Custom DNA Product: McBox luc minicircle and plasmid DNA Applications: Transfection optimization Features: The McBox luc kit includes 100 µg each of certified minicircle and plasmid DNA, both including the firefly luciferase reporter gene. A vial with endotoxin-free water for injection ensures high quality after dilution. Scientists can now directly compare minicircle DNA with a corresponding “classical” plasmid in individual applications. Minicircle DNA contains almost exclusively the gene of interest and its regulating sequence motifs. This provides a safe and…
Author Archives: BPI Contributor
New Validation Guidance Causes a Stir
In November 2008 the US FDA finally issued a new draft guidance on process validation (1). The original guidance on this topic was published in May 1987, and the FDA explained that “since then, we have obtained additional experience through our regulatory oversight that allows us to update our recommendations to industry on this topic.” The new guidance is intended to reflect some goals of the FDA’s Pharmaceutical GMPs for the 21st Century, an initiative that was finalized in 2004.…
Single-Use, Continuous-Countercurrent, Multicolumn Chromatography
Over the past decade, improvements in the biopharmaceutical manufacturing industry have resulted in a dramatic rise in the expression levels from animal cell cultures – some mAb titers have increased 30-fold over the last 15 years. However, increased titers have led to an increase in downstream bottlenecks. To address this challenge, some manufacturers are turning to multicolumn chromatography.
The principles of simulated moving-bed technology can be applied to create a continuous-countercurrent process. The first column in a loading train is allowed to break through, and material coming off it is captured on a second column. Binding capacity can thus be exploited beyond dynamic binding capacity. These processes often significantly improve media use – and hence significantly reduce consumption of media and buffers.
A Presanitized, Purpose-Designed, Single-Use TFF Strategy
As downstream processing accounts for about 70% of the total biomanufacturing cost, it is easy to see why improvements in product recovery and purification are urgently needed. One possible response to this need is the implementation of a single-use TFF process strategy.
Sius “single-use†cassettes provide a unique solution for a cost-effective downstream processing, with measurable cost-in-use savings, while eliminating a significant amount of time performing burdensome clean-in-place (CIP) procedures. This case study outlines the experimental design, development studies, and proposed single-use commercial TFF process based on work performed by Mike LaBreck at Groupe NovaSep.
Case Study: Evaluation and Implementation of a Single-Stage Multimedia Harvest Depth Filter for a Large-Scale Antibody Process
While in the process of transferring to a new manufacturing facility, scientists and engineers at Genentech, Inc. performed small-scale studies to evaluate several candidates for a single-stage depth filter train to accommodate existing equipment at the new facility.
After testing several dual-layer, single-stage filter media, the team chose a robust filter and implemented it at commercial scale. By replacing the traditional two-stage filtration train, they were able to provide significant cost savings relative to piping reconfiguration, new equipment purchase, and new equipment validation. To learn more about the testing methods and results of this study, download the PDF linked below.
FDA 21 CFR Part 11 Revisited
Six years after the US FDA applied a narrower scope to its interpretation of 21 CFR Part 11 on electronic records and signatures (1), the agency is ready to release the revised Part 11. The 2008 release of a draft revision of Annex 11 — Europe’s version of Part 11 (2) — put pressure on the FDA to complete its long-overdue Part 11 revision. As I made clear to members of my SmarterCompliance executive advisory group in May of last…
Development of a High-Capacity MAb Capture Step Based on Cation-Exchange Chromatography
Protein A affinity chromatography is traditionally used as the capture step for monoclonal antibodies (MAbs) (1,2,3). It yields high purity because only the fragment-crystallizable (Fc) region of an antibody (IgG1 or IgG2) or Fc-containing fusion protein can bind to the protein A ligand. The resulting specificity provides substantial reduction in impurities such as host cell proteins (HCPs) and DNA (4,5,6,7,8). The dynamic binding capacity of protein A chromatography resins is generally ≤40 g/L and depends highly on residence time because…
Increasing MAb Capture Productivity
Continually increasing bioreactor titers is placing pressure on downstream processing, especially chromatography steps, to process the greater mass of protein produced. Whereas an order of magnitude increase has been seen in titers over the last few years, no similar increase has yet been achieved in the capacity of chromatography resins. Meanwhile, the industry is coming under rising pressure to reduce manufacturing costs and the resulting cost per gram of monoclonal antibodies (MAbs) produced. Because of the specificity it offers, protein…
Global Marketplace
Depth-Filtration Platform Product: Stax disposable depth filter platform Application: Downstream processing Features: Simplicity, intuitive operation, safety, and speed improve the efficiency of depth filtration processes. A stack of single-use depth filter capsules are configured in an ergonomic, vertical design to enable a single operator to load, operate, and unload within a reduced footprint. Single-use capsules eliminate the need for cleaning and associated validation. Interlocking modules are interchangeable and scalable. Contact Pall Life Sciences stax@pall.com Clean-in-Place (CIP) Product: RotaCIP cleaning equipment…
IBC’s Sixth AnnualSingle-Use Applications for Biopharmaceutical Manufacturing
IBC’s Single-Use Applications for Biopharmaceutical Manufacturing conference is well known in the industry as the largest, most well-respected event focused solely on disposables. This year’s program provides a thorough education on topics such as equipment technologies, and processes through validation; integrating disposables into facilities; implementation tools; and new data from vendors on how plastics are manufactured. Our faculty of experts will present their most up-to-date knowledge and proven strategies you can implement at your company to ensure it is maximizing…