Change Control Overview

Transcription

1 Change Control Overview Kelly Thomas Atlantic Technical and Validation Services Copyright 2014 by Atlantic Technical and Validation Services, LLC. 1

2 Session Outline Discuss Regulations Governing Change Control Review Elements of a Robust Change Control Program Avoiding Pitfalls Review recent FDA 483s in regards to change control deficiencies 2

3 FDA Regulations governing Change Control CFR 21 CFR Document controls Each manufacturer shall establish and maintain procedures to control all documents 21 CFR Responsibilities of Quality Control The quality control unit shall have the responsibility for approving or rejecting all procedures or specifications impacting on the identity, strength, quality, and purity of drug product. 21 CFR Written Procedures These written procedures, including any changes, shall be drafted, reviewed, and approved by the appropriate organizational units and reviewed and approved by the quality control unit. 3

4 European Regulations governing Change Control changes can be found in Annex 15 to the EU GMP Guide. The Annex includes the following passage:... All changes that may affect product quality or reproducibility of the process should be formally requested, documented and accepted. The likely impact of the change of facilities, systems and equipment on the product should be evaluated, including risk analysis.... 4

5 Elements of a Robust Change Control Program: CCRB Develop a SOP to govern the change control process Establish a change control review board to review both proposed and completed changes. QA and EHS are essential members of the CCRB. CCRB MUST review and approve changes PRIOR to implementation. Emergency changes are allowed; however, timely approval is required (i.e. next business day) CCRB members MUST have the knowledge to determine the impact the change will have on product quality and regulatory filings 5

6 Elements of a Robust Change Control Program: Classification Classify change controls as MAJOR or MINOR Major changes have the potential to impact the quality of the product (i.e changing specifications, modifications to cleanrooms, test method changes) Major changes may require testing or re-validation to justify the change. First batches post change should be placed on stability Minor changes DO NOT impact product quality (i.e administrative SOP revisions, like for like equipment changes) 6

7 Elements of a Robust Change Control Program: Justification All proposed changes should be accompanied by a justification as the why the change is needed. Process improvement to increase output Design improvement to improve product quality. Safety Operating convenience CAPA as a result of an OOS or Deviation Continuous Improvement (cost effective) 7

8 Elements of a Robust Change Control Program: Implementation Develop a project plan with detailed milestones and timelines. Important to assess impact to ALL relevant SOPs and documents Cleaning SOPs Test methods Drawings 8

9 Elements of a Robust Change Control Program: Evaluation First batches post MAJOR changes should be placed on accelerated stability. Enhanced sampling plans may be appropriate Incoming EM / Water monitoring 9

10 Elements of a Robust Change Control Program: Close Out Change control owner should provide evidence to the CCRB that all requirements have been successfully implemented Supporting documentation should be attached to the change control record. Work orders Revised SOPs 10

11 Recent FDA 483s Changes to written procedures are not drafted, reviewed and approved by the appropriate organizational unit and reviewed and approved by the quality control unit [21 CFR (a)] and [21 CFR (b)]. Deviations from written production and process control procedures are not justified. [21 CFR (b)] and [21 CFR (a)(2)]. Specifically, a deviation from the approved procedure "Sterile Filtration of Product" was not appropriately recorded and justified. The process was changed to include in each of the [ ]nozzles used in the aseptic filling of saline solution in room [ ] with no assessment of the impact of the change on sterile finished products. 11

12 More Recent FDA 483s Failure to follow your procedure related to your Change Control Program as required by 21 CFR (a). For example, many instances were reported as lacking the required signatures prior to the implementation of a change requested. The inspection revealed inadequate process validation of drug manufacturing (as required by 21 CFR , (a), and (b)), failure to follow Standard Operating Procedures for change controls and process validation (as required by 21 CFR (b) and (d)) 12

13 Avoiding Pitfalls Obtaining signatures from multiple people / departments can delay approval turn around time. Identify members of the Change Control Review Board (CCRB) in the SOP. Do NOT list names, list departments Important to have the right people in the right roles Identify designees for each department to ensure adequate coverage during vacations Establish standard meeting time / days for CCRB to meet Include time to present proposed change controls ideas Time to Review and Approve change control records Change Control Closure approval 13

14 Questions? Feel free to contact either of us at: 14