1.
Phosphorus limitation in nitrifying groundwater filters.
Source
Oasen Drinking Water Company, PO box 122, 2800 AC Gouda, The Netherlands; Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft, The Netherlands; Department of Water Management, Delft University of Technology, Stevinweg 1, 2628 CN Delft, The Netherlands.
Abstract
Phosphorus limitation has been demonstrated for heterotrophic growth in groundwater, in drinking water production and distribution systems, and for nitrification of surface water treatment at low temperatures. In this study, phosphorus limitation was tested, in the Netherlands, for nitrification of anaerobic groundwater rich in iron, ammonium and orthophosphate. The bioassay method developed by Lehtola et al. (1999) was adapted to determine the microbially available phosphorus (MAP) for nitrification. In standardized batch experiments with an enriched mixed culture inoculum, the formation of nitrite and nitrate and ATP and the growth of ammonia-oxidizing bacteria (AOB; as indicated by qPCR targeting the amoA-coding gene) were determined for MAP concentrations between 0 and 100 μg PO(4)-P L(-1). The nitrification and microbial growth rates were limited at under 100 μg PO(4)-P L(-1) and virtually stopped at under 10 μg PO(4)-P L(-1). In the range between 10 and 50 μg PO(4)-P L(-1), a linear relationship was found between MAP and the maximum nitrification rate. AOB cell growth and ATP formation were proportional to the total ammonia oxidized. Contrary to Lehtola et al. (1999), biological growth was very slow for MAP concentrations less than 25 μg PO(4)-P L(-1). No full conversion nor maximum cell numbers were reached within 19 days. In full-scale groundwater filters, most of the orthophosphate was removed alongside with iron. The remaining orthophosphate appeared to have only limited availability for microbial growth and activity. In some groundwater filters, nitrification was almost totally prevented by limitation of MAP. In batch experiments with filtrate water from these filters, the nitrification process could be effectively stimulated by adding phosphoric acid.
Copyright © 2011 Elsevier Ltd. All rights reserved.
License Compliance Issues For Biopharmaceuticals: Special Challenges For Negotiations Between Companies And Non-Profit Research Institutions.
Source
National Cancer Institute, Technology Transfer Center, Fellow, Rockville, MD, USA.
Abstract
Biopharmaceuticals are therapeutic products based on biotechnology. They are manufactured by or from living organisms and are the most complex of all commercial medicines to develop, manufacture and qualify for regulatory approval. In recent years biopharmaceuticals have rapidly increased in number and importance with over 400() already marketed in the U.S. and European markets alone. Many companies throughout the world are now ramping up investments in biopharmaceutical R&D and expanding their portfolios through licensing of early-stage biotechnologies from universities and other non-profit research institutions, and there is an increasing number of license agreements for biopharmaceutical product development relative to traditional small molecule drug compounds. This trend will only continue as large numbers of biosimilars and biogenerics enter the market.A primary goal of technology transfer offices associated with publicly-funded, non-profit research institutions is to establish patent protection for inventions deemed to have commercial potential and license them for product development. Such licenses help stimulate economic development and job creation, bring a stream of royalty revenue to the institution and, hopefully, advance the public good or public health by bringing new and useful products to market. In the course of applying for such licenses, a commercial development plan is usually put forth by the license applicant. This plan indicates the path the applicant expects to follow to bring the licensed invention to market. In the case of small molecule drug compounds, there exists a widely-recognized series of clinical development steps, dictated by regulatory requirements, that must be met to bring a new drug to market, such as completion of preclinical toxicology, Phase 1, 2 and 3 testing and product approvals. These steps often become the milestone/benchmark schedule incorporated into license agreements which technology transfer offices use to monitor the licensee's diligence and progress; most exclusive licenses include a commercial development plan, with penalties, financial or even revocation of the license, if the plan is not followed, e.g., the license falls too far behind.This study examines whether developmental milestone schedules based on a small molecule drug development model are useful and realistic in setting expectations for biopharmaceutical product development. We reviewed the monitoring records of all exclusive Public Health Service (PHS) commercial development license agreements for small molecule drugs or therapeutics based on biotechnology (biopharmaceuticals) executed by the National Institutes of Health (NIH) Office of Technology Transfer (OTT) between 2003 and 2009. We found that most biopharmaceutical development license agreements required amending because developmental milestones in the negotiated schedule could not be met by the licensee. This was in stark contrast with license agreements for small molecule chemical compounds which rarely needed changes to their developmental milestone schedules. As commercial development licenses for biopharmaceuticals make up the vast majority of NIH's exclusive license agreements, there is clearly a need to: 1) more closely examine how these benchmark schedules are formed, 2) try to understand the particular risk factors contributing to benchmark schedule non-compliance, and 3) devise alternatives to the current license benchmark schedule structural model. Schedules that properly weigh the most relevant risk factors such as technology classification (e.g., vaccine vs recombinant antibody vs gene therapy), likelihood of unforeseen regulatory issues, and company size/structure may help assure compliance with original license benchmark schedules. This understanding, coupled with a modified approach to the license negotiation process that makes use of a clear and comprehensive term sheet to minimize ambiguities should result in a more realistic benchmark schedule.
Drought tolerance through biotechnology: improving translation from the laboratory to farmers' fields.
Source
Monsanto Company, 1920 Fifth Street, Davis, CA 95616, United States.
Abstract
Water availability is a significant constraint to crop production, and increasing drought tolerance of crops is one step to gaining greater yield stability. Excellent progress has been made using models to identify pathways and genes that can be manipulated through biotechnology to improve drought tolerance. A current focus is on translation of results from models in controlled environments to crops in the field. Field testing to demonstrate improved yields under water-limiting conditions is challenging and expensive. More extensive phenotyping of transgenic lines in the greenhouse may contribute to improved predictions about field performance. It is possible that multiple mechanisms of drought tolerance may be needed to provide benefit across the diversity of water stress environments relevant to economic yield.
Copyright © 2011. Published by Elsevier Ltd.
Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members.
Source
Applied Biotechnology and the Department of Applied Genomics, Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, Pennington, NJ, 08534, USA.
Abstract
SGLT2 (for "Sodium GLucose coTransporter" protein 2) is the major protein responsible for glucose reabsorption in the kidney and its inhibition has been the focus of drug discovery efforts to treat type 2 diabetes. In order to better clarify the human tissue distribution of expression of SGLT2 and related members of this cotransporter class, we performed TaqMan™ (Applied Biosystems, Foster City, CA, USA) quantitative polymerase chain reaction (PCR) analysis of SGLT2 and other sodium/glucose transporter genes on RNAs from 72 normal tissues from three different individuals. We consistently observe that SGLT2 is highly kidney specific while SGLT5 is highly kidney abundant; SGLT1, sodium-dependent amino acid transporter (SAAT1), and SGLT4 are highly abundant in small intestine and skeletal muscle; SGLT6 is expressed in the central nervous system; and sodium myoinositol cotransporter is ubiquitously expressed across all human tissues.
Gallionella spp. in trickling filtration of subsurface aerated and natural groundwater.
Source
Oasen Drinking Water Company, Post Box 122, 2800 AC Gouda, The Netherlands; telephone: +31610927947; fax: +31152782355; Department of Biotechnology, Delft University of Technology, Delft, The Netherlands; Department of Water Management, Delft University of Technology, Delft, The Netherlands. w.w.j.m.devet@tudelft.nl.
Abstract
The growth of iron-oxidizing bacteria, generally regarded as obligate microaerophilic at neutral pH conditions, has been reported in a wide range of environments, including engineered systems for drinking water production. This research focused on intensively aerated trickling filters treating deep anaerobic and subsurface aerated groundwater. The two systems, each comprising groundwater abstraction and trickling filtration, were monitored over a period of 9 months. Gallionella spp. were quantified by qPCR with specifically designed 16S rRNA primers and identified directly in the environmental samples using clone libraries with the same primers. In addition, enrichments in gradient tubes were evaluated after DGGE separation with general bacterial primers. No other iron-oxidizing bacteria than Gallionella spp. were found in the gradient tubes. qPCR provided an effective method to evaluate the growth of Gallionella spp. in these filter systems. The growth of Gallionella spp. was stimulated by subsurface aeration, but these bacteria hardly grew in the trickling filter. In the uninfluenced, natural anaerobic groundwater, Gallionella spp. were only present in low numbers, but they grew extensively in the trickling filter. Identification revealed that Gallionella spp., growing in the trickling filter were phylogenetically distinct from the species found growing during subsurface aeration, indicating that the different conditions in both systems selected for niche organisms, while inhibiting other groups. The results suggest a minor direct significance for inoculation of Gallionella spp. during filtration of subsurface aerated groundwater. Biotechnol. Bioeng. © 2011 Wiley Periodicals, Inc.
Copyright © 2011 Wiley Periodicals, Inc.
Rectal single dose immunization of mice with Escherichia coli O157:H7 bacterial ghosts induces efficient humoral and cellular immune responses and protects against the lethal heterologous challenge.
Source
Bird-C GmbH&CoKG, A-3420 Kritzendorf, Austria. State Research Centre of Virology and Biotechnology 'Vector', 630559, Novosibirsk Region, Koltsovo, Russia. Federal State Unitary Company 'Microgen Scientific Industrial Company for Immunobiological Medicines', Moscow, Russia. The Republican Research and Practical Center for Epidemiology and Microbiology, Minsk, Belarus.
Abstract
Bacterial ghosts (BGs) have been applied through oral, aerogenic, intraocular or intranasal routes for mucosal immunization using a wide range of experimental animals. All these applications required a booster after primary immunization to achieve protective immunity against the lethal challenge. Here we report for the first time that a single rectal dose of BGs produced from enterohaemorrhagic Escherichia coli (EHEC) O157:H7 fully protects mice against a 50% lethal challenge with a heterologous EHEC strain given at day 55. BGs from EHEC O157:H7 were prepared by a combination of protein E-mediated cell lysis and expression of staphylococcal nuclease A guaranteeing the complete degradation of pathogen residual DNA. The lack of genetic material in the EHEC BGs vaccine abolished any potential hazard for horizontal gene transfer of plasmid encoded antibiotic resistance genes or pathogenic islands to the recipient's gut flora. Single rectal immunization using EHEC O157:H7 BGs without any addition of adjuvant significantly stimulated efficient humoral and cellular immune responses, and was equally protective as two immunizations, which indicates the possibility to develop a novel efficacious single dose mucosal EHEC O157:H7 BGs vaccine using a simplified immunization regimen.
© 2011 The Authors. Microbial Biotechnology © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.
- PMID:
- 22103353
- [PubMed - as supplied by publisher]
Exploiting nature's rich source of proteasome inhibitors as starting points in drug development.
Source
Center for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, Technische Universität München, Lichtenbergstraße 4, 85748 Garching, Germany. michael.groll@ch.tum.de melissa.graewert@tum.de.
Abstract
Cancer is the No. 2 cause of death in the Western world and one of the most expensive diseases to treat. Thus, it is not surprising, that every major pharmaceutical and biotechnology company has a blockbuster oncology product. In 2003, Millennium Pharmaceuticals entered the race with Velcade®, a first-in-class proteasome inhibitor that has been approved by the FDA for treatment of multiple myeloma and its sales have passed the billion dollar mark. Velcade®'s extremely toxic boronic acid pharmacophore, however, contributes to a number of severe side effects. Nevertheless, the launching of this product has validated the proteasome as a target in fighting cancer and further proteasome inhibitors have entered the market as anti-cancer drugs. Additionally, proteasome inhibitors have found application as crop protection agents, anti-parasitics, immunosuppressives, as well as in new therapies for muscular dystrophies and inflammation. Many of these compounds are based on microbial metabolites. In this review, we emphasize the important role of the structural elucidation of the various unique binding mechanisms of these compounds that have been optimized throughout evolution to target the proteasome. Based on this knowledge, medicinal chemists have further optimized these natural products, resulting in potential drugs with reduced off-target activities.
Compositional equivalence of insect-protected glyphosate-tolerant soybean MON 87701 × MON 89788 to conventional soybean extends across different world regions and multiple growing seasons.
Source
Monsanto Company, 800 North Lindbergh Boulevard, St. Louis, Missouri 63167, United States. kristina.h.berman@monsanto.com
Abstract
The soybean product MON 87701 × MON 89788 expresses both the cry1Ac gene derived from Bacillus thuringiensis and the cp4 epsps (5-enolpyruvylshikimate-3-phosphate synthase) gene derived from Agrobacterium sp. strain CP4. Each biotechnology-derived trait confers specific benefits of insect resistance and glyphosate tolerance, respectively. The purpose of this study was to compare the composition of seed and forage from this combined-trait product to those of conventional soybean grown in geographically and climatically distinct regions. Field trials were conducted in the United States during the 2007 growing season, in Argentina during the 2007-2008 growing season, and in the northern and southern soybean regions of Brazil during the 2007-2008 and 2008-2009 growing seasons. Results demonstrated that the compositional equivalence of MON 87701 × MON 89788 to the conventional soybean extended across all regions and growing seasons. Further evaluation of the data showed that natural variation (region and growing season) contributed more to compositional variability in soybean, particularly for such components as isoflavones, fatty acids, and vitamin E, than transgene insertion.
Company profile: PGXIS Ltd.
Source
PGXIS Ltd, Aston Court, Kingsmead Business Park, Frederick Place, High Wycombe, Bucks HP111LA, UK. alun.mccarthy@pgxis.com
Abstract
Pharmacogenomic Innovative Solutions Ltd (PGXIS) was established in 2007 by a group of pharmacogenomic (PGx) experts to make their expertise available to biotechnology and pharmaceutical companies. PGXIS has subsequently established a network of experts to broaden its access to relevant PGx knowledge and technologies. In addition, it has developed a novel multivariate analysis method called Taxonomy3 which is both a data integration tool and a targeting tool. Together with siRNA methodology from CytoPathfinder Inc., PGXIS now has an extensive range of diverse PGx methodologies focused on enhancing drug development.
Personal profile: interview with Bill Andrews, Ph.D.
Abstract
Dr. William H. Andrews has worked in the biotech industry for 31 years, focusing the last 19 years on finding ways to extend human life span through the intervention of telomere shortening in human cells. Dr. Andrews earned his Ph.D. in Molecular and Population Genetics at the University of Georgia. He was a Senior Scientist at Armos Corporation and Codon Corporation, Director of Molecular Biology at Codon and at Geron Corporation, and Director of Technology Development at EOS Biosciences. He is presently the founder, President, and CEO of Sierra Sciences, a biotechnologycompany focused exclusively on finding drugs that will transiently induce the expression of endogenous telomerase in human cells. Sierra Sciences has already identified more than 30 such drugs and is presently characterizing their mechanism of action. While Director of Molecular Biology at Geron Corporation, Dr. Andrews was one of the principal discoverers of both the RNA and protein components of human telomerase and was awarded second place as "National Inventor of the Year" in 1997 for this work. He is presently a named inventor on 43 U.S- issued telomerase patents.
C-S targeted biodegradation of dibenzothiophene by Stenotrophomonas sp. NISOC-04.
Source
Biotechnology & Biology Research Center, Shahid Chamran University, Ahvaz, Iran. moslempapizadeh@yahoo.com
Abstract
Crude oil-contaminated soil samples were gathered across Khuzestan oilfields (National Iranian South Oil Company, NISOC) consequently experienced a screening procedure for isolating C-S targeted dibenzothiophene-biodegrading microorganisms with previously optimized techniques. Among the isolates, a bacterial strain was selected due to its capability of biodegrading dibenzothiophene in a C-S targeted manner in aqueous phases and medium mostly consisting of separately biphasic water-gasoline. The 16S rDNA of the isolate was amplified using eubacterial-specific primers and then sequenced. Based on sequence data analysis, the microorganism, designated NISOC-04, clustered most closely with the members of the genus Stenotrophomonas. Gas chromatography indicated that Stenotrophomonas sp. NISOC-04 utilizes 82% of starting 0.8 mM dibenzothiophene within a 48-h-long exponential growth phase. Growth curve analysis revealed the inability of Stenotrophomonas sp. NISOC-04 to utilize dibenzothiophene (DBT) as the exclusive carbon or carbon/sulfur source. Gibbs' assay showed no 2-hydroxy biphenyl accumulation, but HPLC confirmed the presence of 2-hydroxy biphenyl as the final product of DBT desulfurization. Under sulfur starvation, Stenotrophomonas sp. NISOC-04 produced a huge biomass with untraceable sulfur and utilized atmospheric insignificant sulfur levels.
Interview: commercial translation of cell-based therapies and regenerative medicine: learning by experience. Interview by Emily Culme-Seymour.
Abstract
Dr Haseltine speaks to Emily Culme-Seymour, Assistant Commissioning Editor William A Haseltine, PhD has an active career in both Science and Business. He was a professor at Harvard Medical School and Harvard School of Public Health (MA, USA) from 1976 to 1993, where he was Founder and Chair of two academic research departments. He is well known for his pioneering work on cancer, HIV/AIDS and genomics. He has authored more than 200 manuscripts in peer-reviewed journals and is the author of several books. He is the founder of Human Genome Sciences, Inc. and served as the Chairman and CEO of the company until 2004. He is also the founder of several other successfulbiotechnology companies. William Haseltine is currently Chairman and President of ACCESS Health International, Inc., which supports access to affordable, high-quality health services in low, middle and high income countries, and Chairman of the Haseltine Foundation for Science and the Arts, which fosters a dialog between sciences and the arts. He is an Adjunct Professor at the Scripps Institute for Medical Research and the Institute of Chemical Engineering, the University of Mumbai, India. He is a member of the Advisory Board of the IE University, Madrid, the President's Council of the Cold Spring Harbor Laboratory, the Advisory Council for the Koch Institute of MIT, a member of the University Council Committee on technology transfer, Yale University, and is a Lifetime Governor of the New York Academy of Science (NY, USA). He is an honorary member of the Board of Trustees of the Brookings Institution, a member of the Board of Trustees of the Center for Emerging Markets of the Indian School of Business, a member of the Council on Foreign Relations, a member of the Board of AID for AIDS International, and a member of the Chairman's Circle of the Asia Society. He is a member of the Advisory Board of the Metropolitan Opera (NY, USA), the Chairman's Council of the Metropolitan Museum (NY, USA), the International Council of the Guggenheim Museum, the International Council of the Tate Modern, the Board of Directors of the Young Concert Artists, Inc. and the Youth Orchestra of the Americas.
Nonprofit pharma: solutions to what ails the industry.
Source
SRI International, Menlo Park, California 94025, USA. walter.moos@sri.com
Abstract
Nonprofit organizations (NPOs) play an increasingly important role providing solutions to the significant challenges faced today by both large pharmaceutical and smaller biotechnology companies, not to mention academia. NPOs chartered for the public benefit are common in the USA and in selected other parts of the world. SRI International, originally founded as the Stanford Research Institute in 1946, is one of the largest and most successful independent NPOs. To provide a perspective on NPO business models, a number of SRI case studies spanning a broad range of technical and business initiatives will be summarized, including basic and contract research, discovery and development of new drugs and biologics, pharmaceutical and biotech research and development and contract services, technology pivots,company spin-ins and spin-outs, and the creation of new NPOs. How to bridge the National Institute of Health's "Valley of Death" and how to navigate the Food and Drug Administration's "Critical Path" will be discussed. We conclude with lessons learned about collaborations and routes to commercialization, along with food for thought for bioscience companies and outsourcing participants. Throughout, we attempt to explain why the role of NPOs is important to both the scientific and business communities and to patients and caregivers.
Genetic control of biosynthesis and transport of riboflavin and flavin nucleotides and construction of robust biotechnological producers.
Source
Archer Daniels Midland Company, Decatur, Illinois 625261, USA.
Abstract
Riboflavin [7,8-dimethyl-10-(1'-d-ribityl)isoalloxazine, vitamin B₂] is an obligatory component of human and animal diets, as it serves as the precursor of flavin coenzymes, flavin mononucleotide, and flavin adenine dinucleotide, which are involved in oxidative metabolism and other processes. Commercially produced riboflavin is used in agriculture, medicine, and the food industry. Riboflavin synthesis starts from GTP and ribulose-5-phosphate and proceeds through pyrimidine and pteridine intermediates. Flavin nucleotides are synthesized in two consecutive reactions from riboflavin. Some microorganisms and all animal cells are capable of riboflavin uptake, whereas many microorganisms have distinct systems for riboflavin excretion to the medium. Regulation of riboflavin synthesis in bacteria occurs by repression at the transcriptional level by flavin mononucleotide, which binds to nascent noncoding mRNA and blocks further transcription (named the riboswitch). In flavinogenic molds, riboflavin overproduction starts at the stationary phase and is accompanied by derepression of enzymes involved in riboflavin synthesis, sporulation, and mycelial lysis. In flavinogenic yeasts, transcriptional repression of riboflavin synthesis is exerted by iron ions and not by flavins. The putative transcription factor encoded by SEF1 is somehow involved in this regulation. Most commercial riboflavin is currently produced or was produced earlier by microbial synthesis using special selected strains of Bacillus subtilis, Ashbya gossypii, and Candida famata. Whereas earlier RF overproducers were isolated by classical selection, current producers of riboflavin and flavin nucleotides have been developed using modern approaches of metabolic engineering that involve overexpression of structural and regulatory genes of the RF biosynthetic pathway as well as genes involved in the overproduction of the purine precursor of riboflavin, GTP.
- PMID:
- 21646432
- [PubMed - indexed for MEDLINE]
- PMCID: PMC3122625
- [Available on 2012/6/1]
Using osteoclast differentiation as a model for gene discovery in an undergraduate cell biology laboratory.
Source
Department of Biology, Merrimack College, North Andover, Massachusetts 01845. mark.birnbaum@merrimack.edu.
Abstract
A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. This article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory providing students, within a framework of bone cell biology, with a modern approach to gene discovery. Students are introduced to the topics of bone cells, bone synthesis, bone resorption, and osteoporosis. They then review the theory of microchip gene arrays, and study microchip array data generated during the differentiation of bone-resorbing osteoclasts in vitro. The class selects genes whose expression increases during osteoclastogenesis, and researches them in small groups using web-based bioinformatics tools. Students then go to a biotechnology company website to find and order small inhibitory RNAs (siRNAs) designed to "knockdown" expression of the gene of interest. Students then learn to transfect these siRNAs into osteoclasts, stimulate the cells to differentiate, assay osteoclast differentiation in vitro, and measure specific gene expression using real-time PCR and immunoblotting. Specific siRNA knockdown resulting in a decrease in osteoclastogenesis is indicative of a gene's physiological relevance. The results are analyzed statistically and presented to the class in groups. In the past 2 years, students identified several genes essential for optimal osteoclast differentiation, including Myo1d. The students hypothesize that the myo1d protein functions in osteoclasts to deliver important proteins to the cell surface via vesicular transport along microfilaments. Student response to the new course was overwhelmingly positive. Biochemistry and Molecular Biology Education Vol. 38, No. 6, pp. 385-392, 2010.
Copyright © 2010 International Union of Biochemistry and Molecular Biology, Inc.
- PMID:
- 21567867
- [PubMed - in process]
Drug discovery and development for neglected diseases: the DNDi model.
Source
Drugs for Neglected Diseases Initiative (DNDi), Geneva, Switzerland.
Abstract
New models of drug discovery have been developed to overcome the lack of modern and effective drugs for neglected diseases such as human African trypanosomiasis (HAT; sleeping sickness), leishmaniasis, and Chagas disease, which have no financial viability for the pharmaceutical industry. With the purpose of combining the skills and research capacity in academia, pharmaceutical industry, and contract researchers, public-private partnerships or product development partnerships aim to create focused research consortia that address all aspects of drug discovery and development. These consortia not only emulate the projects within pharmaceutical and biotechnology industries, eg, identification and screening of libraries, medicinal chemistry, pharmacology and pharmacodynamics, formulation development, and manufacturing, but also use and strengthen existing capacity in disease-endemic countries, particularly for the conduct of clinical trials. The Drugs for Neglected Diseases initiative (DNDi) has adopted a model closely related to that of a virtual biotechnology company for the identification and optimization of drug leads. The application of this model to the development of drug candidates for the kinetoplastid infections of HAT, Chagas disease, and leishmaniasis has already led to the identification of new candidates issued from DNDi's own discovery pipeline. This demonstrates that the model DNDi has been implementing is working but its DNDi, neglected diseases sustainability remains to be proven.
Cervical chordoma managed with multidisciplinary surgical approach.
Source
Department of Otolaryngology, Head & Neck Surgery, Christchurch Hospital, New Zealand.
Abstract
BACKGROUND:
This paper describes the interdisciplinary management of a 62-year-old man who presented with a cervical chordoma of C2/3. This is a rare neoplasm of the axial skeleton which is usually treated surgically. This is technically challenging due to the surrounding anatomy and requirement for wide exposure. A number of surgical approaches have been described to access the clivus and upper cervical spine.
METHODS:
This case involved both the Orthopaedic and Otolaryngology Head and Neck Surgery departments. Trotter's surgical technique was used to gain access for excision of the cervical chordoma and there was collaboration with an Orthopaedic Biotechnology Company in which a bio-model of the spine was created and a corpectomy cage specific to the patient developed.
RESULTS:
This approach allowed excellent visualisation of the tumour and the unique cage and plate achieved immediate stability and long term fusion.
CONCLUSION:
An interdisciplinary approach should be used in the management of upper cervical chordomas to facilitate tumour resection and reduce the potential for recurrence.
© 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.
Indian vaccine innovation: the case of Shantha Biotechnics.
Source
McLaughlin-Rotman Centre for Global Health, University Health Network and University of Toronto, 101 College Street Suite 406, Toronto ON, M5G 1L7 Canada. peter.singer@mrcglobal.org.
Abstract
BACKGROUND:
Although the World Health Organization had recommended that every child be vaccinated for Hepatitis B by the early 1980s, large multinational pharmaceutical companies held monopolies on the recombinant Hepatitis B vaccine. At a price as high as USD$23 a dose, most Indians families could not afford vaccination. Shantha Biotechnics, a pioneering Indian biotechnology company founded in 1993, saw an unmet need domestically, and developed novel processes for manufacturing Hepatitis B vaccine to reduce prices to less than $1/dose. Further expansion enabled low-cost mass vaccination globally through organizations such as UNICEF. In 2009, Shantha sold over 120 million doses of vaccines. The company was recently acquired by Sanofi-Aventis at a valuation of USD$784 million.
METHODS:
The case study and grounded research method was used to illustrate how the globalization of healthcare R&D is enabling private sector companies such as Shantha to address access to essential medicines. Sources including interviews, literature analysis, and on-site observations were combined to conduct a robust examination of Shantha's evolution as a major provider of vaccines for global health indications.
RESULTS:
Shantha's ability to become a significant global vaccine manufacturer and achieve international valuation and market success appears to have been made possible by focusing first on the local health needs of India. How Shantha achieved this balance can be understood in terms of a framework of four guiding principles. First, Shantha identified a therapeutic area (Hepatitis B) in which cost efficiencies could be achieved for reaching the poor. Second, Shantha persistently sought investments and partnerships from non-traditional and international sources including the Foreign Ministry of Oman and Pfizer. Third, Shantha focused on innovation and quality - investing in innovation from the outset yielded the crucial process innovation that allowed Shantha to make an affordable vaccine. Fourth, Shantha constructed its own cGMP facility, which established credibility for vaccine prequalification by the World Health Organization and generated interest from large pharmaceutical companies in its contract research services. These two sources of revenue allowed Shantha to continue to invest in health innovation relevant to the developing world.
CONCLUSIONS:
The Shantha case study underscores the important role the private sector can play in global health and access to medicines. Home-grown companies in the developing world are becoming a source of low-cost, locally relevant healthcare R&D for therapeutics such as vaccines. Such companies may be compelled by market forces to focus on products relevant to diseases endemic in their country. Sanofi-Aventis' acquisition of Shantha reveals that even large pharmaceutical companies based in the developed world have recognized the importance of meeting the health needs of the developing world. Collectively, these processes suggest an ability to tap into private sector investments for global health innovation, and illustrate the globalization of healthcare R&D to the developing world.
Evaluation of oxygen transfer rates in stirred-tank bioreactors for clinical manufacturing.
Source
Biologics Pilot Plant, Merck Research Laboratories, Merck & Company, Inc., P.O. Box 4, West Point, PA 19486, USA.
Abstract
Several methods are available for determining the volumetric oxygen transfer coefficient in bioreactors, though their application in industrial bioprocess has been limited. To be practically useful, mass transfer measurements made in nonfermenting systems must be consistent with observed microbial respiration rates. This report details a procedure for quantifying the relationship between agitation frequency and oxygen transfer rate that was applied in stirred-tank bioreactors used for clinical biologics manufacturing. The intrinsic delay in dissolved oxygen (DO) measurement was evaluated by shifting the bioreactor pressure and fitting a first-order mathematical model to the DO response. The dynamic method was coupled with the DO lag results to determine the oxygen transfer rate in Water for Injection (WFI) and a complete culture medium. A range of agitation frequencies was investigated at a fixed air sparge flow rate, replicating operating conditions used in Pichia pastoris fermentation. Oxygen transfer rates determined by this method were in excellent agreement with off-gas calculations from cultivation of the organism (P = 0.1). Fermentation of Escherichia coli at different operating parameters also produced respiration rates that agreed with the corresponding dynamic method results in WFI (P = 0.02). The consistency of the dynamic method results with the off-gas data suggests that compensation for the delay in DO measurement can be combined with dynamic gassing to provide a practical, viable model of bioreactor oxygen transfer under conditions of microbial fermentation.
Copyright © 2011 American Institute of Chemical Engineers (AIChE).
Real time monitoring of multiple parameters in mammalian cell culture bioreactors using an in-line Raman spectroscopy probe.
Source
Process Sciences, Worldwide Medicines Group, Bristol-Myers Squibb Company, Syracuse, New York 13221, USA.
Abstract
The FDA's process analytical technology initiative encourages drug manufacturers to apply innovative ideas to better understand their processes. There are many challenges to applying these techniques to monitor mammalian cell culture bioreactors for biologics manufacturing. These include the ability to monitor multiple components in complex medium formulations non-invasively and in-line. We report results that demonstrate, for the first time, the technical feasibility of the in-line application of Raman spectroscopy for monitoring a mammalian cell culture bioreactor. A Raman probe was used for the simultaneous prediction of culture parameters including glutamine, glutamate, glucose, lactate, ammonium, viable cell density, and total cell density.
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