SHANGHAI INSTITUTE OF BIOLOGICAL PRODUCTS (SIBP) SIBP PROJECT EXECUTION PLAN

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chapter 1 management summary ............................................................................. 3 chapter 2 introduction ............................................................................................... 3 chapter 3 project background.................................................................................... 3 chapter 4 goals .......................................................................................................... 4 chapter 5 execution strategy...................................................................................... 4 chapter 6 schedule .................................................................................................... 5 chapter 7 project organization.................................................................................... 6 project management................................................................................................. 8 chapter 8 engineering design..................................................................................... 8 chapter 9 procurement plan....................................................................................... 9 chapter 10 qualification and validation....................................................................10 chapter 11 appendices............................................................................................. 11

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chapter 1 management summary This Project Plan has been established to give a clear understanding to all parties involved in the project on how this project is going to be executed. The plan addresses all critical areas, which may be decisive upon the success of this project. This plan is based on Engineering Guidelines and takes into account the special type and size of this project as well as the project objectives described in this plan and the available resources (time, money, personnel, etc). The execution strategy, the related activities and the authorisations described in this document are crucial and require approval by all parties.

chapter 2 introduction The purpose of this project execution plan is to define the principal objectives for the project with relative priorities, specific strategies and action plans that will lead to the desired result in terms of implementing the User Requirements with regard to GEP. The User Requirements define what has to be built (Technical Project Scope), whereas the plan defines how the project GEP is to be executed. It is a requirement that all the participating parties, i.e. as the Owner, Engineering, Contractors, etc. agree to establish and to live with the objectives, scope of work, opportunities, critical issues, schedules, organisations, resources, roles and responsibilities. Nevertheless, the plan is a living document that has to be updated and changed throughout the life of the project to reflect major changes in priorities, objectives, critical issues as the project progresses through the design and construction phases. This plan must be approved and represents the agreement and commitment to the plan. Once approved, it is the Project Manager's responsibility to achieve understanding and commitment to the plan by communicating it to the involved parties in a form that is clear, concise and readily usable. Preparing and updating the plan as necessary helps the Project Manager and his team to get and maintain a clear picture of the project GEP (refer to SIBP GEP SOP for details) and its execution strategy. At the same time, the approved plan and the Project Managers approval authority directive set the limits within which the project manager has full authority to make his own and final decisions. To the other parties, the plan serves as a tool to make sure that the project has a suitable execution approach and that Pharma Engineering Guidelines is followed. chapter 3 project background The Shanghai facility is located at Fengxian district of Shanghai. Total plan area of the production site is 312,778 square meters. Including the first phase: No. 103 hazardous goods warehouse, No.111 production building of BCG vaccine injection, No.112 transformation rooms, boiler rooms and engineering department

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building, No.113 transformation room, boiler room and engineering department building, No.114 administration building, No.115 gate rooms A, B, C(three ones), No.116 QA, medium building, No.119 Logistics centre building, No.120 measles vaccine and mumps vaccine production building, No.121 rubella vaccine, varicella vaccine production building, No.122 outer packaging, dilution preparation building, No.126 gate rooms and pump rooms. Second phase: No. 101 blood products facility, No.102 blood bank, No.104 ethanol recovery facility, No.105 laboratory, No.106 diagnostics production building, No.107 interferon building, No.117 logistics building(inlucdng central control), No.123 influenza vaccine production building, No.124 Rabies vaccine production building. Third phase: No.118 New Drug Pilot Plant R&D Center and reserved production workshops. Main products for the first phase: BCG vaccine injection, attenuated live varicella vaccine, measles, mumps and rubella attenuated live vaccines, Main Products for the second phase: long-acting interferon, rabies vaccine, influenza vaccine, blood products, etc. chapter 4 goals PROJECT GOALS 1. Flexibility concerning new products and new technologies. 2. Provide sufficient capacity and the right technologies to cope with the forecasted demand of the defined product list. 3. Enable smooth transfer to the new production site. 4. Provide facilities that are able to met recognized quality objectives and pass inspections. 5. Enable phase out of the existing Shanghai Facilities.

chapter 5 execution strategy The execution strategy of the project includes: 1. Development of Concept Design will be based on approved User Requirements. 2. Concept Design will be established. The project organization will be supported by an Architectural/Engineering-Contractor (A/E1) with experience in pharma facilities. The integrated team will be lead by SIBP. The result of the Concept Design phase (list of deliverables to be established and attached to this plan) will serve as the scope definition for the next project phase. 3. Basic and Detail Design will be accomplished by an Architectural/Engineering-Contractor (A/E2) who will be evaluated during Concept Design. This contractor may (but not

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necessarily) be identical with the A/E1-contractor for Concept Design. The design-lead within Basic Design will be with SIBP. Based on the list of deliverables established in Basic Design the contractor will perform Detail Design including the integration of suppliers packages. Detail Design of package units will be performed by the suppliers and integrated into the design package. The design lead within Detail Design will be with the contractor. SIBP will review Detail Design progress and quality. Final acceptance of Detail Design will be made by SIBP. 4. Detail Design and Construction of equipment (package units) will be performed by suppliers. 5. Construction and Qualification of building and infrastructure. Construction and Commissioning of the building including infrastructure (Sanitary, HVAC, Electrical) will be performed by a General Contractor (GC). Construction Management services overseen by SIBP to coordinate the GC and the suppliers of the package units. 6. Construction Management and Qualification Management including coordination of subcontractors will be performed by the SIBP approved co-ordinator. 7. Commissioning and supervision will be performed by SIBP and approved third parties 8. Qualification and supervision will be performed by SIBP and approved third parties 9. Final acceptance of work performed will be made by SIBP 10. The Technical Project Manager will ensure that all contractors employed have a clearly defined work scope and a complete definition of applicable tools, procedures and standards. 11. In order to optimize and challenge the value of engineering third party expert(s) may be recruited for a review of critical areas.

chapter 6 schedule OVERALL PROJECT SCHEDULE The current project timeline is shown below: PROJECT END DATE Definition of the project end date for the project is the handover of the facility to the owner. This requires completion of start up and commissioning and approval by local authorities. Additional activities will follow, e.g. Qualification, relocation of personnel, start up of product transfers, process validation, operator training, etc. which are not part of the initial project.

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chapter 7 project organization The organization chart for the phases of Project Initiation and Concept Design is provided below. The project is headed by XXXXXXXXX. The organization will be revised and adapted to the new requirements when changing the project status. Current Project Organisation Chart

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ROLES AND RESPONSIBILITIES

PROJECT OWNER Responsible for project execution conformance with approved scope and objectives. Responsible for execution of the project according to the approved execution plans and procedures. Establishes the business case for the project. Approves the user requirements, which define the scope and requirements for the project. Establishes, together with the Technical Project Manager, the prioritized project objectives. Establishes, together with the Technical Project Manager, the Project Organization. Assigns Owner/User Representatives to the Project Management Team (as required). Signs-off the Transition Plan and the handover-plan of the new facility to the user. Approves Concept Design.

TEAM LEADERS Responsible for the definition of the User Requirements, which define the scope and requirements of the facility. Verifies/confirms process requirements, production information and impacts. Reviews concepts and design documents. Reviews and approves critical design deliverables. Gives guidance on regulatory affairs. Establishes the Transition Plan from the old into the new facility.

TECHNICAL PROJECT MANAGER Directly accountable to the Project Owner for the successful delivery of the project. Establishes, together with the Project Owner, the Project Organization. Responsible for project design and execution including cost, schedule, quality and safety Ensures compliance with local laws and building codes. Manages the Engineering and Construction Contractors as well as the Engineering Team Members and the engineering discipline support including project approved consultants.

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Responsible for Contracting, Project Controls, Project Financial Controls and Project Reporting. Supports establishment of user requirements and key data Establishes the execution strategy. Represents the Owners interests in all phases of the project and achieves the project objectives for cost, schedule, quality and safety. Prepares/issues monthly project progress reports in accordance with the Project Controls Plan. Reports to Project Owner / Senior management, providing project status & performance information on a regular basis. Keeps costs, time schedule and technical characteristics on target as approved. Ensures appropriate consulting and provision of the necessary approvals of technical experts, such as Quality Control & Assurance; Safety, Health & Environmental Protection, Information Technology.

project management CHANGE MANAGEMENT Change Management will be implemented starting from the approval or user requirements. STANDARDS Standards applicable for this project (e.g. industry standards, ISPE etc) will be defined as necessary during Concept Design. DOCUMENT AND DATA MANAGEMENT Technical Documentation is handled according to the GEP SOP and Project Quality Plan requirements. Project documentation (electronic and hardcopies) is handled according to the Project Quality Plan.

chapter 8 engineering design REVIEW AND APPROVAL OF DESIGN WORK Periodic reviews of design work will be conducted to ensure compliance with the user requirements and the project objectives. The Technical Project Manager will define the reviews to be made on an as needed basis and nominate the members of the review team.

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VALUE ENGINEERING Value Engineering will be incorporated into design reviews order to optimise the added value of this project. Focus will be on functionality requirements and the standard of technical solutions.

chapter 9 procurement plan Procurement of package units (process equipment) will be performed by the experienced and skilled organisation of the project team. Individual Detailed Specifications will be written for each package to facilitate procurement. Procurement of remaining construction equipment/material (building + infrastructure) will be performed by the selected construction contractor(s) in accordance with the specifications and guidelines specified in the design phases. A detailed procurement plan will be established in the early Basic Design Phase to timely cover Long Delivery Items and to ensure coordination of procurement activities. CONTRACTING STRATEGY The contracting strategy for the project is based on the project execution strategy described in chapter 5. The project scope will be split into the following main contracts: Main Contracts A/E Project Phase and scope Concept Design Comment Contractor resources to be integrated into a project organisation. Process know how and key disciplines (e.g. qualification etc) to be provided by main contractor. All other disciplines to be subcontracted. Subcontractors to be approved by SIBP. Contractor will provide all main services for BD and DD. Missing resources will be subcontracted. Subcontractors to be approved by SIBP. Supervision of contractor services and final acceptance of work will be performed by SIBP according to execution strategy (see chapter 5).

A/E and GC

Basic Design of process, building, utilities, infrastructure and external works Detail Design of building, utilities, infrastructure and external works Design Coordination Construction Management Construction Quality Control Qualification Management

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Suppliers

Detail Design of process package units (PPU) Delivery, Construction, Commissioning & Qualification of process package units including all critical infrastructure systems (e.g. water supply and CIP)

(Interfaces to Building/Infrastructure to be defined in BD)

chapter 10 qualification and validation The products produced by the facility will be launched and need to be produced according to cGMP rules. The facility and the production processes have to meet SIBP Guidelines as well as the regulations of SFDA, WHO and other relevant agencies. A Validation Execution Plan will be established during the basic design phase to cover all qualification and validation issues of this project and to allocate ownership of the activities and compilation of subsequent documents. QUALIFICATION Resource has been assigned to the project to assure that Qualification is being performed according to standards and procedures and to supervise qualification work being performed by contractors and suppliers. On time delivery and quality of qualification work to be performed by contractors and suppliers will be safeguarded by contractual terms and conditions. PROJECT QUALITY PLAN A project quality plan will be established and issued during the Basic Design Phase. The major sections of the Project Controls Plan will include:

Work break down structure/organisation List of deliverables of each project phase (concepts, specifications, etc) Budgeting of hours to be spent on development of the deliverables. Project Estimates and Schedules Progress Control Change Management Reporting (e.g. project monthly report, quarterly report)

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chapter 11 appendices

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