Pharmaceutical Manufacturing Technology Centre (PMTC) Detailed Description of Needs Document April 2012

Transcription

1 Pharmaceutical Manufacturing Technology Centre (PMTC) Enterprise Ireland & IDA Ireland an industry led, industry driven research programme Detailed Description of Needs Document April 2012 PAGE 1

2 Contents 1. Introduction and Background 2. Vision and Goals 3. Research Programme 4. Governance and Management 5. IPR Framework 6. Impacts and Metrics 7. Financial Model Appendices A. Other research areas of interest to the Irish Pharmaceutical sector PAGE 2

3 1 Introduction and Background The Irish Pharmaceutical industry is a very significant and important sector of the Irish economy with an estimated 50,000 employees and accounting for over 50% of Irelands exports. Eight of the ten largest pharmaceutical companies in the world have manufacturing operations in Ireland. Cost competitiveness and patent expiry are the two most critical issues facing the international Pharmaceutical industry generally and Irish manufacturers in particular. Irish sites of Multinational companies are increasingly anxious to improve the value proposition to corporate and late stage Research and Development as well as commercial stage Research & Development. This is a key mandate of the Irish operations. Analytics and in particular Process Analytical Technology (PAT) has had an increasing focus in the industry in recent years. Better understanding and control of the manufacturing process can lead to improved cost competitiveness through Reduced reworking and batch rejections Reduced sampling and laboratory costs Improved process yields Reduced cycle and changeover times Shorter development times The regulatory agencies have been supporting and promoting these industry initiatives under the Quality by Design (QbD) framework and there have been several successful improvements and regulatory filings in recent years. However, there remains considerable technical and research challenges in developing and adopting these technologies and this work will be the early focus of the Pharmaceutical Manufacturing Technology Centre (PMTC). The initial focus of the centre will be on the development of advanced analytical technology solutions to provide real time, relevant data and information which enables high levels of process and product quality control, with faster concurrent and end product testing with consequent benefits to the competitiveness of the pharmaceutical industry sector. With more process control comes more process understanding and opportunities invariably arise for better yields, shorter cycle time, fewer mis operations, all resulting is cost savings that add immediate value to the Irish operations. In particular in its first year of operation the centre will look to examine how PAT can be applied to: PAGE 3

4 1) Advanced Rapid Micro Analytical Techniques 2) Powder Processing control through PAT 3) Enabling and control of continuous processing 4) Soft sensor modelling tools 5) API (Active Pharmaceutical Ingredient) Real time release PAT 6) Pharmaceutical packaging design for product traceability, utility and integrity protection These research themes are outlined in further detail in Section 3. The companies supporting the establishment of this Technology Centre have a series of wider research interests which are detailed in Appendix A. Some of these are currently being investigated by other publicly funded research organisations in Ireland and it is proposed that the PMTC would play a role in leveraging this research work for the benefit of the Pharmaceutical Industry in Ireland. The PMTC is funded under the EI/IDA Technology Centre Programme, an industry led research initiative. PAGE 4

5 2 Vision and Goals The vision of the PMTC is to support and develop the Irish pharmaceutical industry (small and large molecule) by improving manufacturing competitiveness and enhancing the research and development mandate and activity of Irish pharmaceutical manufacturing sites and companies. The Goals of the Centre are 1) The PMTC will conduct and coordinate research in advanced pharmaceutical manufacturing technologies which have a wide application across the Irish pharmaceutical industry. 2) The PMTC will assist in the coordination and be an easy access point for the Irish pharmaceutical industry to other pharmaceutical related research facilities and researchers in Ireland. 3) The PTMC will work closely with other Irish research centres and academic institutions to source additional funding for Pharmaceutical Manufacturing related research through company specific projects, EI and IDA research funding and EU framework programmes. 4) The PTMC will be a one stop shop to showcase advanced pharmaceutical manufacturing expertise and support academic industry collaboration in relation to advanced pharmaceutical manufacturing technologies and know how for manufacturing industry and related service providers. 5) The PMTC will liaise with regulatory authorities to provide assistance to Irish pharmaceutical sites on the research and introduction of new manufacturing technologies. 6) The PMTC will provide a global Technology Watch function for its members and will liaise with global networks in pharmaceutical manufacturing innovations to ensure that Irish pharmaceutical sites are updated on research trends. PAGE 5

6 3 Initial research programme Process Analytical Technology (PAT) has had increasing focus from Industry over the last 10 years and in the last 5 years the number of PAT devices installed in commercial manufacturing equipment has increased considerably. This investment in PAT was carried out because it delivers value in process understanding and control thus maximising operating efficiency and confidence in quality. Increased interest in the introduction of continuous manufacturing to replace batch processes has also led to the need for better process analytical technologies. Table1 below shows the types of PAT technology which the pharmaceutical industry is currently using in batch and continuous manufacturing. TABLE 1 Process Analytical Technology currently in use by industry API synthesis Formulation Packaging Distribution PAT Monitoring Technology Advanced control/automation Benefits Raw material ID hand held raman Raw material ID hand held raman Raw material ID hand held NIR Raw material ID hand held NIR RM QC (NIR, MIR) RM QC (NIR, MIR) Vaccuum integrity Reaction monitoring (NIR, Raman) Crystallisation (FBRM) Drying NIR Drying NIR/Mass Spec Mass spectroscopy Granulation control NIR/FBRM FTIR Blending control NIR API RTL Electronic lab notebooks Electronic lab notebooks Bar coding Bar coding Bar coding Bar coding DP RTR Solid dose Product based Energy usage optimisation Energy usage optimisation Energy usage optimisation Enviromental protection Enviromental protection Enviromental protection Operator safety Operator safety Operator safety Cycle time reduction Cycle time reduction Cycle time reduction Lean manufacturing Lean manufacturing Lean manufacturing Process Knowledge Process Knowledge Process Knowledge However there are important areas for industry where further analytical technology improvements are required. Progress on novel PAT devices and methodology has been slower because the technical challenges and instrumentation capability are limiting factors. Progress has also been slow because PAGE 6

7 many interested parties (end users, instrumentation and control companies, academics) are working in isolation. There is a compelling case to pool all the know how and resources and collectively develop and apply the next wave of PAT technology. For Ireland there is an equally compelling case to lead the way in this research and confirm our status as the premier location for advanced pharmaceutical manufacturing. Industry has identified several areas where further PAT development is required. (shown in table 2 below). TABLE 2 Areas where industry believes PAT could be used if developed API synthesis Formulation Packaging Distribution PAT Monitoring Technology Counterfeit proofing Blisterpack tablet location/presence confirmation Reaction monitoring (NMR, MS) Soft sensors Soft sensors Soft sensors Low cost rxn monitoring solutions Crystallisation (MIR) Drying packaging sizing Drying packaging sizing Bio process API Bio sensors Real time impurity monitoring and control Spectroscopic cleaning verification/swab replacement Spectroscopic cleaning verification/swab replacement Continuous process monitoring Continuous process monitoring in line Rapid micro testing Counterfeit ID Patient diagnostics Custom dosing Advanced control/automation Value statements Model predictive control/advanced Process control API CQV RTR Eliminate sampling for high potency, low volume, high cost products PAT enabled rapid, flexible manufacturing for new product launch Flexibility to move within design space Patent extension based on novel technology Model predictive control/advanced Process control DP RTR Platform/ease of transfer Parametric release/rtr aseptic processes Eliminate sampling for high potency, low volume, high cost products PAT enabled rapid, flexible manufacturing for new product launch Flexibility to move within design space Patent extension based on novel technology Model predictive control/advanced Process control Industry also recognises that some of these are very challenging targets but with industry and academia working as one focused centre the probability of success is significantly enhanced. PAGE 7

8 Research themes for Initial Call for Proposals The Centre will focus on advanced pharmaceutical manufacturing technologies with an initial focus on process analytical technologies (PAT) and continuous manufacturing. These themes have been specified by the pharmaceutical companies in Ireland who are interested in becoming members of the Pharmaceutical Manufacturing Technology Centre. The chosen research themes for the initial research programme are shown below. The themes are necessarily broad and intended to underpin the research direction of the centre long term. 1) Advanced rapid micro analytical techniques 2) Powder processing control through PAT 3) Enabling and control of continuous processing 4) Soft sensor modelling tools to maximise process robustness and operational efficiency 5) Active pharmaceutical ingredient API real time release PAT 6) Pharmaceutical packaging technologies for product traceability, utility and integrity protection PAGE 8

9 Research Theme 1 Advanced Rapid Micro Analytical Techniques Objective: The aim of this theme is to research new analytical approaches for the microbial control of Pharmaceutical ingredients, intermediates and finished products. Research should focus on quantitative and qualitative tests which could ultimately replace the standard Pharmacopoeia tests for total counts and sterility testing respectively and be applied in the monitoring and control of pharmaceutical processes. Background and Significance: Total microbial count testing and sterility testing is employed widely across the pharmaceutical and food industry to control the quality of end products and precursors. The microbiological methods described in the current Pharmacopoeias for the detection, enumeration and identification of micro organisms have been in use for almost a century and are very slow. Typical microbial count tests take up to 7 days and typical sterility tests range from days. Thus the results from conventional methods seldom enable proactive corrective action to be taken and increase product throughput times and lead time to the patient. Rapid techniques would facilitate real time or near real time release with earlier intervention for corrective action. Alternative analytical techniques for rapid micro analysis are suggested in the Pharmacopoeias but due to their limitations (i.e. mainly qualitative and very difficult to validate) have not been widely adopted within the Pharmaceutical sector. Research scope: Project duration is expected to be months with research focus as follows: To research new analytical approaches, including nanosensing technologies, to develop alternative rapid micro testing solutions which deliver valid results that are equal to or more accurate than current methods, and reduce the reliance on removing samples for lab analysis. Methods should be quantitative and very sensitive due to the low bioburden of pharmaceutical ingredients and finished products i.e. typical level of detection should be 1CFU/g for Sterile products and 100CFU/g for bioburden testing. Note Sterility tests are normally qualitative. Methods should be rugged and be applicable to a wide range of sample matrices including single and multicomponent powders, semi solids and liquids. Methods should be able to identify if possible any viable organisms detected. Expected results: Rugged, robust alternative rapid analytical techniques for the microbial count and sterility testing of Pharmaceutical materials. Rugged robust biosensors to monitor biocatalysis and pharmaceutical processes Methods are reviewed and approved by industry and regulatory approval bodies New methods are adopted by the Pharmacopoeias PAGE 9

10 Research Theme 2 Powder Processing Control through PAT Objective: To gain a better understanding of the root cause of powder processing issues and define in line analytical techniques to measure performance during processing Background and significance: Solid Phase Powder Processing is carried out widely within the Pharmaceutical industry but lack of understanding of key material attributes / variability in materials results in processing problems which in turn results in downtime, loss of product. Powder processing involves activities such as milling, blending of different powder materials, drying, conveying metered doses into equipment such as reactors, hoppers, tablet presses, dosing into final packs. Problems consistently arise and result in interrupted manufacturing operations due to blockages or quality problems with product uniformity leading to process down time, lengthy and costly investigations and loss of product. The scientific root causes of these often intermittent issues are rarely understood and often repeat themselves across different products. Ideally such problems should be designed out of the process for new products. Several international research consortia, e.g. in the USA Rutgers Purdue, and in Europe, University of Eastern Finland have been focussing on the development of continuous manufacturing platforms and PAT analysers with the pharmaceutical industry. Research scope: Project duration is expected to be months with the following focus: 1) Technology Watch function is an overarching activity for this theme with the Lead Research Group liaising with international research consortia to inform the companies in Ireland of advances in international research and industry implementation of commercially available PAT systems for powder control. The Lead research group will determine the most effective, inexpensive tests which could generate a model with which one could determine how much of a problem existing / new materials are likely to pose. 2) Evaluate available PAT tools to characterize powder properties, flowability and segregation (demixing). Select the most relevant tools and characterize a number of widely used materials individually, e.g. API and carrier and as formulated mixtures. (One paste formulation to be included in the sample set). Determine the critical parameters to be measured as predictors of powder flowability, blend performance, blend uniformity, segregation risk etc. Compare laboratory and PAT inline tools where necessary. 3) Integrate a PAT solution following GMP and QbD for a defined process, e.g. roller compaction / milling at a pharmaceutical site as agreed by the companies. Expected results: Better understanding of what and how to measure material characteristics which affect various process steps for milling, blending, equipment feeding and tableting operations. A model developed to use as a predictor of problems. Demonstration and integration of a PAT solution in cooperation with the pharmaceutical group of companies and in liaison with the regulatory authorities. PAGE 10

11 Research Theme 3 Enabling and control of continuous processing Objective: This theme aims to define the particular attributes which enable dry granulation (DG) to be used as a green manufacturing approach with consequent benefits in terms of process efficiency and energy usage. Background and significance: Granulation is a widely used process step in pharmaceuticals formulation in order to improve the flow properties of active ingredients thus enabling accurate and repeatable dosing into tableting or other dose filling equipment. Dry granulation avoids the use of wetting agents such as water or solvents to bind the ingredients, by compacting mixtures of powders at high pressure to form a solid flake which when milled forms a free flowing granular powder suitable for tableting, capsule filling or other dose filling. Dry granulation is an old technology which predates more sophisticated alternatives such as wet granulation and Fluid Bed Granulation. Its advantages are its relative simplicity compared to wet granulation (no addition of solvents and/or heat), requiring more compact equipment, facilitates (semi) continuous processing with resultant lower operating costs. The challenge is that it is not always applicable and depends on the physical attributes of the components being granulated both individually and as a mixture although the precise impacts of these are not well characterized using modern analytical tools. Process development tends to focus on particular features of different compaction equipment and operating parameters of same. With the application of good science this approach could be more widely applied as a cost efficient manufacturing process. For clarity a DG process includes premixing of ingredients, compaction to dry flake, and milling to produce a free flowing powder fit for further processing to tablet, capsule or powder for rehydration form. Several international research consortia, e.g. University of Purdue, University of Bonn & Atacama Labs, Abo Akademi University, Finland, etc have been focussing on the development of dry granulation technologies with the pharmaceutical industry. This theme is intended to apply the principles of Quality by Design (QbD) as defined in ICH Q8 Pharmaceutical Development to Dry Granulation (DG) processing which systematically aims to Define the desired product performance required from the process. Define Critical Quality Attributes (CQA s) Design the formulation and process to achieve these product CQA s Understand the material attributes and process parameters to achieve these CQA s Identify and control the sources of variability in the materials and process Monitor process and adjust the process to optimize control. The result will define a set of operating parameters and controls for the process which will ensure consistent product quality output, less waste, and eliminate or reduce the need for end of line testing. PAGE 11

12 The potential also to implement semi continuous processing offers significant cost advantages to industry over batch methods. Research scope: Project duration is expected to be months involving the following suggested tasks: Define the principles which enable the selection of DG as a first choice process option for oral solid dosage drug product forms. Define an appropriate set of characteristics which appropriately define the properties of materials relevant to dry granulation processing. Identify process analytical technologies (PAT) which can measure variation in critical material and process parameters and enable feedback control to adjust equipment such that the desired process performance is maintained. To prove this approach at a pilot scale level examining any issues arising during scale up from the bench. Expected results : By building a coherent body of scientific principles which model this process and defining the tool kit of modern analytical technologies which enable good process design and control, this will create a centre for OEM s of relevant equipment, instrumentation and control, and manufacturing technologies to collaborate and innovate more openly with industrial partners. The approach developed and outputs delivered from the above challenges will establish a template to be applied to develop similar expertise in other relevant processes widely applied in drug product formulation, especially for solid and semi solid forms where physical properties play a significant role in process performance. PAGE 12

13 Research Theme 4 Soft Sensor modelling tools to maximise process robustness and operational efficiency Objective: Modelling using existing process data to provide improved process control and robustness Background and significance: Process robustness is critical in the Pharmaceutical industry yet it is an ongoing challenge and leads to operational inefficiency. Manufacturing in the pharmaceutical industry is supported by the most advanced automation controls and monitoring available. A lot of this capability is not fully used in the industry because the tools to extract maximum value are not available. As part of the manufacturing process, multiple routine measurements are collected (e.g. temperatures, pressures, ph, torque, power consumption etc.). With the continuing adoption of Process Analytical Technology, the ability to monitor direct and indirect product quality attributes and process parameters in real time is also expanding. The evaluation of any of these measurements univariately may provide some information, however, adopting a more holistic approach and monitoring these parameters multivariately may provide significantly more. The creation of soft sensors (or virtual sensors), combining the available parameters in either an openloop or as part of closed loop controls could greatly enhance operational efficiency. The sensors can be used as diagnostic tools to rapidly identify multivariate process deviations. They can further be used as inputs for control to ensure required process performance. Multivariate analysis is still regarded as a specialist tool and will remain so unless we release its potential and add additional value through real demonstrations. Research scope: Project duration is expected to be months, focussed as follows: Develop a user friendly methodology or system that can be used by operators and supervisors on plant floors that will provide a step up in process control and robustness. Statisticians, automation engineers, modellers, mathematicians, programmers may be required to collaborate to bring forward a solution. It may be valuable to identify a specific manufacturing process for demonstration. Accurate data must be available for the specific process to develop the model, which may require data cleaning prior to use. Offline data is also required to verify the performance of the soft sensor. Expected results: A software solution that sits on an automation system that takes data from all measuring devices (including agitation, torque, pressure, PAT etc) and translates it to process performance. PAGE 13

14 Research Theme 5 API Real Time Release PAT Objective: Extend the successful application of real time release in solid dose drug product into active pharmaceutical ingredient (API) manufacturing with consequent benefits for manufacturing flexibility and control. Background and significance: Real time release of solid dose drug product is now well established in the pharmaceutical industry with a number of commercial examples. Real time release has been achieved not only by replacing end product testing with online testing but also by elimination of testing requirements using process knowledge derived from the application of Quality by Design principles. To date real time release has proven difficult to apply to the release of active ingredients (API). While process monitoring using existing technology can give the ability to understand and control our processes the elimination of offline tests has proven difficult primarily due to the requirement to test for low levels of specific impurities. Today, with lean practices in QC laboratories, very often there are multiple batches maybe even a full campaign of 20 batches, awaiting analysis. If a problem is identified during testing there could be a market stockout or significant plant rescheduling to rework batches. Technology that could, in real time, evaluate key product quality attributes without sampling, would represent a significant advance for API manufacturing. In particular, a device that could detect, identify and quantify impurities in API would be invaluable. Research scope: Combine latest technologies, process analytic / spectroscopic / process chromatographic technologies and develop new technologies to assemble robust PAT device(s) for rapid at line/in line API impurity monitoring Expected results: Development of new applications of existing technology, or completely new technology that would facilitate real time release of API. PAGE 14

15 Research Theme 6 Pharmaceutical packaging technologies for product traceability, utility and integrity protection Objective: This theme is aimed at supporting ongoing efforts by the pharmaceutical industry and its regulators to ensure that product integrity is maintained over the supply chain to the end user. Background and Significance: It is estimated by the main global regulatory agencies that counterfeit medicines account for more than 10% of pharmaceutical sales and is a major illegal industry globally today. A particular source is the introduction of counterfeit packs of product into the supply chain after the product leaves the manufacturer and up to the point of sale. The European Medicines Agency currently have a guidance document out for consultation to industry which will aim to implement regulations and better control in this area. They specify what is needed but not how to get there. Packaging costs represent a significant portion of the cost of a drug product and the above mentioned moves to increased controls and prevent counterfeiting will add further to this. Input at the pre launch stage of drug development is critical since any such design features must be presented to regulators for approval in advance of implementation. Given the importance of this industry to Ireland Inc, it makes sense that relevant ICT and advanced analytical expertise and know how be developed by the Centre and made available to companies to enable technically elegant, cost efficient, solutions to be devised which will embed this important last step of pharmaceutical processing in this country. Recent advances have been reported, e.g. Sproxil s item unique 2D variable bar coding which can be scanned using smartphones. Novel anticounterfeiting solutions could also be applicable to the Medtech sector. Research Scope: Project duration is expected to be months and might include the following approaches: Design and selection of unique Physical Chemical Identifiers (PCID s) which would be embedded in the drug product and/or primary packaging as a verification that the product is genuine and not counterfeit. A PCID is defined by US FDA as a substance or combination of substances possessing a unique physical or chemical property used to identify and authenticate a drug product or dosage. In addition to inks, pigments, and flavours, specific chemicals may be used as molecular tags in a PCID. In some cases, the PCID may be easily detected by wholesalers or pharmacists to determine if they have authentic products. In other cases, special analytical instruments may be necessary to identify whether the PCID is present. Define widely available detection tools/technologies (NIR, Raman etc) for the PCIDs which verify product authenticity at plant and retail levels and in between. Assessment and selection of technologies (RFID, 2 D matrix barcoding, etc) to manage serialization of product packaging to the single package level uniquely defining the pack in terms of batch, date of manufacture, position within the lot and encoded printing of such data on each box and at secondary pack level. Integration of same with packaging PAT data management and analysis to capture the full batch history during the manufacturing cycle and facilitate QA overview. PAGE 15

16 Integration with (existing or new) point of sale scanning technologies, such that it can be read and verified at the pharmacy level as the genuine article, preferably in conjunction with PCID detection as per above. Consultation with and involvement of the Irish Medicines Board with respect to the compliance of any proposed solutions to regulatory expectations will also be sought and will enhance the global roll out of same. Expected Results: By addressing the challenges presented by the particular driver for innovation which is to prevent counterfeiting of medicines a one stop shop of expertise can coherently advance the application of technologies in this area which is a global need, and will benefit Ireland by being located close to the Irish pharmaceutical manufacturing sector. It will help embed anti counterfeiting pharmaceutical packaging technology know how in Ireland, which is a critical activity during product launch and ongoing supply. Close involvement of the IMB in supporting the work of the centre will also benefit the sector. Test facilities for new packaging developments will be provided by the packaging companies in the Centre. PAGE 16

17 4 Centre Governance and Management The centre will be an independent, industry driven entity to carry out research of importance to the Irish Pharmaceutical industry, with a view to the commercialization of that research. It is envisaged that the centre will be hosted at a Third Level Institution, with other third level partners also participating in the projects. Once the initial research projects have been awarded, the call for applications to Host the Centre will be advertised. This two stage approach will provide a means of getting the centre started reasonably quickly with the initial research agenda, while a parallel negotiation process takes place on the longer term hosting of the centre and development of the full business plan. The overall structure will be such that the centre is run by a Board with a majority industry membership in order to maintain the commercial focus and ensure that the centre is operated independently. The Technology Leader of the centre will report directly to the Board. There will be other committees appointed by the Board, as deemed necessary for the operation of the centre. These committees will also report to the Board. The Centre Board When the centre is fully established the centre will be managed by a Board made up of representatives of the participating companies, an independent Chair and, where applicable, the research institutions. The membership of the Board will be chosen by the initial participants, but it is recommended that it should not initially exceed 11 members. For the Initial Research Programme an Interim Steering Committee will be put in place. Board membership will be rotated amongst the general membership on a regular basis, with board members serving a two or three year term. It is anticipated that a third or half the board members would rotate every two years. These detailed board arrangements will be decided by the initial board in conjunction with EI/IDA and the participating research institutions. The Board will be in charge of all matters relating to the centre and its activities, including, by way of example: Strategic planning of all aspects of the centre Direction and scope of the research programme Selection of key positions within the centre Authorization of centre expenditures Support increased interactions with the greater industry and academic community. The establishment of other committees as are needed for the operation of the centre e.g.: Intellectual Property Committee; Scientific Advisory Board. PAGE 17

18 The Chair of the Board is a key position in the operation of the centre, and it is recommended that an independent person be chosen carefully for this position. The Chair will be a respected industry figure and will ideally not be associated directly with any participating company or research institute. The Board will meet quarterly. Standard agenda items will be Review of work programme Research & Project updates & new proposals IP update Budget review Public awareness issues Market developments Technology Developments Brokerage activity A representative from SFI will be invited to be an observer at the board (together with observers from EI and IDA) to ensure alignment of the centre s activity with other publicly funded pharmaceutical related research. Functions of the Centre Board The Centre Board will be in charge of all matters relating to the Centre and the Centre Activities including, by way of example: (a) Policy matters and strategic planning in respect of all aspects of the Centre Activities; (b) Direction and scope of the Research Programme, and any changes to same; (c) Selection of the Technology Leader; (d) Development of networks with the greater academic and industrial community (both nationally and internationally) through workshops and such other ways as may be appropriate; (e) Monitoring compliance by the Participants with this Agreement and the Grant Agreement, specifying the steps which the Participants need to take in order to ensure compliance with same, and approving actions to be taken against a defaulting Participant; (f) Authorisation of Centre expenditures; (g) Identification of potential new industry and university members to the Consortium; (h) Valuation of non cash component of the Participant Contributions of each Participant; PAGE 18

19 (i) Issuing instructions to the TL, the IP Committee, the Programme Committee,; and (j) All other matters, decisions and other acts and things which the Grant Agreement and/or this Agreement specifies should be made, dealt with or carried out (as the case may be) by the Centre Board. In carrying out its functions, the Centre Board may establish such other procedures, committees or offices as it considers necessary in order to ensure the proper management of the Centre and of the Centre Activities including, by way of example, a scientific advisory committee and/or a commercial director. Industry Involvement in Management of the Centre The involvement of industry at the strategic and operational levels within the Centre is a key characteristic of the Centre and a major asset when developing and delivering services to the commercial sector. At the board of management level, industry is represented by a majority of full voting members of the board. The role of industry board members is to ensure that the type of services that the Centre is offering, and the service models which are being used, are commercially realistic and attractive. The policies and procedures which govern the working of the Centre are developed at board level; industry members of the board are tasked to ensure that these policies and procedures are enablers for industry cooperation, rather than obstacles. Industry partners are actively involved in the review of research agendas. Industrial partners are encouraged to identify research areas and specific research topics which will be of strategic or competitive value to them; these are then integrated into the research agenda. Where industrial researchers are already addressing these areas, collaborative research initiatives can be put in place. These may include the placement of industrial researchers in centre premises, where appropriate. Technology Leader The Board will appoint the Technology Leader. He/she will act as the public face of the organisation and will be the top level management liaison with industrial partners, with funding agencies, regulatory authorities, with PIs (Principal Investigators) within the Centre and with academic collaborators. The TL must have Credibility and profile with companies and researchers in the sector Extensive industrial experience Political and policy awareness Management and people skills The ability to balance research, financial, social and political imperatives PAGE 19

20 The TL s most important role is to provide the centre with the industry profile which it needs in order to optimally develop its relationships with commercial partners. The TL will be a senior industry figure with a proven track record of success in the sector. The ability of the TL to fully understand the Irish and International Pharmaceutical Industry context and to network smoothly with senior management of Pharmaceutical companies in Ireland is a priority. The TL will have proven experience in managing research teams and technology/product development, managing external collaborations including industrial collaborations, strategic planning, business development, input into the commercialisation of research and new technologies, identification of intellectual property, leadership of people and project teams in complex organisations, pursuit of national and international grant support, publishing and patenting. The TL will report to the Chair and Board of Management. IP Committee Technology Steering Committee Centre Membership A Process will be implemented to bring in additional members to the centre. These new member companies will be proposed and approved by the Board. An annual cost of membership will be agreed and the privileges of this membership will include inclusion at programme meetings, access to non IP PAGE 20

21 sensitive data, access to alerts of centre activities. The following companies have already confirmed their willingness to participate in the Centre. Some of these companies have agreed to nominate a representative to serve on the interim board of management for the Centre. Multinational Pharmaceutical companies Allergan Alkermes BMS Swords Helsinn Birex Leo Pharma Janssen J&J Pfizer Servier Teva Pharma Indigenous companies Applied Process Consulting, APC Innopharmalabs Steripack Topchem Pharma Linking and building on the work of other related research groups The PMTC will develop strong links to other centres and research groups currently supporting research for the Pharmaceutical industry. In particular the current activities and research of the SSPC (Solid State Pharmaceutical Cluster), NIBRT (National Institute of Bioprocessing Research and Training) and IDDN (Irish Drug Delivery Network) have been identified by the participating companies as being of relevance. It is proposed that the PMTC could play an important coordinating role, with the agreement of the main funding agencies (EI/SFI/IDA) to simplify industry s access to the Irish research community and to PAGE 21

22 put together multi group proposals and projects for EU Framework research or other publicly funded research schemes. PAGE 22

23 5) Intellectual Property Management IPR Framework Agreement This section sets out the understanding regarding the IP generated by the Centre. It has the support of the companies currently planning to be members of the Centre. A similar IP model has been used in other publicly funded research undertaken by a number of the supporting companies in Ireland and so the legal agreement to underpin the model should be reasonably straightforward to agree with both the multinational and Irish member companies and any participating research organisations. A member is a company who signs the Centre s Agreements and pays the annual membership fee. The IPR model is interdependent with the funding arrangements therefore the following IPR models will apply: Platform Projects, 100% State funded Projects in the Initial Research Programme of the Technology Centre are Platform projects which have a wide applicability to all companies involved. These initial projects are 100% State funded and do not include any company funding contributions. The IP will be owned by the Public Research Organisation (PRO) as outlined in the National Code of Practise for Management of IP from Publicly funded Research, and in compliance with EU State Aid Rules. Industry members will have first right to licence the IP at fair market rate. Should the industry members decide not to exercise their right to licence the IP, the Centre may offer an option to Irish or European non member companies at fair market rate. Platform Projects, industry co funded As the Centre becomes fully established, industry co funded projects will be introduced with access rights relating to the funding contribution provided by the members. Platform multi industry member projects are seen as the preferred mechanism to leverage inter member collaboration, as these projects have the potential to provide the most widely applicable results. Common, non competing, research themes will be outlined for Platform Projects which may be carried out by one PRO or multiple PROs. One or multiple PROs + multiple industry members One PRO + multiple industry members The PRO which generates the IP will own it, and the co funding industry members will have first option to license it. The licensing fee will be based on fair market value less the cash and in kind contribution which the member has made to the project. Should the co funding industry members decide not to exercise their right to exploit the IP, the Centre may offer an option to other Centre members at fair market rate. If none of the industry members wish to exploit the IP, the Centre may offer an option to Irish or European non member companies at fair market rate. PAGE 23

24 Where the co funding industry members of a project group determine that an exclusive licence is agreeable and preferable for maximum exploitation, a process will be agreed in the consortium agreement for this. Such exclusive licence shall be at fair market rate. Targeted Projects, industry co funded While most projects in the Centre are expected to be Platform multi industry member / single (or multiple) PRO projects, provision will also be made for sole industry member projects, i.e. Targeted projects. Targeted projects for a sole industry member must seek advance approval from the Board through the facilitation of the Technology Leader. The funding contribution to be provided by the industry member will be in line with EU State Aid Rules and the industry member may negotiate exclusive rights to the results of the targeted project at market rate. IP Committee The IP Committee will be set up during the Initial Research Phase after the Hosting contract has been awarded. The Host PRO, though the facilitation of the Technology Leader shall act as sole agent for all IP negotiations and shall make appropriate arrangements with collaborating PROs. The Host PRO is the sole agent for the exploitation of all IP generated under the Centre for the term of the Centre. The IP Committee will be led by the Host PROs TT Office and will comprise the Technology Leader, a representative from each PRO, an industry member and a funding agency observer. The reporting and documenting of results will be the responsibility of each PRO reporting to the Host PRO in accordance with the IP Schedule. PROs are responsible for the keeping of records, documenting of background IP, protection of foreground IP and for informing the industry members of project results through the facilitation of the Technology Leader. As part of the IP Schedule, background IP being non exclusively made available for projects will be registered on a project by project basis. PROs will provide an option to non exclusively licence background they introduce to the project where that background is needed and necessary to exploit foreground IP. Such licence shall be at fair market rate. PAGE 24

25 6) Impacts and metrics The impacts and metrics expected of the centre will be a critical measure of its success. The impacts and metrics detailed here will be considered in more detail by the centre board during its initial first year of operation and modified, quantified and developed further as required. Company Impacts Extent to which the companies involved in the centre are sustaining or increasing employment numbers. Amount of R & D investment and activity secured by Irish sites of MNC s and engaged in by Irish companies. Cost competitiveness of the Irish Pharmaceutical Industry Extent of contact and liaison with the regulatory authorities on centre projects. IP and Research Quality The number of invention disclosures, patents filed, prototypes developed and new technologies demonstrated. The effectiveness of the centre s IP Steering Committee and IP Agreements in managing new intellectual property developed by the research partners thus facilitating effective and timely technology transfer for centre members. Technology Transfer The number of licenses completed with company members The number of knowledge transfers, including researcher to company knowledge transfers, company to researcher knowledge transfers and company to company knowledge transfers Technology adoption rate for completed licences, resulting in full commercial implementation Industry Engagement Membership and Governance The extent to which centre membership is growing and developing each year. The level of engagement by industry members with the centre, as measured by the number of co funded platform and co funded targeted projects. The extent of company to company cooperation and networking arising from the centres activities. PAGE 25

26 The number of exchanges, visits and recruitment/staff placements between industry and academic members. Number of wider industry events (conferences and open meetings) organised by the centre. Satisfaction of membership with the overall activities and running of the centre. Leveraged Funding The number of EU Framework research projects developed by the centre. The amount of other industrially relevant projects developed by the centre assisted by funding agencies (EI/IDA/SFI). The centre board will provide funding agencies with a comprehensive report on an annual basis. This report must include progress against metrics and deliverables for the previous year, a financial report for the previous year, work programmes for the next year, metrics and deliverables for the next year, and a detailed budget for the next year. A major review of the progress of the centre will be carried out in year 3. This review will include all the annual reports in addition to a site visit by an international panel of experts, and an industry survey to gauge the reputation of the centre in the industrial sector. PAGE 26

27 7) Financial model A detailed financial model will be developed based on the EI/IDA commitment of 1m per annum over five years, funding including overhead contribution, once the initial engagement with the research organisations occurs. It is also the expectation of the industry group that the centre would look at other sources of project funding (EU Framework, company contributions, other EI funding mechanisms, IDA research funding) in addition to the EI/IDA core funding. A more detailed budget and funding model will be developed as part of the year 2 6 Business Plan which will be prepared once the centre is fully established. PAGE 27

28 Appendix A Summary of all research themes of interest to Irish Pharmaceutical Manufacturers (as identified at the Industry workshop in January 2012) Synthesis/ Biosynthesis (Small molecule and biomolecule) Catalysis (inorganic and enzymatic, biocatalysis), ionic liquids Continuous manufacturing Single use/modular/portable manufacturing technologies (Wave reactions / plug and play) Biological manufacture of API Anti counterfeiting technology Reducing raw material variability analytics for fingerprinting Interaction with material aggregation Elimination of a process step Research on novel equipment/ plant set up/design/system integration Lean manufacturing Isolation/ Purification ( Small molecule and biomolecule) Continuous crystallization Downstream bioprocessing Analytics (Includes in process testing and finished product, development and routine) PAT in line/at line Process control PAGE 28

29 Process modelling predictive modelling Science of scale up modelling approach to scale up Automation data analytics Real time release High throughput chromatography Rapid sterility/micro assays Formulation (Includes solids, liquids, semi solids, sterile/non sterile, primary packaging/filling) Oral delivery of biologics Primary contact materials Combination meds Dry granulation Flavours and taste masking Oral delivery of large molecules Extended release How to integrate API and formulation QbD connecting development and manufacturing Adaptable scale up centre for novel drug delivery systems Packaging technology (Secondary packaging, printed components, bulk packing and transport) Automation Serialization and traceability PAGE 29

30 Anti counterfeiting Cold chain Patient friendly packs for compliance Integrate with healthcare to deliver market needs Patient centric/friendly packaging development PAGE 30