The following case studies illustrate some of the past and current industry collaborations at the PMBRC.
Case Study 1: Innovation Partnership with Teva Pharmaceuticals Ireland
Teva Pharmaceuticals Ireland is part of Teva Pharmaceutical Industries Ltd, the world's leading generic pharmaceutical company. Teva’s Waterford plant is responsible for the manufacture and development of respiratory products for supply to the United States and other global markets. The Spiromax® Dry Powder Inhaler (DPI) is a proprietary technology developed by Teva for the treatment of respiratory conditions. DPIs contain fine drug particles blended with a carrier material (usually lactose). In order to work properly the drug must stick to the lactose particles, but not adhere too strongly such that they do not detach on actuation. The physicochemical properties of the drug and lactose are critical to getting this balance right. This project aimed to help Teva understand the critical material properties required for the optimum performance of the Spiromax® DPI.
The PMBRC Technology Gateway used a variety of characterisation techniques to understand the properties of the raw materials involved and probe the interactions between the drug and carrier. In particular the researchers were able to understand the effect of certain formulation and processing factors which affected the performance of the device. The work in this project focussed on a single DPI product and the work has enabled Teva to understand the optimal formulation and process parameters for the manufacture of that product. The analytical techniques developed as part of the project and the knowledge gained can now be applied to all other DPI products currently in development in Teva, Waterford. A number of invention disclosures and academic publications are currently in preparation. Teva have agreed to fund the continuation of the research for a further two years.
“The work carried out by the PMBRC on the project has significantly enhanced our understanding of the drug-carrier interactions in our DPI product. Pharmaceutical regulators demand a thorough understanding of the factors affecting drug product performance. The knowledge gained in this project will help us to meet our regulatory obligations and will also have a knock-on effect on products currently in development. We are so pleased with the research that we have agreed to fully fund the continuation of the work for a further two years”.
Dr. Julian Blair, Senior Director of R&D, Teva Pharmaceuticals Ireland
Case Study 2: Co-funded Innovation Voucher with Xeolas Pharmaceuticals
Xeolas Pharmaceuticals is a cutting edge start-up Irish speciality pharmaceutical company based in Dublin. Xeolas develops medicinal products for niche markets, specialising in value-added, innovative or novel formulations of established active substances. Xeolas is an R&D based, technology focussed company. The Dublin base focusses on project management, development planning, clinical development, regulatory, quality and logistics with an expansion plan in 2014 bringing R&D, clinical and small-scale manufacture in-house.
Xeolas is developing a novel, liquid formulation of a drug for the treatment of cardiovascular disease. The drug is normally supplied as a tablet, but Xeolas wish to develop a liquid formulation for use in paediatric patients or patients that are unable to swallow tablets. The drug is not very stable in water however and tends to degrade over time in liquid formulations.
In collaboration with Xeolas, researchers at the PMBRC prepared a number of prototype formulations designed to prevent degradation of the drug in water. The researchers developed analytical methods and used these to assess the stability of the prototype formulations over a period of time. The results have been promising and have proved that a stable formulation of this drug can be prepared if the formulation components are carefully controlled. Xeolas now wish to develop this product further and it has become an important part of the company's R&D portfolio.
Case Study 3: Direct Funded Collaboration with Waters Technologies Ireland
Case Study 4: Innovation Partnership with Genzyme Ireland Ltd.
The PMBRC completed a 3-year Enterprise Ireland innovation partnership research project with Genzyme Ireland Ltd. in June 2013. The project involved relating critical quality attributes of incoming raw materials to the performance of the manufacturing process. Further details of this collaboration remain confidential between Genzyme and the PMBRC.
Case Study 5: Identification of impurities in a tablet product for EirGen Pharma Ltd.
EirGen Pharma Ltd. required assistance with the identification of three unknown impurities in a tablet product, Eir-010, which were observed to form during stability testing. The company did not have the analytical equipment or expertise required to identify the compounds and approached the PMBRC to help.
The PMBRC has a suite of analytical equipment and trained researchers ideally suited to tackle this problem. Firstly the tablets were analysed by HPLC-MS and GC-MS to determine the molecular weight of each impurity. Tablets were then subjected to forced thermal degradation and appreciable quantities of each impurity were isolated using preparative chromatography. The 1H NMR spectra of the extracted impurities were measured at 400 MHz. The mass spectrometry and NMR data were then used to determine the identity of each impurity. The results were presented to the company in the form of a technical report.
The impurity problem was a significant hurdle in the development of Eir-010 and threatened to halt the filing of the product. EirGen were able to use the data generated to support the filing of Eir-010 with the European Medicine Agency (EMA). Eir-010 will be commercially launched in key European markets, with sales worth €20m forecast over the next five years. See IOTI flyer of this case study.
Case Study 6: Fluid Bed Drying Trials for Temmler Ireland Ltd.
Temmler Ireland Ltd. were looking to introduce a new product to their manufacturing site and requested the PMBRC to conduct fluid bed drying (FBD) trials on a granulate. The purpose of the trials was to determine the feasibility of drying the granulate using FBD prior to scale up in their manufacturing plant. The trials were successfully completed and the granulate characterised using the analysis equipment available in the PMBRC. Temmler are now planning to proceed with the new product introduction.