progress

View full text Add to dashboard Cite

Biologics produced from CHO cell lines with endogenous virus DNA can produce retrovirus‐like particles in cell culture at high titers, and other adventitious viruses can find their way through raw materials into the process to make a product. Therefore, it is the industry standard to have controls to avoid introduction of viruses into the production process, to test for the presence of viral particles in unclarified cell culture, and to develop purification procedures to ensure that manufacturing processes are robust for viral clearance. Data have been accumulated over the past four decades on unit operations that can inactivate and clear adventitious virus and provide a high degree of assurance for patient safety. During clinical development, biological products are traditionally tested at process set points for viral clearance. However, the widespread implementation of platform production processes to produce highly similar IgG antibodies for many indications makes it possible to leverage historical data and knowledge from representative molecules to allow for better understanding and control of virus safety. More recently, individualized viral clearance studies are becoming the rate‐limiting step in getting new antibody molecules to clinic, particularly in Phase 0 and eIND situations. Here, we explore considerations for application of a generic platform virus clearance strategy that can be applied for relevant investigational antibodies within defined operational parameters in order to increase speed to the clinic and reduce validation costs while providing a better understanding and assurance of process virus safety.

show abstract

Viral clearance by flow‐through mode ion exchange columns and membrane adsorbers

Cited by 37 publications

References 27 publications

Adapting viral safety assurance strategies to continuous processing of biological products

Adapting viral safety assurance strategies to continuous processing of biological products

Cation exchange chromatography performed in overloaded mode is effective in removing viruses during the manufacturing of monoclonal antibodies

Suitability of a generic virus safety evaluation for monoclonal antibody investigational new drug applications

Contact Info

Product

Resources

About