Posters

A Single-Use Bioreactor for Both Cell and Microbial Cultures: A Dream Becomes Reality

Application of single-use equipment is common practice in the biopharmaceutical industrial and academic field. Compared to the traditional glass or stainless steel bioreactors, single-use bioreactors offer clear advantages: a quicker turnaround time; minimal utilities required; greatly reduced risk of cross contamination; more operational flexibility; reduced validation requirements. However, until recently, single-use bioreactors have a restricted application, only to animal cell cultures due to limitations in mixing and mass-transfer. As single-use technology not only has significant benefits for cell culture processes,…

Effect of process condition on the Mycoplasma rentention of cell culture media filtersMethods

A Mycoplasma contamination event can have a major impact on a biopharmaceutical manufacturer. The loss of a cell culture due to a contamination incurs significant costs that can be attributed to both the initial bioreactor set-up and to the subsequent decontamination. Production facility throughput may be affected and in the worst cases the ability of the manufacturer to supply patients with medicines. Mycoplasma are extremely small in size and lack a cell wall giving the cells some flexibility that enables…

Salt-tolerant cation exchanger for direct capture of proteins

Ion-exchange chromatography is widely used for the purification of biotherapeutic proteins. Usually, cation exchangers are applied in the primary capture step of proteins with alkaline pI. Conventional ion-exchange chromatography has the advantage of high-binding capacity, but it requires low salt conditions for protein binding and consequently adjustment of conductivity of clarified culture supernatant. An alternative method to maintain some binding capacity at higher conductivity levels is working at low pH condi¬tions notwithstanding that some proteins are sensitive to acid treatment.…

Engineering Analysis of Mixing in ATMI’s Bioreactors Using Computational Fluid Dynamics

The Integrity® PadReactor™ and Nucleo™ systems are a single-use bioreactors specifically designed to fulfill the needs of cell culturists. They are perfectly suited to laboratory environments, process develop¬ment centers, clinical material supply and flexible GMP manufacturing. The bioreactor vessel, which offers comparable functionality to classical stirred tank bioreactors, is a single-use bag integrating an internal paddle mixing and sparger system. This innovative bag design allows a non-invasive connection to the system. The paddle is enclosed in a medical grade ULDPE…

Viral Vaccine Manufacturing Scale Using the iCELLIstm Disposable Fixed-Bed Reactor

Viral vaccines are usually produced by anchorage-dependent cell lines. At industrial scale, these cells are either cultivated in static mode on multiplate systems (Roller bottles, Cell Factories, Cell Cube, etc.) or on suspended micro-carriers (porous or non-porous) in in bioreactors. Multiplate systems are bulky and require a lot of handling operations, whereas microcarrier cultures require numerous operations (sterilization and hydration of carriers,bead-to-bead transfers) from pr eculture to final process. However most of the currently available disposable reactors are not well…

The Effect of Conductivity on Dynamic Binding Capacity on CEX Resins

In an effort to improve the antibody manufacturing platform, newer Cation Exchange Resins were evaluated. Dynamic binding studies were conducted using 2 different monoclonal antibodies at a stable pH and varying conductivities across nine resins to determine the differences in binding capacity. DBC Studies were performed at a pH of 5 and conductivities of 5, 10 and 15 mS/cm for the nine cation exchange resins with breakthrough criteria set at 10%. While most of the resins provided excellent binding capacity…

Albumin: A robust pharmaceutical excipient in the stabilization of protein therapeutics

Optimal formulation of peptide and protein pharmaceuticals into efficacious dosage forms to ensure sufficient stability and provide acceptable shelf life is critical. To achieve a stable pharmaceutical drug product, excipients are often added to the protein drug substance. In this study, we investigate recombinant human albumin (rAlbumin) for its ability to prevent or minimize physical and chemical degradation of two allelic variants of the recombinant malaria vaccine candidate, merozoite surface protein 2 (MSP2), in various test formulations. The studies establish…

Improved purification of biotherapeutics using CaptureSelect® affinity ligands

BAC BV – The Affinity Experts – develops novel & cost-effective solutions for affinity purification challenges. Affinity chromatography is one of the simplest and most effective methods for purifying protein therapeutics, offering reduced process steps and higher yields than non-affinity methods can provide. For standard MAb purification Protein A is a well established affinity ligand which clearly has demonstrated the benefits of a highly selective primary capture step. However, for non antibody based therapeutics and novel antibody formats lacking a…

Cell Culture Design Space Modeling using a Scale-Down Approach

As an industry initiative to “provide assurance of quality,” the ICH Q8 guideline proposes building quality into the design of experiments by defining the process design space within which critical product quality attributes are within an acceptable range. A characterized design space not only enhances process knowledge but also can later be utilized for process validation and regulatory filings, saving on the time and cost of additional filings if process changes are implemented in the future. Because it is neither…

A New, Robust Method for Protein Elution from Ceramic Hydroxyapatite

Ceramic hydroxyapatite (CHT™) is used for protein purification owing to its superior removal of all process-stream impurities (aggregates, HCP, viruses, endotoxin, protein A, DNA, etc.). At commercial scale CHT performance can be impacted due to the release of protons during elution. This proton release lowers mobile phase pH which may impact the robustness of CHT particles. We have developed a novel, patent-pending technology called the surface neutralization system (SNS), which desorbs protons from the surface of CHT prior to elution.…