Implement an Effective Change Management System throughout GMP and Validation Environments. Eileen Cortes February 23, 2017

Transcription

1 Implement an Effective Change Management System throughout GMP and Validation Environments Eileen Cortes February 23, 2017

2 Agenda Change Management Principles Change Management Process and Change Control Change Management Process Atypical Change Management Process Flow Case Study Open Discussion

3 Change Management Principles It is not the strongest of the species that survive, nor the most intelligent, but the one most responsive to change

4 Why We Need Change Management? Because we DO! What is change management? Per ICH Q10 Innovation, continuous improvement, outputs of process performance, product quality monitoring and CAPA drive change. To evaluate, approve, and implement these changes properly an effective change management process must be in place Ensures continual improvement is undertaken in a timely and effective manner. Provides a high degree of assurance there are no unintended consequences of the change. Change Management is a more broad concept that change control. Change Management includes the oversight of how we drive changes in our sites and how the change process is implemented. Not only Change Management has direct impact in our processes effectiveness but also in our financial outcome. Regulations enforce them, Change Management applies to the whole product lifecycle per ICH Q10.

5 Change Management through Lifecycle Stages Quality Risk Management shall be applied to evaluate changes Proposed changes shall be evaluated against the complete product lifecycle: Design / System Engineering Product Development / Portfolio Manufacturing / Data Management Regulatory Marketing Patient / Sales

6 Application of Change Management through Lifecycle

7 Regulations and Change Management ICH Q10 Change Management: A systematic approach to proposing, evaluating, approving, implementing, and reviewing changes. (ICH Q10) FDA Change control: is another well-known CGMP concept that focuses on managing change to prevent unintended consequences. The CGMP regulations provide for change control primarily through the assigned responsibilities of the quality control unit. Certain major manufacturing changes (e.g., changes that alter specifications, a critical product attribute or bioavailability) require regulatory filings and prior regulatory approval (21 CFR , 514.8, and ) Change control: with regard to pharmaceuticals is addressed in more detail in the CGMP regulations. A firm may want to revisit the adequacy of the design of the manufacturing facility ( ), the design of the manufacturing equipment ( ), the design of the production and control procedures ( ), or the design of laboratory controls ( )

8 Regulations and Change Management ISO 9001:2015 Focus on Quality Management Evaluation / Risk Assessment Implementation Integrity Resources Planning and Control Communication

9 Regulations and Change Management ICH Q8 Pharmaceutical Development ICH Q9 Quality Risk Management ICH Q10 Quality Systems Knowledge understanding - the use of quality risk management principles, supported by the implementation of ICH Q8, ICH Q9 and ICH Q10 principles provides the opportunity to be Science based and execute risk based post-approval changes Drive innovation and Continuous improvement ICH Q10

10 Change Management Cycle Risk Assessment Monitor / Continuous Verification Knowledge Collect Data & Evaluate Variation Implement Change

11 Change Management vs. Change Control The scope of change management is much broader than change control, which was typically applied to one change at a time Change management includes the oversight and management of the entire portfolio of changes and the change process, including all the components of change control

12 Change Management Process and Change Control

13 Roles and Responsibilities Roles and Responsibilities must be clearly defined. Per ICH Q10 Proposed changes should be evaluated by expert teams contributing the appropriate expertise and knowledge from relevant areas (e.g., Pharmaceutical Development, Manufacturing, Quality, Regulatory Affairs, and Medical) to ensure the change is technically justified Minimum Roles Originator Change Owner Change Subject Matter Expert (SME) Regulatory Affairs Functional Areas Quality Assurance

14 Change Management Main Components Change Proposal Regulatory Assessment Impact Assessment Implementation Plan Change Evaluation Implementation Process Closure Effectiveness Check

15 Change Proposal Develop Change Proposal Description of Change Includes a detailed description of the proposed change including the current state (pre- change) and the future state (post-change) with a summary of planned outcome (as left operating state of control). Define change boundaries, which is what is in scope of change. A gap assessment of current vs. proposed may be used to highlight change points when current state of change is being revised/optimized and aid with construction of risk identification. Justification of Change: Provides the circumstances that prompted the change proposal, giving rationale and expected benefit of the proposed change and assessment of past released lots to ensure equivalency of lots released.

16 Regulatory Assessment Regulatory Affairs will determine impact on: Regulatory Risks Regulatory Licensing Policies Regulatory Submissions Product Labeling

17 Risk / Impact Assessment Risk Assessment must be performed to assess potential impact of change. The facility in which will accommodate the change should be considered under a facility assessment that assesses the change relative to the capability of the classified facility to uphold product safety, identity, strength and/or quality that is at least comparable to the state prior to change or intended state. Changes to specifications, sample plans test methods, product controls, reference standards, standard curve standards, etc. should be assessed for comparability to state prior to change and equivalency risks should be identified. Changes initiated at contract manufacturing organizations, contract laboratory or suppliers should be assessed for comparability to state prior to change and equivalency risks should be identified. Assessors are to assess impact to Documentation, Trainings, Validation, Equipment/Systems, Product, Product License/Dossier, Product Hold Times, Stability, GMP Processes or Computerized Systems (Functionality, Security, Integration and Interfaces)

18 Implementation Plan & Target Dates The Implementation Plan Key Areas are: Target Implementation Date Date that Change will be employed. Be realistic! Implementation Plan The implementation plan should list all steps required to implement change Contingency Plan Rollback plan, as applicable

19 Change Evaluation and Approval for Implementation The Change Owner employs implementation tasks according to approved plan. The Change Owner ensures completion of the implementation actions outlined in the parent record by the implementation due date and begins routing for approval. If target implementation date cannot be met, owner is to request an extension and provide justification. The Quality task approver ensures completion of the assigned tasks by the date due. The Change Owner confirms required data, evidence of performance of the implementation plan (QC data summary, validation summary report, work orders, etc.) are attached to the change record, as necessary.

20 Implementation Process Implementation Process minimum checks: The Owner and/or Task Owners employ implementation tasks according to approved plan. The Owner ensures completion of the implementation actions outlined in the record by the implementation due date and begins routing for approval. If target implementation date cannot be met, owner is to request an extension and provide justification. The Quality approver ensures completion of the assigned tasks by the date due. The Owner confirms required data, evidence of performance of the implementation plan (QC data summary, validation summary report, work orders, etc.) are attached to the record, as necessary.

21 Closure Summary Summary, results and deliverables of the changes that are implemented as part of the implementation plan Identify whether the change is executed to plan. If No, provide justification Route The owner routes the change record for closure to department Approvers who are manager level and above and Quality with all supporting documentation by target implementation due date Approvals The record approvers and Quality ensures that the Change Completion is approved within XXX calendar days of the completion of the implementation plan (XXX: recommended - 30 days)

22 Effectiveness Check What is an Effectiveness Check? Predetermined criteria to assess the effectiveness of the change Ensures there are no other unforeseen consequences on other classified areas or state of control (which might not have been apparent with change proposal approval) Owner Opens the Effectiveness check record, identifies acceptance criteria and targets completion date Quality Quality approver reviews the Effectiveness Check Summary to confirm satisfactory completion of the Effectiveness Check by ensuring all acceptance criteria are met and the adequate objective evidence is referenced and attached

23 Change Management Process Atypical

24 Emergency Changes What is an Emergency Change? A change implemented, without prior assessment by the change review team or SMEs in response to a failure. The change restores operation where failure to do so would have posed a likely or imminent adverse impact to product quality, operator safety, data integrity or equipment. Deviation should be linked to the record. All emergency changes require at a minimum: Approval from respective functional area management Quality and can be implemented once verbal approval has been received Change Owner initiates change record within 24 hours of emergency change Change proposal must be completed and submitted to change review team within X business days (X days recommended, 5 business days)

25 Amendments If a change to the approved implementation plan is needed owner will initiate an amendment and document: A proposed due date (new target implementation date), as applicable to accommodate new record scope Description of the proposed change Description of activities performed to date Justification for amendment Attachments supporting amendment, if applicable Approvers as designated functional area management and Quality

26 Case Study

27 Q&A Open Discussion

28 Thank You!