In order to underpin the competitiveness of the UK pharmaceutical industry, a step change improvement in manufacturing efficiency is needed. This project aims to deliver this for production of the largest proportion of dosage forms (tablets). The efficiency gains are targeted at improved manufacturing precision, improved productivity and improved mass yield, and will be deliverable at approximately 70% of the capital cost of conventional technology. In developing this capability, significant technical knowledge to be delivered which will enhance the offering of the equipment manufacturers who are part of our consortium. The project will use advanced manufacturing equipment, process measurement, control and information management to deliver the claimed benefits. Previous work has been fragmented; this project will deliver an integrated advanced manufacturing / product release data acquisition platform. It is proposed to set up and use test facilities to prove the feasibility of the required manufacturing platform, enabling the optimal design of a commercial plant capable of making saleable product. The key deliverables are (i) an optimised integration strategy, (ii) performance benchmarks, (iii) a de-risked design for a full scale integrated facility, and (iv) data to demonstrate design effectiveness to key stakeholders including regulatory agencies. The process uses continuous twin screw granulation, fluid bed drying, inline blending and tablet compression, whilst PAT instruments along with standard process parameters such as temperature, pressure and work input are used to monitor the stability and control the process Product release is focused around real time continuous process monitoring and control. It is based on an understanding of the process acquired during the experimental trials following DfM/QbD principles. A concept factory of the future will be designed for the layout and operation of continuous OSD pharmaceutical manufacture. Peripheral work to the above this project will also is deliver a POC continuous tablet coater that coats at a rate to compliment the continuous trial equipment and a continuous powder blender.

The project consists of three elements and seeks to determine the ability of fibrinogen to identify patients with COPD who have muscle and/or cardiovascular disease manifestations. The first part is focused on supporting Regulatory acceptance of clinical biomarkers representing the non-pulmonary disease subtype of COPD with the aim to ensure that assets in our Portfolio are not discarded due to an inappropriate clinical development plan. The second part includes a clinical trial with a novel Phase II anti-inflammatory in a selected subset of COPD patients with elevated blood fibrinogen to assess its effect on our chosen clinical biomarkers. The third part is an experimental medicine study with a Phase I novel drug candidate with an unprecedented mechanism of action which, together with the 2 other parts, may provide a path for a novel therapy for COPD patients at risk of cardiovascular-related events.

Mupirocin is an example of an antibiotic that is the product of a complex synthetic factory found naturally in bacteria. It is currently made industrially using bacteria that have been through successive rounds of selection to find strains that produce more antibiotic during controlled fermentation. It is particularly used against the well known superbug MRSA. The current problems with antibiotic resistant hospital superbugs means that we need more antiobitcs and new antibiotics. Current studies on the bacterial factories that make antibiotics and other products suggest that by changing gene order and improving the signals that switch these genes on it may be possible to increase production. In addition, by combining genes from different pathways one can create new antibiotics or other pharmaceutically active compounds. This project will explore how synthetic biology can be used to build better pathways using our knowledge of how these pathways are programmed.

Awaiting Public Project Summary

This project involves a consortium of a UK based healthcare company (GlaxoSmithKline), a UK based university (King's College London), and a European based fruit extract producer (BerryPharma). Strategic partners of GSK are also being consulted as part of this project. These include a UK based crop research institute (James Hutton Institute) and a European beverage development company (Doehler). The aim of this project is to develop novel fruit beverages with proven health benefits, by sharing plant breeding, food science and nutrition expertise held within the consortia. A number of animal studies have shown metabolic health benefits of polyphenols. This project will help deliver evidence of this effect in humans. Recent technological developments have enabled the extraction and solubilisation of fruit polyphenols, however technical challenges still exist with high acidity, bitterness and the need for integration in a high sugar base, when incorporating the current extracts into food products. A critical aim of this project will be to prove the health benefits of these fruit polyphenols in stable products that are acceptable from a sensorial and nutritional (low sugar) basis.