DocusSign Envelope ID: 22842231-8F 88.46 15-AFES.2145ES34DCDC, * Biogen USCS Sra ro Biogen and ICON GSS Data Management, Biostatistics, and Statistical Programming Functional Service Provider (FSP) Engagement Handbook Version 3.0 Effective 10MAR2022 BIOGEN-ICON Engagement Handbook Version 3.0 1 of 24DocusSign Envelope ID: 22842231-8F 88.46 15-AFES.2145ES34DCDC, Table of Contents 1.0 Overview 1.4 Approvals: 1.2 Change Contra 2.0 — Governance and Communication 24 Governance Model. Level 1: Executive Steering Committee (ESC) Level 2: Outsourced Operations Committee Level 3: FSP Team Meetings — Data Management Level 3: FSP Team Meetings - Biostatistics Level 3: Team Meetings — Statistical Programming Level 4: Lessons Learmedi/Improvements (Ad Hoc Only) = Data Management Level 4: Lessons Leamed/Improvements (Ad Hoc Only) - Biostatistics Level 4: Lessons Learnedi/Improvements (Ad Hoc Only) ~ Statistical Programming 2.2 Communication & Escalation Plan Somarvonns O ou w TABLE 4 Escalation Plan 10 23 Escalation Rules for Raising Issues and Communicating Solutions. 1" 24 Escalation Principles. TABLE ta IT Escalation Plan "1 2.5 ICON GSSGSS Operational Management Structure and Oversight. 2.6 Contract Management 3.0 Quality 16 3.4 FSP Audit of ICON GSSby Biogen. 3.2. Regulatory Inspections of Biogen studies at aclitios. 3.3. Regulatory Inspections of Biogen facilities where ICON GSS services are included, 3.4 Regulatory Inspections of ICON GSS that may impact Biogen servi 3.5 Issue Management / Escalation and CAPA Management. 3.6 Serious Breach 4.0 Project Planning & FSP Management 17 4.1 Resource Management. 4.2 Toam Assignment List 43° Training. 4.4 Resource Utilization and idle Time Management... 4.5. Performance Feedback and Staff Changes. 48 Performance Metrics and Service Level Assessments 47 Risk Mitigation 48 Process Improvements. 49° IT Equipment & Set-up. 4.410 Technology.. 5.0 Relationship Management 2 5.4 Communication Principles. 5.2 Team Absences and Changes 5.3. Meeting Minutes, Agendas and Action Logs. 5.4 Guidelines for FSP Travel 55 Holidays 5.6 Vacation Coverage. 5.7 BIOGEN Global Data Management Collaboration Site / ICON WorkSpace. 5.8 Biogen Biostatistics and Statistical Programming Collaboration SitelCON WorkSpace 5.9 Contracting Process. Appendix 1: Change Control BIOGEN-ICON Engagement Handbook Version 3.0 2of 24Docusign Envelope ID: 22842231-8F 88.46 16-AFES.2145ESt4DCDC, 1.0 Overview: This Engagement Handbook (EHB) Is created collaboratively between Biogen and ICON GSS. The purpose of the document is to describe the interactions for Data Management (including data provisioning and Database Development across Functional Service Provision (FSP) assignments in Data Management for Biogen), as well as for Biostatistics and Statistical Programming. In addition, this handbook will serve as a relationship manual that specifies the oversight activities to ensure that all work performed safeguards pationt safety, rights and data integrity and complies with regulations and procedures. The scope of activities outsourced to the FSP is documented in the MCRO Agreement, dated 29Mar2018, and its amendments ("Agreement") and subsequent Statements of Work. In this FSP, ICON GSS staf will follow Biogen SOPs and Procedures and utilize Biogen systems in the management of studies, This document does not describe trial specific procedures or processes undertaken or involved at the individual trialtrial delivery level. Trial specific procedures, processes and details are documented in the respective trial specific documentation, 14 Approvals: This document will be approved by both a Biogen (BIOGEN) and ICON GSS representative. A copy of the complete Engagement Handbook, including signature pages will be stored in the Biogen Global Data Management Collaboration site/ICON WorkSpace, 12 Change Control The Biogen Analytics and Data Sciences Vendor Manager (ADS VM) responsible for this specific ‘engagement will update the Engagement Handbook in conjunction with feedback from BIOGEN and ICON GSS managers. The Engagement Handbook will be reviewed as updates are required and published with a new version as necessary. Major changes will be highlighted and/or logged on Appendix 1 - Change Control, 2.0 Governance and Communication ‘The goal of the Governance Framework is to build and maintain a successful collaboration between Biogen and ICON GSS by outlining clear communication and escalation pathways. There are three levels ‘of Governance that encompass the overall relationship management: The tiers of governance are: = Level 1: Steering Committee (Data Management, Biostatistics, Statistical Programming) — ‘combined meeting for all functional areas + Level 2: Outsourced Operations Committee (Data Management, Biostatistics, Statistical Programming) — separate meetings for each functional area + Level 3: FSP Team Meetings (Data Management, Biostatistics, Statistical Programming) — separate meetings for each functional area + Level 4: Lessons Learned/Improvements (Ad Hoc Only) (Data Management, Biostatistics, Statistical Programming) - separate meetings for each functional area ‘The goal of having multiple tiers of governance is to ensure collective success of the relationship and of individual projects. Governance members will be designated as core or as agenda driven by mutual agreement of both companies. Core members or designees are required attendees. Agenda-driven members will be included on an ad-hoc basis, Note: Each team is accountable to the next level up for performance management & escalation of issues. BIOGEN-ICON Engagement Handbook Version 3.0 of 24Docusign Envelope ID: 22842231-8F 88.46 16-AFES.2145ESt4DCDC, ‘The relationship between these groups and their responsibilities are depicted in the following figure: 24 Governan: lod ‘The Parties will manage the overall engagement through the following management groups, consisting of three layers: Level 1: Executive Steering Committee (ESC) BIOGEN (Sponsor) ICON GSS (FSP) Members Members Lead ADS VM ‘VP Operations/Director of Program Management Required Attendees Head, Data Management or | Director of Program Designee Management/Designee Head, Biostatistics or Designee Head, Statistical Programming or Designee ‘Optional Attendees IT Representative, Quality ‘Operations Representative, IT Representative, Head of Data | Representative, Qualily Sciences and Operations —_| Representative Executive Steering Committee Meeting Schedule and Responsibilities The BIOGEN ADS VM schedules 2meetings per year (target is for atleast one face-to-face meeting), and co-chairs the Executive Steering Committee meetings with the ICON GSS Lead. ICON GSS Lead documentsidistributes Meeting Minutes. ICON GSS Lead is responsible for BIOGEN ESC meeting ‘materials (including agenda) and will work with all participants to coordinate ESC meeting materials. BIOGEN-ICON Engagement Handbook Version 3.0 4 of 26Docusign Envelope ID: 226A2231-6F 88-66 15-AFES-2145E5340000, NOTE: ADS VM and ICON GSS Lead will meet on an as-needed basis to discuss on-going issues related to resources, contracts, finances, unresolved escalation and any other topic as needed to maintain the working relationship, ‘The ESC will have oversight of this program. ESC members may consist of a senior/executive management representative from both Biogen and ICON GSS, The ESC is responsible for identifying key risks and development of mitigation strategies for areas including, but not limited to: Overall Service Performance Providing Strategic Direction for Data Management, Biostatistics, and Statistical Programming Outsourced Operations Committee (OC) including the review of high-level operational issues escalated from the OOC and approval of associated response plans. Business Plan and Goals Capacity Capability development Defining/communicating upcoming needs across Biogen Proactively working across organizations to ensure alignment Resourcing and change management Identification of key risks and contingency plans Presentation of new services or technical capabilities to expand collaboration (only as requested by Biogen). For each ESC meeting, the Outsourced Operations Committee Leads (OC) will update the ESC in advance on any current risks, issues, and associated contingency plans. Level Outsourced Operations Committee (OO0C) Data Management Outsourced Operations Committee (DMOOC) BIOGEN (Sponsor) Members ICON GSS (FSP) Members Lead Head, Dala Management Director of Program Management Operations or Designee. Required ‘Select members of the Data Operation Manager Attendees Management Lead Team Optional Atiendees ‘ADS Vendor Manager, Quality Representative, TMF Representative Line Manager, Quality Representative, IT Representative, Training Representative Biostatistics Outsourced Operations Committee (B0OC) BIOGEN (Sponsor) Members ICON GSS (FSP) Members Lead Head, Biostatistics or Designee | Director of Program Management Required ‘Select members of the Operation Manager Attendees Biostatistics Lead Team Optional Attendees | ADS Vendor Manager Line Manager, Quality Representative, IT Representative, Training Representative Statistical Programming Outsourced Operations Committee (SPOOC) ‘BIOGEN (Sponsor) Members ICON GSS (FSP) Members Lead Head, Statistical Programming or | Director of Program Management Designee Required ‘Select members of the Stalistical | Operation Manager Attendees Programming Team Optional Atfendeos ‘ADS Vendor Manager Line Manager, Quality Representative, IT Representative, Training Representative BIOGEN-ICON Engagement Handbook Version 3.0 5 of 24Docusign Envelope ID: 22842231-8F 88.46 16-AFES.2145ESt4DCDC, Outsourced Operations Committee Meeting Schedule and Responsibilities ICON GSS schedules monthly meetings, provides the Agenda, chairs the Operations Committee meetings {DMOCC), and documentsidistributes Meeting Minutes. The agenda will include additional items {performance status update, staff monthly accolades, study updates and training, TMF, process improvement etc.). ‘The OOC is the high-level management team responsible for operations within the Biogen and ICON GSS relationship. The OOC will consist of senior level functional representatives from both ICON GSS and Biogen. The OC is responsible for: ‘Management of operational issues escalated from the FSP Team Meetings Agreement on resourcing projections via agreed Statement of Work Collaboration at a relationship-wide level on initiatives to identify & mitigate risks. Monitoring performance of relationships and creating efficiencies. Issue diagnosis, management, and resolution, which include the escalation of issues to the SC where resolution is not possible at the OOC. Designing and monitoring of metrics for milestones, timelines, and quality. * Ongoing evaluation of Key Performance Indicators (KPIs), Service Level Agreements (SLAs), and resolution of issues arising from KPI/SLA analysis, ‘+ Review assessment of resource requirements & capacity planning in relation to Biogen needs for successful portfolio delivery. ‘The agenda topics may include, but not be limited to: + Partnership accomplishments. + Review of performance through KPIs or metrics. + Issue management & escalation + Project Team Health, + Study or service delivery concems: + Standardization of services. + Resource, scope and change management. * Monitoring and escalation of utilization of staff and review of SOW requirements. + Contingency plans. + Contractual issues. + Hot topies/accompishments + Highlight process improvements implemented. + Status of upcoming Portfolio related milestones. + Training compliance and knowledge gap review. Level 3: FSP Team Meetings — Data Management ‘BIOGEN (Sponsor) Members | ICON GSS (FSP) Members Lead ‘Assigned Data Management Operations Lead (DMOL), Required ‘Assigned Data Management Assigned Trial Data Manager (TDM) Attendees Operations Lead (DMOL), Assigned Lead Clinical Programmer Analyst Optional Data Management Porfofo Lead | Sludy Builder, Data Manager, Attendees (DMPL), Quality Representative, Coding Specialist, Validation Lead Validation Analyst, Reports | Analyst, Clinical Programmer, Developer Extemal Data Analyst FSP Team Meeting Schedule and Responsibilities BIOGEN-ICON Engagement Handbook Version 3.0 6 of 24Docusign Envelope ID: 226A2231-6F 88-66 15-AFES-2145E5340000, ‘The ICON GSS TDMs will attend regular FSP Team meetings for their assigned projectiprogram and will also attend any additional meetings as assigned by Biogen Leads. ‘The purpose of the FSP Team Meeting is to provide study related management and oversight of study activities, including issue resolution with escalation to the OOC as required. FSP team members are responsible for communicating information regarding administrative and functional process issues to their respective management. Example agenda items include but not limited to: + Project status. = Data and performance quality. * Resourcing needs. + Timelines. * Critical deadiines. + System performance and issues. + Process issues. Level 3: FSP Team Meetings - Biostatistics BIOGEN (Sponsor) Members | ICON GSS (FSP) Members Lead ‘Assigned Biostatistics Lead NA Required ‘Assigned Biostatistics Lead ‘Assigned Biostatistician Attendees Optional Biostatistics Project Lead ‘As required additional FSP team Attendees members FSP Team Meeting Schedule and Responsibilities The ICON GSS Biostatistician will attend regular FSP Team meetings for their assigned project/program and will also attend any additional meetings as assigned by Biogen Leads. ‘The purpose of the FSP Team Meeting is to provide study related management and oversight of study activities, including issue resolution with escalation to the OOC as required. FSP team members are responsible for communicating information regarding administrative and functional process issues to their respective management, Example agenda items include but not limited to: Project status. Data and performance quality. Resourcing needs. Timelines. Critical deadiines, ‘System performance and issues. Process issues. Level 3: Team Meetings — Statistical Programming [BIOGEN (Sponsor) Members | ICON GSS (FSP) Members Lead ‘Assigned Statistical Programming | NA Lead Required ‘Assigned Statistical Programming | Assigned Statistical Programmer Attendees Lead BIOGEN-ICON Engagement Handbook Version 3.0 7 of 24Docusign Envelope ID: 226A2231-6F 88-66 15-AFES-2145E5340000, ‘Optional ‘Sialistical programming study ‘As required additional FSP team Attendees team members members Team Meeting Schedule and Responsibilities The ICON GSS Statistical Programmers will attend regular Study Team meetings for their assigned projectiprogram and will also attend any additional meetings as assigned by Biogen Statistical Programming Leads. ‘The purpose of the Team Meeting is to provide study related management and oversight of study activities, including issue resolution with escalation to the OOC as required. FSP team members are responsible for communicating information regarding administrative and functional process issues to their respective management. Example agenda items include but not limited to: + Project status. Data and performance quality. Resourcing needs. Timelines. Critical deadiines. ‘System performance and issues. Process issues. Level 4: Lessons Learned/Improvements (Ad Hoc Only) - Data Management BIOGEN (Sponsor) Members TCON GSS (FSP) Members ] Lead Assigned DMOL ‘Assigned OMOLITOM Required ‘Assigned DMOL, Assigned TDM, Assigned Study Bullder, Assigned Attendees Assigned Statistician, Assigned |_| Data Manager, Assigned Coding Statistical Programmer, Assigned | Specialist, Assigned Validation SDTM Lead, Assigned Lead Analyst, Assigned Clinical Clinical Programmer Analyst, Lead | Programmer, Assigned External Validation/Quality Analyst, Reports | Data Analyst Developer Optional Assigned DMPL, Qualiy Operation Manager Attendees Representative Meeting Schedule and Responsibilities ‘The Biogen DMOLs and/or Subject Matter Experts may schedule lessons leamed or other meetings that focus on process improvement or identification of training needs. The Operations managers will be informed of these suggested improvements to focus on any operational or general relationship improvements. If necessary, a follow-up meeting may be scheduled to ensure proper implementation of any action items. Level 4: Lessons Learned/Improvements (Ad Hoc Only) - Biostatistics ‘BIOGEN (Sponsor) Members ICON GSS (FSP) Members Lead [Assigned Biostatistics Lead [Assigned Biostatisticians. BIOGEN-ICON Engagement Handbook Version 3.0 Bof 24Docusign Envelope ID: 226A2231-6F 88-66 15-AFES-2145E5340000, Required ‘Assigned Bioslalisics Lead ‘Assigned Biostatistician Attendees Optional Quailly Representative Operation Manager Attendees Meeting Schedule and Responsibilities The Biogen Biostatistics Lead and/or Subject Matter Experts may schedule lessons learned or other meetings that focus on process improvement or identification of training needs. The Operations managers will be informed of these suggested improvements to focus on any operational or general relationship improvements. If necessary, a follow-up meeting may be scheduled to ensure proper implementation of any action items. Level 4: Lessons Learned/Improvements (Ad Hoc Only) - Statistical Programming ‘BIOGEN (Sponsor) Mombors | ICON GSS (FSP) Membars | Toad ‘Assigned Slatistical Programming | Statistical Programmers Lead Required Assigned Stafstcal Programming | Operation anager ‘Attendees Lead, Statistical Programing team members Optional ‘Management ‘Sialiacal Programming Manager Attendees Meeting Schedule and Responsibilities ‘The Biogen Statistical Programmers and/or Subject Matter Experts may schedule lessons learned or other meetings that focus on process improvement or identification of training needs. The Operations managers will be informed of these suggested improvements to focus on any operational or general relationship improvements. If necessary, a follow-up meeting may be scheduled to ensure proper implementation of any action items. 2.2 Communication & Escalation Plan ‘A documented communication plan is critical to operational success as it ensures team members understand the expectations of their role and are informed of various issues. A detailed escalation plan (See Table 1) outlines the communication pathway for issue escalation and resolution and coincides with the FSP governance model. NOTE: Study specific communication and escalation plans will also be followed to address study-specific matters. BIOGEN-ICON Engagement Handbook Version 3.0 of 24DocuSign Envelope ID: 22842231-8F 88.46 15-AFES.2145ESt4DCDC, TABLE 1 — Escalation Plan rey or TT People tobe informed veer recor of Director Busters | Avafected say eam ered Program Stategy sd Imenbers & menage Becta Management Operators iy BIOGEN esr Involeing | Dieaarat abs var] Fanaa Manage ‘Contac Petmweeseenioge com eed Drcieriead— | A afocied ay tart aol Pros Data Managerrant_| members & managers Ponies (Copy 08 UM for Pract ramp upranp sown erect) ‘Tasocate Drea | ADS WNT ‘Arafoces way oar ae DataMaragemen | Direcorttoad— | members managers ee reid Dparatone to" Data Managersent | ForTrainag Cony Designo) (or Designo {raining Coornator Forduatty Quatiy | For Qualy: Quay Represoriawwe | Reprosonacwe Pee Program Bioatscan er | Browatsbean Hemet Management | Desigreatead Pome ent Sowtttlar ‘Nata aay eae ‘members & anager Po “asocate Dress | ADS VIE ‘Rr afocod way oar are Bisttstcian or | Drocortlos— | mombore managers peer tro Dosigeet ong Biosatstean Gr | ForTrinag Cony Blosintsian) Designee) ‘rang Goordnator Forduaty:Quatty | For Guaty: Gantt, Represertawe | Represenacwe ras ‘recor? | Aasodite Dredar= | DrecotHead - | Al afoctos say tar pee Program Stoeea! Sts! ‘mombors & managers Ponies Management | Programming Programing BIOGEN-ICON Engagement Handbook Version 3.0 10 of 24DocuSign Envelope ID: 22842231-8F 88.46 15-AFES.2145ESt4DCDC, ory ‘Dreciorof | AseoeateDresos= [ADS VN ‘aoc say oar cet Program Stateteal Drectetead— | mombore & managers ee Management | Progemmag or | Sttstcal Fortraneg: copy pees ood Destaee) Pregrarming or | Train Goorinator Decsgos) For Quali: Guay Fordualy:qualiy | Represenacwe Represoratve 23 Escalation Rules for Raising Issues and Communicating Solutions All teams must adhere to the following rules: + Allteam members are charged with identifying issues proactively + Any team member may raise an issue of concem at any time + Study related issues are expected to be addressed within the Study Management Team (SMT). The Ciinical Projects Lead (CPL) should also be consulted in the resolution of study specific issues. + Issues that are escalated to level 2 (0x. unresolved at the study level) will be documented and tracked to resolution + Trending of documented issues will allow Biogen and ICON GSS to identify best practices and process improvement opportunites. + Documentation of the resolution should include: Date and author(s) of the plan Corrective action plan Preventative action plan, as applicable Timetine(s) for resolution The lead responsible for resolution Where appropriate, a cost benefit analysis. 24 Escalation Principles TABLE 1: ‘+ First priority is to deliver the milestone with quality and in compliance, * Before an issue is escalated, © aroot cause analysis should be performed by the escalating individual. © all efforts to resolve the issue directly with the responsible resource should be exhausted + The escalation should include information and supporting documentation. + Escalations need transparency. Communications and transparency increase the level of trust among functions and organizations. ‘+ Once escalated, communication of progress is critical + Final decisions and how issues are resolved need to be Documentedishared + Remember, escalation is not a bad thing -IT Escalation Plan Identifying the malfunctioning application will lead to better resolution. 2. Escalate any time you do not get a satisfactory response. BIOGEN-ICON Engagement Handbook Version 3.0 of 24Docuion Emon ib 228n2i94asB tere’. 2asesaococ Recommended | Escalation language Contact You goto | IT Service Centre (SC) Pankaj the Workflow Kumar homepage and itdoes not load T T Your IT Service Centre (SC) Pankaj usemame Kumar and password do fot work in Workflow but do clsowhero T T You are in| Create a bug repor in the application Please mention | Pankaj Worktiow | Workflow Click the prioty of Kumar and you are your request tencountering Tr an error or there is something unexpected or you have a question You get TSC Teannot open an | Chris Kania thrown out of application Citrix oF through Citrix, cannot open and it causes| an me to not be application able to do my in Citrix work. Thisis a Citi problem (Mention if you know it affects multiple people) Youcan get | IT SC {cannot run Chris Kania into Cire SAS. Please and open route this to the SAS EG but R&D SAS. running VAIGRID SAS does Queue. not work. (Mention if you know it affects rmuttple people) You needa | Complete Wingspan internal Contributor On-tine traning Laura Wingspan | in BIU. Request a Wingspan account through BAM Putnam eTMF account BIOGEN-ICON Engagement Handbook Version 3.0 12 0f 24DocusSign Envelope ID: 22842231-8F 88.46 16-AFES-2145ESS4DCDC, USER ACCOUNT Complete pre tecorded traning in hoger Univers: Wiegrean eTME Overview Training: Internal Contrtor(Ontine Course) Create a BAM request to set up 8 ‘Wingspan account: BAM Request ~Cincal Agpications = Wingspan eTMF = internal Contributor Walt for an email with a ink to Wingspan 23a) You have an | IT SC Laura issue with Putnam your Wingspan TMF account. Any ITsc lam unable to | Derrick questions access my Halbur regarding Biogen your Biogen university University OR (BU) Tam unable to training, see any missing trainings being training assigned tome. assignments in Biogen or not University loading OR Trainings are not loading/opening forme. Calling the IT SC will always put your ticket into a higher priority queue than any other method. BIOGEN-ICON Engagement Handbook Version 3.0 13 of 24Docusign Envelope ID: 22842231-8F 88.46 16-AFES.2145ESt4DCDC, IT contact information US & Canada x 8-HELP (x84357), option 1 1-617-670-4357 1-877-447-2442 Intemational Offices x 46030 (Internal) #1-617-914-6030 (External) 25 ICON GSS Operational Management Structure and Oversight ICON GSS Director of Program Management GSS has assigned a primary point of contact responsible for ICON GSS delivery of services to Biogen. This roles ultimately accountable to the Biogen Global Heads of Data Management, Biostatistics, and Statistical Programming. The ICON GSS Directoridesignee is primarily responsible for: Recruitment: working with Biogen to understand requirements and subsequently overseeing the ICON GSS recruitment process to ensure timely identification of candidates ‘Overseeing the management of all resources hired and the Line Managers assigned to the program ‘Overseeing the assignment of resources: Working with the Primary Point of Contact at Biogen to assign resources, Ensuring all resources are assigned and fully functioning in the Biogen teams Metric Management: Reviewing ICON GSS outputs in line with agreed KPIs and SLAs. Reporting con these metrics and discussing either with the relevant counterpart. Quality oversight: ensuring the entire DM, Biostatistics, and Statistical Programming teams in ICON GSS are performing as expected and addressing any issues identified either by ICON GSS or by Biogen promptly Collaboration: working with the Biogen team to collectively work on overall best practice in Data management, Biostatistics, and Statistical Programming. Data Management, Biostatistics, and Statistical Programming Outsourced Operations Committee management: working with Biogen at the OOC level Steering Committee participation: Participating in SC and bringing forward any matters from OOC that need to be highlighted to the SC. ICON GSS Operation/Line Manager ICON GSS provides Line/Operation Managers (LM) to provide line management, career development and mentoring support to all ICON GSS employees. The Ops/Line manager will ensure that the performance or each resource assigned meets Biogen expectations and will work with Biogen to implement corrective action plans for individual employees if needed. Line Managers are assigned on a local / regional basis as much as possible to ensure that they understand local employment laws and cultural requirements / sensitivities. BIOGEN-ICON Engagement Handbook Version 3.0 14 of 24Docusign Envelope ID: 22842231-8F 88.46 16-AFES.2145ESt4DCDC, Main Responsibilities of the Operations/Line Manager: Recruit manage and lead Biogen FSP staff across their respective region. Ensure FSP staff is adequately trained on ICON GSS and Biogen training plans. Facilitate FTE assignments in conjunction with Biogen team, Provide regular feedback to Biogen management about operations of the FSP staff. Evaluate performance metrics to identify process improvement areas. Act as point of contact for Biogen DM, Biostatistics, and Statistical Programming operations leads Carry out performance management for staff not meeting appropriate expectations. Issue Escalation (performance & project) to ICON GSS Director of Program Management. Any quality and/or compliance issue(s) must follow the Biogen deviation and escalation processes. Career management (retention, etc.) Implement Reward & Recognition programs towards retention strategies. The ICON GSS Line ManageriBiogen Manager/OL RACI for DM services The ICON GSS Line Manager/Biogen Manager/OL RACI for Biostatistics and Statistical Programming is located in the Biogen Biostatistics and Statistical Programming Collaboration site/lCON WorkSpace (To be developed) 26 Contract Management A copy of the specific FSP FTE contract is held with each BIOGEN and ICON GSS and is available by request for approved personnel. On an annual basis, the Biogen ADS VM will work with internal departments to review and revise the contract as needed in Q4. Purchase orders will be requested accordingly for the next calendar year. Change Orders (Contract Modifications) ‘There are three items that may drive contract changes and the ADS VM will follow an established process to make changes if any of the following instances occur throughout the year: 41) General contract changes (ie. performance metrics, language) 2) The PO is almost fully utilized ‘The Biogen ADS VM will initiate any official change orders and obtain signatures for approval. Reference the MCRO and its amendments for further details. Invoicing After the month's completion, the ICON GSS Operations Lead should provide BIOGEN ADS VM and invoice reviewers with a draft invoice and the associated backup information as agreed between the parties, Upon BIOGEN ADS VM and invoice reviewer approval of draft invoice, FSP should emall monthly invoices to the following email address: (POInvoices@Biogen.com) with a copy to the BIOGEN ‘ADS VM, invoice reviewers, and Finance. Upon receipt in the BIOGEN system, the BIOGEN invoice reviewer will review and approve the invoices. ICON GSS Operations Lead and ADS VM will work collaboratively to manage the overall budget in relation to monthly/yearly spend, ICON GSS will also contribute to any reforecasts required by Biogen throughout the year. In addition to formal invoice submission, a summary of hours per month per associate will be provided to Biogen Operations to support invoicing. An activity timesheet report that contains time spent, per activity, per resource, by study will be provided by ICON GSS to support operational requirements. BIOGEN-ICON Engagement Handbook Version 3.0 16 of 24Docusign Envelope ID: 22842231-8F 88.46 16-AFES.2145ES@4DCDC, 3.0 Quality 3.1__FSP Audit of ICON GSS by Biogen GCP audits are conducted by the BIOGEN R&D Quality department or a contractor performing the audit on their behalf. These audits typically occur approximately every two years. The ADS VM is to be made aware when this is occurring and answers any general relationship management questions if necessary. 3.2 Requlatory inspections of Biogen studies at ICON GSS Facilities When Biogen learns of a regulatory agency's intent to inspect services provided by ICON GSS, where ICON GSS inspection support may be required, Biogen will notify ICON GSS Program Lead, in a timely manner. This will be case dependent and will be based on a number of factors including scope of inspection, inspection support expertise and exposure within ICON GSS (global and facility level) In situations where ICON GSS is inspected by a Health Authority (HA) in relation to one or more Biogen sponsored trials Biogen wil: + Inconsultation with ICON GSS, provide inspection preparation support as required and agreed wit Biogen. As required, this support may be remote or physically onsite at an ICON GSS facility ‘+ Prior to any inspection, provide any documentation and/or data as requested by the HA to support such inspection. + During any inspection of a Biogen trial at an ICON GSS facility, ICON GSS will provide direct support as appropriate, ‘+ During the actual conduct of an inspection by a HA, where one or more Biogen trials are the primary {focus of the inspection, e.g., marketing application submission, for cause (triggered), Biogen reserves the right to have Biogen associates physically present at the ICON GSS facility during such inspection. These associates will provide consultation and/or support as required and will work with ICON GSS to ensure all HA questions relating to the Biogen trials, and ICON GSS services supporting those trials, as suitably addressed. ‘+ During the actual conduct of an inspection by a HA, where one or more Biogen trials are the secondary focus of the inspection, e.g., GCP inspection of ICON GSS facility, Biogen will work with ICON GSS to ensure that all HA questions relating to the Biogen trials, and ICON GSS services supporting those trials, as suitably addressed. In consultation with ICON GSS, and if appropriate, Biogen may provide onsite support during the inspection. ‘+ Following any inspection involving a Biogen trial, ICON GSS will share any Biogen related inspection findings/report with Biogen. ICON GSS and Biogen will collaboratively work on any related responses prior to submission to a HA. ICON GSS will provide Biogen with a copy of the submitted response; follow up HA correspondence and the final inspection findings/report, 3.3 Requlatory inspections of Biogen fac jos where ICON GSS services are included For regulatory inspections of Biogen, Biogen Inspection process and procedures for managing regulatory inspection will be followed. When Biogen learns of a regulatory agency's intent to inspect services provided by ICON GSS where ICON GSS inspection support may be, required Biogen will notify ICON GSS Program Lead, in a timely manner ‘+ ICON GSS to provide complete and accurate documents to fulfl an inspection related request ‘+ ICON GSS to provide documentation as required by Biogen to support regulatory responses following the inspection ICON GSS to make appropriate ICON GSS associates available for consultation and/or interview in a timely manner ‘As appropriate, ICON GSS associates will participate in Biogen submission/inspection readiness activities as part of their role as members of Biogen clinical tral teams BIOGEN-ICON Engagement Handbook Version 3.0 16 of 24Docusign Envelope ID: 22842231-8F 88.46 16-AFES.2145ESt4DCDC, 3.4 Requlatory inspections of ICON GSSGSSthat may impact Biogen services For regulatory inspections of ICON GSS, ICON GSS will follow ICON GSS SOP GENO13: Audits or Inspections of ICON GSS Operations by External Partios. When ICON GSS learns of a regulatory agency's intent to inspect an ICON GSS facility that may impact, Biogen studies, ICON GSS Quality will notify Biogen by email in timely manner after receiving notice. ICON GSS will update Biogen on any support required or findings that impact Biogen services in timely manner. ICON GSS QA will liaise with Biogen QA on inspection findings relevant to Biogen. 3.5 Issue Management / Escalation and CAPA Management Quality Issues identified at a study level and program level will be escalated as per the Biogen process! SOPs. Biogen SOPs will be followed for managing the CAPA. ICON GSS study team will provide CAPA, implementation plan as per Biogen SOPs. Biogen QA will be managing the CAPA process and inform ICON GSS QA as required. Quality Issues related to ICON GSS performance as described in the Agreement will be escalated to ICON GSS program management and will follow ICON GSS CAPA management process. Biogen QA will be kept informed of any critical issues noted by ICON GSS QA. If such an issue is likely to impact a Biogen process, this will also be covered by the Biogen deviation and escalation process, ICON GSS study team will work with Biogen Quality Assurance for CAPA implementation Plan according to Biogen SOPs. 3.6 Serious Breach To ensure Biogen timely reporting of all Serious Breaches to relevant Regulatory Authorities, ICON GSS shall follow the agreed Biogen process and notify Biogen within agreed timelines for making the determination of an actual or potential ICON GSS Serious Breach that may directly impact services under this agreement. Biogen is responsible for reporting Serious Breaches of GCP andior the protocol to applicable Regulatory Authority as per required timelines 4.0 Project Planning & FSP Management! 4.4 __ Resource Management ICON GSS assigns qualified personnel to perform Services as specified in the Agreement and associatedStatement of Works. ICON GSS personnel will use Biogen procedures (which are essential for the provision of the Services), processes and systems. ICON GSS is solely responsible for the management, training, travel and expense management, expense management and other employer-employee related tasks in connection with ICON GSS personnel performing FSP services for Biogen ICON GSS is solely responsible for the management of all of its employer-related obligations in connection with its personnel. These obligations may include but are not limited to: ‘+ Human resource issues, including hiring practices, training (with the exception of specific training related to Biogen procedures), establishment of employee policies and administration of health and benefits plans. * Project Planning & Vendor Management describes how work is managed. BIOGEN-ICON Engagement Handbook Version 3.0 17 of 24Docusign Envelope ID: 22842231-8F 88.46 16-AFES.2145ESt4DCDC, ‘+ Work performance and work behaviour issues, including probationary period, annual appraisals, ‘employee discipline, replacement and termination ‘Administration of systems for timekeeping, payroll and employee expense reimbursement Monitoring of specific performance expectations, in alignment with ICON GSS acceptance criteria, including operations status and timelines Communication of work assignment changes (i.e. notification of assignment end date) Day to day management including management of vacation time or leave of absences and supervision of employment issues in connection with performance of the Services. Itis the responsibility of ICON GSS to ensure that adequate means and resources are put.in place to ensure the delivery of services in a timely and quality manner. ICON GSS is responsible for sourcing suitable candidates to fulfil the requirements of each role adhering to the Job Descriptions andlor Role Profiles shared by Biogen. Biogen is not involved in the hiring process. At the outset of this FSP engagement, ICON GSS and Biogen were in agreement on the resource requirements. Biogen will provide ICON GSS with the number of resources per role required for the FSP. ‘The location of associates is also determined as per Biogen requirements. 42 Team Assignment List Each engagement’s Task Assignment is directed from Biogen. ICON GSS provides the FSP resource name and start date in the monthly invoice provided to Biogen. The Task Assignment list will be updated by the FSP Manager when any change occurs in resourcing or staffing on a monthly basis. 43 Training ‘The FSP staff will be following Biogen SOPs and processes. The FSP Manager is responsible for ensuring all appropriate FSP staff is trained in BIOGEN UNIVERSITY, Training requirements are defined using the standard FSP curricula. Biogen ADS Business and Performance Management will perform regular training record review to ensure compliance, Biogen and ICON GSS training and operations management teams have defined the requirements for training for each role, ICON GSS employees will access the Biogen Training System to complete the required training for their role. ‘Once a new ICON GSS employee is identified and communicated to Biogen for account set-up, the Biogen training team will assign the appropriate curricula for the employee's role in the Biogen Training System. A “ICONIGSS — New Hire Onboarding Document’ has been created by Biogen and ICON GSS representatives which outlines the on-boarding and training requirements for all ICON GSS staff working with Biogen under the (FSP) for DM, Biostatistics, and Statistical Programming, Refer to the Blagen/ICON GSS Training and Onboarding Guideline for further details, 44 Resource Utilization and Idle Time Management Managing idle time is a joint responsibilty between ICON GSS and BIOGEN. There are some sequential steps the team has implemented to assist in collaborating on idle time management: 1. ICON GSS Line Managers report weekly on study assignments and any idle hours to relevant BIOGEN Line Managers 2. Biogen Line Managers will review and utilize any idle time to support study work and or internal initiatives, 3. Ifidle time issue continues, ICON GSS staff will continue to report the idle work issue to the relevant BIOGEN Lead until further assignments are received. BIOGEN-ICON Engagement Handbook Version 3.0 18 of 24Docusign Envelope ID: 22842231-8F 88.46 16-AFES.2145ESt4DCDC, 4, Ifthe problem exists (a solution is not being implemented) beyond two business days, then ICON GSS Lead (s) will escalate the issue directly to the BIOGEN Functional Operations Lead. 5. ICON GSS staff should not remain passively awaiting assignments. 45 Performance Feedback and Staff Changes ‘The Biogen and ICON GSS teams agree on a spirit of good intention whereby both parlies communicate regarding progress on projects and problems or delays, with the intent that ICON GSS will promptly address and resolve any performance concems, Biogen Lead provides periodic feedback to ICON GSS for ICON GSS associates performing services to Biogen, Biogen Lead provides a summary of any issues & communicates to ICON GSS Lead as promptly as possible if problems arise. ICON GSS Lead develops and implements an appropriate remediation andlor improvement plan and conveys outcome to Biogen lead. When concerns are raised by Biogen staff or management or are proactively identified by ICON GSS Line Managers, ICON GSS shall diligently and proactively address the identified issues with the resources. Biogen Managers will co-operate with further information requests from ICON GSS LMs to assist in addressing any concerns. Further details can be found in the current MCRO and its Amendments, Itis acknowledged that staff changes will occur on this FSP for many reasons. While ICON GSS will ensure to minimise turnover, a metric that is measured both as an SLA and KPI, there will be some resource changes that need to be handled within the ICON GSS and Biogen teams. ‘Once a potential staff change has come to ICON GSS's attention (e.g. handed notice, confirmation of maternity leave date, confirmed promotion / department move), the ICON GSS Manager will review potential options to ensure continuity of delivery. This can include recruiting suitably experienced resources to join the team, ‘The ICON GSS Line Manager advises the Biogen Lead if an employee is leaving the program. For each resource change, details will be communicated to the Biogen Lead on how the change will be implemented, including potential succession candidates (considering a backfill within the same study if possible), timelines for replacements, documented transition plan, and back-up plans in the event that a replacement is not in place when the leaving staff member is becoming unavailable. ICON GSS is responsible for ensuring that all assigned study related activities are completed to Biogen satisfaction despite resource changes. In case of unplanned absence of a staff member e.g. sick leave the ICON GSS Line Manager should inform the Biogen Lead as soon as they are made aware of the unplanned leave. If deemed required by the ICON GSS Line Manager and the Biogen Lead, the ICON GSS Director of Program Management should also be informed so that adequate cover within the study team can be organized on a short-term basis, if required. 4.6 Performance Metrics and Service Level Assessments Performance and quality are key measures of relationship satisfaction and are integral to the long-term ‘success of the relationship. Biogen and ICON GSS have developed SLAs and KPIs that are reported on and reviewed at the OC, ‘The SLAs are documented in the Agreement and are reported on and reviewed on a quarterly basis. The KPls are documented in the Agreement and are reported on and reviewed on a monthly basis. BIOGEN-ICON Engagement Handbook Version 3.0 19 of 24Docusign Envelope ID: 22842231-8F 88.46 16-AFES.2145ESt4DCDC, ‘The functional level KPIs and the mechanism of reporting for both SLAs and KPIs are located on the Biogen Global Data Management Collaboration site/ICON WorkSpace and the Biostatistics and Statistical Programming Collaboration site/ICON WorkSpace (TBD). ‘The Biogen ADS VM and the Operations Managers reviow the quarterly/monthly performance metrics and raise any concems at the appropriate governance meeting, These performance metrics should be summarized al the steering committee meeting and exist in Schedule C of the existing Agreement. 47 _ Risk Mitigation If provision of performance metrics causes concern to BIOGEN, the Parties will work together to establish a process to mitigate the issue inclusive of the appropriate amount of quality review commensurate with the need as identified by the parties. 4.8 Process Improvements Biogen expects continuous improvement from its suppliers and ICON GSS is committed to working collaboratively with Biogen in implementing any improvement to processes that will result in not only an improved relationship but ultimately results in speedier, high quality clinical trial data ready for analysis. ICON GSS will leverage their experience and will work with Biogen on implementing any process cfficiencies identified, Process improvements identified by ICON GSS will be discussed at Outsourced Operations Committee Meeting, a dedicated process site improvement meeting, and/or with the relevant Biogen PoC and will be tracked. Biogen, will as required, assign resources to assess and decide on whether suggested improvements are something that should be implemented. ICON GSS will support Biogen with roll out of any agreed process improvements, 49 IT Equipment & Set-up IT equipment is provided by ICON GSS to all ICON GSS employees. IT teams in Biogen and ICON GSS have defined the requirements for set-up; these steps are outlined in the IT on-boarding process Outlined in the Training and Onboarding manual. IT team in Biogen will roview these documents quarterly and update as appropriate. Once a new employee is identified, a ticket is logged into ICON GSS's IT ticketing system (Service Now) with the relevant employee details, 410 Technology + System Connectivity All FSPs work on a Citrix connection and have access to BIOGEN’s SAS desktop, This desktop includes all the applications needed to perform Data Management activities such as WorkFlow, ‘TeamNET site, Wingspan eTMF, SAS Enterprise Guide, and email + Account Management Process Requests for new accounts must be entered into the Biogen Account Management (BAM) system. New User account access requests to Biogen's network are submitted to adshelp@biogsn.com, Please see the ICON GSS Training and Onboarding Manual for details. + Medidata Issue Management Process. BIOGEN-ICON Engagement Handbook Version 3.0 20 of 24Docusign Envelope ID: 22842231-8F 88.46 16-AFES.2145ESt4DCDC, All Medidata Rave EDC and Coder application issues can be reported to Medidata Help Desk by submitting a ticket to helpdesk@mdsol.com. If urgent, Medidata Help Desk should also be notified by calling 1-866-MEDIDATA (633-4328). Alternatively, issues can be brought to the attention of Biogen IT Support Centre at itse@biogen.com (1-877-447-2442), + Medidata System Outages and Downtime For Medidata Rave EDC and Coder applications, when there is a planned system downtime or an unexpected system outage, a message will be displayed on the application login screen. 5.0 Relationship Management Relationship Management is focused on ensuring we have all the components necessary for a successful partnership. 5.1 Communication Principles Effective communication is an essential element of a good working relationship. The Govemance structure supports consistent and regular communication between Biogen and ICON GSS with regard to operational and strategic issues. The following communication guidelines should be adhered to: + All team members must maintain clear and open communication in the management of their projects and must solicit issues from within their functional area. + Ad hoc phone calls and email communication to discuss new tasks or timelines, or changes to existing tasks or timelines, processes, and clarification of issues may occur in addition to scheduled meetings and teleconferences. ‘+ Team members should be thoughtful of those team members travelling and/or working in different time zones and should adjust their mode of communication accordingly. 5.2___ Team Absences and Changes Biogen and ICON GSS teams are expected to inform each other of all key personnel absences & annual leave with sufficient notice to allow for proper resource planning and appropriate back-up coverage. Unplanned absences are to be communicated as soon as possible. National/Company holidays for both partners should be cascaded annually, as applicable. 5.3 Meeting Minutes, Agendas and Action Logs ICON GSS is responsible for meeting minutes, agendas and action logs for all joint meetings. Meeting minutes are reviewed and approved by Biogen before finalization. The action log is reviewed as a standing item at future meetings and updated in the interim by the ICON GSS representative. 54 Guid es for FSP Travel BIOGEN Operations Management will determine when travel is required by an FSP team member on a case-by-case basis. When travel is required by an FSP team member (e.g. an investigator meeting, training, project meetings, etc.) and a meeting planner is used, the FSP team member should use the meeting planner services.” If a meeting planner is not used, then BIOGEN requires the FSP team member to finalize travel arrangements using BIOGEN's Travel Agency. For all travel, ICON GSS should be following Biogen’s Travel and Reimbursement Process for Non-Employees. When booking through Biogen’s Travel Agency, ICON GSS staff will pay using an ICON GSS corporate credit card or other approved means of payment through ICON GSS and this will be invoiced back to Biogen in accordance with the terms outlined in the MCRO and its amendments. When booking, if the nightly rate for any hotel stay exceeds $350inight, ICON GSS is to immediately contact BIOGEN ADS VM for guidance prior to proceeding with booking, BIOGEN-ICON Engagement Handbook Version 3.0 21 of 24Docusign Envelope ID: 22842231-8F 88.46 16-AFES.2145ES@4D0DC, * Biogen preferred hotels in the Cambridge area consist of the following: ‘© Marriott Cambridge Marriott Residence Inn Cambridge The Liberty Hotel Royal Sonesta Hotel Hotel Marlowe Renaissance Boston Waterfront ‘The Partios will share holiday schedules and document recognition of ICON GSS holidays and Biogen holidays accordingly, BIOGEN Holidays vs. ICON GSS Holidays and process for billing BIOGEN project leads should work with ICON GSS staff members to assign an adequate number of tasks where possible aver the BIOGEN holidays when ICON GSS is conducting normal business hours to ensure appropriate usage of FTE, 5.6 Vacation Coverage Vacation days will be discussed in advance with Biogen and with reasonable notice period. The Biogen Data Management Lead, Biostatistics Lead, and Statistical Programming Lead and/or Operations Manager should review study deliverables and milestones scheduled during the requested leave period and determine whether they are in agreement with the proposed leave, 5.7__ BIOGEN Global Data Management Collaboration Site/ICON WorkSpace, ‘The engagement has a Global Data Management site setup to allow team members (as applicable) to communicate and share FSP project information, 5.8 Biogen Biostatistics and Statistical Programming Collaboration Site/ICON WorkSpace ‘The engagement will also include a Biostatistics and Statistical Programming Collaboration within the ICON WorkSpace site to allow team members (as applicable) to communicate and share FSP project information 5.9 Contracting Process 4, Once the Biogen Operational Lead and ICON GSS have identified a need for a change to the level of resources or resource type needed, ICON GSS to natify VM of pending change and then ICON GSS to route all questions and discussions through the VM. 2. Biogen requires ICON GSS to provide the Study Budget and Study Contract Draft (Statement of Work or Amendments) at the same time as part ofthe initial submission. 3. Costing for work to be provided based on agreed upon contracted rates within the respective Statement of Work, ICON GSS commits to responding to all VM follow-up requests within 3 (three) Business Days. ICON GSS to send budget excel file and word file, if required, within five (5) business days of intial request, Any revisions to be sent within three (3) business days of Biogen request. 6. ICON GSS commits to responding to Contract signatures requests within 2 (two) Business Days. All Contracts will be sent for Vendor signature through Biogen's Part 11 Compliant DacuSign system, BIOGEN-ICON Engagement Handbook Version 3.0 22 of 24DocuSign Envelope I: 22842231-6F 88.46 16-AFES.2145ES@4DCDC, The signatures below confirm that the BIOGEN and ICON GSS approve of the content in this FSP Engagement Handbook. Doeusigeay: Link Ngo 10-Mar-2022 nh Ngo SO BIOGEN Analytigg,and Data Sciences Date Vendor Mj fondo "Ee et 14-mar-2022 cast Lisa Hegarty ICON GSS Client Manager Date BIOGEN-ICON Engagement Handbook Version 3.0 23 of 24DocuSign Envelope ID: 22642231-6F 88.06 15-AFES-2145E534000C, Appendix 1: Change Control Date of Requested Effective Change Requested By Section Topic Effective Date_| Version Addition of Biostatistics and ICON GSS and | Entire Engagement | Statistical 09Dec2020 Biogen Handbook Programming 16Dec2020 | v2.0 Aaministrative corrections throughout; Table ta - addition of Biogen ICON GSS and| Entire Engagement | University Training 260c12024 Biogen Handbook. escalation pathway | 10Mar2022__| v3.0 BIOGEN-ICON Engagement Handbook Version 3.0 24 of 24