Harmonizing Manufacturing across Multiple Sites and Regions

Transcription

1 Harmonizing Manufacturing across Multiple Sites and Regions ISCT North America Regional Meeting Philadelphia, Pennsylvania Byron T. McAllister B.T. McALLISTER ASSOCIATES, INC. Tuesday, 10 September 2013

2 Harmonizing Manufacturing across Multiple Sites and Regions The Change Control Management Process (A Tutorial): An Essential Element for Successful Transition to Commercialization (Read: Product Approvals, Prescriptions Equal Positive Cash Flow) It must include: 1. Prospective written and approved change management plan; 2. Project management deliverables; and 3. Periodic effectiveness checks.

3 The Change Control Management Process Why You Need A Comprehensive Change Control Management Process To ensure that all changes to GMP and GMP-related activities are: Documented, Reviewed, Approved, Implemented, and Controlled

4 The Change Control Management Process There must be clear rules for: Proposing, Classifying, Reviewing, Approving, Implementing, Closing, Follow-up, and Reporting of Changes

5 The Change Control Management Process CCMP applies to: The management of changes to a GMP or GMP-related activity CCMP Does Not apply to: Unexpected / unplanned result or action (deviation) occurring during a GMP or GMP-related activity, which must be treated through the Deviation Management Process N.B.: Yes, the CCMP process may be invoked as part of the deliverables in terms of Corrective and / or Preventive Action(s) (CAPA) as the result of a material Deviation [legal definition], but this is a topic for another day Pre-scheduled calibration and preventative maintenance events.

6 The Change Control Management Process DEFINITIONS: A Change: Is any prospective addition, modification or deletion with respect to raw material, components, process, product, method, equipment (including computerized system), specification, responsibility and / or facility used to perform a GMP related activity

7 The Change Control Management Process GMP Related Activity Any activity/system which may potentially impact the equipment or system design and operation, validation status, process performance, safety or product quality attributes

8 The Change Control Management Process When Is GMP Compliance Expected / Required? The Process / Product Development Life Cycle EU versus U.S. FDA Controversy remains, but Flexibility in Design Decision-Making Is Paramount Patient Safety and First-in-Man considerations Validity of Tests Sterility, Apryrogenicity, Freedom from Other Adventitious Agents

9 The Change Control Management Process What Is A Locked Process? Processes Related To Patient Safety for Phase 1 Objectively, Processes Related To Manufacturing and Control for Phase 2 and beyond Certainly, for Phase 3 Pivotal Efficacy Trials Absolutely, for Product Consistency Batch Production Bio-Batches, Demonstration Batches, Process Validation Batches Pre-Approval Inspection (PAI) to Demonstrate Full GMP Compliance

10 The Change Control Management Process Examples of Different Types of Quality System Changes: Administrative Change: change to a document- format, spelling, typographical error correction, or clarification which does not include any change to the intent or meaning Emergency Change: change which must be implemented immediately due to an issue of safety or immediate product loss Local Change: a change in which the scope is limited to one site/facility only Permanent Change: change is not temporary in nature. Major Change: any change that impacts a regulatory filing or commitment (i.e., the Registered Details ) Minor Change: any change that does not impact regulatory filings Multisite Change: a change that impacts more than one site Temporary Change: any change of a specific duration or number of batches after which the initial conditions will be restored

11 Multi-Site Change Control Management Why Is Multi-Site Change Control Management So Complicated? Changes May Originate From Many Different Sources A Request for Change may be initiated by: 1. Sponsor 2. Supplier (manufacturer of the raw or starting material)* 3. Clinical site* 4. CMO, CRO or CTL* * Must be accepted and implemented by the Sponsor in any event

12 Multi-Site Change Control Management Drivers of Complexity: Never Be Single Sourced Golden Rule of Quality Assurance Catastrophe Backup Planning Additional Site(s) of Manufacture Manufacturing Formula Master Control One Product for Worldwide Market Raw Materials and Components Grades and Quality Specifications Products Requiring Manipulation at Clinical Administration Site Sponsor Must Supply Everything Needed for Consistency

13 Multi-Site Change Control Management Regulatory Categories: Classification of regulatory action required before a change can be made effective. Type A: Changes can be implemented immediately and need no notification of the Health Authorities Type B1: Changes can be implemented immediately, but require subsequent notification of the Health Authorities. Type B2: Changes can be implemented immediately AFTER notification of the Health Authorities. Type C: Changes require approval by Health Authorities PRIOR to implementation.

14 Multi-Site Change Control Management Process Elements for the CCMP: Request Must Have a Proponent Drives the entire process QA is only the information traffic controller, i.e., facilitator, communicator Implementation Planning Deliverables (a comprehensive Project Management list of all affected processes and products) Expected Timeline (Often a matter of hurry up and wait!) Actions to maintain quality and compliance to GMP Validation considerations Stability confirmation

15 Multi-Site Change Control Management Review of Multi-Site Changes: Requests Must Be Reviewed by the Respective Heads of QA and RA Assess the Impact On Each Site Data Requirements for Eventual Submission Approve or Deny the Change Request

16 Multi-Site Change Control Management Process Elements for the CCMP (Cont): Implementation of the Change Material Quarantined Until Changes Verified All Activities Completed All Deliverables Available and Approved Changes Made Effective Date of First Implementation Batch Number(s) Involved

17 Multi-Site Change Control Management Process Elements for the CCMP (Cont): Effectiveness Checks Audit, Audit, Audit! Corrective Action Where Necessary See the CAPA Process Close Out the Change Request Archive Update the Registered Details as appropriate See Ongoing Process / Product Monitoring Management Process

18 Multi-Site Change Control Management The Value Proposition: The Obvious: GMP Compliance, it s the Law! ICH Q10 requires it Departmental System Owner of the GMP System/Activity for technical approval of comprehensive implementation plan, identification of deliverables, revalidation requirements, if applicable, etc. Local/Site QA for accuracy, adequacy, completeness and compliance to Quality Policies, Standards and SOP s. If you are a CMO or CRO or CTL, customer approval of implementation plan, revalidation requirements, etc. (as required) Safety, Health & Environment (SHE) for compliance to applicable company and regulatory SHE requirements.

19 The Value Proposition (Con t): The Not So Obvious: Provides for a continuum of process and product development progress (Development History), and Provides for a link back to the original R&D Scientist(s)

20 And Finally...

21 QUESTIONS??