August 2012

New EXP-Pak™ Closed-System Disposable Cell Expansion Bags

      Clinical cellular therapy applications often times require a cell expansion or maturation step before use. Traditionally, cell expansion or cell culture is performed in “open” systems including multiwell culture dishes or tissue culture flasks. These “open” steps present risks and are not ideal for larger-scale manufacturing. The new EXP-Pak™ cell expansion container is a closed-system, gas permeable bag intended for expansion and culture of nonadherent cells. EXP-Pak™ bags are made from a unique polyolefin film that permits…

Innovative, Scalable, Single-Use Depth Filtration System

Clarifying cell culture broth is the first downstream unit operation in an elaborate sequence of steps required to purify a biological therapeutic. The availability of large-scale, single-use depth filtration technology in recent years has given process developers the capability to improve and simplify downstream processes. The Zeta Plus™ Encapsulated System is a single-use depth filtration system designed for the bioprocessing industry where upstream cell culture clarification or downstream impurity removal is required. The Zeta Plus Encapsulated System consists of a…

Turn-Key Bioreactor Solutions

      In order to reduce scale-up costs and facility capital expenses, biotechnology companies are adopting single-use systems. To fully enable the single-use paradigm, automation software, hardware, and single-use sensors must be optimized; moreover, both validation documents and materials certifications must be readily available for cGMP implementations. Finesse provides turn-key, configure-to-order measurement and automation solutions for many single-use bioreactor types: “stirred-tank,” “paddle,” or “rocker” systems. The Finesse turn-key system is optimized for each bioreactor type to maximize product yields.…

Managing the Challenges of Cell Therapy Product Delivery in Clinical and Commercial Settings

      Unlike traditional pharmaceuticals, cell therapy products (CTPs) require geographically dispersed networks of cell/tissue collection, manufacture, distribution, and clinical treatment facilities. Regardless of source (allogeneic, autologous) or formulation (e.g., fresh, frozen, scaffold), the vast majority of CTPs are clinically administered on a per-patient basis. A CTP will be clinically effective, and therefore commercially viable, only if it is robust enough to be delivered to the patient in an efficient, controlled, and reproducible manner. In the context of CTPs,…

Understanding the Relationship of Bacterial Retention and Growth Media in Biopharmaceutical Processes

  Background     Tryptic soy broth (TSB) is a general-purpose medium used for cultivating numerous microorganisms including Serratia marcescens, a Gram-negative rod commonly found in water and involved in pharmaceutical contaminations (1, 2). This study examines the growth characteristics and bacterial retention of S. marcescens (ATCC #14756) in five types of TSB: EMD TSB (type 1), EMD Irradiated TSB (type 2), EMD Non-Animal Origin TSB (type 3), EMD Non-Animal Origin Irradiated TSB (type 4), and Competitor ATSB (type 5).…

Fujifilm Diosynth Biotechnologies

One of the major bottlenecks in the production of biopharmaceuticals is the efficient expression of therapeutic proteins in microbial or mammalian cells. The Escherichia coli pAVEway™ expression system described here has been developed to ensure high product titers and efficient scale up to GMP manufacture while minimizing many common issues seen in other expression systems, such as “leaky” expression (expression of recombinant protein in the absence of inducer). How It Works The use of a number of powerful E. coli…

Culture of Normal Human Dermal Fibroblast Cells

      The large numbers of ex vivo expanded cells that are required in many clinical cell therapy protocols (>100 million per patient) make standard culture conditions problematic and expensive, resulting from the need for extensive personnel and facilities resources and the high potential of contamination. To meet such clinical demand, a robust, automated, and closed cell-expansion method is optimal. The Quantum Cell Expansion System (CES) is a functionally closed, automated, hollow-fiber bioreactor system designed to reproducibly grow both…

Constraints on Vaccine Production

      Influenza vaccine has historically been produced in embryonated chicken eggs. However, to meet the needs for pandemic preparedness and the scalability of vaccine production, cell-based processes are now being developed and implemented in the industry. The methods for purification processes have typically involved a combination of sucrose density gradient ultracentrifugation, ultrafiltration/diafiltration (UF/DF) with hollow-fiber membranes, and chromatography using affinity, ion-exchange, and/or gel filtration media (resins). In these processes, both sucrose density gradient ultracentrifugation and gel filtration have…

Intelligent Tools to Facilitate Bioprocess Development

    Figure 1: ()   Continously new bioprocesses are evolving, and bioprocessors are searching for the easiest way to process samples in R&D. Currently, a huge trend toward disposable production systems is notable. For these purposes plastic bags, stirred tank reactors, and storage tanks established on the market. Unfortunately, these reactor types are not suitable to perform sophisticated bioprocess development. In bioprocess R&D, throughputs of 50 to 1,000 fermentations are needed. Therefore, m2p-labs developed intelligent new tools at microscale…

Scalable Packaging Systems for Cell Therapy

Daikyo Crystal Zenith® vials provide an ideal solution for low-temperature or cryogenic storage and transport of high-value biological drugs. () Many current cell-based products are produced, frozen, stored, and delivered to the clinical site in intravenous (IV) bags or polypropylene screw-cap containers. Although IV bags are sufficient for small-scale processes, they may not be suitable for commercial scale. Bag failures can lead to microbial contamination of the cell product, increased product preparation time, increased antibiotic use, and increased resource expenditure…