SubscribeIreland has one of the world’s fastest growing pharma/biotech sectors and delegates from over 40 major companies followed Werum’s invitation to their MES Day in Cork; they gained deep insights how MES (Manufacturing Execution Systems) are meeting the industry’s aspirations to go electronic in its manufacturing operations.
The benefits of MES
Liam O'Brien of Enterprise System Partners, a Cork-based consultancy in life sciences manufacturing, described the concept and benefits of MES, which integrates overall enterprise resource planning (ERP) and event/shop floor based automation and control systems. Typically, MES cover aspects such as recipe management, material tracking, weighing and dispensing, deviation management, warehouse management, equipment management, and electronic batch recording (EBR) - this being a 'crucial' aspect of where pharma manufacturing is going.
The key advantages of MES are many, and include reduced labour and increased quality of operations through the elimination of the generation, verification and management of paper batch records, said O'Brien. It also makes compliance with regulatory demands, including 21 CFR Part 11, easier.
MES have several attractive features which can streamline workflows. For example, in terms of warehouse management, the main benefit is the significant reduction in labelling activity, while wireless devices and bar-coding decrease errors. 'We are talking here about an e-warehouse, which is fully automated,' he explained.
In the equipment and container management module, which works closely with material management, the functionality to define and enforce cleaning rules means that equipment can only be used if its status is correct. Diarmuid Quinn, also of Enterprise System Partners, went on to discuss the elements involved in the successful introduction of MES into a plant.
A good System Master Plan is an essential starting point. 'This should ideally be a live document reviewed on an annual basis, looking five years ahead and considering the plant or corporation's needs' he stated. After this a Front End Study is needed, followed by vendor selection. The MES project team should be formed as early as possible - ideally playing some role in the Front End Study and vendor selection.
'This is probably the single biggest issue, for MES has impact across the whole organization,' said Quinn. The individuals on the team must have the power to make change and decisions, be IT system aware, and be fully committed to the long duration of the project. When it comes to MES implementation, a phased approach is desirable with prioritisation of the modules to be installed.
There are a number of cautions, Quinn explained, such as checking at the maturity of vendors and their applications, being aware of the impact of MES on standard SOPs, regulatory impact and validation requirements. 'Training requirements must take into account the existing level of PC awareness among staff, which can be low in the work environment, the complexity of the software, and the understanding of 21 CFR Part 11.
For some staff, this will be the first time they have encountered an e-signature.'Simon Bragg, European Research Director, ARC Advisory Group, which advises upon manufacturing and supply chain issues, commented upon trends in the pharma industry and how these will affect manufacturing operations.
The production environment is changing fast. Companies will no longer be relying on two or three blockbusters but will have portfolios of products with hundreds of different recipes and much smaller, almost personalised, batch sizes. These trends will demand changes in manufacturing practices where there will be a leading role for Process Analytical Technology (PAT) and Collaborative Production Management (CPM).
In terms of market share and capabilities, ARC regards Werum as Europe's leading supplier of CPM solutions to the pharma industry. In conclusion, Bragg said, pharmaceutical manufacturing will move from a supply chain to a value chain model, which will lead to a need to place CPM at the heart of the enterprise to improve productivity.
Case study Nycomed (formerly ALTANA)
Graham Clarke, Production Manager of Nycomed's Carrigtohill site, near Cork, described the experience of installing MES from the start in this brand new plant. The site was been designed as a back-up to one of the company's German sites and manufactures tablets of the proton pump inhibitor pantoprazole and a product currently in Phase III. The tabletting process involves the following operations: weigh, blend, granulate, blend (a complex step), compressing, coating, printing to give finished product ready for shipping.
‘My advice is to include as many manufacturing personnel as possible in the qualification stages of MES,' said Clarke. 'This builds up local expertise on site.' In this instance, plant start up - including tech transfer - and the MES project had to run in parallel.
Getting MES to go 'live' while at the same time going into commercial production at the same time presented Nycomed with a 'huge challenge'. 'The key thing is training of users,' he added. 'The more of them are involved in the early stages, the better.' For, while the MES system is an excellent means of controlling material weighing, containers and scales, problems can occur if users are not completely familiar with all the required transactions.
Jim Lambe, IT Manager of the Carrigtohill plant explained why they had decided to install an MES platform. It was seen as the way forward in managing the manufacturing process in a compliant, safe, effective and efficient manner. Key benefits include a more predictable process with minimal risk of deviation - for instance, because material flows are so tightly controlled. MES also integrates with SAP, LIMS and other environments; in short, MES is an essential part of any state-of-the-art, cost-effective manufacturing plant.
The following modules of the Werum PAS-X platform have been installed in the plant: MBR (Material Master Data), EBR (Electronic Batch Recording), WD (Weighing and Dispensing), WMS (Warehouse Management & Raw Material Sampling). The MES installation project began in February 2005 with the award of the purchase order to Werum and was finished by May 2006 with completion of the validation report.
In answer to questions, Lambe commented that although Nycomed was using the EBR component, they currently still had some paper batch records as well. They had appointed a full time systems administrator. 'We placed this post within IT because it is such as key focal area and its people are well known in the plant,' said Lambe. And, yes, Nycomed has developed a disaster plan. 'We built the plant with two servers which are totally separate from one another, connected by two types of fibre optic cable. There is a massive amount of redundancy. If one server goes down, production can go on with data in real time - we monitor and test this on a regular basis.'
Case Study Genzyme
In a second case study, Eamonn O'Mathuna, MES Owner at the Genzyme Waterford site in Waterford, described gWAP (the genzyme Waterford Automation Program). The vision of gWAP is to achieve paperless manufacturing in warehouse, oral dose, packaging, quality control, and fill finish. This involves the installation of the PAS-X system for the production management incl. Electronic Batch Recording/EBR, Material tracking and Warehouse Management, along with a Data Historian System, Product Data Management System and interfacing and integrating these with the existing ERP.
The plant manufactures Renagel, which is used to bind phosphate and reduce the need for kidney dialysis, and various other products. O'Mathuna explained that Genzyme was anticipating significant change and growth at Waterford which would involve an increase of manual data entries from 750,000 in 2005 to 2.5 million in 2010 for batch records alone, with materials and quality data entries being additional to this. gWAP has proceeded, with tabletting and packaging already being completely paperless since April.
Kevin Brady, OD Manufacturing Manager, explained that gWAP has realised benefits in the oral dose product, with 31 paper documents and 1,000 entries being eliminated per batch. There has also been an improvement in Right First Time results, with the target of over 93 per cent being realised and the need for a second signature has been all but eliminated.
Other benefits include real time update of information on batch status and improved container and equipment management. The phased implementation continues to expand. Therefore, production has reached new heights of 1.3 batches per eight hour day, which is the highest output since the commencement of Renagel.
There have been many challenges along the way - over 263 SOPs have been updates and training has involved over 200 man days. 'It has been a challenge to change mind sets and let go of the paper,' Brady said. 'However, our future business is very much focused upon the electronic environment.' In response to questions, the Genzyme team pointed out that regulatory authorities are comfortable with the use of a hand held scanner to 'read' a label.
The gWAP implementation team had been led by IT, and then taken over by manufacturing. They had not lost any data and their concerns about putting all their faith in the system had been unfounded - it had never let them down.
The future of MES Finally, Christian Woelbeling, Director Marketing and Sales with Werum, commented on the future of MES - as Werum sees it. The Pharmaceutical MES market is growing at 10-15 per cent per annum. 'To fully achieve operational excellence and lean manufacturing strategies in pharmaceutical production, you need independent, but integrated, MES,' he said. The company is committed to full integration of their products with SAP ERP which, after all, accounts for 90 per cent of market share.
Furthermore, in his view, MES is now a global roll out and is a manufacturing excellence strategy, and no longer only a system. Also the FDA paradigm shift to QbD (Quality by Design) and PAT calls for improved process understanding and control which Werum's products are able to support.
Accordingly, they are working towards a real time release eWorkflows. Woelbeling's prediction is that in ten years time, every pharmaceutical company will be operating paperless, with EBR systems. Since the PAS-X user conference and user forum is said to be the largest user community within the pharmaceutical industry, this suggests that companies are already quite some way down the paperless road.