Attachment C. Site Management and Control

Transcription

1 Attachment C. Site Management and Control EPA Export :22:43:46

2 Attachment C Management of the Installation C.1 Site Management and Control The organisation chart for the management of the Alexion biopharmaceutical manufacturing campus when in operation is provided as follows: Executive Vice President of Global Operations Vice President of Alexion Pharma International Trading - Manufacturing Director of Operations While the full leadership team shall be accountable for environmental performance, specific functional responsibility for environment management will be the responsibility of the EHS & Security Manager. Specific duties in that regard are listed below. The management team will be provided all the appropriate training and resources to effectively manage and control environmental compliance. The Alexion EHS Policy is shown in Attachment C.1. Specific Duties of the EHS & Security Manager EHS & Security Manager The EHS & Security Manager, reporting to the Director of Operations, will have overall responsibility for maintenance and implementation of the Environmental Management System (EMS), including the compilation, distribution, amendment and maintenance of all EMS documentation at the installation. The EHS & Security Manager will develop the site EHS strategy for the start-up phase and extend into long term sustainable model. Specifically, the duties and responsibilities of the EHS & Security Manager include: - Provide effective hands on, operational environmental health & safety support and advice to management and site personnel in all areas - Ensure compliance with existing and evolving regulatory and company Environmental, Health and Safety requirements & expectations - Ensure that new processes and associated equipment modifications are assessed from an environmental health and safety point of view through risk assessment - Provide a point of contact for communication and correspondence with the EPA - Ensure compliance with Industrial Emissions Licence conditions - Ensure provision of Annual Environmental Report to the EPA to include, amongst others, selfmonitoring data, environmental management programme, schedule of environmental objectives and targets and licence specific reports Attachment C Site Management & Control.DOC Page 1 of 4 EPA Export :22:43:46

3 - Ensure compliance with REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), Health & Safety Authority (HSA) and Dangerous Goods Safety Adviser (DGSA) requirements - Establish and document the environmental standards and criteria to be applied for each production and process - Ensure that each department s responsibility for environmental performance is suitably documented - Ensure that adequate records are maintained for demonstration of conformance to environmental requirements - Conduct internal audits of the Environmental Management System to ensure continued adherence to documented requirements - Ensure that adequate resources are available to maintain the environmental system at its required level - Ensure the health and safety regulations are catered for in the Environmental Management System. Ongoing Assessment of Environmental Performance The Alexion campus will be subject to the following principles and conditions: - Best Available Technologies (BAT): BAT is a key principle in the Industrial Emissions Directive where emphasis is placed on pollution prevention techniques, including cleaner techniques and waste minimisation, rather than end-of-pipe treatment. Alexion will subscribe fully to the principles of BAT in the design and operation of the campus. Table I.8 contains supporting information in relation to the BAT conclusions. - Waste Management: Production and associated activities at the campus will unavoidably generate waste. Alexion will operate and maintain a well-developed waste management, minimisation and auditing strategy at the campus (further details in Section F Materials Handling). The IEL will set out a series of requirements/conditions with respect to waste in terms of recording, reporting, and waste contractor requirements. Alexion will comply fully with their obligations in terms of waste management as set out in the IEL. - Environmental Management System (EMS) / Environmental Management Programme (EMP): Improvements in environmental performance are encouraged in the EMP associated with the IEL by setting a series of objectives and targets commonly associated with reducing resource material use (e.g. water, energy etc.) and waste production generally. Alexion will undertake the establishment of meaningful and aggressive targets for improvements in the areas of waste reduction throughout the lifetime of the operation of the biopharmaceutical manufacturing campus. Quality Control System A Quality Management System (QMS) will be developed to meet quality guidelines and regulatory requirements. C.2 Environmental Management System An Environmental Management System (EMS) will be developed for the campus in line with the ISO standard. A decision on whether the management system will be certified to the ISO standard will be made once the management system is in place. The EMS will monitor environmental performance and set objectives and targets to reduce environmental impact. The EMS and Environmental Management Programme (EMP) will encourage improvements in environmental performance by setting a series of objectives and targets commonly associated with reducing material use (e.g. raw materials, water, energy, etc.) and waste production. Alexion will undertake the establishment of meaningful targets for improvements in the areas of waste reduction throughout the lifetime of the operation of the campus. Attachment C Site Management & Control.DOC Page 2 of 4 EPA Export :22:43:46

4 A copy of the EMP for each year will be included in the Annual Environmental Report submitted to the EPA, along with the proposed programme or objectives and targets for each forthcoming year. The EMS will be audited on an on-going basis, both internally and externally. C.3 Hours of Operation (a) Proposed Hours of Operation The Alexion campus will operate 24 hours. Day staff will be on site from Monday to Friday, from 8 am to 5 pm each day. Site operatives will have a 24/7 four cycle shift with shift change at 07:00 and 19:00. There will be a 24 hours security presence on site throughout the year. (b) Proposed Hours of Construction and Development Works and Timeframes Construction will occur for a period of 24 months. Normal construction working hours will be Monday to Friday 8:00am to 6:00pm however longer working hours and potentially shift work is envisaged during peak construction periods. (c) Not Applicable. (d) Not Applicable. For waste activities, the proposed hours of waste acceptance Any other relevant hours of operation expected C.4 Fit and Proper Person - Indicate whether the applicant or other relevant person has been convicted under the Environmental Protection Agency Act 1992, as amended, the Waste Management Act 1996, as amended, the Local Government (Water Pollution) Acts 1997 and 1990, the Air Pollution Act 1987 and the Air Pollution Act 1987 (Environmental Specifications for Petrol and Diesel Fuels)(Amendment) Regulations Neither Alexion nor any Director of Alexion has been convicted of any offence under the Environmental Protection Agency Act 1992, as amended, the Waste Management Act 1996, as amended, the Local Government (Water Pollution) Acts 1997 and 1990, the Air Pollution Act 1987, and the Air Pollution Act 1987 (Environmental Specifications for Petrol and Diesel Fuels)(Amendment) Regulations Provide details of the applicant s technical knowledge and/or qualifications, along with that of other relevant employees. The knowledge and skills that Alexion staff has built up in the design, operation and management of facilities around this technology will ensure that any potential environmental risks associated with the process will be minimised, in comparison with a situation where a new technology or manufacturing process is being introduced. The current EHS & Security Manager has the following experience: - BSc. Environmental Science, MSc. Energy Management and a Diploma in Legal Studies - A minimum of 10 years EHS experience and a proven track record operating in a EHS role in a bio-pharmaceutical manufacturing environment - Experience working with the HSA and EPA - A high level of initiative, energy and motivation are key role requirements, as well as organisational skills - Knowledge of pharmaceutical manufacturing - IT Skills, Communication Skills, People Management Skills. The management and staff of the Alexion campus will be supported by equipment vendor personnel for the purposes of commissioning and installation, training, maintenance and equipment replacement/repair. This Attachment C Site Management & Control.DOC Page 3 of 4 EPA Export :22:43:46

5 will be formalised through the operation of service / maintenance contracts, as appropriate following completion of the construction phase. - Provide information to show that the person is likely to be in a position to meet any financial commitments or liabilities that may have been or will be entered into or incurred in carrying on the activity to which the application relates or in consequence of ceasing to carry out that activity. Alexion is aware that as part of grant of the IEL that it may be requested to complete a Decommissioning Management Plan (DMP) and an Environmental Liabilities Risk Assessment (ELRA). These reports will identify the necessary costs required to cover these liabilities and at that point in time Alexion will put in place the necessary financial provisions, following EPA approval. A detailed ELRA and DMP will be developed and submitted to the EPA within six months of commencement of operations, or as otherwise agreed with the EPA, in accordance with the relevant Guidance on assessing and costing environmental liabilities (EPA, 2014). The plans will be reviewed in accordance with IEL conditions. Decommissioning of all aspects of the campus will be validated by the EPA in the event of a surrender of the IEL. Attachment C Site Management & Control.DOC Page 4 of 4 EPA Export :22:43:46

6 Attachment C.1 Alexion EHS Policy EPA Export :22:43:46

7 Environment, Health & Safety Policy Alexion s mission is to prolong and improve the quality of human life, by providing products and services for major unmet medical needs. We incorporate our competencies into the way we do business to implement the EHS policy for all operations at our sites. OUR COMPETENCIES Accountability All employees are accountable for their own health and safety. Employees are encouraged to actively participate in EHS matters and work in partnership with management to assure compliance and support continuous improvement. We are all empowered to challenge any activity if there is an unacceptable risk of a safety or environmental incident. Drive for Results By setting and achieving challenging EHS objectives based on the principles of Risk Avoidance and Pollution Prevention, we demonstrate our commitment to continuous improving EHS performance. Decision Quality We are committed to complying with the spirit and letter of all legal and regulatory requirements relating to protection of all employees, members of the public and the environment. We implement best practices to safeguard our workplaces and the environment. Perseverance We drive for world-class EHS performance by encouraging everyone to engage with the EHS systems, provide leadership and to comply with policies and practices. We provide workplace policies, standards, procedures and training to ensure that employees can perform their jobs in a safe, healthy and environmentally responsible manner. Problem Solving We believe that all workplace incidents, illnesses and adverse environmental impacts are preventable. We drive down the EHS impact of our operations by continuously improving the way we do business to improve safety, reduce emissions, waste, and energy use. Collaboration We promote and maintain open, constructive dialogue and good working relationships with employees, regulatory agencies, customers, third parties and local communities. We share information and openly communicate our EHS performance. We want everyone to go home safe everyday Julie O Neill, EVP Global Operations Rev 01 EPA Export :22:43:46

8 Attachment D. Infrastructure & Operation EPA Export :22:43:47

9 Attachment D Infrastructure and Operation D.1.1 Operational History The Alexion site is a biopharmaceutical manufacturing campus located on a 16.8 Ha. plot within the IDA College Business and Technology Park (i.e. College Park), approximately 12km north-west of Dublin City Centre, adjacent to the Institute of Technology, Blanchardstown (ITB). Phase 1 of the campus i.e. the construction of a 5 storey office building and roof top plant room, QC laboratories, packaging / warehouse building, utility building and spine corridor on a greenfield site was granted planning permission by Fingal County Council (FCC) in May 2014 (Planning Ref. FW14A/0020). A further planning permission was granted in January 2015 (Planning Ref. FW14A/0138) for amendments to the previously approved planning application. The Phase 1 development is due for completion in Q Phase 2 of the Biopharmaceutical Campus comprise the construction of a manufacturing building supported by a warehouse extension to the east and north sides of the Phase 1 warehouse building; a central utilities building (CUB) located to the north of the Phase 1 warehouse; a utilities yard and waste water treatment area to the rear (north) of the Phase 2 area. The ancillary external utilities within the utility yard will consist of; a single storey control building, single storey pump house, single-storey drum storage building, single storey electrical building, process water and waste water storage tanks, bunded water treatment chemical tanks, bunded diesel storage tank and back-up electrical generators. Phase 2 was granted planning permission by Fingal County Council (FCC) in August 2015 (Planning Ref. No. FW15A/0067). Figure D.1 shows a 3D representation of the campus site showing both Phase 1 and Phase 2. Attachment D Infrastructure & Operation.DOC Page 1 of 18 EPA Export :22:43:47

10 Figure D.1 3D Representation of College Park Biopharmaceutical Campus (Phase 2 marked in red) Attachment D Infrastructure & Operation.DOC Page 2 of 18 EPA Export :22:43:47

11 D.1.2 Products Alexion is a global biopharmaceutical company focused on serving patients with severe and ultrarare disorders through the innovation, development and commercialisation of life-transforming therapeutic products. The proposed manufacturing building has been designed to manufacture cell culture derived drug substances - Soliris (eculizumab) and Strensiq (asfotase alfa) with capability for future products, assumed to be based on Soiliris. It will be a multiproduct facility producing mammalian cell culture based protein therapeutics including monoclonal antibodies with both campaign and concurrent manufacturing capabilities. The campus will manufacture these products suitable for sale globally in all major regions and achieve regulatory compliance in accordance with HPRA (Formerly IMB), FDA, EMA, Japanese and other global requirements. D.1.3 Soliris (eculizumab) works by inhibiting terminal complement, a normal part of the immune system that, when activated inappropriately, plays a role in serious diseases like Paroxysmal Nocturnal Hemoglobinuria (PNH) and atypical Hemolytic Uremic Syndrome (ahus). Soliris (eculizumab) is presently manufactured at Alexion s Rhode Island Manufacturing Facility in the US, and at a Contract Manufacturing Organisation (CMO) site. Strensiq (asfotase alfa) is a first-in-class bone-targeted enzyme replacement therapy designed to address the underlying cause of HPP deficient alkaline phosphatase (ALP). By replacing deficient ALP, treatment with Strensiq aims to improve the elevated enzyme substrate levels and improve the body's ability to mineralise bone, thereby preventing serious skeletal and systemic patient morbidity and premature death. Strensiq (asfotase alfa) is manufactured at a CMO site. Overview of the Production Process The manufacturing processes to be employed by Alexion in the manufacturing building will follow what are now considered as industry standard techniques for the production of medicines for patients using biotechnology derived processes. Today, this approach is favoured over traditional organic chemistry routes used in the past because it is capable of yielding more complex molecules for medicinal applications, is more efficient in terms of productivity, poses lower safety risks, and has less environmental impact in terms of hazardous chemicals used or waste generated for disposal. The primary process steps per production train (of which there will be 3 seed trains for cell culture and two trains for purification) are as follows; - Upstream: Inoculum Prep, Cell Culture & Harvest - Downstream: Purification and Product Formulation The overall process is represented in a block flow diagram in Figure D.2 Attachment D Infrastructure & Operation.DOC Page 3 of 18 EPA Export :22:43:47

12 Media Cell Bank Vial Thaw CO 2 Incubators Flasks 125ml 15l Biowaste to Heat Inactivation/WWTP Seed Culture Preparation 20l, 50l, 200l Biowaste to Heat Inactivation/WWTP Buffer Preparation Cell Culture Bioreactors l,6 5000l l Biowaste to Heat Inactivation/WWTP Harvest 22,000l Centrifuge Biowaste to Heat Inactivation/WWTP Buffers Buffers Buffers Buffers Purification 1 Pre Viral Crude Protein Purification 2 Pre Viral Crude Protein Purification 3 Viral Free Protein Product Formulation & Bulk Fill OFF SITE FOR FINAL FILL Waste to ph Adjust/ WWTP Waste to ph Adjust/ WWTP Waste to ph Adjust/ WWTP Waste to ph Adjust/ WWTP Figure D.2 Overall Process Flow Diagram Attachment D Infrastructure & Operation.DOC Page 4 of 18 EPA Export :22:43:47

13 All of these primary process steps will be located within cleanrooms to be constructed within the footprint of the new 4 storey manufacturing building. These operations will be supported by the following process areas; - Media preparation (internal) - Buffer preparation (internal) - Column packing (internal) - Component preparation (internal) - Waste water management (internal and external) - Process utility supplies (internal and external) D.1.4 Development of the Plant Phase 1 of the biopharmaceutical campus consists of: - Administration building - QC Laboratories - Warehousing (goods shipping & receipt and waste handling) - Packaging - Data Centre - Central utilities - Car parking (approx.300 bays) - Entrance gatehouse The site is arranged on a central spine concept that connects all buildings via a 5m wide central corridor. All personnel will enter the main administration building via the main entrance and proceed down the spine corridor to the different buildings. Phase 2 comprise the construction of the following building and facilities as an extension to the Phase 1 development; - New manufacturing building: 4 storey building with intermediate level mezzanines - New 2 storey central utilities building (CUB) located to the north of the Phase 1 warehouse (black utilities and electrical distribution, with associated utility yard) - New single storey warehouse extension to the east and north sides of the Phase 1 warehouse building and contains; raw materials, finish product and dispensing. - A utilities yard and waste water treatment area to the rear (north) of the Phase 2 area. The ancillary external utilities within the utility yard will consist of; a single storey control building, single storey pump house, single storey drum storage building, single storey electrical building, process water and waste water storage tanks, bunded water treatment chemical tanks, bunded diesel storage tank and back-up electrical generators; Each of these facilities will be accessible via a single-storey internal access corridor running through the spine of the campus with elevated utility rack; - A staff entrance lobby extension to the western elevation of the Phase 1 internal access corridor; - Car parking for an additional 220 vehicles is proposed in an area to the west of the campus; - An electrical substation building with separate access off Cruiserath Road; - Provision of temporary construction access off Cruiserath Road to be maintained as an emergency vehicle access and egress following construction; Attachment D Infrastructure & Operation.DOC Page 5 of 18 EPA Export :22:43:47

14 - Ancillary site works including additional internal access roads, an additional fire water sprinkler tank, underground services, lighting, CCTV, soft and hard landscaping and increase to size of surface water attenuation pond to the southeast of the site. Phase 2 site enabling works are expected to commence in September 2015 with construction due to commence in January 2016 and scheduled to be complete by December See Figure D.3 for site layout (Phase 1 shown in shaded red). Attachment D Infrastructure & Operation.DOC Page 6 of 18 EPA Export :22:43:47

15 Figure D.3 Site Layout Plan Attachment D Infrastructure & Operation.DOC Page 7 of 18 EPA Export :22:43:47

16 D Plant Layout Manufacturing Building D The manufacturing building has been designed to house a total of six 22kL production bioreactors plus associated scale up trains, downstream processing and support functions such as media and buffer prep as well as clean utility generation. The design allows for multiple products to be run concurrently in the bioreactor suite. The manufacturing building is designed with process equipment placed is an optimal arrangement to reduce product and liquid transfers. The optimal layout consists of the following stack up arrangement which creates a natural segregation of flows: - Level 3: Inoculum Prep Room, Bioreactor Hall (Cell culture) and Media and Buffer Preparation - Level 2: Buffer hold and access from Harvest (Centrifuge Room) - Level 1: Purification (Purification rooms 1 to 4) - Level 0: Utilities The following bioreactors will be located within the bioreactor hall: - Six 50L seed bioreactors - Six 200L seed bioreactors - Six 1,000L seed/production bioreactors - Six 5,000L production bioreactors - Six 22,000L production bioreactors - Two 22,000L harvest vessels Plant Layout Warehouse and Packaging Area The warehouse is designed to support the packaging and final product storage and distribution. The Phase 1 warehouse consists of: - Shipping - Receiving (associated kitting area) - Waste handling - QC storage - Packaging - Packaging material storage - Finished product storage (cold rooms) - Gowning for packaging area - Engineering stores The packaging area has been designed to cater for different products. It is required that the packaging area has the flexibility to handle various different lot sizes and as a result the packaging area has taken the following approaches: - Fully automatic packaging and labelling - Semi-automatic / manual packaging Phase 2 includes an extension to the existing phase 1 warehouse and will provide storage and logistics support for the manufacturing operations in the manufacturing building. The warehouse facilities for the new manufacturing operations (Phase 2) include: Attachment D Infrastructure & Operation.DOC Page 8 of 18 EPA Export :22:43:47

17 D Receiving/shipping - Ambient GMP warehouse staging - Chemical storage (HAZMAT) for GMP materials Chemicals to be stored will include corrosives (CIP materials Caustic/HCl, and flammables) plus waste water dosing chemicals - A bunded area suitable for segregated storage of pallets is to be provided. - Cell bank storage room - Warehouse locker/toilet facility - Weigh & dispense - QC Sample - Compressed gas storage and hook up - Ethanol storage and associated dilution - HVAC plant room and electrical distribution - Retain sample storage (2-8 degree cold room) - Decontamination waste autoclave - Chemical waste handling - General waste handling - Fork truck charging The building also contains an internal mezzanine floor that houses the mechanical plant and storage for retain samples. Plant Layout CUB Building The CUB building contains all associated black utilities generation equipment for the manufacturing building. This CUB building does not support the Phase 1 development which includes its own utility building. The building consists of 2 main floors and houses the following services; - Electrical room - LV Distribution - Boiler room - Chiller room - Compressors - Comms room - Others; cooling towers, water treatment systems for boilers and cooling towers, etc. - Utility yard; process water storage, brine tank, liquid CO 2, liquid oxygen, diesel storage, backup generators, etc. The cooling towers (5 no.) will be located on a recessed part of the roof of the CUB above the chillers (3 no.). The building has a 6m clear floor-to-floor height and an overall height of 14m. There will be boiler flues through the roof to a height of 3m above roof. All services from the CUB will travel along a rack located above the central spine corridor to the various buildings. Attachment D Infrastructure & Operation.DOC Page 9 of 18 EPA Export :22:43:47

18 D Phase 1 Utility Building The Phase 1 utilities building located adjacent to and to the north of the laboratory building comprise a chiller room and boiler room. This building is flanked by an external utilities yard to the east that houses the cooling towers and emergency generator. Plant Layout Administration and Laboratory Building The administration area has been designed as a functional, efficient multi-story office based around a relatively deep floor plan which maximises occupancy per floor. The following sections detail each floor. - The lower ground floor (Level 0) includes large draught lobby, reception/security, storage room, office for visitors outside of security, changing area (incl. showers), meeting room outside security, lift access and stairs to the upper levels. The reception is a feature volume, double height. The key design elements will be the large stair to the level one and the wall along the edge of the spine corridor. - The upper ground floor (Level 1) includes laboratories, offices, kitchen, staff restaurant (with external terrace), plant room space, open plan offices and a meeting room suite (which can be removed if the canteen expands), entrance to the link corridor and laboratory area. - The office level 2 incorporates the plant room for the laboratories and the campus information technology suite. - The office levels 3 and 4 are open plan with cellular office space. The administration plant room is also located in level 4. - Level 5 will accommodate a plant room with air handling units for the administration area. Initially, the laboratories will support the product from the Alexion supply chain and will expand as the site is developed in future phases to support the drug substance manufacture, drug product manufacture, and development facilities. The laboratories and functional areas to be included in the proposed development are as follows: - Sample receipt and Sample preparation (Stability) - Stability storage - Microbiology laboratory - Immunology laboratory - Sterility laboratory - PCR lab (DNA testing) - Chemistry laboratory - Instrument laboratory - Metrology - Glass wash Office write-up areas will also be provided in the laboratory area. The laboratories will accommodate up to 40 staff initially and up to a maximum of 100 at full fit out in the future. D.1.5 Detailed Description of the Production Process As noted previously the primary process steps per production train (of which there will be three seed trains (with six production bioreactors for cell culture) and two trains for purification) are as follows; - Upstream: Inoculum Prep, Cell Culture & Harvest (Refer to Figure D.4) - Downstream: Purification and Product Formulation (Refer to Figure D.5) Attachment D Infrastructure & Operation.DOC Page 10 of 18 EPA Export :22:43:47

19 Figure D.4 Upstream Block Flow Diagram Attachment D Infrastructure & Operation.DOC Page 11 of 18 EPA Export :22:43:47

20 Figure D.5 Downstream Block Flow Diagram Attachment D Infrastructure & Operation.DOC Page 12 of 18 EPA Export :22:43:47

21 Segregation is provided in the design between upstream processes handling cells and downstream processes which are cell free. The system is considered media free after the Protein-A capture chromatography step described below. Pre-viral inactivation and post-viral inactivation segregation is also provided. The facility will have the capacity for a batch production rate of 3 batches every 8 days and a batch volume of 1,345L. The following is a breakdown of each step within upstream and downstream bulk drug substance (BDS) manufacturing: D Cell Culture (Inoculum Prep, Bioreactor Suit (Seed Bioreactors & Production Bioreactors) (Upstream) The manufacturing process starts with the growth of genetically modified mammalian cells (GMM s) in a series of shaker flasks and cell bag bioreactors to seed bioreactors of increasing size and on to three large scale (1,000L, 5,000L and 22,000L) production bioreactors. These are the cells that are used to produce the therapeutic proteins used as medical products. Cell culture commences with thawing of the working cell bank vial and expanding the cells in suspension cultures containing growth medium. Cells are expanded in shake flasks, roller bottles and/or spinner flasks of increasing size until enough cells are available for transfer to a stainless steel bioreactor or cell bag bioreactor. Cells from multiple larger spinner flasks or a cell bag bioreactor can be used to inoculate a stainless steel bioreactor. The cell bag bioreactor and incubators and shakers for the shake flasks are located in the inoculum laboratory. Continued seed expansion (three to five-day growth cycle per step) is completed in the bioreactor hall. The culture (spinner flask or cell bag) from the inoculum lab is used to inoculate the appropriate size stainless steel bioreactor. The culture from each stainless steel bioreactor is used to inoculate the next stage of cell growth. After inoculating the 22,000 L production bioreactor, the cells continue to grow and product is expressed extracellularly. Protein expression may be continuous or may require an induction step (thermal shift, change in media, etc.) Growth phase is typically 11 to 14 days until target harvest parameters are reached. If required in the future, the 5,000L bioreactor can be used as a production bioreactor and harvest from this vessel may be sent to the centrifuge. D Harvest (Upstream) The purpose of the harvest step is to remove cells and suspended cell debris from the productcontaining conditioned media (from the 22,000L or 5,000L production bioreactors). Cells and cell debris are removed by centrifugation. Cell debris from the centrifuge will be discharged to the biowaste system for decontamination. The process stream is then clarified by depth filtration and clarifying filtration prior to the first purification step in the downstream area. D Purification (Downstream) In the downstream area the harvested cell culture solution is purified using a series of chromatography skids and columns, a viral inactivation procedure, ultrafiltration skids (for concentration and diafiltration) and viral filtration skid. After purification, the product solution is then adjusted to the final bulk concentration and transferred to bulk drugs substance containers. The purification process consists of four main areas: - Purification Room 1 where Ultra Filtration UF-1, Virus Inactivation and Protein A Liquid Chromatography are located - Purification Room 2 where Chrom 2, UF-2 and Virus Removal by Nanofiltration are located - Purification Room 3 where Chrom 3 is located - Purification Room 4 where Final Formulation and Bulk Fill are located Purification Room 1 The primary objective of the ultrafiltration UF-1 step is to concentrate and diafilter (if necessary) the harvested cell culture solution. After the concentration and diafiltration step is completed the product solution is filterd into the protein A load vessel and viral inactivated in viral inactivation No. 1 vessel if required (i.e. for Strensiq (asfotase alfa) product) prior to performing protein A chromatography. Attachment D Infrastructure & Operation.DOC Page 13 of 18 EPA Export :22:43:47

22 The primary objective of the protein A step is to remove cell-derived impurities, such as host cell proteins and nucleic acids. The protein A column is cycled multiple times to purify the entire batch of product. At the conclusion of the process, the column and skid are stored in a bacteriostatic solution. The eluate is then filtered and transferred to the viral inactivation No. 2 vessel, by cycle, if required (i.e. for Soliris ) for virus inactivation. Virus inactivation is a low ph step. After virus inactivation, the solution is transferred to purification room 2 for the next purification step. Purification Room 2 The primary objective of the ultrafiltration UF-2 step is to concentrate and diafilter the product solution for the next purification phase. When the product solution is ready it is transferred into the chromatography 2 load vessel. The primary objectives of the chromatography 2 step are the removal of host cell proteins and other process derived impurities. At the conclusion of the process, the column and skid are stored in a bacteriostatic solution. As required by the process, the UF-2 step may be completed before or after the chromatography 2 step. The concentrated product is then transferred from the UF-2 retentate tank (Strensiq (asfotase alfa)) or the chromatography 2 pool vessel (Soliris ) through the virus filtration skid and the filtered pool is collected in the virus filtration pool vessel, the chromatography 3 load vessel both located in purification room 3, or UF-3 retentate tank in purification Room 4 for further processing. Purification Room 3 The primary objectives of the chromatography 3 step are the removal of impurities. The product is eluted from the column and collected into the chromatography 3 pool vessel (Soliris ) or UF-3 retentate tank (Strensiq (asfotase alfa)) and diluted with buffer. At the conclusion of the process, the column and skid are stored in a bacteriostatic solution. As required by the process, the viral filtration step may be completed before or after the chromatography 3 step. Purification Room 4 (Formulation and Bulk Fill) The objectives of the final ultrafiltration/dia-filtration purification step are to concentrate the protein from the previous step and to diafilter the product into the formulation buffer to the correct concentration, producing the BDS. The final Strensiq (asfotase alfa) product is then filtered into a series of 1L BDS bags for product storage. The final Soliris product is then filtered and filled into 100L BDS bags for product storage. Each product stored BDS is transferred to a 2-8 o C cooler, quarantined and stored within cold rooms within the final product storage area of the warehouse until final release for filling at the off-site finish/fill facility. D.1.6 D D Key Support Functions Media Preparation The purpose of the media preparation area is to make up and supply media, nutrient feed solutions, and other supplemental feeds (e.g., alkali and antifoam) for the cell culture bioreactors and inoculum labs. Section G of the IE Licence Application provides a comprehensive list of all raw materials used in the process. Buffer Preparation The purpose of the buffer preparation area is to make up and supply buffer to the buffer hold vessels. Buffer prep and supply solutions of inorganic salts and other solids are mixed with water in the buffer preparation area. Mix tanks are used to prepare aqueous buffer solutions used in the purification steps for chromatography and ultra and dia-filtration. These solutions are used for cleaning and conditioning of the chromatography resins as well as for containing the products in a stable solution. Section G of the IE Licence Application provides a comprehensive list of all raw materials used in the process. Attachment D Infrastructure & Operation.DOC Page 14 of 18 EPA Export :22:43:47

23 D D D D D D D.1.7 Ethanol Preparation Ethanol is used for column storage in downstream processing. The ethanol preparation area will be located in a separate room within the Warehouse, where the ethanol will be diluted in WFI to 18% to bring the mixture to outside its flammable range. Larger quantities of ethanol will be stored externally within IBCs in the drum store, north of the utility yard. Column Packing Downstream includes areas for column packaging and column storage. Weigh and Dispense In the dispensary located in the warehouse, powders for media and buffer solution make up are weighed out from vendor provided raw material containers for each process solution (media or buffer). The powders are directly weighed into stainless steel transfer containers or into small plastic bags that are placed inside the stainless steel containers. Equipment Cleaning / CIP The following cleaning strategies will be implemented within the manufacturing building: - Clean-In-Place (CIP) systems - Clean-Out-of-Place (COP) systems - Manual cleaning (minimal) - Autoclave sterilization - Steam-In-Place (SIP) In order to maximise productivity, all of the major processing equipment will be cleaned via an automated CIP system. The equipment will be rinsed with purified water and residual soil is removed by use of recirculating cleaning solutions. All aqueous waste water is recovered from the cleaning systems and directed to the site waste water treatment area. SIP is employed after CIP when process sanitisation or sterility is required. Equipment Wash Equipment preparation upstream and downstream areas will be provided containing necessary COP systems, autoclaves and sinks with utility drops for manual cleaning. Dedicated washrooms are provided to cell culture, to downstream, and a dedicated wash for media and buffer Prep on Level 3 of the manufacturing building. A sterilisation autoclave will be provided in cell culture captive wash and also in downstream wash. Waste Management Area All process waste from cell containing areas is routed through and managed in this area and includes: - An area for bio-waste management to accommodate bio-waste heat inactivation skids, tanks, and containment. This is described in further detail in Section F of the IE application form. - An area for one pass through style decontamination autoclave along with areas for staging of pre and post autoclaved material. The waste handling area and waste compactor area are described in more detail in Section H of the application form. Site Utilities Special high purity utility systems will be provided at the facility which will be used in all locations that could potentially come in contact with product. The following service supplies will be generated; Attachment D Infrastructure & Operation.DOC Page 15 of 18 EPA Export :22:43:47

24 D Black Utilities - CUB, Utility Yard & Manufacturing Building The following black utilities will be generated within the central utilities building (CUB) and distributed via the spine pipe rack to the manufacturing building: - Chilled glycol (2/5 deg. C) - Chilled water (8/15 deg. C) - Plant steam (10barG) - Low temperature hot water (LTHW) (45/35 deg.c) - Cooling tower water (22/32 deg. C) - Instrument air (6.5barG) The following black utilities will be generated within the yard and distributed via the spine pipe rack to the manufacturing building: - Water for operation (WFO) - Brine - Liquid nitrogen - Liquid oxygen - Liquid carbon Dioxide The utility yard located immediately north of the CUB will contain: - Liquid gas storage area for nitrogen, carbon dioxide, oxygen and associated evaporators, - A single storey control building, - Single storey pump house and water softening plant, - Single-storey chemical storage building, - Bunded water treatment chemical tanks (acids and bases) along with CIP storage vessels will be located within segregated concrete containment bunds, - A large process water storage tank, - Electrical compound, process water and waste water storage tanks, - Bunded diesel storage tank, - 5 no. back-up electrical generators; The following black utilities will be generated within the manufacturing building for internal distribution to users: - Tempered glycol water - Sanitary hot water - Process air - Pressure reducing stations for plant steam (8barG + 4barG) - BDS condensate recovery skid. D Clean Utilities The following clean utility systems are provided within the manufacturing building: - Purified water (PW) - Hot water for injection (HWFI) - Ambient water for injection (AWFI) Attachment D Infrastructure & Operation.DOC Page 16 of 18 EPA Export :22:43:47

25 - Clean steam (CS) D Chilled Water System An extensive chilled water system is required in order to provide the cooling requirements for the manufacturing processes. There will be water cooled liquid chillers complete with external cooling towers located in the new CUB building. Chillers are also installed within the utility plant room north of the laboratory, within a dedicated chiller plant room. Externally located cooling towers are located adjacent to the utility plant room in a plant compound to the west of the utility plant room, at ground level. D D D Heating System The heating demand is provided using gas-fired boilers. The campus will consist of 4 No. 7.3 MW natural gas-fired steam boilers, operated on a 3 duty and 1 standby basis. There will be 3 No. 1MW natural gas fired boilers used to generate low pressure hot water supply (LPHW) to the Phase 1 buildings. The emissions from the gas fired boilers will include oxides of nitrogen (NOx) and carbon monoxide (CO). Water Supply Public water supply to the site will be utilised to produce water for operations (WFO). To generate water for operations the mains water hardness will require softening to achieve a nominal 60ppm of hardness. This will require a softening skid, with pumps, filters and softener. The water for operations is then stored within a large glass lined steel tank which is capable of 24 hours storage. All the above equipment is located in the utilities yard north of the CUB. A bulk flow meter has been installed on the water main at the southern site entrance as part of Phase 1. The Phase 2 development will be supplied from a separate Irish Water watermain, with its own flow meter, on the eastern boundary. The rainwater harvesting system installed as part of Phase 1 will be extended to cover supply to all WC cisterns and urinal cisterns within the Phase 2 development. This will reduce the requirement for mains potable water on an intermittent basis (as affected by actual rainfall frequency). Natural Gas An existing 125mm, 4 bar gas pipeline is located at the south of the site. The Phase 2 facility s internal gas supply will be serviced from the new above ground installation (AGI), which is currently being installed by Gas Networks Ireland. D Firewater Main A fire hydrant ring main will be provided around the perimeter of the buildings. The ring main will be fed from the Phase 1 firewater storage tank and associated pump house located at the east of the development. An additional second firewater storage tank will be provided as part of the Phase 2 development. The underground fire main will connect to the building at various points to provide a supply for the internal sprinkler system through a number of branch entry pipes. The facility s hydrant main will be designed to comply with the Insurer s specifications. A 200mm internal diameter cement lined ductile iron main will be provided around the site. All details relating to hydrants and fire fighting requirements will be detailed and agreed with the Fire Officer during the preparation of the fire certification for the facility. D Electrical Distribution The current ESB Networks supply for Phase 1 terminates at an ESB Switch room at the southern end of the Alexion site. The adjacent MV switch room supplies 2 no. unit substations (Admin & Attachment D Infrastructure & Operation.DOC Page 17 of 18 EPA Export :22:43:47

26 CUB) via MV ring main arrangement. A new 10kV substation, to be located off Cruiserath Road, to the north of the site, will serve the Phase 2 development. Additional electrical infrastructure required for Phase 2 will be accommodated in the new CUB and utility yard area. D.1.8 D.1.9 Underground Drainage Systems Please refer to Section E for details on foul, process and storm water drainage and their associated emission points. Abatement, Recovery and Treatment Systems to be used On-Site Please refer to Section F for information on abatement, recovery and treatment systems to be used on site Attachment D Infrastructure & Operation.DOC Page 18 of 18 EPA Export :22:43:47

27 Attachment E.1 Emissions to Atmosphere EPA Export :22:43:47

28 Attachment E.1 Emissions to Atmosphere The emissions to atmosphere are classified according to: - Boiler Emissions - Main Emissions - Minor Emissions - Fugitive and Potential Emissions The following Air Emission tables in the IEL Application form have been completed: - Table E.1 (i) for boiler emissions. - Table E.1 (iv) has been completed for all minor emissions from the facility - Table E.1 (v) has been completed for all potential emissions All emission points are shown on Drawing 3: Air Emission Points (1 of 2) and Drawing 4: Air Emission Points (2 of 2). Boiler Emissions The campus will consist of 4 No. 7.3 MW (heat output) natural gas-fired steam boilers, operated on a 3 duty and 1 standby basis. These boilers will produce steam to service production operations, air handling units (AHUs) and low-pressure hot water generation. Of the substances listed in the schedule of EPA (Industrial Emissions) (Licensing) Regulations 2013 (S.I. 137 of 2013), emissions from these gas-fired boilers will include the products of combustion, oxides of nitrogen and other nitrogen compounds (NOx) and carbon monoxide (CO). As these boilers are natural gas-fired, the emission of particulates (PM 10 / 2.5 ) and of SO 2 is negligible. A summary list of these emission points to atmosphere is provided in Table E1.1. Table E1.1 Boiler Emission Points Emission Ref A1-1 A1-2 A1-3 A1-4 Description Type of Emission Location Steam Boiler No. 1 (Natural Gas fired) Steam Boiler No. 2 (Natural Gas fired) Steam Boiler No. 3 (Natural Gas fired) Steam Boiler No. 4 (Natural Gas fired) Boiler (NO X, CO) Boiler (NO X, CO) Boiler (NO X, CO) Boiler (NO X, CO) Exhaust stack enclosure east of Manufacturing Building Exhaust stack enclosure east of Manufacturing Building Exhaust stack enclosure east of Manufacturing Building Exhaust stack enclosure east of Manufacturing Building Main Emissions There are no main emissions to atmosphere from the proposed campus. Minor Emissions Minor emission points are those which on the basis of their concentration and mass are not considered environmentally significant to be classified a main emission or boiler emission. General clean air HVAC vents along with exhausts which consist solely of air, steam or water vapour are not listed. Attachment E.1 Emissions to Atmosphere.DOC Page 1 of 11 EPA Export :22:43:47

29 The following sub-sections summarise the minor emission points associated with the campus: It should be noted that as detailed design progresses, consolidation of emission points may be possible as well as the addition of further minor emission points. CHP Plant There will be 1 No. 4.1 MW (gross thermal input) natural gas fired CHP plant located within the CUB used to generate approximately 1.5MW of electricity. The CHP plant will also have the potential to produce 950 kg/hr of steam along with hot water. LPHW Boilers There will be 3 No. 1MW natural gas fired boilers used to generate low pressure hot water supply (LPHW) to the Phase 1 Buildings. These LPHW Boilers will operate on a 2 Duty/ 1 Standby basis and will be located in the Phase 1 Utilities area to the west of the link corridor between the Administration and Warehouse buildings. Cell Culture Process Equipment All vents from cell culture process equipment will be equipped with 0.2 µm sterile vent filters to remove any genetically modified mammalian cells (GMMs) greater than 0.2 µm that may be present. The CIP (cleaning in place) of the cell culture process vessels occurs after each batch. Cleaning chemicals used may give rise to small quantities of potassium hydroxide and phosphoric acid vapours. The cleaning chemicals used have a relatively low volatility. Similarly, the extract vent lines from bio-safety cabinets (BSCs) will contain HEPA (high efficiency particulate air) filters to remove GMMs in the extract air. Other Process Equipment & Process Support Equipment Vents from the harvest vessel and purification vessels will be fitted with 0.2 µm sterile vent filters, along with the vents from the biowaste drainage system. The harvest and purification vessels will be cleaned after each batch which may give rise to small quantities of potassium hydroxide and phosphoric acid vapours. Ethanol Storage/Use 18% ethanol solution will be used for sanitisation and storage of chromatography resin. An ethanol storage vessel (3000L) located in the chemical drum/store area will provide the ethanol for these operations. The vessel will be fed from ethanol IBCs (intermediate bulk containers). The ethanol dilution will occur in a vessel located in Level 0 of the Phase 2 Central Utilities Building adjacent to the clean utilities area. This dilution vessel will have a nitrogen blanket and conservation vent which will help reduce ethanol vapour breathing losses. The ethanol vapour emissions associated with these activities are expected to be minor. Laboratory Fumehoods & Biosafety Cabinets It is expected that small quantities of solvent will be used in various laboratory fumehoods, both within the laboratory building and also laboratories located in the manufacturing building. Volatile Organic Compound (VOC) emissions arising from these operations are expected to be minor. The bio-safety cabinets located within the laboratory building will similarly to those within the manufacturing building contain HEPA filters to remove any potential GMMs vapours in the extract air A summary list of the minor emission points to atmosphere is provided in Table E1.2. Attachment E.1 Emissions to Atmosphere.DOC Page 2 of 11 EPA Export :22:43:48

30 Table E1.2 Minor Emission Points Emission Ref Description Type of Emission Location A3-1 LPHW Boiler No. 1 (Natural Gas fired) Boiler (NO X, CO) Phase 1 Utilities Compound A3-2 LPHW Boiler No. 2 (Natural Gas fired) Boiler (NO X, CO) Phase 1 Utilities Compound A3-3 LPHW Boiler No. 3 (Natural Gas fired) Boiler (NO X, CO) Phase 1 Utilities Compound A3-4 Ethanol dilution tank vent Ethanol vapour A3-5 Ethanol dilution tank room Extract Ethanol vapour A3-6 TMS Lab Fume hood Extract Fan A3-7 Air with potential for solvent vapours/particulates North side of Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Inoculum 3 Biosafety Cabinet exhaust 1 Vapour with potential for GMM Manufacturing Bld. A3-8 TMS Lab Biosafety Cabinet Extract Fan 1 Vapour with potential for GMM Manufacturing Bld. A3-9 Waste sump vessel vent A3-10 Purification Room #1 vent A3-11 Purification Room #2 vent A3-12 Purification Room #3 vent A3-13 Purification Room #4 vent Vapour with potential for potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid North of Manufacturing Bld Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Attachment E.1 Emissions to Atmosphere.DOC Page 3 of 11 EPA Export :22:43:48

31 Emission Ref Description Type of Emission Location A3-14 Harvest Vessel vent A3-15 Buffer Hold Vessels Vent #1 A3-16 Buffer Hold Vessels Vent #2 Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for potassium hydroxide/phosphoric acid Vapour with potential for potassium hydroxide/phosphoric acid Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. A3-17 Buffer Hold Vessels Vent #3 A3-18 Buffer Hold Vessels Vent #4 A3-19 N-4 Seed Bioreactor #1 vent A3-20 N-3 Seed Bioreactor #1 vent A3-21 N-2 Seed Bioreactor #1 vent Vapour with potential for potassium hydroxide/phosphoric acid Vapour with potential for potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. A3-22 N-1 Seed Bioreactor #1 vent A3-23 Production Bioreactor #1 vent A3-24 N-4 Seed Bioreactor #2 vent A3-25 N-3 Seed Bioreactor #2 vent A3-26 N-2 Seed Bioreactor #2 vent Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Attachment E.1 Emissions to Atmosphere.DOC Page 4 of 11 EPA Export :22:43:48

32 Emission Ref Description Type of Emission Location A3-27 N-1 Seed Bioreactor #2 vent A3-28 Production Bioreactor #2 vent A3-29 N-4 Seed Bioreactor #3 vent Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. A3-30 N-3 Seed Bioreactor #3 vent A3-31 N-2 Seed Bioreactor #3 vent A3-32 N-1 Seed Bioreactor #3 vent A3-33 Production Bioreactor #3 vent A3-34 N-4 Seed Bioreactor #4 vent Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. A3-35 N-3 Seed Bioreactor #4 vent A3-36 N-2 Seed Bioreactor #4 vent A3-37 N-1 Seed Bioreactor #4 vent A3-38 Production Bioreactor #4 vent Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Vapour with potential for GMM/potassium hydroxide/phosphoric acid Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. A3-39 Inoculum 1 Biosafety Cabinet exhaust 1 Vapour with potential for GMM Manufacturing Bld. Attachment E.1 Emissions to Atmosphere.DOC Page 5 of 11 EPA Export :22:43:48

33 Emission Ref Description Type of Emission Location A3-40 Inoculum 2 Biosafety Cabinet exhaust 1 Vapour with potential for GMM Manufacturing Bld. A3-41 CHP Plant Emissions NO X, CO Exhaust stack east of Manufacturing Building A3-42 Small Scale Buffer Prep Fumehood exhaust Air with potential for particulates/solvent vapours Manufacturing Bld. A3-43 Buffer Prep Vessels vent A3-44 Small Scale Media Prep Fumehood exhaust A3-45 Media Prep Vessels vent A3-46 A3-47 Bioreactor Train #1 Feed Vessels vent Bioreactor Train #2 Feed Vessels vent Vapour with potential for particulates/solvent vapours Air with potential for particulates/solvent vapours Air with potential for particulates Vapour with potential for particulates/potassium hydroxide/phosphoric acid Vapour with potential for particulates/potassium hydroxide/phosphoric acid Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. Manufacturing Bld. A3-48 Bioreactor Train #3 Feed Vessels vent Vapour with potential for particulates/potassium hydroxide/phosphoric acid Manufacturing Bld. A3-49 Bioreactor Train #4 Feed Vessels vent Vapour with potential for particulates/potassium hydroxide/phosphoric acid Manufacturing Bld. A3-50 Sodium hydroxide vessel vent Sodium hydroxide vapour Chemical store & distribution area A3-51 Ethanol IBC vent Ethanol vapour Chemical store & distribution area A3-52 Ethanol Storage Vessel vent Ethanol vapour Chemical store & distribution area Attachment E.1 Emissions to Atmosphere.DOC Page 6 of 11 EPA Export :22:43:48

34 Emission Ref Description Type of Emission Location A3-53 Ethanol Storage Room Exhaust Ethanol vapour Chemical store & distribution area A3-54 CIP100 Storage Vessel Vent Vapour with potassium hydroxide Chemical store & distribution area A3-55 CIP130 Storage Vessel Vent Vapour with potassium hydroxide Chemical store & distribution area A3-56 CIP200 Storage Vessel Vent Vapour with phosphoric acid A3-57 A3-58 A3-59 Phase 2 Emergency Generators Diesel Tank Vent - breathing losses Phase 1 Emergency Generator Diesel Tank Vent - breathing losses QC Solvent Store/Waste Staging Extract Fan Exhaust A3-60 Sterility Lab 1 Isolator Fan Exhaust Diesel vapours Diesel vapours Potential for solvent vapours Air with potential for hydrogen peroxide vapour/particulates Chemical store & distribution area Phase 2 Utility Yard Phase 1 Utilities compound Warehouse Laboratory Building A3-61 Chemistry Prep Lab Benchtop Fumehoods Extract Fan Exhaust Air with potential for solvent vapours Laboratory Building A3-62 Chemistry Prep Lab Benchtop Nederman Extract Fan Exhaust Air with potential for solvent vapours Laboratory Building A3-63 Chemistry Prep Lab Fumehood #1 Extract Fan Exhaust Air with potential for solvent vapours Laboratory Building A3-64 Chemistry Prep. Lab Fumehood #2 Extract Fan Air with potential for solvent vapours Laboratory Building A3-65 Labs Chemical Storage Cabinets Extract Fan Exhaust Air with potential for solvent vapours Laboratory Building Attachment E.1 Emissions to Atmosphere.DOC Page 7 of 11 EPA Export :22:43:48

35 Emission Ref Description Type of Emission Location A3-66 Raw Materials Lab Chemical Storage Cabinet #1 Extract Fan Exhaust 1 Air with potential for solvent vapours Laboratory Building A3-67 Raw Materials Lab Chemical Storage Cabinet #2 Extract Fan Exhaust 1 Air with potential for solvent vapours Laboratory Building A3-68 Raw Materials Lab Chemical Storage Cabinet #3 Extract Fan Exhaust 1 Air with potential for solvent vapours Laboratory Building A3-69 Biowaste Drain Vent #1 Vapour with potential for GMM A3-70 Biowaste Drain Vent #2 Vapour with potential for GMM A3-71 A3-72 A3-73 Phase 1 Fire Water Pump Diesel Tank Vent - breathing losses Raw Materials Lab Nederman Extract Fan Exhaust 1 WWTP Alkaline Storage Tank - breathing/filling losses Diesel vapours Air with potential for solvent vapours Air with potential for alkaline vapour Manufacturing Bld. Manufacturing Bld. Fire Water Pump house Laboratory Building Waste Water Treatment Area A3-74 WWTP Acid Storage Tank - breathing/filling losses Air with potential for acidic vapour Waste Water Treatment Area A3-75 Phase 2 Emergency Generator No. 1 - Diesel Tank - breathing/filling losses Diesel vapours Phase 2 Utility Yard A3-76 Phase 2 Emergency Generator No. 2 - Diesel Tank - breathing/filling losses Diesel vapours Phase 2 Utility Yard A3-77 Phase 2 Emergency Generator No. 3 - Diesel Tank - breathing/filling losses Diesel vapours Phase 2 Utility Yard A3-78 Phase 2 Emergency Generator No. 4 - Diesel Tank - breathing/filling losses Diesel vapours Phase 2 Utility Yard Attachment E.1 Emissions to Atmosphere.DOC Page 8 of 11 EPA Export :22:43:48

36 Emission Ref Description Type of Emission Location A3-79 Diesel Rotary Uninterrupted Power Supply (DRUPS) Unit #1 - Diesel Day Tank - breathing/filling losses Diesel vapours Phase 2 Utility Yard A3-80 Diesel Rotary Uninterrupted Power Supply (DRUPS) Unit #2 - Diesel Day Tank - breathing/filling losses Diesel vapours Phase 2 Utility Yard 1. The following emission points are to be confirmed/omitted during detailed design: A3-7/8/39/40/66/67/68/72 Fugitive and Potential Emissions Fugitive emissions - vapour: There are a number of storage vessels for ethanol, CIP (cleaning in place) chemicals (potassium hydroxide solution, phosphoric acid solution), sodium hydroxide and diesel (for emergency diesel generators and fire water pumps). The vents from these storage vessels have been listed under the minor emissions. In addition to those minor emissions some fugitive emissions could arise during their filling from transfer route connections. These potential fugitive emissions primarily relate to the ethanol and diesel bulk storage vessels as opposed to the less volatile bulk material storage tanks of caustic and phosphoric acid solutions. These emissions are considered to be fugitive and will not give rise to negative air quality impacts off-site. Other volatile organic chemicals (VOCs) associated with the process that may result in fugitive emissions include IPA (isopropyl alcohol) and ethanolamine. Small quantities of IPA will be used for filter integrity testing and the cleaning of various surfaces. Ethanolamine is used in Media preparation solutions but given its relatively low vapour pressure (approximately C) and the fact that its use will be tightly controlled (as it has the potential for respiratory irritation) associated fugitive emissions are expected to be minimal. The campus will be designed to minimise the potential for fugitive emissions, for example by minimising the numbers of components from which minor leakages could occur. The use of low-leak equipment (valves, pumps etc.) in the plant will significantly reduce the potential for fugitive emissions. Fugitive emissions particulates: In the dispensary located in the Warehouse, powders for Media and Buffer solution make up will be weighed out from vendor provided raw material containers. These operations will take place in down flow booths which will operate 100% recirculation of air i.e. no external exhaust point to the atmosphere. Each downflow booth will be fitted with a coarse filter, pre-hepa (high efficiency particulate arrestor) and HEPA to collect any particulates generated during the dispensary operations. As such any fugitive particulate emissions are expected to be minimal. Potential Emissions Potential emission points are points from which there is no emission during normal operations but emissions to atmosphere may result from equipment malfunctions or accidents. To reduce the possibility of such emissions, current good manufacturing practice (cgmp) and international standards are used for the specification, design and construction or manufacture of plant equipment. The potential emission points consist of the following: - Emergency Generators & Diesel Rotary Uninterruptible Power Supply Units (DRUPS) - In the event of a loss of electrical power 4 No. 2,500 kva Emergency Generators (includes 2 No. future generators), 2 No kva DRUPS units (includes 1 No. future unit) and 1 No kva Emergency Generator (from Phase 1) will provide back-up power. The emissions from these diesel fired generators, when operational, will include the products of combustion - NO x / Attachment E.1 Emissions to Atmosphere.DOC Page 9 of 11 EPA Export :22:43:48

37 NO 2, CO, PM 10 / 2.5 and SO 2. These generators will only be used for emergency cover. Under normal circumstances, they will be run for short periods estimated at a maximum of 30 minutes per week, for test and maintenance purposes. - Fire Water Pump A diesel fired firewater pump together with an electrical jockey pump located in the sprinkler pump-house building will supply fire-fighting water to the site firewater ring main. The firewater pump will not be run during normal operation other than for testing purposes (approximately 30 minutes per week). Low sulphur diesel (maximum 0.1% sulphur by mass) will be used as a fuel for the firewater pump. When operational, these diesel supplied fire water pumps will emit combustion exhaust gases containing NO x /NO 2, CO, PM 10/2.5 and S0 2 to atmosphere. - Pressure Relief Vents from Chillers and Storage Vessels - The over-pressurisation of chillers as well as storage vessels (Ethanol, O 2, CO 2, and N 2 ), results in the activation of their associated pressure relief device/s and a discharge of material to atmosphere. The equipment will be designed to reduce the frequency of occurrence of such over-pressurisation events to a minimum. - Chiller Rooms Extract Fans In the event of a leakage of refrigerant being detected in the Chiller Rooms (Phase 1 and Phase 2 Chiller Rooms) an extract fan will be activated to dilute the workplace concentration of the refrigerant. This is expected to be an infrequent occurrence. A summary list of these emission points to atmosphere is provided in Table E1.3. Table E1.3 Potential Emission Points Emission 2 Description Type of Emission Location Ref A4-1 A4-2 A4-3 Ethanol Storage Vessel Emergency Relief Vent Liquid Oxygen Storage Vessel Emergency Relief Vent Liquid Carbon Dioxide Storage Vessel Emergency Relief Ethanol vapour/liquid Oxygen liquid/vapour Carbon dioxide liquid/vapour Chemical store & distribution area Phase 2 Utility Yard Phase 2 Utility Yard A4-4 Liquid Nitrogen Storage Vessel Emergency Relief Vent Nitrogen liquid/vapour East of Manufacturing Bld A4-5 Phase 2 Emergency Generator No. 1 (Diesel) NO X, CO, SO 2, PM10/2.5 Phase 2 Utility Yard A4-6 Phase 2 Emergency Generator No. 2 (Diesel) NO X, CO, SO 2, PM10/2.5 Phase 2 Utility Yard A4-7 Phase 2 Emergency Generator No. 3 (Diesel) NO X, CO, SO 2, PM10/2.5 Phase 2 Utility Yard A4-8 Phase 2 Emergency Generator No. 4 (Diesel) NO X, CO, SO 2, PM10/2.5 Phase 2 Utility Yard A4-9 Phase 1 Emergency Generator No. 1 (Diesel) NO X, CO, SO 2, PM10/2.5 Phase 2 Utility Yard A4-11 Phase 1 Firewater Pump Exhaust NO X, CO, SO 2, PM10/2.5 Fire Water Pump house Attachment E.1 Emissions to Atmosphere.DOC Page 10 of 11 EPA Export :22:43:48

38 Emission 2 Description Type of Emission Location Ref A4-12 Phase 2 Chiller #1 Emergency Relief Vent #1 Refrigerant (R134a) Phase 2 CUB North side A4-13 Phase 2 Chiller #1 Emergency Relief Vent #2 Refrigerant (R134a) Phase 2 CUB North side A4-14 Phase 2 Chiller #2 Emergency Relief Vent #1 Refrigerant (R134a) Phase 2 CUB North side A4-15 Phase 2 Chiller #2 Emergency Relief Vent #2 Refrigerant (R134a) Phase 2 CUB North side A4-16 A4-17 A4-18 A4-19 A4-20 A4-21 Phase 2 Chiller #3 Emergency Relief Vent #1 Phase 2 Chiller #3 Emergency Relief Vent #2 Phase 2 Chiller #4 Emergency Relief Vent #1 Phase 2 Chiller #4 Emergency Relief Vent #2 Phase 2 Chiller #5 Emergency Relief Vent #1 Phase 2 Chiller #5 Emergency Relief Vent #2 Refrigerant (R134a) Refrigerant (R134a) Refrigerant (R134a) Refrigerant (R134a) Refrigerant (R134a) Refrigerant (R134a) Phase 2 CUB North side Phase 2 CUB North side Phase 2 CUB North side Phase 2 CUB North side Phase 2 CUB North side Phase 2 CUB North side A4-22 Phase 2 Chiller Room Emergency Extract Fan Exhaust Air containing refrigerant (R134a) Phase 2 CUB North side A4-23 Phase 1 Chiller #1 Emergency Relief Vent Refrigerant (R134a) Phase 1 Utility Building A4-24 Phase 1 Chiller #2 Emergency Relief Vent Refrigerant (R134a) Phase 1 Utility Building A4-25 Phase 1 Chiller #3 Emergency Relief Vent Refrigerant (R134a) Phase 1 Utility Building A4-26 Phase 1 Chiller Room Emergency Extract Fan Exhaust Air containing refrigerant (R134a) Phase 1 Utility Yard A4-27 Diesel Rotary Uninterrupted Power Supply (DRUPS) Unit #1 NO X, CO, SO 2, PM10/2.5 Phase 2 Utility Yard A4-28 Diesel Rotary Uninterrupted Power Supply (DRUPS) Unit #2 NO X, CO, SO 2, PM10/2.5 Phase 2 Utility Yard 2. Emission point reference A4-10 is not used Attachment E.1 Emissions to Atmosphere.DOC Page 11 of 11 EPA Export :22:43:48

39 Drawing 3: Air Emission Points (1 of 2) EPA Export :22:43:48

40 KEYPLAN N ELECTRICAL SUBSTATION TO ROSEMOUNT N EXISTING FINGAL COUNTY COUNCIL PUMPING STATION DRUM STORE FFL WASTE WATER TREATMENT AREA CONTROL BUILDING NOTES EXISTING 110kV SUB-STATION SITE AREA 41.3 ACRES 16.8 HECTARES UTILITY YARD ELECTRICAL BUILDING FFL CENTRAL UTILITY BUILDING FFL A1-N A3-N A4-N LEGEND MANUFACTURING BUILDING FFL WAREHOUSE EXTENSION FFL SHEET 1 OF 2 WAREHOUSE & PACKAGING BUILDING (UNDER CONSTRUCTION) FFL FIRE WATER SPRINKLER TANK SHEET 1 OF 2 FORMAL ISSUE DATA CENTRE (UNDER CONSTRUCTION) FFL EX. BINS STORE YARD EX. WASTE MANAGEMENT EX. LOADING DOCKS EX. FIREWATER PUMP HOUSE EX. SPRINKLER TANK CAR PARK UTILITIES COMPOUND (UNDER CONSTRUCTION) ALEXION EX. FIRE ACCESS ROAD No. 2 EX. KITCHEN DELIVERIES Ordnance Survey Ireland Licence No. EN c Ordnance Survey Ireland/Government of Ireland PROPOSED MANUFACTURING FACILITY INDUSTRIAL EMISSIONS LICENCE APPLICATION DRAWING 3: ATMOSPHERIC EMISSION POINTS SHEET 1 OF 2 IE :1500 IE DR-0003 EPA Export :22:43:48

41 Drawing 4: Air Emission Points (2 of 2) EPA Export :22:43:48

42 SHEET 1 OF 2 SHEET 1 OF 2 WAREHOUSE & PACKAGING BUILDING DATA CENTRE EX. BINS STORE YARD EX. WASTE MANAGEMENT EX. LOADING DOCKS EX. FIRE ACCESS ROAD No. 2 EX. KITCHEN DELIVERIES ADMINISTRATION BUILDING LABORATORY BUILDING TEMP. PUMP PUMP EX. GAS AGI INSTITUTE OF TECHNOLOGY BLANCHARDSTOWN FORMAL ISSUE NOTES LEGEND KEYPLAN N A1-N ALEXION A3-N A4-N Ordnance Survey Ireland Licence No. EN c Ordnance Survey Ireland/Government of Ireland PROPOSED MANUFACTURING FACILITY INDUSTRIAL EMISSIONS LICENCE APPLICATION DRAWING 4: ATMOSPHERIC EMISSION POINTS SHEET 2 OF 2 IE :1500 IE DR-0004 EPA Export :22:43:48

43 Attachment E.3 Emissions to Sewer EPA Export :22:43:48

44 09/09/2015 Attachment E.3 Emissions to Sewer Waste water generated will arise from a number of sources, namely process/manufacturing, laboratories, utilities and sanitary. As shown in Figure E.3.1 below it is proposed that process waste waters (non-sanitary) arising from the Alexion development will undergo preliminary treatment on-site which will render the waste water amenable for discharge to the local Irish Water sewer and subsequent downstream treatment at the Ringsend Waste Water Treatment Plant (WWTP) which discharges into Dublin Bay. Figure E.3.2 shows (schematically) the route of waste water from the site. Drawing 5: Sewer Emission Points includes details of the locations of emission points SE1 and SE2, and all associated underground drainage networks within the site. Tables E.3 (i) and E.3 (ii) have been completed in full. SE1 will include waste water from the laboratories and sanitary / domestic foul waste water from toilets, showers, lockers and canteen facilities. Grease traps meeting the requirements of BS EN 858 will be installed at the point of use in the kitchen area at the sinks, ovens and washing equipment. Pretreatment/retention is not required as the waste water will be low level and non-process related. SE2 will include waste water from process/manufacturing, utilities and laboratories. Please note treatment will be provided on site before discharge to the Irish Water sewer. There will be no List I or List II substances, as listed in the Annex to EU Directive 2006/11/EC (as amended) contained in any emission to sewer from the site. Figure E.3.1 Sources of Waste Water IE REF-0035_1_08.DOC Page 1 of 4 EPA Export :22:43:48

45 09/09/2015 Figure E.3.2 Route of Waste Water from the site Ringsend Waste Water Treatment Plant Irish Water has advised that the existing treatment works at Ringsend has a capacity of 1.65 million population equivalent (PE) but is currently receiving and treating a daily load of approximately 1.75 million PE. To accommodate current loads and to allow for future growth of the Dublin region, it is necessary to increase the capacity to at least 2.1 million PE. In addition to an increase in capacity, the treatment works must also be upgraded to treat effluent to a higher standard than the original design. Planning permission (An Bord Pleanala Ref. PL29C.YA0010) has been granted to upgrade the plant to 2.1 million PE capacity and Irish Water is committed to developing the plant as an urgent national priority. The upgrade and expansion of the treatment works will be implemented in 3 phases. Phase 1 immediate upgrades has already commenced and comprises advanced works to improve certain aspects of the existing works, including additional odour treatment and improved sludge handling capacity. Phase 2-400,000 PE Extension the construction is programmed to commence in the second half of 2016 with the new extension available for waste water treatment in Phase 3 existing works nutrient removal upgrade is planned to commence when Phase 2 is available, in 2018 and is expected to take 2 years to complete, with an anticipated completion timescale of the end of 2020, subject to obtaining relevant permits for the project. The Greater Dublin Drainage Project, currently being prepared to go for planning approval, is a regional waste water project to serve the Greater Dublin Area, with a planned treatment plant at Clonshaugh, Fingal. The project includes an orbital sewer and two pumping stations which will divert drainage from the north of Dublin City to the new treatment plant. Subject to being granted planning approval, it is anticipated that this project will be operational in Waste water from the entire Dublin 15 area, including College Park, will ultimately be diverted from the Ringsend WWTP to the new plant at Clonshaugh. Characteristics of the Site Waste Water Table E.3 (ii) in the application outlines the expected characteristics of the emissions to sewer from the facility as SE1, following on-site collection, management, and preliminary treatment. IE REF-0035_1_08.DOC Page 2 of 4 EPA Export :22:43:48

46 09/09/2015 The location of the proposed development in College Park to a large extent defines the manner in which waste water from the facility will be handled. The site is currently connected to an existing public sewer system serving College Park that eventually connects to the 1200mm 9C interceptor trunk sewer from Blanchardstown. The 9C trunk sewer in turn discharges to the sewerage system transporting sewage across Dublin City to the Ringsend Waste water Treatment Plant. Waste water treated at Ringsend is discharged to Dublin Bay in accordance with their EPA licence. As such, the only viable disposal route for waste water arising at the proposed development site is via public sewer to Ringsend. There are no watercourses in proximity to the site with capacity to assimilate treated waste water from the proposed development. Accordingly, in considering the most appropriate strategy for management of waste water generated at the site, the following options were evaluated; 1. Direct disposal of all waste water to the public sewer for subsequent downstream treatment at Ringsend WWTP 2. Pre-treatment only on the Alexion site, with balanced and neutralised waste water going to public sewer for subsequent downstream treatment in Ringsend 3. Primary treatment with chemically enhanced sedimentation on the Alexion site, with partially treated waste water going to Ringsend 4. Secondary biological treatment on the Alexion site, with treated waste water going to Ringsend Note: For all the above options, heat inactivation treatment (and subsequent cooling) of the cell-contented waste streams will be carried out on the Alexion site, prior to combining with the other effluent streams before discharging to the local public sewer. In evaluating the options, the following key issues were considered; Options 3 and 4 above would require development on the Alexion site of significant waste water treatment infrastructure comprising large tankage, typically involving aeration and activated sludge processes, chemical addition as well as sludge processing and associated storage and handling. The scale of plant and tankage likely to be required to accommodate primary sedimentation and/or secondary treatment on the Alexion site would be significant and unlikely to be accommodated within the subject property without compromising the ability of the site to maintain the manufacturing operations proposed. In addition, potential environmental issues associated with the installation of such plant in College Park would be potentially significant and require the implementation of mitigation measures for the management of odour, bio-aerosols release, sludge handling and associated traffic. In consultation with Irish Water, it has been confirmed that Ringsend WWTP has the capacity to treat the projected waste water volumes when they arise from the development in In addition, Irish Water have confirmed that the sewer network external to the College Park site has the capacity to cater for the projected waste water volumes, subject to the site complying with the following condition; During storm events no discharge will be permitted to the network for periods of up to 7 hours. It will be the Customers responsibility to provide onsite storage to cater for this. Once storm conditions have abated a maximum discharge rate of 81.9l/s from the site would be permitted to facilitate emptying of the on-site storage. Accordingly, Option 2 (including allowance to address the above condition) is deemed to be the most environmentally sustainable approach to management of waste water from the site. Proposed On-Site Waste Water Management System The proposed on-site waste water management system will provide pre-treatment to the process effluent only and will consist of the following component treatment steps: - Screening - Waste Water Balancing IE REF-0035_1_08.DOC Page 3 of 4 EPA Export :22:43:48

47 09/09/ Cooling - Neutralisation - Monitoring Note: Sanitary effluent from the facility (from lockers and toilets) will combine with the sanitary and laboratory effluent prior to separately entering the foul sewer in College Park. Effluent Screening: Upstream coarse screening to remove shoe covers; hair nets, gaskets etc. which may have a detrimental impact on downstream mechanical equipment will be employed. Waste Water Balancing: The main purpose of the balance tank system is to provide buffering capacity to smooth out variations in the flow and pollution loads. This will allow a uniform discharge to the public sewer, and provide natural buffering to ph fluctuations allowing the effluent feed to the downstream neutralisation stage to remain steady. An additional buffer tank will also be provided to cater for periods of peak load or abnormal concentration requiring retention. Peak loads can be diverted to the buffer tank away from the balance tank and bled back into the system over time allowing for a more uniform treatment and discharge profile. The buffer tank will also cater for storing waste water during specific storm events (to be notified via telemetry by Irish Water) where no discharge will be permitted to the external sewer network for periods of up to 7 hours. Once storm conditions have abated a maximum discharge rate of 81.9l/s from the site would be permitted to facilitate emptying of the on-site storage. Overall up to 5 tanks are envisaged, each of approximately 400m 3 working capacity. Cooling: Process effluent from the production facility will be at elevated temperatures due to the thermal deactivation of production wastes and the potential use of high temperature utilities such as Water for Injection (WFI). IEL conditions are likely to restrict effluent temperature to a maximum of 40 o C, therefore it may be necessary to reduce effluent temperature. Cooling will naturally occur during effluent transfer and equalisation. Neutralisation: The ph control will be achieved utilising inline dosing, with a PLC controlled chemical dosing system (acid and caustic). There will be upstream and downstream ph sensors installed allowing for effective ph adjustment. The recirculation loop will be provided downstream of the monitoring point to reverse waste water back to the balancing tanks if the quality of discharge waste water does not comply with licence requirements. Odour Control: Under normal circumstances it is not expected that odours will arise from the waste water management system. However, given the biological nature of the process effluent, any risk of odour would be monitored on an on-going basis to determine the requirement of either corrective actions or abatement. Monitoring: Flows and loads will require monitoring to ensure compliance with IEL requirements. As a minimum, flow, temperature and ph will require continuous monitoring. A 24 hour proportional flow composite sampler, with refrigeration, will also be installed. IE REF-0035_1_08.DOC Page 4 of 4 EPA Export :22:43:48

48 Drawing 5: Sewer Emission Points EPA Export :22:43:48

49 CAR PARK EXISTING FINGAL COUNTY COUNCIL PUMPING STATION EXISTING 110kV SUB-STATION LEGEND KEYPLAN N N ELECTRICAL SUBSTATION TO ROSEMOUNT DRUM STORE FFL WASTE WATER TREATMENT AREA CONTROL BUILDING NOTES UTILITY YARD ELECTRICAL BUILDING FFL SITE AREA 41.3 ACRES 16.8 HECTARES EX. FIRE ACCESS ROAD No.1 MANUFACTURING BUILDING FFL DATA CENTRE (UNDER CONSTRUCTION) FFL UTILITIES COMPOUND (UNDER CONSTRUCTION) CENTRAL UTILITY BUILDING FFL EX. FIRE ACCESS ROAD No.1 WAREHOUSE EXTENSION FFL WAREHOUSE & PACKAGING BUILDING (UNDER CONSTRUCTION) FFL FIRE WATER SPRINKLER TANK EXISTING FIREWATER PUMP HOUSE EXISTING SPRINKLER TANK LABORATORY BUILDING (UNDER CONSTRUCTION) FFL ADMINISTRATION BUILDING (UNDER CONSTRUCTION) FFL Ordnance Survey Ireland Licence No. EN c Ordnance Survey Ireland/Government of Ireland FORMAL ISSUE EXISTING ATTENUATION POND EXISTING CAR PARK (UNDER CONSTRUCTION) ALEXION EX. GAS AGI EXISTING ESB & CLIENT SWITCH ROOM PROPOSED MANUFACTURING FACILITY INDUSTRIAL EMISSIONS LICENCE APPLICATION DRAWING 5: SEWER EMISSION POINTS IE :2500 IE DR-0005 EPA Export :22:43:48

50 Drawing 6: Wastewater Process Flow Diagram EPA Export :22:43:48

51 NOTES ³ ph TOC ³ ³ ³ TOC ph FORMAL ISSUE ALEXION PROPOSED MANUFACTURING FACILITY INDUSTRIAL EMISSIONS LICENCE APPLICATION DRAWING 6: WASTEWATER PROCESS FLOW DIAGRAM N.T.S. IE DR-0006 EPA Export :22:43:48

52 Attachment E.5 Noise Emissions EPA Export :22:43:48

53 E.5 Noise Emissions The main sources of noise have been identified in Table E.5 (i) of this application and are shown in Drawing 7 and 8: Noise Emission Sources. In line with the attached EIS and Attachment I.7 of this application, noise attributable solely to onsite activities shall not exceed the below criteria: - Daytime (07:00 to 19:00hrs): 55dB LAr,T; - Evening time (19:00 to 23:00hrs): 50dB LAr,T; - Night time (23:00 to 07:00hrs): 45dB LAeq,T. The nearest noise sensitive locations to the Alexion facility are shown in Drawing 9: Noise Sensitive Locations and shown in the following table. Table E.5-1: Description of Noise Sensitive Locations Noise Sensitive Location (NSL) Monitoring Period Description National Grid Coordinates NSL1 NSL2 NSL3 NSL4 NSL5 Day/Evening/Night Day/Evening Day/Evening Day/Evening Day/Evening Outside nearest residential dwelling along Dromheath Drive ~330m south west of the proposed facility boundary East corner of Lady s Well park ~50m south west of the proposed facility boundary ~300m west of the proposed facility boundary at the rear of Mulhuddart Cemetery Outside the Bright Horizons early childhood care and education centre ~200m east of the proposed facility boundary Outside of the Institute of Technology Blanchardstown (ITB) Learning and Innovation Centre ~15m south of the proposed site boundary E, N E, N E, N E, N E, N Operational Noise Emissions There will be a number of noise generating equipment and activities associated with the operation of the proposed development. Any noise from production and utilities equipment located inside/within the site buildings will be mitigated by both equipment design and/or the building structure to prevent any external noise impact. The externally located utility equipment items which could potentially impact on ambient noise levels, are as follows: - 4 No. Cooling Towers located on the roof of the central utilities building - 1 No. main fresh air intake louver located on southern elevation of main process building - 1 No. main exhaust air louver located on eastern elevation of main process building - 2 No. warehouse air intake louvers on northern elevation of warehouse building - 5 No. pumps associated with waste water treatment area - 4 No. cooling towers in utilities yard - 12 No. cold room compressors (4 No. located on roof of warehouse building; 8 No. located on external wall of the lab building in Phase 1 utilities yard) - 14 No. AHUs associated with the administration, canteen, warehouse and laboratory buildings (overall 22 No. separate fan noise sources located at various points at external intake and exhaust louvers) Attachment E.5 Noise Emissions.DOC Page 1 of 2 EPA Export :22:43:49

54 For the purposes of the impact assessment, only the main noise sources were included in the noise model. Noise from site emergency equipment, i.e. fire water pump, emergency generators etc., is not considered normal operational noise for the purposes of this assessment. See Section of NG4 for further justification details. No significant noise is anticipated from the process water pump-house and with respect to the emergency equipment (i.e. firewater pumps and emergency generators), this equipment was not included in the noise model, because other than for testing purposes (ca minutes testing per week during daytime hours only), this equipment will only be run during emergency situations. The firewater pumps will be located in a pump-house which will attenuate noise from the pumps, and the emergency generators will incorporate acoustic enclosures/sound insulation material to attenuate noise. Therefore noise from this emergency equipment is not considered normal operational noise for the purposes of this assessment. For the purposes of the impact assessment, vendor noise source data was available for the majority of the equipment listed above. Where vendor data was not yet available, sound power levels were estimated for the equipment based on design data for similar equipment. Where required construction materials and cladding for the buildings housing noise generating plant and equipment will have an appropriate Sound Reduction Index (SRI). Based on the existing noise levels and noise impact assessment (as detailed in Attachment I of this application) it is predicated that the additional noise contribution from the facility will not cause a significant negative impact at the nearest noise sensitive locations. The minimisation of noise will form an integral part of the detailed design. The various noise control and attenuation measures to be employed at the plant can be summarised as follows: - As part of the detailed design and tendering process, stringent noise level criteria will be specified for all plant and equipment; - Acoustic insulation / enclosures and attenuation will be provided on plant and equipment as necessary; - Plant and equipment will be maintained and serviced on a maintenance schedule; - Site access roads will be of smooth hard standing surface to reduce vehicular noise. Attachment E.5 Noise Emissions.DOC Page 2 of 2 EPA Export :22:43:49

55 Drawing 7: Noise Emission Sources (1 of 2) EPA Export :22:43:49

56 KEYPLAN N N LEGEND FORMAL ISSUE ALEXION Ordnance Survey Ireland Licence No. EN c Ordnance Survey Ireland/Government of Ireland PROPOSED MANUFACTURING FACILITY INDUSTRIAL EMISSIONS LICENCE APPLICATION DRAWING 7: NOISE EMISSION SOURCES (SHEET 1 OF 2) IE :1500 IE DR-0007 EPA Export :22:43:49

57 Drawing 8: Noise Emission Sources (2 of 2) EPA Export :22:43:49

58 BUILDING FFL WAREHOUSE EXTENSION FFL N EX. FIRE ACCESS ROAD No.1 DATA CENTRE (UNDER CONSTRUCTION) FFL UTILITIES COMPOUND (UNDER CONSTRUCTION) WAREHOUSE & PACKAGING BUILDING (UNDER CONSTRUCTION) FFL FIRE WATER SPRINKLER TANK EXISTING FIREWATER PUMP HOUSE EXISTING SPRINKLER TANK CAR PARK ADMINISTRATION BUILDING (UNDER CONSTRUCTION) FFL LABORATORY BUILDING (UNDER CONSTRUCTION) FFL EXISTING CAR PARK (UNDER CONSTRUCTION) EX. GAS AGI EXISTING ESB & CLIENT SWITCH ROOM EXISTING ATTENUATION POND Ordnance Survey Ireland Licence No. EN c Ordnance Survey Ireland/Government of Ireland FORMAL ISSUE NOTES NOTES NOTES NOTES N ALEXION LEGEND PROPOSED MANUFACTURING FACILITY INDUSTRIAL EMISSIONS LICENCE APPLICATION DRAWING 8: NOISE EMISSION SOURCES (SHEET 2 OF 2) IE :1500 IE DR-0008 EPA Export :22:43:49

59 Drawing 9: Noise Sensitive Locations EPA Export :22:43:49

60 EXISTING DITCH EXISTING SOUTHERN PERIMETER BERM TO BE REMOVED BY OTHERS PRIOR TO COMMENCEMENT OF DEVELOPMENT CAR PARK 2.5m X 5.0m PARKING SPACE U.N.O. EXISTING FINGAL COUNTY COUNCIL PUMPING STATION EXISTING 110kV SUB-STATION KEYPLAN N ELECTRICAL SUBSTATION TO ROSEMOUNT AREA SUBJECT OF SEPARATE PLANNING APPLICATION FW15A/0043 N AREA SUBJECT OF SEPARATE PLANNING APPLICATION FW15A/0038 DRUM STORE FFL WASTE WATER TREATMENT AREA CONTROL BUILDING UTILITY YARD ELECTRICAL BUILDING FFL NOTES SITE AREA 41.3 ACRES 16.8 HECTARES CENTRAL UTILITY BUILDING FFL LEGEND EX. FIRE ACCESS ROAD No.1 EX. FIRE ACCESS ROAD No.1 MANUFACTURING BUILDING FFL DATA CENTRE (UNDER CONSTRUCTION) FFL UTILITIES COMPOUND (UNDER CONSTRUCTION) WAREHOUSE & PACKAGING BUILDING (UNDER CONSTRUCTION) FFL ADMINISTRATION BUILDING (UNDER CONSTRUCTION) FFL LABORATORY BUILDING (UNDER CONSTRUCTION) FFL WAREHOUSE EXTENSION FFL EXISTING DITCH TO BE MAINTAINED FIRE WATER SPRINKLER TANK EXISTING FIREWATER PUMP HOUSE EXISTING SPRINKLER TANK Ordnance Survey Ireland Licence No. EN c Ordnance Survey Ireland/Government of Ireland EXISTING ATTENUATION POND EXISTING CAR PARK (UNDER CONSTRUCTION) FORMAL ISSUE EX. GAS AGI EXISTING ESB & CLIENT SWITCH ROOM ALEXION PROPOSED MANUFACTURING FACILITY INDUSTRIAL EMISSIONS LICENCE APPLICATION DRAWING 9 : NOISE SENSITIVE LOCATIONS IE :2500 IE DR-0009 EPA Export :22:43:49