Process Management Framework SCENARIOS

1. Process Management Framework SCENARIOS TransCelerate Quality Management System Initiative Process Management Sub-Team

2. Overview of Scenario Tool Purpose: Assist in building sponsorship for and understanding of Process Management • This scenario tool uses examples to illustrate how effective Process Management Framework can ensure the efficient and effective delivery of clinical development programs. • Each slide covers different stages of process development to assist in tailoring the message. • Intended to allow selection of relevant slides for different purposes and audiences. • These scenarios may be customized by presenters to reflect actual instances experienced within their organization. • Not intended to be a “how-to” guide for what Process Management solution to use for a given scenario nor how to design a particular solution. • Note that similar types of Process Management potential solutions apply in many different scenarios. An integrated and overarching Process Management program enables consistent design and implementation of solutions to address multiple needs. SCENARIO DESCRIPTION BUSINESS IMPACT PROCESS MANAGEMENT POTENTIAL SOLUTIONS PROCESS MANAGEMENT BENEFITS • EACH SCENARIO IS PRESENTED IN FOUR PARTS

3. Examples of Scenarios • Selecting an Organizational Structure • Unifying a fragmented process for protocol development by applying a process-centric approach • Identifying E2E Processes • Identifying core, sub-processes, and enabling processes for site start up activities Mapping and Modelling a Process • An organization is seeing lengthy delays in the site start up process, specifically the part following ethics approval and prior to site activation • Determining Process Risk • Following successful identification and mapping of site start up processes, an organization wishes to identify areas of risk so that mitigation steps can be built into the process • 1 • 2 • 3 • 4 • Controlled versus Managed Documents • Following the identification of core processes for site start up activities (scenario 2), an organization has no documented methodology for determining if process content should be in a controlled or managed document • Determining Training Needs • An organization is updating numerous procedures around study start up and is unsure what delivery type, detail level, and assessment of training is required • Identifying Process Measures and Controls • Following successful mapping of trial start up activities, the organization wants to develop metrics to monitor and improve each part of the process • Management of Process Changes • Following unification of fragmented processes for protocol development (scenario 1), an organization needs to secure stakeholder “buy-in” and ownership to ensure ongoing support • 5 • 6 • 7 • 8

4. Scenario • 1 Selecting an Organizational StructureKey Concepts

5. Scenario • 1 Selecting an Organizational StructureUsing the Tool - Real World Scenario (slide 1 of 2) Scenario: An organization’s conventional structure means that the process for protocol development and approval is fragmented, with each function independently managing their own responsibilities. • Problem: • Investigational Supplies as part of their process may only review the protocol section entitled ”IMP”, but ClinOps may not be aware of this and assume that they review the entire protocol. • ClinOps may have changed the protocol template so that additional IMP labelling information is now captured in a new section elsewhere in the protocol. Investigational supplies, not being aware of this, might still only review the “IMP” section of the protocol, but upon providing their approval, ClinOps assume both sections have been reviewed and are fine. • Clinical Operations (ClinOps) • Authoring, Review & Approval of Protocols • Drug Safety • Review of Protocol Safety Measures • Statistics • Review of Protocol Statistical Techniques • Investigational Supplies • Review of Protocol IMP Section • Office of the Medical Officer • Medical Office Review and Approval of Protocols

6. Scenario • 1 Selecting an Organizational StructureUsing the Tool - Real World Scenario (slide 2 of 2) Scenario: An organization’s conventional structure means that the process for protocol development and approval is fragmented, with each function independently managing their own responsibilities. • Potential Solution: • The organization changes its structure so that the process of ”Protocol Development” is the driving factor. • Each function still has its own responsibilities, but the process-centric model includes accountability for each process. This ensures collaboration across all individual functions with the bigger picture in sight – the end goal of producing a robust protocol that will receive regulatory/ethics approval and will therefore allow the organization to get their drug to the people that need it…the patients! Process Accountable Responsible

7. Scenario • 2 Identifying E2E ProcessesKey Concepts

8. Scenario • 2 Identifying E2E ProcessesUsing the QMS Initiative — Toolkit for Implementing Processes - Real World Scenario Scenario: An organization conducts many clinical trials but all procedural activities and the processes that govern them are grouped under the umbrella of “Clinical Trial Conduct”. An inspection results in findings around study start up activities. • Problem: • “Clinical Trial Conduct” is a very high level process as almost all activities within clinical operations will fall under such a broad category. • By using such a general umbrella structure, the organization is not able to identify or assign subject matter experts for key processes. Therefore, Quality & Compliance cannot be achieved or improved through regular review, metrics, and other continuous improvement activities. • Key responsible roles for key activities cannot be effectively trained because all staff under the umbrella of “Clinical Trial Conduct” are expected to be trained on all aspects of the wider process – much of this will not be relevant to the role individual teams and sub-functions perform. • Potential Solution • By identifying core processes, sub-processes, and enabling processes which constitute the core process, the organization begins to map its own structure, allowing it to allocate experts to each process, monitor quality & compliance on a much more granular level and direct training and improvement activities. As the organization starts to grow, or the pipeline begins to enter different phases of development, strain on resources can be identified on a process level, which assists in recruiting the correct type of additional resources.

9. Scenario • 3 Mapping and Modelling a ProcessKey Concepts

10. Scenario • 3 Mapping and Modelling a ProcessUsing the QMS Initiative — Toolkit for Implementing Processes - Real World Scenario (slide 1 of 2) Scenario: An organization is seeing lengthy delays in the site start up process, specifically the part following ethics approval and prior to site activation. Ethics approval notifications are not being received by everyone who needs this information, and outdated copies of Protocols and ICFs are being used and shared resulting in the need for re-approvals. • Problem: • The organization doesn't have a clear understanding or overview of the functions and activities involved in this part of the process, and therefore the team members don’t have this overview either. The regulatory team for example, are not aware of whose submissions should be communicated to, and the ClinOps team do not have any listing of all functions/team members that protocol/ICF updates should be communicated to. • Potential Solution: • The organization needs to map the process by getting all SMEs around the table and developing an initial Suppliers, Inputs, Process, Outputs, and Customers (SIPOC) diagram. This simple diagram begins the shift to process thinking, by getting SMEs to see the process through “customers” (anyone who receives a deliverable or output from the process, such as the protocol or ICF) and what the process requires as Inputs (e.g. the docs for compiling a Reg submission).

11. Scenario • 3 Mapping and Modelling a ProcessUsing the QMS Initiative — Toolkit for Implementing Processes - Real World Scenario(slide 2 of 2) Scenario: An organization is seeing lengthy delays in the site start up process, specifically the part following ethics approval and prior to site activation. Ethics approval notifications are not being received by everyone who needs this information, and outdated copies of Protocols and ICFs are being used and shared resulting in the need for re-approvals. • Potential Solution (continued): • Having mapped the process, it is now possible for each individual function to see where their part of the start up process falls within the “bigger picture” and who requires the documents they are creating. It also automatically establishes the scope of the process so each function can now identify correctly those key areas and stakeholders of the process that they need to engage in order to drive business deliverables and performance.

12. Scenario • 4 Determining Process RiskKey Concepts

13. Scenario • 4 Determining Process RiskUsing the QMS Initiative — Toolkit for Implementing Processes - Real World Scenario (slide 1 of 2) Scenario: Following successful identification and mapping of site start up processes, an organization wishes to identify areas of risk so that mitigation steps can be built into the process. • Problem: • Without a methodology for RISK assessment of the process, the organization cannot identify critical steps in order to ensure quality & compliance. This is part of a Sponsor’s responsibilities under ICH E6 which states: “… the sponsor should identify those processes and data that are critical to ensure human subject protection and reliability of trial results”. Revision 2 of ICH E6 also added an explicit section (5.0.2) on “Risk Identification” which states: “The sponsor should identify risks to critical trial processes and data. Risks should be considered at both the system level (e.g., standard operating procedures, computerized systems, personnel) and clinical trial level (e.g., trial design, data collection, informed consent process).” • Potential Solution: • Use the TransCelerate risk scoring methodology to identify and classify risks across the process from three different aspects: compliance risk, process complexity risk and process operational risk.

14. Scenario • 4 Determining Process RiskUsing the QMS Initiative — Toolkit for Implementing Processes - Real World Scenario (slide 2 of 2) Scenario: Following successful identification and mapping of site start up processes, an organization wishes to identify areas of risk so that mitigation steps can be built into the process. • Potential Solution (continued): • Establishing the correct process performance measures and controls assures that the process is working as designed and has objective evidence for evaluating performance and driving continuous improvement. Effective Process Measures: • 1) A clear definition of what is “critical to quality” (CTQ) and how to consistently measure it, 2) agreed performance targets, and 3)ownership for the performance of the metric using process. Time Measures: • Cycle time from when study documentation is completed until Regulatory approval is obtained; time from when the first subject is enrolled until the recruitment is completed. Cost Measures: • What is the cost for the company to initiate sites, complete the recruitment for the study; what is the cost for the company if the recruitment is delayed and additional sites and countries need to be added to the study? Quality measures: • Study documentation completeness, on time reporting to external authorities and the number of data errors.

15. Scenario • 5 Controlled versus Managed DocumentsUsing the QMS Initiative — Toolkit for Implementing Processes - Real World Scenario (slide 1 of 1) Scenario: Following the identification of core processes for site start up activities (scenario 2), an organization has no documented methodology for determining if process content should be in a controlled or managed document. • Problem: • Managed documents are key in that they enable individual functions to retain ownership of documentation around best practices, internal workflows etc. However, any high risk or key compliance aspects of a process require more robust control to ensure quality & compliance – if this balance cannot be determined, the organization risks consistency/quality issues and fragmentation of core compliance tasks across the document landscape. • Potential Solution: • Using the risk based approach, the organization will have much more confidence in the criticality of document content, and can use this to make the separation on where they are willing to “draw the line” in terms of what becomes managed information versus controlled information. Utilize the risk scorecard to make an assessment of the content of the document itself. Note: Figures are for guidance regarding controlled documentation and managed information. The specific documentation types are for illustrative purposes only. Company naming conventions may differ.

16. Scenario • 6 Determining Training NeedsUsing the QMS Initiative — Toolkit for Implementing Processes - Real World Scenario (slide 1 of 2) Scenario: An organization is updating numerous procedures around study start up and is unsure what delivery type, detail level, and assessment of training is required. • Problem: • Different processes have different sizes of impacted people/ functions. In addition, some process changes may include updates to systems or use of new systems. There is no one size fits all solution for ensuring adequate training. • Potential Solution: • Utilizing a learning plan allows the business to maintain an inventory of existing knowledge as well as identifying what information will be created as part of the updates, who will own this information, and what learning plan is needed.

17. Scenario • 7 Evaluate Process Health Performance as Part of Management ReviewKey Concepts

18. Scenario • 7 Management Review for Existing Processes Which Do Not Have Measures and Controls in PlaceReal World Scenario • What is the cycle time for when study documentation is completed until the ERC/ Regulatory approval is obtained? How does this vary on a regional level? Are the variations due to additional complexities in the approval process? Or because of resource limitations? Or maybe a training issue? How many deviations from the process have been logged for the regions that take significantly longer? • What is the cost for the company to initiate sites? How does this compare to the total cost for recruitment for the study? How does this ratio change across countries? What are the additional costs related to? • What is the cost for the company if the recruitment is delayed and additional sites and countries need to be added in the study? • How long does it take from when the first subject is enrolled until the recruitment is completed? Scenario: Following successful mapping of trial start up activities, the organization wants to develop metrics to monitor and improve each part of the process. • Problem: • There are currently no metrics in place, so although the process is mapped and it’s possible to see the key inputs/outputs/ interdependencies, etc., there is still no way to identify which aspect of that mapped process is causing delays, is inefficient, etc. • Potential Solution: • Using the process map as a start, the organization can identify time cost and quality measures by asking the right questions: Start with the highest level process and work left to right to complete the table. Define the process goal(s), critical to quality metrics (time, cost, quality), roles responsible to review the metrics, frequency (how often the information is to be reviewed), forum, and focus (what activities are to be reviewed). After the table is complete for the high level process, repeat for each sub-process.

19. Scenario • 8 Management of Process ChangesReal World Scenario • Responsible • The person who actually carries out the process or task assignment • Responsible to get the job done Scenario: Following unification of fragmented processes for protocol development (scenario 1), an organization needs to secure stakeholder “buy-in” and ownership to ensure ongoing support. • Problem: • Processes are living representations of the way in which an organization conducts its core work – to ensure alignment and efficiency but more importantly quality & compliance. Without the correct culture of process ownership by both senior management as well as subject matter experts and stakeholders, processes can quickly turn from guiding a process to restricting it. • Potential Solution: • The RACI principles are well used and understood in the corporate world, even outside the clinical research environment. By associating accountabilities and responsibilities to key levels of seniority and key stakeholders within an organization, this automatically builds a sense of ownership of processes and procedures, and the motivation to ensure they remain robust and effective, changing to accommodate the ever changing needs of the organization and the regulatory environment. • The person who is ultimately accountable for process or task being completed appropriately • Responsible person(s) are accountable to this person • Accountable • Consulted • People who are not directly involved with carrying out the task, but who are consulted • May be stakeholder or subject matter expert • Informed • Those who receive output from the process or task, or who have a need to stay informed

20. Scenario • 8 Management of Process ChangesReal World Scenario Senior Management Oversight Committee Scenario: Following unification of fragmented processes for protocol development (scenario 1), an organization needs to secure stakeholder “buy-in” and ownership to ensure ongoing support. • Potential Solution (continued): • Different levels of senior management within an organization and located within different aspects of an organization can be utilized in different ways to ensure a culture of change is understood and becomes a normal part of the way of working. Where functions understand that process changes are undertaken to assist their day to day work, this culture becomes easily accepted. ACCOUNTABLE for Quality & Compliance of Processes and Procedures within their respective functions Controlled Process Owners RESPONSIBLE for the management of processes including updates to address quality/compliance issues (e.g. through deviations, CAPAs etc.) Business Process Owners RESPONSIBLE for managed documents to ensure alignment and efficiency Process Subject Matter Experts Key SMEs with in depth knowledge on the process/procedure through management or experience. These representatives of their functions are CONSULTED to ensure functional issues/concern with updates/changes are raised and addressed Upstream/ Downstream Process Owners INFORMED of changes to neighboring processes (e.g. where there may be handoffs) to ensure they have the vision of their process within the wider context of business activities (i.e. their part in the bigger picture)

21. Process Management – Conclusion • The Process Management Framework referenced herein represents an integral part of an effective QMS. • Common understanding of the steps required to implement can provide greater organization success in implementing process management in a robust way. • They will ensure our key and critical processes associated with clinical development are identified, defined and have clear and concise procedural documentation that is consistent and fit for purpose and that our staff are effectively trained and are able to excel at executing the process “Right First Time”. • This is “must have” for today’s competitive landscape.