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Scale-Up of Single-Use Depth Filtration Systems

Process development engineers are responsible for developing scale-up strategies for efficient and cost-effective manufacture of biological and bioprocess-derived products at bench-scale, pilot scale and at manufacturing scale. A central unit operation in the production of these various therapeutic proteins is cell clarification using depth filtration. Recently, single-use depth filtration technologies have been developed, at scales ranging from the lab, to R&D, process development and on to manufacturing.

In this educational webcast, Laura Brown, Scientific Application Support Specialist II with 3M Purification, will provide guidelines for scaling-up of single-use depth filtration systems, and will review the commonly used single-use depth filtration products used for biopharmaceutical manufacturing.

Rapid Development of Chemically Defined Media and Feeds through Replacement of Basal Hydrolysates

Protein hydrolysates are widely used in mammalian cell culture to improve cell growth and recombinant protein production. However, use of the hydrolysates can lead to significant process variability, due to the limited control of their source and final composition during manufacturing. On the other hand, development of chemically defined media and feeds requires a tremendous amount of work, including comprehensive library screening and spent media analysis.

In this educational webcast, Dr. Hao Chen, Associate Principal Scientist, BioProcess Development at Merck, describes a rapid method for developing chemically defined media and feeds for Chinese hamster ovary (CHO) cell lines from existing proprietary media and feeds by the replacement of basal protein hydrolysates with novel supplements. In the case studies presented, Dr. Chen shows that after two rounds of optimization, the protein hydrolysate was successfully replaced. The resulting cell growth, protein productivity, and product quality were similar in the chemically defined and original media. The entire development process was completed within six weeks.

Production of CGMP-Grade Lentiviral Vectors

Lentiviral vectors are important tools for gene transfer because of their ability to transduce a number of cell types without the need for host cells to be dividing. As a result, investigators are using them as gene delivery vehicles in clinical applications. Since lentiviral vectors play such a vital role in gene therapy, they need to be manufactured at large scale for clinical trials. But, large-scale production using CGMP methods can present a number of challenges.

To address these challenges, the authors of this case study developed a process that allows for extensive scale-up in a safe, sterile, and reproducible system to produce clinical-grade lentivirus. This manufacturing process is very efficient and can be carried out using minimal staff (two operators for production of each subbatch). It provides the extensive scale-up capacity necessary to produce CGMP-grade lentivirus, and it has been used successfully in several completed and on-going phase 1–2 ex-vivo gene therapy clinical trials.

Applied Biosystems® GoPure™ Prepacked Chromatography Columns

Convenient, flexible, and efficient purification of biomolecules

GoPure™ Pre-packed Columns: A high performance, flexible purification platform

Single-use technologies have been widely utilized in upstream processes for many years. Interest in improving operational efficiency, speeding facility turn around and elimination of product carryover risk is now driving adoption of ready-to-connect filtration and purification modules in downstream processing.For chromatography, performance and flexibility that is equivalent to traditional self-pack columns is a prerequisite for use in multiproduct facilities. This webcast will describe GoPure™ Pre-packed Chromatography Columns and a custom packing process for third party resins. Case studies will be presented that demonstrate column packing process stability and scalability.

Evaluating Library Databases for Microbial Identification: Critical Aspects and Recommendations

A thorough evaluation process for microbial identification systems should consist of both a technical and financial review, regardless if you are performing internal testing and outsourcing. Assessment of the library database used for microbial identifications is a critical component of evaluating a system or service in its ability to generate accurate identifications. Comprehensive depth of entries, accuracy and coverage of relevant species frequently found in aseptic and sterile manufacturing environments have a significant impact on both performance and cost. Databases…

Characterization and Performance of the Mobius® CellReady 200 L Bioreactor System: The next Generation of Single-Use Bioreactors

Successful bioprocessing relies on the ability to accurately and effectively monitor and control critical process parameters. The Mobius® CellReady 200 L single-use bioreactor is uniquely designed with the novel Mobius® Mobius® SensorReady technology, an external loop that enables configurable, flexible and functional monitoring and control. Bioreactor characterization properties such as mixing time, volumetric mass transfer capabilities, temperature mapping and power input define the process design space wherein accurate and effective monitoring and control can occur. Each of the aforementioned characterization…

Efficient Production of Recombinant Antibody Derivatives in Pseudomonas flourescens

P. fluorescens serves as an attractive expression host for the production of stable and biologically active antibody fragments. A proprietary strain of P. fluorescens has been specifi cally developed as a protein production platform to enable rapid identification of strains capable of expressing high titers of soluble, active protein, and refl ects the additional sophistication required of engineered antibody derivatives being developed today. Pfēnex Expression TechnologyTM employs a toolbox of defined P. fluorescens strains containing custom-designed combinations of genetic elements…

Evaluation of Ultra Performance Size Exclusion Chromatography for the Analysis of Proteins and Higher Order Aggregates

Complete characterization and analysis of biopharmaceuticals includes size exclusion chromatography (SEC) to measure protein aggregates and other size variants. Current silica-based HPLC-SEC methods can be time-consuming and unreliable. New advances in packing materials and instrumentation have allowed faster and more reproducible separations to be achieved. Improvements in resolution, sensitivity and throughput will be demonstrated for sub-2 μm SEC packing materials as compared to traditional silica-based columns. The effect of pore size and particle size for the analysis of aggregates and…

Towards the Use of Statistical Modeling to Predict Cell Culture Performance of Hydrolysates

Hydrolysates are complex media supplements composed of many as well as different types of components. Predicting cell culture performance of a particular lot remains an elusive target, other than by small scale cell culture testing which consumes valuable time, effort and resources. In order to reduce the need for incoming acceptance tests by our customers, FrieslandCampina Domo plans to develop a simple analytical assay that accurately predicts cell culture performance. Our Quality by Design project has provided information at the…

Performing Quality by Design on hydrolysates: a DOE case study

Hydrolysates provide increased cell growth and titers. The aim of FrieslandCampina Domo is to re-define hydrolysates and re-design their quality profile. The Quality by Design concept as put forward by the FDA proves to be an excellent framework for achieving these goals. In addition it will also enable FrieslandCampina Domo to provide a Design Space of this critical raw material for the biopharmaceutical industry and so making process changes easier and cost effective. FrieslandCampina Domo has analysed protein hydrolysates at…