The following case studies illustrate some of the current and past industry collaborations at the PMBRC:
Case Study 1: Directly Funded Study with GSK (Dungarvan Site)
Project Title: Relating material properties to manufacturing performance and product quality.
Profile of Company: GSK’s Dungarvan manufacturing site started operations in 1981 and is now one of the largest employers in the south east of Ireland. The site supplies more than 70 global markets with pain relief and denture care products. A centre of packaging excellence, the site boasts a committed workforce with technical, engineering, quality and operational expertise.
How the PMBRC delivered a solution for the Company: GSK Dungarvan manufactures high-volume products such as Panadol (6.5 billion tablets a year) for international export. The high-volume nature of the operations requires a consistent and reliable supply chain of active ingredients and excipients. While there are many potential suppliers for these ingredients, not every source is suitable for GSK’s products and manufacturing processes. Certain physico-chemical properties such as particle size, powder flow, porosity, crystal polymorphs, water sorption and dissolution are required for high throughput manufacturing and to ensure the quality of the finished product.
The PMBRC Technology Gateway has a highly experienced team of solid-state pharmaceutical scientists backed up by academic staff that are actively involved in drug product formulation and materials characterisation research. Using a suite of advanced characterisation techniques, the Technology Gateway works with the GSK team to investigate the material properties and determine the ingredient sources most suitable for their products and manufacturing processes. For example, the recent acquisition of an X-ray Diffractometer with an Environmental Chamber (funded by the Enterprise Ireland Capital Infrastructure Programme) allows the study of ingredient polymorphs (crystal forms) as a function of temperature and relative humidity. This, in turn, allows GSK to understand, optimise and trial materials most likely to best perform during manufacture and yield a good shelf-life on storage.
Impact for the Company: Collaboration with the PMBRC Technology Gateway has allowed GSK Dungarvan to identify the best raw material sources for key products in their portfolio and has supported maintenance of the highest quality standards.
Company Testimonial: “The PMBRC offers GSK Dungarvan a local, highly professional and agile materials characterisation support, with timely data generation, thus helping GSK maintain and meet our business expectations. The PMBRC has allowed GSK conduct critical materials characterisation, supporting supplier introductions, along with root cause analyses investigations, ensuring ongoing supply of GSK Consumer Healthcare Products” – Dr. Patrick Mooney, Raw Materials Technical Change Specialist, GSK, Dungarvan, Co. Waterford.
Case Study 2: Innovation Voucher with TriviumVet
Project Title: Development of an analytical method for the detection of a disease biomarker in horses.
Profile of Company: Based in Waterford, TriviumVet uses cutting-edge healthcare and pharmaceutical technologies to create clever, highly effective and functional products for the veterinary market. The TriviumVet pipeline comprises innovative treatments for diseases where there are no specific veterinary approved drugs. TriviumVet Diagnostics, a division of TriviumVet, is developing novel diagnostic tools with applications in both animal and human healthcare.
The company focuses on adapting cutting edge technology developed for human medicine to improve the accessibility for pets. Therapeutic candidates are formulated for species specific suitability, tested for safety and efficacy and are then submitted to the FDA (Centre for Veterinary Medicine) and the EMA European Medicines Agency (CVMP) for approval. The company has a product development pipeline targeting a range of canine, feline and equine conditions.
How the PMBRC delivered a solution for the Company: TriviumVet are developing a product to treat a debilitating condition in horses for which there is no approved treatment on the market. As part of this work, the company needed a sensitive analytical method which could detect and quantify a biomarker in blood samples. This task was made difficult by the low levels of the biomarker in the blood coupled with a range of interfering compounds and sample matrix components. The PMBRC Gateway developed a sample clean-up technique and demonstrated that the target biomarker could be quantified at low levels using ion chromatography.
Impact for the Company: The success of the project allowed TriviumVet to proceed with clinical studies of their treatment which are currently underway.
Company Testimonial: “The PMBRC helped us progress this project from a concept to a working diagnostic aid that can be used not only to progress our internal development work, but also to benefit veterinary patients in the field. Niall, Gautam and the wider PMBRC team went above and beyond our expectations to deliver on a challenging brief. We will certainly be working with this group again on other R&D projects in the future” – Stuart Fitzgerald, Head of Clinical Affairs, TriviumVet.
Case Study 3: Innovation Partnership (Feasibility Study) with PepsiCo
Project Title: Characterisation of raw materials used in concentrates.
Profile of Company: PepsiCo is a leader in the global food and beverage industry, operating in 200 markets, with annual revenues in excess of $60 bn. The PepsiCo Cork site is home to 700 manufacturing and R&D personnel. The Research and Development (R&D) team includes product and packaging developers, and quality and regulatory personnel with a special focus on dairy, beverages, fruits and vegetables.
How the PMBRC delivered a solution for the Company: PepsiCo work with a diverse range of ingredients including sweeteners, flavourings, acids, buffers and preservatives. These ingredients come from a wide range of global suppliers. To ensure smooth running of the manufacturing process, ingredients are required to have certain physico-chemical properties such as rheometry (flow), particle size, particle shape, crystallinity and moisture sorption behaviour. Understanding how these properties affect the manufacturing process and the resulting product quality is critical for PepsiCo.
Working with the company, the PMBRC Technology Gateway selected three key ingredients from the PepsiCo supply chain and conducted a comprehensive characterisation of their properties. Differences between suppliers were identified and these differences were mapped onto process performance. Using the data generated, the project team were able to identify the ideal quality attributes of the incoming raw materials and likewise flag potential problematic batches of incoming ingredients.
Impact for the Company: Using the data generated from the project, PepsiCo were able to approach suppliers with a target profile for incoming raw materials. Potential new suppliers would have to meet certain ingredient specifications prior to being approved for use in PepsiCo manufacturing plants. PepsiCo are now expanding the project to other ingredients in their supply chain.
Company Testimonial: “The work done by the PMBRC provided a real insight into how material properties impact our manufacturing process. It helped explain why some materials have historically caused problems during manufacturing and allowed us to take steps to avoid these problems in the future. During the project regular progress updates were provided. The team explained the results comprehensively which was helpful to my team as we build our knowledge in this area” – Paula Lyons, R&D Concentrate Stewardship Manager, PepsiCo R&D.
Case Study 4: Directly Funded Contract Research with MEDITE SMARTPLY
Project Title: Characterisation of novel wood products.
Profile of Company: MEDITE SMARTPLY is a market leading manufacturer of innovative medium density fibreboard (MDF) and oriented strand board (OSB) panels. Combining the very latest technologies, sustainable raw materials sourced from our own forests and customer-led innovation allows MEDITE SMARTPLY produce products of the highest quality, defining the standards of engineered timber panels. Their manufacturing sites in Clonmel, Co. Tipperary (MEDITE) and Waterford City (SMARTPLY) in Ireland feature the latest production technology to deliver quality products and customer service unparalleled within the industry. Continuous development and investment over the past 30 years has enabled MEDITE SMARTPLY to enter new diverse markets and sectors, ensuring that there is always a fresh pipeline of new products to address market demands.
How the PMBRC delivered a solution for the Company: MEDITE SMARTPLY believe that the next generation of wood panels products will be determined by scientific-led research and enabling technologies. The PMBRC has been an important R&D partner with MEDITE SMARTPLY since 2012, providing technical support to the product development process with an increasingly important role in our development of “Intelligent Engineered Wood Panels”. In particular, their enthusiasm and expertise combined with a wide range of analytical equipment such as DSC, TGA, DVS, HPLC-MS, and GC-MS have been used to solve complex problems and characterise new prototype products.
Impact for the Company: The equipment and expertise of the PMBRC is not available in-house in MEDITE SMARTPLY. By partnering with the PMBRC, the company has been able to develop new solutions and products and get them to market quicker than would have been possible otherwise. This in turns helps MEDITE SMARTPLY maintain its market leading position.
Company Testimonial: “The PMBRC provide skills and expert knowledge essential for MEDITE SMARTPLY to deliver our growth strategy through a “Value Add” based product and service approach. Key to this strategy is the development of innovative new product solutions through scientific-led research where PMBRC are a key collaborator. It is very important that we have the expertise and facilities of PMBRC on our doorstep in the South East as this accelerates our rate of innovation” – Dr. Rory Rice, Technical Development Specialist, MEDITE SMARTPLY.
Case Study 5: 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.
Company Testimonial: “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 6: Direct Funded Collaboration with Waters Technologies Ireland
Waters Technologies Ireland, located in Drinagh, Wexford, is the primary manufacturing infrastructure for Waters Corp Mass Spectrometry Instruments, LC Chemistry consumable, Clinical testing and Data Informatics products worldwide. Specifically Waters generates business advantages for laboratory-dependent organizations by delivering practical and sustainable scientific innovation to enable significant advancement in healthcare delivery, environmental management, food safety, and water quality and employs over 300 people. Waters products are used by pharmaceutical, life science, biochemical, industrial, academic and government organizations working in research and development, quality assurance and other laboratory applications.
The PMBRC has established an ongoing relationship with Waters, supporting their manufacturing and R&D activities. Central to this relationship is the strong analytical capability in the PMBRC including HPLC, LC/MS, GC/MS, NMR, AFM and thermal analysis techniques. The centre has supported Waters in a range of process optimisation, quality investigation and product development projects. The strong research activity in the PMBRC in the area of analytical science has also benefitted the R&D programme at the Waters Technologies Ireland site.
Company Testimonial: “Having the PMBRC on our doorstep has been really important for us in Waters over the last number of years. The ease of access to the equipment and scientific team in the centre has enabled us to rapidly progress quality investigations and R&D projects which were urgent for the site. We have a very good relationship with the team in the centre and now see their capability almost as part of the overall capability of the Wexford site” – Pat Curtis, Principal Process Chemist.
Case Study 7: 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.