vaccines – Page 2 – BioProcessing Journal

Investigation of an Adventitious Agent Test False Positive Signal in a Plant-Derived Influenza Vaccine

Medicago manufactures influenza vaccine virus-like particles (VLPs) in an unusual production platform consisting of Nicotiana benthamiana plants. During the in vitro adventitious agent test (AAT) of certain Medicago B strain influenza vaccine VLP test samples, positive hemagglutination of guinea pig red blood cells was observed on day 14, but not on day 28. The positive result in the assay was surprising because the production process uses no animal-derived raw materials and contains a viral inactivation step. Plant-associated viruses would not be expected to infect the mammalian cell-based assay. No cytopathic effects or hemadsorption of red blood cells was observed in these AATs. The positive hemagglutination was observed at 2–8°C, but not at 36–38 °C, and only in a few of the six detector cell lines used in the assay. Because this is quite an unusual pattern of responses for an AAT, Medicago and the contract testing lab, Eurofins Lancaster Laboratories (ELLI) investigated the positive responses thoroughly for the presence of an adventitious agent or an alternative explanation not involving a viral contaminant. Investigation results indicated that the hemagglutinating activity associated with the vaccine test sample itself was responsible for the positive hemagglutination response. The positive hemagglutination on day 14 of these AATs was deemed an assay artifact, and preventive actions were taken to prevent recurrence of this type of false positive response…

Biologics Production Regulatory Risk Analysis and Management

adventitious agent test adventitious agents contaminant control false-positive hemagglutination vaccines virus-like particles

A Suspension Vero Cell Line for Production of Viral Vaccines and Viral Therapeutics

Fujifilm Diosynth Biotechnologies (FDB) is a global contract development and manufacturing organization (CDMO) with over 25 years of experience in process development and/or manufacturing of greater than 310 molecules at sites in: Billingham, England; Research Triangle Park, North Carolina; and College Station, Texas. At our College Station location, we specialize in the development and manufacture of virus-based vaccines (attenuated or recombinant viruses), oncolytic viral therapies (such as adenovirus, polio) and gene therapy vectors (such as adeno-associated virus [AAV])…

Cell & Gene Therapy Viral Vectors

contract manufacturing scale-up serum-free media suspension cell line vaccines Vero cells

Hepatitis B Surface Antigen Particle Purification by Immunoaffinity Chromatography Based on CDI-CB.Hep-1 mAb Monolithic Supports

Bead matrices have been used in affinity chromatography to purify molecules in multiple applications. For instance, the hepatitis B surface antigen (HBsAg) is one of the molecules purified by this technique for human vaccine development programs. However, the use of monolithic supports have emerged as the advantageous choice for affinity chromatography based on convective mass transfer, a high number of channels, and low backpressures at high flow rates. For this reason, several experiments were conducted to determine the suitability of CB.Hep-1 monoclonal antibody (mAb) immunosorbent developed on carboxyimidazole (CDI)-monolithic supports (ligand concentrations: 0.5, 1.0, and 7.0 mg/mL) for HBsAg particle purification. Key results from this study show the highest amounts of HBsAg adsorbed (3059.31 ± 865.71 µg HBsAg/mL immunosorbent, n = 2), and HBsAg eluted (2884.50 ± 541.01 µg HBsAg/mL immunosorbent, n = 2), were estimated in the 1.0 mg/mL-CDI-CB. Hep-1 mAb monolithic support immunosorbents. In addition, the ligand leakage was always < 3 ng mAb/µg HBsAg (approved limit) in the 1.0 mg/ mL-CDI-CB.Hep-1 mAb immunosorbents. Experiments also evidenced the high purity and molecular homogeneity of purified HBsAg particles (< 95 %) across 20 purification cycles. Therefore, the ligand concentration could be reduced up to 1.0 mg/mL, which would enable a notable decrease in the mAb amount required for vaccine manufacturing, as compared to bead matrices (4.0 mg/mL). This study demonstrated that CDI-CB.Hep-1 mAb monolithic support immunosorbents are best suited for assessing the large-scale purification performance of HBsAg particles for human vaccine development programs at low ligand concentration and high flow rates...

Biologics Production

immunoaffinity chromatography immunosorbents monoliths purification vaccines

Inactivation of Adventitious Agents by UVC Irradiation in a Plant-Based Influenza Vaccine Production Process

Biologics are often produced in or derived from matrices that harbor the potential for introduction of adventitious agents to the drug product. This potential is not strictly theoretical, as viruses such as hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), porcine circovirus (PCV), and minute virus of mice (MVM) have been detected in biological products in the past. From a regulatory and safety perspective, assurance that adventitious agents are not present in the drug product is a critical measure of product quality. Guidelines for assuring safety, with respect to adventitious agents in blood-derived products and products produced in mammalian cell culture, are addressed in specific guidances from the Food and Drug Administration (FDA) and the Committee for Proprietary Medicinal Products (CPMP). These guidance documents suggest that safety is best assured through screening donor material or production cell lines, by controlling animal-derived raw materials used during manufacture, incorporating viral removal and inactivation steps in the production process, and protecting the product from the environment during manufacture. Even though Medicago develops products that are produced in plants, a host that does not support the replication of viruses that infect mammals, various regulatory agencies have advised that the production process should contain one or more operations that remove or inactivate adventitious agents. Medicago has investigated multiple methodologies to accomplish this goal, and has found ultraviolet C (UVC) irradiation treatment to be effective for adventitious agent inactivation in the production process used to manufacture their quadrivalent influenza vaccine without detrimental impact to the product…

Biologics Production Manufacturing

adventitious agents plant-based protein production ultraviolet C irradiation vaccines viral clearance virus-like particles

FANG Vaccine: Autologous Tumor Cell Vaccine Genetically Modified to Express GM-CSF and Block Production of Furin

Based on our previously published TAG vaccine design and the TAG vaccine clinical results to date (which demonstrate safety and evidence of efficacy — stabilizing disease plus one confirmed complete response; data submitted elsewhere), we have moved forward with a fundamentally new autologous tumor cell vaccine design incorporating a key technical enhancement through our proprietary bifunctional shRNA technology. The resulting FANG vaccine expresses both recombinant human GM-CSF protein and a furin bifunctional shRNA which blocks the expression of furin protein, and then in turn, significantly reduces the expression of both TGFß1 and TGFß2 in all primary human tumors tested to date…

Biologics Production

autologous cancer vaccine autologous tumor vaccine production furin bifunctional shRNA nonviral vector system vaccines

Characterization and Qualification of Cell Substrates for Manufacturing Viral Vaccines in the United States

Cell substrates are used in various stages of viral vaccine manufacturing, as in the isolation, selection, and propagation of the virus seed or virus vector stock, as well as for the amplification of the virus to produce the final vaccine product. The various stages of cell substrate use, including cell banking, are shown in a generic manufacturing scheme in Figure 1. Traditionally, viral vaccines have been produced in animal tissues, primary cell cultures, and cell lines that either have a finite life span, such as normal diploid cells, or a theoretically infinite life span, as achieved with continuous or immortalized neoplastic cells. The cell substrates used in viral vaccines currently licensed in the US are listed in Table 1…

Manufacturing Viral Vectors

cell substrates characterization FDA safety testing vaccines viral vaccines

A Summary of the Manufacture, Biochemical Characterization, and Virological Safety Demonstration of the Mouse mAb CB.Hep-1 Used to Produce the Hepatitis B Vaccine

Monoclonal antibodies (mAb) are highly selective molecules, and an unlimited amount of mAbs with equal quality can be produced using mammalian cell cultures and animals. These molecules have remarkable applications in biomedicine, diagnosis and therapy due to the ability to reproduce exactly the same binding properties. The mAbs have been generated against an ostensible set of compounds such as toxins, drugs, blood proteins, cancer cells, viruses, hormones, environmental pollutants, food products, metals and plant materials. In general, mAbs can also be used for creating sensitive tests to detect small amounts of substances, and in therapies, abzymes, and for isolating specific compounds from complex mixtures by immunoaffinity chromatography (IAC)…

Manufacturing

ascites method characterization immunoaffinity chromatography monoclonal antibody vaccines viral clearance viral safety

Preparation of Haemagglutinin-lgG1 Fc Fusion Proteins in Insect Cells and Evaluation as Influenza Vaccines

ImmBio’s lead development candidate is an influenza vaccine based on the ImmunoBody® platform technology. An ImmunoBody is a fusion of a selected immuno-dominant antigen with a cell-binding domain — the Fc fragment of human IgG1. The use of recombinant Fc fusion proteins is well documented where it can help solubilize hydrophobic proteins, provide a handle for easy detection and purification, as well as improve half-life…

Baculovirus Expression Technology Biologics Production

BEVS influenza insect cell technology recombinant hemagglutinin proteins vaccines

TAG Xenograft Vaccine: Xenograft-Expanded Autologous Tumor Vaccine Genetically Modified to Express GM-CSF and Block Production of TGFβ2 (part 1)

Preliminary studies with a variety of cell-based vaccines suggest target accessibility (potential immunogenicity) to immune-directed approaches in a variety of solid tumors. However, four primary factors limit the generation of effective immune-mediated anticancer activity in therapeutic applications: 1) identifying and/or targeting cancer-associated immunogen(s) (target) in an individual patient; 2) insufficient or inhibited level of antigen-presenting cell (dendritic cell, macrophage) priming and/or presentation; 3) suboptimal T cell activation (potency) and proliferation; and 4) cancer-induced inhibition of the anticancer immune response in both afferent and efferent limbs…

Biologics Production Manufacturing

anticancer immune response autologous tumor vaccine production autologous vaccine gene transduced cell vaccine vaccines

TAG Vaccine: Autologous Tumor Vaccine Genetically Modified to Express GM-CSF and Block Production of TGFβ2 (part 2)

We have designed a novel autologous vaccine by combining two vaccine strategies that have each been previously tested in separate non-small cell lung cancer (NSCLC) clinical trials: 1) a GM-CSF gene transduced tumor cell vaccine; and 2) a TGFβ2 antisense gene transduced cell vaccine. Each has demonstrated similar beneficial effects without any evidence of significant toxicity in advanced cancer patients…

Biologics Production Manufacturing

anticancer immune response autologous vaccine cell viability gene transduced cell vaccine vaccines

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