Engineering Commons^™

The Global Manufacture Of Polio Vaccine In The Endgame Of Eradication, Philip Minor

Vaccine Technology III

The manufacture of medicines is increasingly globalised but biological products such as vaccines are more complex and their production raises significantly different issues to that of chemical entities. New producers in any region of the world may have difficulty in recognising all the concerns involved and can benefit from technology transfer exercises and a strong and scientifically competent regulatory authority. The issues will be discussed in the context of the Global Polio Eradication Initiative in its terminal phases and future needs for the manufacture of polio vaccine.

Manufacturing Flu Vaccine In Mexico: A Major Public Health And Technology Transfer Challenge, Roger Vinas

Vaccine Technology III

As Health partner of Mexican Public authorities initiative, Sanofi Pasteur is committed to build a Flu Bulk Vaccine Site, on Mexican soil, in order, for this country, to be self-sufficient for supplying seasonal vaccine and, especially,in case of a Flu Pandemic event. This presentation will give highlights on key drivers to consider while transferring this kind of Technology from Europe to Mexico: - Technology Transfer guidelines: stepwise process - Getting Permits/Authorizations - Looking for partners/Contractors: Engineering and Construction phases - Staffing ramp-up for Manufacturing (Production and Quality Control) start-up

Production Of Serotype 6-Derived Recombinant Adeno-Associated Virus In Serum-Free Suspension Cultures Of Hek 293 Cells, Érica A. Schulze

Vaccine Technology III

Recombinant adeno-associated virus (rAAV) has become a promising candidate vector for gene therapy. Anchorage-dependent cells are traditionally used to produce rAAV. However, mass production to meet demands for clinical trials requires large-scale and cost-effective manufacturing processes. The key advantages of rAAV vectors are a broader tissue tropism through the use of different serotypes and a good safety profile.

In the present work, a serotype 6-derived rAAV was produced by transfection of suspension HEK293 cells in serum-free medium using three plasmids: one encoding the GFP gene flanked by ITR sequences, the second encoding the replication and capsid genes, and a third …

Development Of Inactivated Polio Vaccine From Attenuated Sabin Strains For Clinical Studies And Technology-Transfer Purposes, Yvonne E. Thomassen, Wilfried A.M. Bakker, Janny Westdijk, Aart G. Van ‘T Oever, Nico Van Den Heuvel, Jan Hendriks, Gideon F.A. Kersten, Leo A. Van Der Pol

Vaccine Technology III

Recently, responding to WHO’s call for new polio vaccines, the development of Sabin-IPV (injectable, formalin-Inactivated Polio Vaccine, based on attenuated ‘Sabin’ polio virus strains) was initated at NVI. This activity plays an important role in the WHO polio eradication strategy. The use of Sabin instead of wild-type Salk polio strains will provide additional safety during vaccine production. Initially, the Sabin-IPV production process will be based on the scale-down model of the current, and well-established, Salk-IPV process. In parallel, process development, optimization and formulation research is being carried out to further modernize the process and reduce cost per dose. The lab-scale …

Building Process Understanding For Vaccine Manufacturing Using Data Mining, Matthew Wiener

Vaccine Technology III

The production of vaccines is a complex biological process, with long cycle times and a high level of variation in raw materials, biological growth rates, and test methods. While long-term shifts or cycles in yield are not unusual, it is important to build understanding of the causes of shifts and cycles, for greater control and predictability. Hundreds of variables are monitored for every batch of vaccine produced; however, the relationships between product quality and the many process variables are difficult to quantify. In this article, we describe how mining historical process data using random forests and partial least squares (PLS) …

Rna Based Plasmid Selection System For Antibiotic-Free Plasmid Dna Vector Production, Aaron E. Carnes, Jeremy Luke, Justin Vincent, Clague Hodgson, James Williams

Vaccine Technology III

Antibiotic resistance markers, typically kanamycin resistance (kanR), allow selective retention of plasmid DNA during bacterial fermentation and are the most commonly utilized selectable markers. However, to ensure safety, regulatory agencies recommend elimination of antibiotic resistance markers from therapeutic and vaccine plasmid DNA vectors. The presence of an antibiotic resistance gene in the plasmid backbone is considered undesirable by regulatory agencies, due to: 1) the potential transfer of antibiotic resistance to endogenous microbial flora; and 2) the potential activation and transcription of the genes from mammalian promoters after cellular incorporation into the genome. Here, we describe the development and application of …

Design Of Experiment Based Japanese Encephalitis Virus Formaldehyde Inactivation Optimisation For A Vero Cell Derived Vaccine, Michael Hughson

Vaccine Technology III

Japanese Encephalitis (JE) is a disease primarily dominant in South East Asia, caused by the Japanese Encephalitis virus (JEV). It is responsible for an estimated 50,000 cases of the disease every year, of which around 10,000 are fatal and approximately 15,000 result in long term neurological sequelae (WHO 2006). Viral inactivation is a main feature in many vaccine manufacturing processes in order not only to inactivate the product itself but also any potential adventitious agents which may have been introduced during manufacture. Chemical inactivation using formaldehyde is one of the most common methods used for inactivated viral vaccines, yet due …

Sustainable And Innovative Processes For Carbon Capture And Recycling, Manuel Alvarez-Guerra

CO2 Summit: Technology and Opportunity

No abstract provided.

New Vaccine Technologies: Promising Advances May Save More Lives, John Boslego

Vaccine Technology III

In the past 20 years, immunization has prevented nearly 20 million deaths from vaccine-preventable infections. Despite this success, poorer countries often lack access to newer and more expensive vaccines, and vaccines are not yet available for many illnesses. PATH is working to narrow the immunization gap between developed countries and developing countries by increasing the availability of existing vaccines, reducing the lag time for adoption of recently-licensed vaccines, developing technology in support of vaccines and immunization (e.g. vaccine vial monitor, Uniject, vaccine stabilization platforms) and working with partners to develop new vaccines.

Vaccine development is expensive and manufacturers often focus …

Poly-Methyl Vinyl Ether-Co-Maleic Anhydride Nanoparticles As Antigen Delivery And Activating Systems, Carlos Gamazo, Ibai Tamayo, Ana I. Camacho

Vaccine Technology III

The incorporation of antigens into poly-methyl vinyl ether-co-maleic anhydride nanoparticles (NP) has demonstrated to enhance the immune responses in terms of a potent Th1-adjuvant capacity. This fact may be explained by the implemented possibilities that NP render to the antigen: controlled release from the vehicle and chemotaxis for APC recruitment. Besides, after oral administration, it was reported that the bioadhesive nature of the polymer enhanced the interaction of the particulate-adjuvant to the gut mucosa. Moreover, these NP allow the adhesion of antigens and ligands to its outer shell, creating high antigen density surfaces that increase the possibilities of antigen recognition …

Microalgae Productivity Potential, Jason Quinn

CO2 Summit: Technology and Opportunity

No abstract provided.

Potent, Rapid And Cost-Effective Influenza Vaccines Made In E. Coli, Thomas Hofstaetter

Vaccine Technology III

The traditional influenza vaccine, trivalent inactivated virus (TIV) has been in use in the United States in one form or another since the 1940s. The system for production involves injecting influenza virus into embryonated hen’s eggs, harvesting the allantoic fluid containing the virus, inactivation with formalin, disruption of the virus with non-ionic detergent, zonal centrifugation to enrich for antigen and a second inactivation step. The recent appearance of the H1N1 swine virus has provided an opportunity to test the pandemic response system established over the past ten years. What we find is that the public health system seems to work …

Iscomatrix™ Adjuvant Links Innate And Adaptive Immune Responses, Debbie Drane

Vaccine Technology III

The ISCOMATRIX™ adjuvant has antigen delivery and presentation properties as well as immunomodulatory capabilities which combine to provide enhanced and accelerated immune responses. The responses are broad, including a range of sub classes of antibodies as well as both CD4+ and CD8+ T cells. A range of ISCOMATRIX™ vaccines (ISCOMATRIX™ adjuvant combined with antigen) have now been tested in clinical trials and have been shown to be generally safe and well tolerated as well as immunogenic, generating both antibody and T cell responses.

The mechanisms by which ISCOMATRIX™ adjuvant facilitates its immune effects is the scope of significant study and …

Clinical Development Of Formulated Therapeutic And Prophylactic Dna-Based Vaccines, Alain Rolland

Vaccine Technology III

Over the recent years, plasmid DNA vaccines have reached licensure against infectious hematopoietic necrosis virus in farmed salmon (Canada), West Nile virus in horses and metastatic melanoma in dogs (United States). A number of approaches are currently evaluated in clinical trials to enhance the potency of DNA vaccines in humans, including formulation of DNA with delivery systems and adjuvants as well as administration of DNA with devices. This presentation will report on the development of TransVaxTM, a poloxamer-formulated therapeutic DNA vaccine against human cytomegalovirus (CMV) in transplant patients. A vaccine that increases CMV-specific T-cell responses could reduce CMV reactivation after …

Development Of Recombinant Protein Based Chemical Conjugate Malaria Vaccines Targeting The Pre-Erythrocytic Stage, Transmission Blocking, Or Both, David L. Narum, Nicholas Macdonald, David Jones, Ruth Ellis, Yimin Wu, Patrick E. Duffy

Vaccine Technology III

The development of a Plasmodium falciparum malaria vaccine is critical for future control and elimination programs. Recombinant protein based chemical conjugate vaccines, covering different parasite stages, are being developed due to complexity of the parasite and sub-optimal immunogenicity of recombinant malaria proteins in humans, respectively. Chemical conjugation of recombinant malaria proteins to carrier proteins improves their immunogenicity in animal studies. A transmission blocking vaccine comprised of the ookinete protein Pfs25 chemically conjugated to Pseudomonas aeruginosa ExoProtein A (EPA) is currently being developed for pilot scale cGMP production. Bulk lots of Pfs25 and EPA have already been produced and released following …

The Challenge Of Developing New Generation Vaccines For Control And Eradication Of Foot And Mouth Disease In South America, Susana Levy

Vaccine Technology III

Foot and mouth disease (FMD) is a highly infectious viral disease that affects food producing animals such as cattle, pigs and sheep. The FMD status given by the World Organization for Animal Health (OIE) has a huge financial impact on countries that have economies based on meat trade. In the past 15 years the MERCOSUR countries (Argentina, Brazil, Paraguay and Uruguay) have consolidated industrial processes to supply the region with safe and efficacious vaccines to prevent FMD in livestock. Control and eradication programs rely heavily on compulsory vaccination with multivalent whole virus inactivated vaccines. Currently, vaccines are industrially obtained by …

Ultra-Scale Down Studies Of Human Cell Bioprocessing For A Prostate Cancer Vaccine Therapy - The Impact Of Capillary Shear, Juan Pablo Acosta Martinez, Katherine Lawrence, Carol Chu Mike Hoare, Stephen Ward

Vaccine Technology III

The scale-up and manufacturing of therapies based on intact whole cells presents a major challenge for development scientists and engineers due to the stress-reactive nature of these cells. The administrated cells may be characterized in terms of their membrane integrity and their surface markers and eventually their biopotency. The challenge is to process the cells at various scales and in a way which maintains these cell properties. Also during formulation the presence of cytokines produced by cells prior to their inactivation is a critical factor. This poster presents an approach to allow the rapid characterization of human cell lines in …

Establishing A Platform For Spray Drying Inhalable Vaccines In South Africa, Willem Germishuizen, L Venter, A Khosa, F Mudau, P.B. Fourie, B Pulliam, M Kabadi, A Schiermeier, D.A . Edwards

Vaccine Technology III

Mycobacterium bovis BCG is the current vaccine for tuberculosis (TB). However, BCG as it is currently administered shows highly variable efficacy in protecting adults against TB. The natural route of infection of TB is via inhalation of bacilli-containing aerosols and it is postulated that immunization by the natural route of infection may lead to a greater immunity given the fact that the lungs are the primary target of infection. By eliciting both local and systemic immune responses, it is anticipated that an inhaled form of BCG will offer greater protection against pulmonary TB.

Current commercial BCG vaccine preparations are filled …

Scale-Up Of An Intensified Process For Rad35 Adenovirus Production Using The Per.C6® Cell Substrate, Alfred Luitjens, Herman Van Herk

Vaccine Technology III

Tuberculosis is the world’s second deadliest infectious disease, with over 9 million new cases diagnosed in 2006. In collaboration with the Aeras Global Tuberculosis Vaccine Foundation, we are developing a recombinant tuberculosis adenovirus based vaccine (rAd35). Currently a series of three Phase I trials are taking place, with the first two studies indicating very promising results, safety and toleration. In November 2008 we started a Phase II study in South Africa. The manufacturing process supporting these clinical studies was developed using the PER.C6® cell substrate. With the productivity of this production process, scale-up to 10,000-liter bioreactor will be required to …

Application Of Animal-Free Recombinant Bioactive Protein Supplements To Improve The Performance Of Cell-Based Viral Vaccine Production, Kenneth Bertram, Marina Ross, Domenica Cavallaro, Larissa Chirkova, Geoffrey Francis

Vaccine Technology III

Animal cell culture for the production of viral vaccines has been performed for more than 50 years, and currently this technology is expanding rapidly to meet present and future demands of the health sector. The development and regulatory approval of continuous cell lines for manufacturing viral vaccines has brought numerous benefits to production processes. However, greater advances in the last decade have been achieved in mammalian cell production of biological therapeutics, including monoclonal antibodies, hormones, growth factors, cytokines and clotting factors. We and others have contributed to these upstream advances by improving cell culture media with the development of animal-free …

Cim Technology: Enabeling Economic Vaccine Purification, Matjaz Peterka, Franci Smrekar, Tony Brazzale, Marko Banjac, Petra Kramberger, Milos Barut, Ales Podgornik, Ales Strancar

Vaccine Technology III

Vaccines are diverse and complex biological molecules, complexes and particles. Different production technologies are used for vaccines manufacturing and every production process require somekind of vaccine purification. Purification of vaccines is technically challenging and was traditionally inefficient and partially neglected due to different economical and technical reasons. Density gradient ultracentrifugation, introduced in1960s is still a major purification step for many vaccines present on the market. As a complementary techniques, cross flow filtration and chromatography has been used. Conventional chromatography supports designed for protein purification have relatively small pore sizes with restricted access for large molecules and viruses. In addition mass …

Comparison Of Various Measurement Techniques For Characterizing The Hydrodynamics Of Gas-Solid Fluidized Beds, Rahmat Sotudeh-Gharebagh, Navid Mostoufi, Reza Zarghami, Mojgan Abbasi, Nasim Salehi-Nik

The 13th International Conference on Fluidization - New Paradigm in Fluidization Engineering

There are various techniques to characterize the hydrodynamic of fluidized beds. Nowadays, sensor development is widely used to determine the hydrodynamic state of a fluidized bed to improve control and safety of the operation of such reactors. The objective of this study was to compare the advantages and disadvantages of the intrusive and novel non-intrusive techniques. The measurement techniques investigated in this work were vibration of the bed, acoustic emission and pressure. Extensive measurements were carried out at different superficial gas velocities with different particle sizes. Vibration and acoustic emissions were recorded at 25 KHz for 30 s using accelerometer …

Preface, Sang Done Kim, Yong Kang, Jea Keun Lee, Yong Chil Seo

The 13th International Conference on Fluidization - New Paradigm in Fluidization Engineering

PREFACE

Bubble-Free Fluidization Of Particles In The Voids Of A Packing Of Coarse Spheres, Bruno Formisani, Rossella Girimonte, Patrizia Bafaro, Vincenzino Vivacqua

The 13th International Conference on Fluidization - New Paradigm in Fluidization Engineering

Confining a bed of relatively fine particles in a packing of coarse spheres prevents the onset of bubbly flow past their point of incipient fluidization. To improve present representations of confined fluidization, experiments on several cuts of solids of various density are analysed and interpreted by adapting some fundamental relationships of the fluidization theory to the peculiar geometry provided by the confining environment.

Motion Of A Large Object In A 2d Bubbling Fluidized Bed, Antonio Soria-Verdugo, L. M. García-Gutiérrez, S. Sanchez-Delgado, U. Ruiz-Rivas

The 13th International Conference on Fluidization - New Paradigm in Fluidization Engineering

The motion of a large object in a bubbling fluidized bed is experimentally studied using digital image analysis. A wide range of fluidized bed applications involves the motion of large objects within the bed, such objects being reactants, catalysts, agglomerates, etc.

The experiments were run in a 2D bubbling fluidized bed with glass spheres as bed material. The object motion is measured using tracking techniques, while independent measurements of the dense phase velocity (using PIV) and bubble velocity were carried out. The effect of the excess gas velocity on the object motion was also analyzed.

It is generally accepted that …

Particle Clusters In Fluidized Beds, Ray Cocco, Frank Shaffer, S.B. Reddy Karri, Roy Hays, Ted Knowlton

The 13th International Conference on Fluidization - New Paradigm in Fluidization Engineering

Accurately predicting the entrainment rate is important in designing a commercial fluidized bed. However, most correlations fall short in providing an accurate prediction of the entrainment rate. Many correlations assume that smaller particles have a higher entrainment rate than larger particles; but, this is often not the case. Smaller particles can, and often do, have lower effective entrainment rates than larger particles. This has been presumed from several different experiments. In one case, the entrainment rate of FCC catalyst fines was measured at different fluidized bed heights and found that higher entrainment fluxes were observed at lower bed heights (i.e., …

Investigation Of The Shifting-Parameter As A Function Of Particle Size Distribution In A Fluidized Bed Traversing From A Fixed To Fluidized Bed, Christo Rautenbach, M.C. Melaaen, B.M. Halvorsen

The 13th International Conference on Fluidization - New Paradigm in Fluidization Engineering

Accurate predictions of pressure drops in fluidized beds are of great importance in the industry. Up to date no satisfactory correlation exists to predict the pressure drop in a fluidized bed as the bed is traversing from one regime to another. In the present study the powered addition correlation [1] is investigated for this particular application. It has been found that this correlation is well suited for the investigated application.

Table Of Contents, Sang Done Kim, Yong Kang, Jea Keun Lee, Yong Chil Seo

The 13th International Conference on Fluidization - New Paradigm in Fluidization Engineering

No abstract provided.

Multiple Orifice Bubble Generation In Gas-Solid Fluidized Beds: The Activation Region Approach, Sergio Sanchez Delgado, J.V. Briongos, A. Acosta-Iborra, D. Santana

The 13th International Conference on Fluidization - New Paradigm in Fluidization Engineering

This work addresses the bubble generation mechanism at multi-orifice distributors in gas-solid fluidized beds (FB). Different measurements techniques such as high speed video camera and Kistler pressure transducers were applied to obtain information from both local, and global bed dynamics. Pressure fluctuation time series are used for dynamic diagnosis of the 2-D facility used during the study. The bed was operated with different distributor plates at several bubbling conditions leading to different bubble flow patterns characterized by digital image analysis of both the dense and the bubble phases.

In order to explain the bubble pattern developed within the bed and …

Mixing Behavior And Hydrodynamic Study Of Gassolid-Solid Fluidization System: Co-Fluidization Of Fcc And Coarse Particles, Zeeshan Nawaz, Yujian Sun, Yue Chu, Fei Wei

The 13th International Conference on Fluidization - New Paradigm in Fluidization Engineering

Gas-solid-solid (GSS) fluidization system is a unique piece of equipment and its features related to better mixing quality. The mixing and hydrodynamic behavior of FCC particles with coarse particles is investigated in 2D and 3D cofluidized beds. The reason of enhancing mixing and fluidization properties by adding coarse particles is particularly due to the movement of coarse particles, those breaks the strong interparticle forces between FCC particles and destroy bubble wake (bubble disassociation strategy), time to time. The attrition mass was measured by using Zeeshan relationship at designated conditions.