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Issue 2 2008
Issue 2 2008 / 19 March 2008 /
The early 21st century has seen a revolution in RNA biology, bringing with it the prospect of a new class of medicines based on RNA. What are the prospects for developing these RNA-based medicines for the growing medical problem of neurodegenerative disease and what are the challenges to making these new medicines work successfully within the complex environment of the nervous system? Recent progress on RNA silencing of neurodegenerative disease targets and RNAi delivery to the nervous system is encouraging and suggests that clinical evaluation of these therapeutic agents is realistic within the next few years.
A spectacular revolution in RNA biology over the last decade has created new tools and opportunities for advancing basic biomedical science as well as the tantalising prospect of RNA-based medicines to treat human disease. The discovery of RNA interference (RNAi) in 1998 by Fire and Mello1 led rapidly to elucidating the biochemical mechanism underlying the phenomenon of RNA-based gene silencing. (more…)
Tagged with: Functional genomics, Matthew JA Wood, RNAi, University of Oxford
Issue 2 2008 / 19 March 2008 /
Most people in molecular biology today are not old enough to remember pre-PCR. But try to do your job without it and you will see what a difference that simple little technique has made.
‘Polymerase Chain Reaction’ is now a word in Merriam Webster’s Collegiate Dictionary and if you put ‘PCR’ into Google, you get 18,000,000 hits. If you type in ‘PCR song,’ you get a lovely little ditty courtesy of Bio-Rad, which will rattle around in your brain like an insane cat in your garage. Try it.
When I stumbled on PCR in the spring of 1983, I was trying to increase the demand for oligonucleotides, which before automation my laboratory had made by hand. Our new machine from my friend Ron Cook at Biosearch across the San Francisco bay had threatened job stability in the laboratory by doing what had taken us about three weeks to do, in eight hours – and it did it every eight hours, no breaks.
My attempt succeeded. The demand went up by about a million and I didn’t have to fire any of my fellow ‘lab’ workers at Cetus. (more…)
Tagged with: Dr. Kary Mullis, Polymerase Chain Reaction (PCR)
Issue 2 2008 / 19 March 2008 /
Type 1 diabetes is an autoimmune disease, characterised by immune infiltration into the islets of Langerhans, resulting in the destruction of insulin producing b-cells. Over recent years, evidence has been collected on the important role of chemokines in the recruitment of immune cells leading to the pathology of this disease. (more…)
Tagged with: Catholic University of Leuven, Laboratory of Experimental Medicine and Endocrinology (LEGENDO), Lut Overbergh, Polymerase Chain Reaction (PCR), Prof. Chantal Mathieu M.D. P.h.D.
Issue 2 2008 / 19 March 2008 /
The complexity of drug discovery faces many challenges; principally, the failure of drug candidates during the development process as a result of adverse effects or lack of efficacy. A key reason for this high attrition rate is that we are only just beginning to understand the complexity of the response(s) from a biological system to perturbations, such as a disease state or drug treatment. Subsequently, a deeper insight into the molecular mechanisms underlying both disease processes and drug action will ultimately contribute to increased productivity through the drug discovery process[1,2].
In recent years, progress has been made in ascribing pathological conditions to defects in molecular pathway components, for example, linking dysregulation of signalling pathways to cancer and inflammatory diseases.
Kinases and phosphatases are key regulators in signalling pathways, so it is not surprising that across the pharmaceutical industry, a substantial percentage of drug discovery efforts are focused on targeting these enzyme classes. In particular, the modulation of cellular kinase activities, which is one of the most rapidly growing areas in the development of novel drugs. (more…)
Tagged with: Bayer (Schweiz) AG, Hans Voshol, Jan van Oostrum, Novartis Institutes for BioMedical Research, Phosphoproteomics, Proteomics, Zeptosens
Issue 2 2008 / 19 March 2008 /
The impact of biomarker technology and biomarker strategies in pharmaceutical development is still in its infancy; but the impact is already proving significant. Biomarker strategy forms the basis for personalised medicine, the industry/regulatory focus centres on improving the success rate and reducing the high attrition rate often encountered in early phases of clinical research. The depth and breadth of knowledge required to successfully implement biomarkers into drug development is generating company collaborations and inclusion of professionals that have not traditionally been part of drug product development.
Today, we are witnessing a revolution in the understanding of health and disease, spurred on by the sequencing of the human genome and the subsequent creation of a map of human genetic variation. This revolution has been given a name: personalised medicine. (more…)
Tagged with: Altus Pharma, Biomarkers, Candida Fratazzi, Claudio Carini, MDS Pharma, Personalised medicine
Issue 2 2008 / 19 March 2008 /
High content screening (HCS) is based on subcellular imaging using automated microscopy, in combination with automated image analysis. High content screening was first introduced over a decade ago as one of the promising new technologies, intended to address the bottleneck of secondary assays in the development of new drugs. Since then, the application has rapidly expanded throughout the entire drug discovery process, from target identification and validation, through to lead optimisation and detailed investigation of the mode of action.[1,2,3]
One main characteristic of HCS is its capability of multiplexing, meaning not only several additional reagents creating several read outs, but also gives the ability to analyse different parameters of each individual cell, within an array of cells. Temporary cellular events which can be analysed via live cell and population analysis deliver sensitive results of rare events within the cell population.
An area where HCS shows its benefits is in the high throughput screening of small molecules for lead finding. Increasingly, pharmaceutical companies successfully screen their full collection; however, the throughput is limited by the assay procedure, including washing and fixation steps4,5. Image collection and data analysis time can be another throughput limiting factor, depending on instrument setup and complexity of the biology to be analysed. (more…)
Tagged with: Dr. Daniela Gabriel, Dr. Marjo Simonen, HCS (High Content Screening), Novartis Institutes for BioMedical Research
Issue 2 2008 / 19 March 2008 /
Over the past 40 years, the development of increasingly powerful computers has played a major role in the advancement of laboratory experimentation. Initially, the high processing capabilities of computers were exploited to perform complex calculations at unprecedented speeds, often offline to a company’s main frame.
Gradually, as digital technologies progressed, and with the development of the microprocessor, computers were brought into the laboratory and used for data acquisition and data processing. As a consequence, a number of laboratory techniques were revolutionised to such an extent that it is now difficult to believe, by modern standards, just how crude certain measurements had been and also what degree of confidence or accuracy they offered. The cutting out and weighing of chromatography peaks to obtain quantitative data is one such example. (more…)
Tagged with: ELNs, John Trigg, LIMS, phaseFour Informatics
Issue 2 2008 / 19 March 2008 /
European Pharmaceutical Review caught up with Mr Neil Kipling, founder and CEO of software giants IDBS, to discuss future prospects and products in advanced solutions software, to serve the ever demanding life sciences industry. (more…)
Tagged with: IDBS, Interviews, Mr Neil Kipling
Issue 2 2008 / 19 March 2008 /
Testing cleaning validation samples requires a validated method. The extent of validation is dependent upon the type of method employed, the capabilities of the method, the scientific and regulatory needs of the resulting data and the anticipated outcome of the testing. A number of test method options are reviewed for their analytical capabilities, along with their method validation parameters.
Cleaning validation is a critical function in pharmaceutical manufacturing. Regulatory agencies have placed great emphasis on demonstrating that a cleaning process prevents cross-contamination1,2. Manufacturing equipment cleanliness does not merely impact the subsequent formulation, but every formulation processed in the equipment and the overall manufacturing program in a facility. A cleaning process is validated and monitored through testing of the equipment. Testing ranges from visual inspection to swab sampling or rinse sampling.
For any test method to be suitable for its intended purpose, it must be appropriate for measuring analytes at and below the acceptable residue limit (ARL). An ARL can be based on available toxicological data such as an allowable daily intake (ADI), an adulteration limit such as 10 ppm and visual cleanliness. The ARL has a direct bearing on the validation parameters of the test method. (more…)
Tagged with: Aseptic Processing, Gas chromatography, HPLC, Mass spectrometry, Merck & Co., Richard Forsyth
Issue 2 2008 / 19 March 2008 /
Thermal analysis techniques cover all methods in which a physical property is monitored as a function of temperature or time, whilst the sample is being heated or cooled under controlled conditions. Calorimetric methods measure the energy involved in every process. The quicker new developments attain the market, such as the progression of micro or nanotechnologies, combinations of different hyphenated techniques, as well as the development of high automated or high throughput systems, the faster new horizons will open in the industrial environment. In addition, the application of sophisticated kinetic software in DSC, calorimetry and reaction calorimetry gives better safety predictions.
Table 1 summarises most thermal analysis and calorimetric methods including coupled and combined techniques, most of which have been introduced in European, US and Japan pharmacopoeias. Every new instrument leads to increased sensitivity, versatility and is constantly expanding the use of automation, therefore giving more robust and reliable results. (more…)
Tagged with: Calorimetry, Danielle Giron, Novartis Pharma AG, Thermal Analysis
Issue 2 2008 / 19 March 2008 /
The process analytical technology guidelines have been a hotly debated topic within the pharmaceutical industry ever since they were made public in 2004. This also holds true at Johnson & Johnson Pharmaceutical Research & Development (J&JPRD), Division of Janssen Pharmaceutical N.V. In recent years, the company has introduced PAT tools in its manufacturing operations and in its development organisation on a project-by-project basis. Several of these projects have resulted in a better insight into critical manufacturing processes and have led to significant optimisations.
Despite these promising results, the company feels a more sector specific approach will be needed to ensure optimal integration of the PAT principles. “Constant monitoring, adjusting, and optimising of manufacturing processes – the very essence of PAT – is not always that obvious in a strongly regulated environment. That is why the implementation strategies that have been successful in other industries do not necessarily apply for the pharmaceutical industry,” says Peter Van Broeck, Senior Director New Product Introductions at Johnson & Johnson.
European Pharmaceutical Review recently brought together four PAT specialists from different departments within Johnson & Johnson. Each of them has their own particular experience with the use and implementation of PAT tools. An interesting conversation on the current view of PAT within Johnson & Johnson ensued. (more…)
Tagged with: Johnson & Johnson, Koen De Smet, Mario Hellings, PAT, Peter Van Broeck, Tom Van den Kerkhof
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