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http://www.webmedcentral.com/images/Header_Logo.giftext/html2011-12-05T08:44:24+01:00http://www.webmedcentral.com/Mr. Robby KumarGenomics in Medical Science: An Overview
http://www.webmedcentral.com/article_view/2580
Genomics is the study of an organism's genome and the use of the genes. It deals with the systematic use of genome information, associated with other data, to provide answers in biology, medicine, and industry.Genomics has the potential of offering new therapeutic methods for the treatment of some diseases, as well as new diagnostic methods. Other applications are in the food and agriculture sectors. The major tools and methods related to genomics are bioinformatics, genetic analysis, measurement of gene expression, and determination of gene function.text/html2010-10-12T15:13:53+01:00http://www.webmedcentral.com/Dr. Hui XiangImproving The Cost Efficiency In Pharmaceutical Outsourcing
http://www.webmedcentral.com/article_view/975
There is a growing demand to contain the sky-rocketing drug costs. The driving forces for such demand come from public awareness of high drug price, rising R & D expenses, tighter FDA regulations, higher NDA/BLA requirements, and competition of generic drugs [1]. Drug companies are looking into ways to cut costs in order to stay competitive. Outsourcing is one of such measures to reduce cost and risk in drug development and production. While enjoying the gains brought by outsourcing, many drug companies do not have a systematic cost evaluation program. Often they are unaware of the significant internal costs associated with outsourcing when making decisions [2].Implementing the Scoring System in Cost/Benefit AnalysisIn brief, cost efficiency is defined to achieve the business goal with minimal cost, or make maximum on the money invested. Cost/benefit analysis, one of the widely used tools, gives a glimpse of what kind of benefit will be generated based on what cost. In order to evaluate cost efficiency in pharmaceutical outsourcing, the scoring system could be adopted to measure both the deliveries[3], as well as the costs [2]. The deliveries are scored in the following five categories: regulatory compliance, supply assurance, quality, service, as well as innovation [3], as summarized in Illustration 1.The costs are scored in the following 3 categories: manufacturing costs, CMO profit margin, and sponsor’s internal costs [2], as shown in Illustration 2. The manufacturing costs and sponsor's internal costs are further traced to material costs, labor costs, and overhead costs. Activity-based cost system should be used to evaluate these costs. Many sponsors are not even aware of such internal costs, thinking that once they contract it out they do not need to do anything about it [2]. Examples of sponsor’s internal costs include project management, relationship building, process transfer, document translation, training/support, as well as studies required by regulatory affairs.Based on Illustrations 1 and 2, the cost efficiency can be estimated by the following calculation:Deliveries = Compliance + Assurance of Aupply + Quality + Service + Innovation (1)Costs = Manufacturing Costs + CMO Profit Margin + Associated Internal Costs (2)Cost Efficiency Index = Deliveries / Costs (3)This scoring system is not the only way to estimate cost efficiency. Other factors could be added in if they need to be considered. Also, the scoring weight could be changed to better reflect the criticality of each factor, as long as it is consistent in the same comparison.Strategies to Improve Cost EfficiencyBased on the above equation, sponsors need to improve deliveries meanwhile reduce the costs in outsourcing. However, the above equation just helps us to compare the cost efficiency from period to period or from options to options. It does not tell what should be done to improve the efficiency in outsourcing. Due to the complex features in pharmaceutical manufacturing, simply say increase the deliveries while reducing the costs is not enough. In order to improve cost efficiency, the following strategies are recommended:1) Commit to quality and regulatory compliance: Improvement in cost efficiency should be built on the pre-condition that quality and compliance are not compromised. With rising bar of drug regulations, cost increase to meet regulatory requirements should be viewed as an absolute requirement. Pharmaceutical business is not purely commercial because any violation of regulation or quality standards will result in tremendous financial loss, even judicial prosecutions [1].2) Perform thorough quotation analysis: At bidding stage, sponsor should list the criteria and perform thorough quotation analysis, requiring contractors to quote costs of materials, labor, overheads, as well as profit [1]. Details, such as pay by hour, by milestones, or by service, need to be discussed. "Beware of low upfront costs that hide high fees of all varieties” [4].3) Balance the capacity and demand: It is important to estimate the contractor’s capacity when making outsourcing decisions. Either over-estimation or under-estimation will have significant financial impacts. As Ransohoff estimated, operation at 50% or 150% capacity could increase costs up to tens of millions of dollars each month for a typical monoclonal antibody product2. “An optimal capacity mix for API [active pharmaceutical ingredient] manufacturing is 70%. The remainder of the time will be needed for clean-up, changovers, validation and training” [3].4) Gain access to new technologies: Pharmaceutical industry is heavily technology driven. New technologies can significantly improve return on investment. Contract companies offer a variety of their in-house technologies, as well as experiences in cGMP manufacturing, process development, scale-up, and validation. Dr. Andrew Racher at Lonza Biologics said, “As a contract manufacturer, we have developed more than 300 robust manufacturing processes…, we leverage our previous experience, which allows us to develop these robust processes more quickly than companies that have less historical data to draw from” [5].5) Manage projects efficiently: Because contract manufacturing needs to use facilities, technologies, and experiences that are often unavailable in-house, efficient project management is very essentiall [1]. However, this does not mean to micro-manage every activity. "For the project to be successful, the sponsor must manage it carefully and competently. It's a fine line to walk between neglecting the project and micromanging it, but walk it you must” [4]. It is good that sponsor and contractor form a joint project management team, which makes decisions on scope of work, specifications, milestones, responsibility, etc. This requires effective communication and clear responsibility.6) Develop long-term partner relationship: A recent survey showed that majority outsourcing goes to preferred contract companies on the basis of good service [6]. The overhead costs to start with the new CMO was enormous: searching, negotiation, relationship building, process transfer, document translation, process modification, training, stability studies, fill and finish modification, comparability study, rewriting the CMC report, and revalidation. In addition to delays in launching the drug, the risk of failure was increased dramatically. Many companies face difficult choices when the contract companies are not performing well or do not fit their need in issues such as capacity, supply, or compliance. At late development or commercial manufacturing stage, it is hard to switch to another contractor [7].7) Incorporate risk assessment in decision making: Several tools, such as discounted cash flow analysis and Monte Calo simulation, could be used to estimate the risk in decision making [2]. It is recommended to defer large capital commitment to a later clinical stage when risk is significantly reduced.8) Review performance periodically: This would help both sponsors and CMOs to identify issues needing improvement in the future. Both sides should agree on performance metrics, and measure the progress against such metrics1. At the same time, sponsors should measure the cost efficiency, and compare it with previous records to see if it is improving. If not, find out the reasons.9) Go international. While currently the majority of drugs are still produced in North America, EU, and Japan, the trend is that pharmaceutical industry is catching up with other industries in moving to developing countries with low labor costs and market potential [1, 8]. Such move is greatly facilitated by global harmonization on drug regulation, as well as electronic communication in data transfer and regulatory filing. It is recommended that pharmaceutical companies actively look for such opportunities for future outsourcing partners.text/html2013-02-05T18:44:30+01:00http://www.webmedcentral.com/Dr. Narotam Sharma Tuberculosis and Molecular Diagnosis
http://www.webmedcentral.com/article_view/3992
The incidence of Tuberculosis varies considerably around the world and most Mycobacterial infections in developing nations are still being caused by Mycobacterium tuberculosis members. A quick and correct diagnosis is of great importance because of the high morbidity. Unfortunately, conventional bacteriological methods are time consuming, their sensitivity is low, and so treatment occasionally becomes empirical. PCR method has high specificity in identifying M. tuberculosis in various specimens. Molecular diagnostic tools for Tuberculosis (TB) have evolved quickly with new innovations which can provide unprecedented opportunities for the rapid, sensitive and specific diagnosis of M. tuberculosis in clinical specimens and the status of its drug sensitivity. Microscopy and culture methods can not be replaced but the molecular assays can be applied in parallel with any new molecular tests for the diagnosis of TB. For extra pulmonary specimens, the use of the amplification methods is advocated, since rapid and accurate laboratory diagnosis is critical. Customization of the diagnostic usefulness of a molecular assay, according to the ease, reliability and need for health care sector is of immense value in a modern clinical Mycobacteriology laboratory. Keywords: Master Mix, Nested PCR, In-House PCR assays, Nucleic acid Amplification.text/html2013-03-07T13:18:22+01:00http://www.webmedcentral.com/Dr. Narotam Sharma High Resolution Melt Curve Analysis- An Innovative Approach for Molecular Diagnosis
http://www.webmedcentral.com/article_view/3998
High Resolution Melting (HRM) is a homogeneous, extremely powerful technique for SNP genotyping, mutation scanning and sequence scanning in DNA samples [1]. Enabled by the recent availability of improved double-stranded DNA (dsDNA)–binding dyes and next-generation real-time PCR instrumentation, High Resolution Melting Analysis is based on PCR melting (dissociation) curve techniques. For several years, various researchers and instrument makers have independently investigated the utility of high-resolution DNA dissociation analysis. The team at Idaho Technology has done an admirable job of vigorously promoting their research through traditional journal publications. Conversely, Corbett Life Science does not pursue publication, but instead relies on the publications of customers to promote the technology. Regardless, both companies have independently advanced the field of high resolution dissociation analysis and successfully introduced what has now become known as high resolution melt (HRM) analysis. Idaho Technology was first to market with an instrument made specifically to do dissociation analysis; the HR-1. The HR-1 was a showpiece for the technology with the singular aim of producing the most detailed melt curve possible [2]. As such, it opened the eyes of many to the potential of HRM and remains the performance benchmark for the acquisition of an individual melt curve. However the HR-1 is not capable of thermal cycling and can only analyze a single sample from within a glass capillary per run making data analysis time consuming. The HRM technology characterizes nucleic acid samples based on their disassociation behavior and detects small sequence differences in PCR amplified sequences, just by direct melting. Samples are also discriminated according to their sequence length, GC content and strand complementarily. With the use of specific DNA dyes, high-end instrumentation and sophisticated analysis software, these differences are detected.text/html2013-08-12T05:20:41+01:00http://www.webmedcentral.com/Mr. Lalit L KharbikarParticle Bombardment: Not a Good Approach for Gene Transfer into Embryonic Axes of Cotton (Gossypium hirsutum L.) Cultivars
http://www.webmedcentral.com/article_view/4305
A particle bombardment mediated transformation protocol for direct gene transfer into cotton (Gossypium hirsutum L.) embryonic axes is described. Bt toxin gene, cry I A(c) under the control of CaMV 35S promoter and the npt-II gene as selectable marker is used for the experiment with cotton cv. NH 545. The embryonic axes explants were bombarded at various parameters of pressure and distance and incubated for 2 days at 28°C on MS medium supplemented with BAP (3 mg/l). Selection of transformed embryonic axes was conducted on MS medium containing 100 mg/l kanamycin supplemented with either BAP or kinetin and NAA after 15 days. A maximum regeneration frequency of 26% was achieved on selection medium when explants were bombarded with 900 psi at 6 and/or 9 cm distance and cultured on MS medium supplemented with BAP (1.6 mg/l) and Kinetin (0.4 mg/l) without NAA. The presence of transgene was detected by polymerase chain reaction (PCR) and southern blotting analysis. Out of total 432 bombarded explants, 112 survived the selection and only 3 transgenic cotton plantlets could be recovered. Overall, the gene transfer efficiency achieved through this method was only 3%.text/html2014-03-24T05:23:51+01:00http://www.webmedcentral.com/Ms. Shaila P ChavanIdentification and Characterization of EST-SSRs in Mungbean
http://www.webmedcentral.com/article_view/4598
Background: Mungbean has great nutritional sense over other cereal crops and supplements the need of protein and carbohydrates. Mungbean crop improvement programmes through marker assisted selection and gene mapping required molecular markers. In this regards simple sequence repeats (SSR) have great utility mostly because of high polymorphism, co-dominance nature, random distribution and ample availability.
Methods: Conventional method for identification of SSRs through enrichment library and sequencing is labour intensive. Available nucleotide sequence data deposited in public domains is one of the major sources for identifying SSRs.
Results: In the present study, nucleotide sequences available from NCBI database for - mungbean including 829 EST (expressed sequence tags), 83 GSS (genomic survey sequence), and 2903 nucleotide sequences were searched for microsatellite identification and then the characterisation of these SSRs as di, tri and tetra, class I, class II and class III were carried out. The frequency distribution of SSRs concludes that ga/tc (518), ca/tg (238) among di nucleotide and caa/ttg (84) and gaa/ttc among trinucleotide are found most abundantin nucleotide sequence.
Conclusions: Moreover EST-SSR markers are also useful to understand population structure and evaluation of genetic diversity which is requisite for the effective utilization of available genetic resources in Vigna species.