Monoclonal antibody (mAb) manufacturers struggling with single-use technology (SUT)-derived impurities should use ultrafiltration and diafiltration as the basis of their removal strategies, according to new research.
Single-use technologies provide a low-cost, flexible means of manufacturing biopharmaceuticals that is free of the time-consuming cleaning and validation steps required when using stainless steel culturing systems.
Unfortunately, the plastic components in SUTs are a major source of impurities, also called process equipment-related leachables (PERLs), which can impact product quality, efficacy, and safety.
As a result, SUT users must develop removal strategies. But, this can be challenging, as current impurity reduction guidelines, specifically ICH Q3A (R2), do not cover mAbs and biologics.
In addition, SUT suppliers can be reluctant to disclose proprietary information about their technologies, which makes it hard for biopharmaceutical firms to perform detailed risk assessments.
Now, however, new research suggests that two established downstream processing techniques—ultrafiltration and diafiltration—can be relied upon to eliminate PERLs from the process stream.
The study by a team at Ireland’s National Institute for Bioprocessing Research and Training (NIBRT) and Johnson & Johnson (J&J) examined how effective the techniques were at removing 22 sample elements added to an mAb process stream.
The key finding, according to the authors, was that UF/DF achieved 97% clearance levels for 18 of the sample elements. The remaining four elements—silver, tungsten, thallium, and lead—showed lower clearance levels.
“This study demonstrated that UF/DF is an efficient mAb downstream stage to remove significant elemental impurity levels that may be accumulated from previous manufacturing steps. This substantially reduces risks associated with elemental leachable species from processing steps before the UF/DF stage in drug substance manufacturing,” they write.
The NIBRT and J&J team are hopeful the findings will aid in the development of guidelines for mAb manufacturers and the wider biopharmaceutical industry.
“Results from this study lay a solid foundation for the understanding and prediction of UF/DF capacity to remove elemental leachables,” they write.
The researchers used their findings to develop digital models that can characterize and predict the clearance behavior of elemental impurities during UF/DF processes.
“Clearance modeling emerges as a valuable platform to support industry and regulatory bodies in developing sophisticated risk-based PERL testing strategies, ultimately, ensuring patient safety.
“The aim is to create an impactful platform that will support industry and regulatory bodies in developing sophisticated risk-based PERL testing strategies, facilitating the appropriate selection of substances for further risk assessments, which will ultimately ensure patient safety and enable trace elemental impurity control for protein stability.”
The post UF/DF Effective Against SUT-Derived Impurities appeared first on GEN - Genetic Engineering and Biotechnology News.
Single-use technologies provide a low-cost, flexible means of manufacturing biopharmaceuticals that is free of the time-consuming cleaning and validation steps required when using stainless steel culturing systems.
Unfortunately, the plastic components in SUTs are a major source of impurities, also called process equipment-related leachables (PERLs), which can impact product quality, efficacy, and safety.
As a result, SUT users must develop removal strategies. But, this can be challenging, as current impurity reduction guidelines, specifically ICH Q3A (R2), do not cover mAbs and biologics.
In addition, SUT suppliers can be reluctant to disclose proprietary information about their technologies, which makes it hard for biopharmaceutical firms to perform detailed risk assessments.
Now, however, new research suggests that two established downstream processing techniques—ultrafiltration and diafiltration—can be relied upon to eliminate PERLs from the process stream.
The study by a team at Ireland’s National Institute for Bioprocessing Research and Training (NIBRT) and Johnson & Johnson (J&J) examined how effective the techniques were at removing 22 sample elements added to an mAb process stream.
The key finding, according to the authors, was that UF/DF achieved 97% clearance levels for 18 of the sample elements. The remaining four elements—silver, tungsten, thallium, and lead—showed lower clearance levels.
“This study demonstrated that UF/DF is an efficient mAb downstream stage to remove significant elemental impurity levels that may be accumulated from previous manufacturing steps. This substantially reduces risks associated with elemental leachable species from processing steps before the UF/DF stage in drug substance manufacturing,” they write.
The NIBRT and J&J team are hopeful the findings will aid in the development of guidelines for mAb manufacturers and the wider biopharmaceutical industry.
“Results from this study lay a solid foundation for the understanding and prediction of UF/DF capacity to remove elemental leachables,” they write.
The researchers used their findings to develop digital models that can characterize and predict the clearance behavior of elemental impurities during UF/DF processes.
“Clearance modeling emerges as a valuable platform to support industry and regulatory bodies in developing sophisticated risk-based PERL testing strategies, ultimately, ensuring patient safety.
“The aim is to create an impactful platform that will support industry and regulatory bodies in developing sophisticated risk-based PERL testing strategies, facilitating the appropriate selection of substances for further risk assessments, which will ultimately ensure patient safety and enable trace elemental impurity control for protein stability.”
The post UF/DF Effective Against SUT-Derived Impurities appeared first on GEN - Genetic Engineering and Biotechnology News.