Two major challenges associated with optimizing biomanufacturing operations remain unresolved. The first is variability: how to understand and improve manufacturing with significant variation in process times throughout all unit operations. The second is complexity: modern biomanufacturing facilities are complex and interconnected, with piping segments, transfer panels, and valve arrays, as well as water for injection (WFI) and other shared resource constraints. That complexity is becoming even greater with the need for process standardization and processing of higher (and…
2012
Large-Scale, Single-Use Depth Filtration Systems
Clarifying cell culture broth is the first downstream unit operation in an elaborate sequence of steps required to purify a biological therapeutic. A combination of centrifugation, depth filtration, or tangential-flow filtration (TFF) is used for that operation. The availability of largescale, single-use, depth filtration technology in the recent years, however, has given process developers the capability to improve and simplify downstream processes. Clarification of Cell Culture Streams The main purpose of clarification is to efficiently separate…
Integrity Testing of Sterilizing-Grade Filters
Integrity testing of sterilizing-grade filters is necessary to reliably prevent damage to these sterile barriers from compromising the production of biopharmaceuticals. Documented integrity test results are essential to a manufacturing audit trail for releasing pharmaceutical products (1, 2). Accordingly, problems encountered during this testing can lead to considerable financial damages and substantial delays or even entirely prevent a production lot from being released to the market. Therefore, filter integrity testing is a critical step with high economic importance…
An Emerging Answer to the Downstream Bottleneck
Biotechnology companies have invested billions of US dollars in new manufacturing infrastructure, expanding the industry’s total mammalian cell culture production capacity from 670,000 L in 2002 to 2,550,000 L in 2010 (Figure 1) (1). This capacity expansion is estimated to have cost the industry about $20 billion (Figure 2) (1). Figure 1: Macroporous structure of Natrix chromatography media (see () Figure 1: () Figure 2: () That production capacity (and the investment it represents) is…
Retention of Highly Penetrative A. laidlawii Mycoplasma Cells
Mycoplasma are infamous for contaminating cell culture lines at rates as high as 80% (1,2,3,4,5). For biopharmaceutical processes, the inadvertent use of contaminated culture medium or medium components can lead to contamination of an aseptic process-validation media fill or cell culture medium for a bioreactor (6,7,8,9,10,11). Thoroughly testing medium components before use is generally impractical because of the large volume of material in use. Frequently, culture media cannot be autoclaved (because of the presence of heat-sensitive components or…
Scaling Up Stem Cells
Cell-based products are becoming increasingly important as potential biotherapies. Cell therapy is predicted to have a huge impact on the healthcare sector over the coming decades. Stem cells, in particular, are investigated as potential treatments for a diverse range of applications (such as heart disease and metabolic and inflammatory disorders) in which they might be used to restore lost biological functions. The cell therapy industry is starting to mature. Several emerging companies are now supporting late-stage clinical trials,…
Global Marketplace
Affinity Chromatography Product: CaptureSelect affinity ligands Applications: Antibody-based separations Features: BAC BV has teamed up with both Life Technologies and GE Healthcare to supply them with CaptureSelect antibodies for use as chromatography ligands. Life Technologies has launched a 0.1- to 7.9-mL range of POROS columns for analytical chromatography for IgG, IgM, human serum albumin fusion proteins, and antibody fragments containing κ or λ light chains. GE Healthcare has added LambdaFabSelect for GMP purification of antibodies and fragments that contain λ…
Reducing the Environmental Impact of Single-Use Systems
Committed to sustainability, EMD Millipore is working to provide solutions for the life sciences industry. This commitment is driven by four global issues: climate protection, global health, clean water, and resource efficiency. The company is designing product and process improvements to address these challenges and meet customer expectations. Figure 1: () Life-cycle assessment (LCA) is one of the most rigorous tools we use to help us understand and quantify our products’ environmental impacts (Figure 1). This holistic,…
IBC’s 9th Annual Single-Use Applications for Biopharmaceutical Manufacturing
This conference offers solutions toward better industry cooperation in standards harmonization and downstream processing. New applications for disposables in fill–finish and bulk storage will be covered through a series of case studies, panel discussions, point–counterpoint debates, and breakout-discussion roundtables. Program Highlights PDA Task Force for Single-Use Systems will outline a technical report overview and concepts focused on extractables and leachables. Genentech will disclose additional data from experiences with disposable bags for cell culture media storage. A panel of experts from…
Biobanking Basics
With increasing large-scale “-omic†and clinical studies, the value and need for large and small biobanks or biorepositories has grown exponentially. Many organizations are processing and storing hundreds, thousands, even millions of biosamples. Those samples are collected from a number of sources, however, and put to end uses that are not always anticipated at collection. Consistent standards thus must be established to collect and store samples. Everyone involved must work toward a common goal of high-quality, consistent, reliable,…