GSK - Articles and news items

GlaxoSmithKline announces start of two phase III studies in advanced/metastatic melanoma

Industry news, News / 24 January 2011 / GlaxoSmithKline

GlaxoSmithKline (GSK) announced today the start of two global Phase III studies in advanced or metastatic melanoma patients with a BRAF V600 mutation. The studies will separately assess the efficacy and safety of two investigational agents, GSK2118436 and GSK1120212, to determine their individual ability to stop or slow the progression of skin cancer in patients whose tumours contain a BRAF V600 mutation, which occurs in 50 to 60 percent of melanoma patients.Commencement of these studies confirms previously announced plans to progress these assets into Phase III.

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Microbiological quality for non-sterile drug product for the 21st century

Industry Focus 2010, Past issues / 22 February 2010 /

For decades microbiological quality has remain dormant while the pharmaceutical industry has continued to evolve. Compendial methods and limits, while now generally harmonised throughout the world, still reflect the same methods utilised 100 years ago. Although there is more clarification around the number and types of organisms permitted in products since routes of administration are better defined, there is little change to what is considered an acceptable number or the types of organisms allowed in product. The good news is, however, in this new environment of Quality by Design (QbD) and the Process Analytical Technology Initiative1 outlined in Quality for the 21st Century, application of a Risk Based approach can provide some flexibility for microbial control. Through an enhanced understanding of the product and process gained during product development, some of the repetitive and inefficient end product testing may be replaced with real time or supportive data to confirm microbial quality. (more…)

Next generation antibody therapeutics: Antibody fragments, dual-targeting strategies, and beyond…

Issue 5 2009, Past issues / 9 October 2009 /

A multitude of novel therapeutic antibody formats based on modification of the conventional IgG format have arisen in recent years. The intensification of interest in this area reflects a pressing need for an additional repertoire of therapeutic molecules which retain the exquisite binding specificity and low intrinsic toxicity of monoclonal antibodies (mAbs), while engineering additional features which enhance clinical efficacy, for example, by improving tissue perfusion or demonstrating increased specificity for a defined cell type. This article briefly reviews the key molecular aspects of therapeutic antibody fragments in development, including single-chain Fv fragments (scFvs), camelid VHH domains, human domain antibodies (dAbs), and an expanding array of bispecific/dual-targeting variants. Such molecules, characterised by unique biophysical and pharmacological properties, are ideally placed to become the next generation of antibody-based therapeutics. (more…)

The increasing use of Microbial Genotypic Techniques for the Identification of Pharmaceutical Isolates

Industry Focus 2009, Past issues / 10 January 2009 /

The historical demarcation of prokaryotes has not been by way of a specific scientific-based concept, but has been defined by a more arbitrary, anthropocentric system, rooted in the practical necessity of the time of its inception, based on the infor­mation available at the time. Therefore, species are historically defined on the basis of the disease they cause. (more…)

Disinfectant validation

Issue 6 2008, Past issues / 3 December 2008 /

The design, validation and implementation of a documented and approved disinfectant programme must form a key part of any pharmaceutical production area qualification. There is significant regulatory interest in this area as it forms a fundamental part of any production facility maintenance schedule. European pharmaceutical companies are required to implement the necessary measures in order to comply with the requirements set out in EudraLex Volume 14 of the “Rules Governing Medicinal Products in the European Union”1. These guidelines are more commonly known as the EU Guide on GMP (EU-GMP). Pharmaceutical companies who supply to the United States are also required to comply with the GMP requirements of 21 CFR 211.56 “Sanitation” and 21 CFR 211.67 “Equipment cleaning and maintenance”.

This article will discuss the key industry standards and guidelines and highlight their significance within the pharmaceutical industry. The tasks that should be considered in order to validate your disinfectant products and cleaning programme will be outlined. (more…)

A practical approach to microbial testing to support non-sterile product stability

Issue 6 2008, Past issues / 3 December 2008 /

During stability, product testing is performed to ensure the product will continue to meet specified criteria of quality and strength through its expiration or shelf-life at the temperature and humidity required by specific markets. This article will not address the other stability requirement of continued efficacy during consumer use which is done by “in-use testing”, an important subject for another article.

Since Microbial Limit Testing (MLT), to include Microbial Enumeration (TAMC and TYMC) and Test for Specified Organisms; and Antimicrobial Effectiveness Testing (AET), if appropriate, are attributes that define the quality of a product, these tests should be considered and included as part of the stability program for both setting expiratio, and supporting on-going commercial stability. The required testing for microbiology is a bit ambiguous as written in ICH 6QA1 which, thankfully, leaves room to define testing conditions that make sense for the product under study. (more…)

Computational prediction of microRNA and targets

Issue 5 2008, Past issues / 29 September 2008 /

MicroRNAs (miRNAs) are small (~21nucleotides), evolutionarily conserved, noncoding RNA molecules that regulate gene expression1. In mammalian genomes, conservative predictions suggest that between 500-1500 miRNAs exist. There miRNAs appear to be capable of regulating the expression of multiple genes, with many genes appearing to be regulated by multiple, different, miRNAs2. Less conservative estimates suggest their may be tens of thousands of miRNAs3 in mammalian genomes, that between 20-30% of all human genes may be subject to regulation by miRNAs, and that each miRNA may contribute to the regulation of 200 or more mRNA targets4. Therefore it is easy to see why miRNA and their potential targets have received a lot of interest in recent times, as they offer a previously unknown mechanism of fundamental molecular biology that can subtly attenuate mRNA / protein expression.

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RNAi therapeutics: addressing targets?

Issue 4 2008, Past issues / 2 August 2008 /

Gene silencing by RNA interference (RNAi) uses double-stranded RNA to shut down gene expression in cells. This provides the possibility that this new methodology could be used in the treatment of disease symptoms and disease processes. A particular attraction of RNAi (as well as other gene knockdown methods of treatment, including antisense) is that, at present, no one class of protein appears to be refractive to silencing using this method and, therefore, it has the potential to make any gene product a target for pharmaceutical intervention. As will be discussed later though, delivery of these large polyanionic molecules to their site of action may pose a significant challenge.

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