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1. OBJECTIVE
1.1. Change control is a quality tool and a management to maintain and keep the records of all changes as a history. Changes can be related to facility, documentation, system, equipment, instrument, procedure, layouts and products etc.
1.2. To lay down a procedure to describe the handling of change control which include the procedure for initiation, evaluation, review, approval/ rejection of proposed change, Implementation of the approved changes and its post implementation.
2. SCOPE
2.1. This procedure is applicable for handling of change control.
2.2. This procedure covers (but not limited to) the change in product quality / reproducibility, facility, utilities and / or support systems, process equipment, / instrument including computer data storage device / software, manufacturing formula, manufacturing / packing process & parameters, process environment or manufacturing site, standard batch size, specification, analytical methods, vendor / suppliers, raw / packing material, artworks, process aids, holding period; storage and distribution of product, documentation including validation master plan, validation reports, qualification protocol and reports, new material / product introduction, SOP’s, site master file.
3. RESPONSIBILITIES
3.1. Initiator :
– Initiating the Change Control Record and ensuring that change is implemented in accordance with this procedure and managing the implementation activities in accordance with stakeholders’ review comments and agreed action items.
– Managing timely execution of activities in conjunction with the stakeholders and Completing risk assessments.
– Adding action items as required.
– Resolving issues, if any, in coordination with stakeholders and Quality Assurance (QA). Escalating issues, such as extensions of Change Controls not being closed in a timely manner to higher management whenever required.
– Initiating variation proposal(s) such as changes being effective (CBE) via CCR, if required, based on CCR evaluation done by regulatory affairs (if required).
– Ensuring that all necessary activities related to the implementation of change, including performing a risk assessment of the change are satisfactory and verified.
– Responsible for discontinuing Change Control Records, as appropriate.
3.2. Regulatory affairs
– Reviewing the proposed change with reference to regulatory impact.
– Communicating the change to the Regulatory Agency/Customer (if applicable) via a variation (CBE, Prior Approval Supplement (PAS) as examples) or annual report.
– Change Control Record evaluator(s) shall be responsible for reviewing the proposed change for possible impact on systems and procedures from respective disciplines, such as process development, validation or material/vendor sourcing.
3.3. Quality head/designee
– Implementing and managing a system for the change control process.
– Ensuring all aspects of the change control process, including management of change proposals, change evaluations, change approvals, change implementations, and effectiveness checks of change(s).
– Obtaining the necessary information from other organizational units to comprehensively evaluate the potential impact of the change(s) on other sites” processes, as appropriate.
– Provide the notification of changes to regulatory affairs (RA), FDD, PDD, ADD, customers, and market representatives.
– Changing classifications. (E.g. Level (Minor) I, (Major) II & (Critical) III).
– Approving or rejecting the proposed change with respect to the impact on quality/GMP compliance.
– Ensuring the adequacy of action items, approving the Change Control Record, assigning the change level classification (I, II, & III) to the CCR.
– Performing impact and risk assessment, Identifying and generating action items, as required.
– Approving the extension of Change Control Record closure, performing document assessment, closure of all action Items, and Performing Trend Analysis of Changes.
– Establishing and maintaining procedures to assure the proposed changes to a system are evaluated for potential impact on the following:
3.4. Documents:
– Standard operating procedures
– Quality agreements
– Training requirements
– Specifications
– Analytical Methods
– Analytical templates
– Worksheets
– Master Batch records
– Master packaging record
– Quality manual
– Protocols
– Labeling
– Methods used in manufacture
– Packaging, Testing, release, and distribution of products
– Manufacturing/packaging instructions, including regulatory commitments for global processes, cGMP engineering drawings.
3.5. Product characteristics:
– Microbial testing
– Identity
– Quality
– Strength
– Purity
– Safety and
– Efficacy of Drug Products.
3.6. Validation Documents:
– Process
– Equipment
– Facilities
– Critical utilities
– Testing analytical methods (chemical, physical, microbiological),
– Cleaning.
4. DEFINITIONS
– Minor change: A change that may not have an impact upon the identity, quality, purity, strength, stability, safety and efficacy or physical characteristic of the product.
– Major change: A change that may have an impact upon the identity, quality, purity, strength, stability, safety and efficacy or physical characteristic of the product.
– Critical change: A change that has a significant impact on quality and /or safety of the final product.
– Cross-Functional Team: A group of people with different functional expertise working towards a common goal. The team is responsible for the review and implementation of the Change Control Record.
– Change: The creation, revision, or discontinuance of a process, software, equipment, facility, utility, product, or document.
– Corrective and Preventive Action: A concept with current Good Manufacturing Practice (cGMP) that focuses on the systematic investigation of root causes of unexpected incidences to prevent their recurrence (corrective action) or to prevent their occurrence (preventive action).
– Closure Date: The date on the proposed changes is implemented and evaluated is the closure date of Change Control.
5. PROCEDURE
5.1. Initiation of change control record (CCR):
– The Initiator shall discuss the proposed change with the Department Head and key stakeholders, including, Quality Assurance and Regulatory Affairs to reach a consensus that the change is necessary, feasible, and supportable whenever required.
– Once the agreement is reached regarding the proposed change, the Initiator shall initiate a Change Control Record (CCR).
– QA shall issue the Change Control Record to the concerned department & shall assign the change control number on the form with signature and date for issuance.
5.2. Numbering system for changes
– All changes shall be numbered as a specific numbering system, as example it shall be CC/XXX/YYYY demonstrated as: CC denotes to change control, XXX denotes to sequential number and YYYY udenotes to year, E.G. CC/001/2017: this shall be the first change control in year 2017.
5.3. Approval and review of change control
– After approval on change initiation form user shall give the intimation for change control form, QA issued the form by assigning change control number.
– User shall fill the form and make available all documents related to proposed changes; all attachments shall flow with the form to HOD than QA.
– QA head review the form, as per assigned category, review all attached documents and planned programs related to changes.
– After a successful review QA shall approve the form. This shall be entered in log book of change control by QA personnel.
– In case change control related to regulatory shall be approved by regulatory in consultation with Head QA
5.4. Evaluation and implementation
– Head QA shall assign the effective date of implementation of the changes and the originating department shall plan for any necessary training and shall update the relevant documents with corrective actions jointly with QA. The status of completion of action shall be mentioned in the change control form by the originating department and shall be forwarded to QA.
– Implemented change control shall be further reviewed by Head QA. After finding all correct the documents undergoing for changes / revisions shall have revised as per the procedure.
– Approved and closed change control forms are then filed and maintained by QA.
5.5. Closing of Change control
– Change control must be close within a specified period in exceeding a proper justification to be done.
5.6. Timeline for change closure
– Product, document, and system-related change controls should be closed within 90 days and facility/equipment related change controls should be closed within 180 days if all impacted actions are completed.
– If any impacted action is not completed within the time limit, then such change controls should be kept open till completion of all impacted actions and fill the “Extension of change control” format for the extension of change control.
– Fill the required details of the form by the user department and HOD give the justification for the extension with a tentative date for closure of change control.
– Reason for the extension should be reviewed and approved by Head QA after consulting the User Department.
– After approval by Head QA for an extension, Quality Assurance person should monitor the status of change controls pending for closure and record every month.
6. Examples on change types
6.1. Level I:
– No impact on control system ensuring SISPQ of product. e.g.
6.1.1. Reduction in Hold time,
6.1.2. Tightening IP / FP limits,
6.1.3. Increased frequency of monitoring and in-process checks.
6.2. Level II:
– The changes do not have a significant impact on the control system however that triggers validation/qualification/stability study etc. e.g.
6.2.1. Establishment/increase of hold time
6.2.2. Introduction of new count / new pack
6.2.3. Change in SOP/Template/Protocol/LIMS documents
6.2.4. Change in Machine/Equipment
6.2.5. Release limit change (e.g. from IH to USP, etc.)
6.2.6. Change in In-process parameters
6.2.7. Change in Pack style/Pack count.
6.3. Level III:
– The changes have a potential impact on product quality/regulatory bodies according to respective guidelines i.e. Changes except for annual notification requirements. e.g.,
6.3.1. Change in Calibration/Stability frequency,
6.3.2. Change in FP limits (Dissolution / Average Wt. etc.)
6.3.3. Batch size change
6.3.4. Updating of pharmacopoeia change
6.3.5. Change in the strength of RM (e.g. Pellets)
6.3.6. Change in Manufacturing formula
6.3.7. Relaxation of FP limit
6.3.8. Launch of new product/system
6.3.9. Change in Storage condition
6.3.10. Change in Primary Packing Material
6.3.11. Product Shelf Life Extension
6.3.12. Deletion and Up-gradation, and repair, replacement of equipment, facility, area, or utility.
