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Change Control Process and Management in Pharma

Standard Operating Procedure (SOP) for Procedure, Process and Management of Change Control (temporary change or permanent change control) in the pharmaceutical drug manufacturing plant.

Change Control Management

1.0   Objective:

  • To lay down the procedure to identify, initiate, evaluate, review, approve, implement, and regularize the change through a change control system.

2.0   Scope – SOP for Change Control:

    • 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,
    • Site Master File.

3.0   Responsibility – Change Control Process:

Initiating Department : The concerned persons from the originating department shall initiate a change control.
Initiating Department Head : Responsible for the review of the proposal to evaluate the impact on their department’s documents/system/activities. To recommend and forward it to QA.Post effective evaluation of change.
Impact assessment team : Shall evaluate and comment on proposed changes.
Head QA or designee : Review of the impact of change, Classification of change, Planning for implementation close the change control.
Head QA : To review the comments on proposed changes and approve and reject the change control.

4.0   Procedure for Change Control Management:

  • Identification of change:

    • A need for change can be identified as an outcome of (but not limited to):
      • Implementation of good practices (commonly called as GxP), like manufacturing/ laboratory/documentation/engineering/distribution etc.
      • The recommendation in product quality review.
      • Up-gradation and/or extension of facility, premises, process, equipment & utility.
      • Self -Inspection, external audit, complaint investigation, or improvement program.
      • Regulatory changes, Pharmacopeial updates, marketing authorization need.
  • Classification of Change:

    • Critical Changes:
    • Change which has a significant impact on product quality and patient safety shall be classified as Critical changes.
    • This covers the Introduction of the new dosage form in an existing qualified facility,
    • Change of Water system/HVAC System etc.
    • Major changes :
    • A change is likely to have a significant impact on quality attributes (safety, identity, strength, purity, quality) either on a process, material, product, procedure, utility.
    • This covers the design change in the existing facility, HVAC, Purified water & generation system, and introduction of new equipment/replacement of existing equipment with a new one in an existing qualified facility.
    • Minor changes:
    • A change is unlikely to have a detectable impact on the quality attribute (safety, identity, strength, purity, quality) on a process, material, product, and procedure.
  • Initiation of Change control:

    • Initiating department shall initiate the change control form (Annexure I), after taking the controlled copy from QA.
    • QA shall issue the change control number and login shall be done in Annexure-III.
    • The initiator shall collect requisite information to initiate the change control.
    • The existing / proposed activity shall be written under specified columns.
    • A change comparison report, wherever required, shall be prepared and shall enclose with change control.
    • The reason for change shall be defined in the change control under the specified column.
    • The reference of change shall be written under column “reference” and if required copy shall be attached with change control.
    • A risk analysis report for all critical & major changes shall be prepared following SOPfor “Quality Risk Management” if necessary and the same shall be enclosed with change control.
    • The initiator shall forward, the duly filled and signed change control along with enclosures to the Head of Department/designee for evaluation and approval.
    • For all major & critical changes (If required) the initiator shall prepare a change implementation plan where applicable and that shall be enclosed with change control.
  • Approval of change by initiating Department Head:

    • The Head of department/designee shall review the feasibility of change with respect to the proposal and its reason for the change, risk assessment, and supporting documents.
    • If the proposed change is not feasible, the head of the department/designee shall reject the change after consulting with Head QA.
    • Any additional information/justification is required from the initiator, change control shall be returned to the initiator (reconsideration) with comments by the head of the department/designee for correction.
    • If the proposed change is feasible / found satisfactory, the head of the department/designee of the initiating department shall enter their consent (regarding the impact on their documents /activities/system), and approve the change, so the change control will be forwarded to QA for next course of action.
  • The first level of evaluation of change control by QA:

    • Designated QA personnel shall review the change control and attached documents for correctness.
    • If the change request needs further clarification or justification, shall be returned to the initiator (reconsideration) for corrections.
    • If change control is acceptable, designated QA personnel shall assess the impact of the proposed change (primary assessment) as per predefined parameters in the change control.
  • Second level evaluation of change control by Impact Assessment Team:

    • After completion of the primary assessment, change control shall be forwarded to the Impact Assessment Team (IAT) for their review and comments along with responsibility.
    • IAT shall be decided, based on the recommendation from the initiating department head, and impact assessment shall be done as per Annexure-II.
    • If required DRA shall inform the authority about the change where approval from the regulatory authority shall be taken prior to implementation.
    • If the change is pertaining to contract manufacturing product, approval from the customer, MA holder / PL / QA shall be taken and communication shall be attached to change control.
    • After receipt of comments from IAT, the designated QA person shall review the comments and forward to head QA for further approval of comments.
  • Review by QA:

    • Designated QA personnel shall review the comments made in the change control by the IAT team and evaluate all content before the approval of Head QA on change control.
    • Head QA put their comment in change control and classify the change as minor/major/critical.
  • Approval of change control:

    • Head QA shall review the comments made in the change control.
    • Head QA shall approve/reject the change as per their assessment.
    • QA Head shall put their comment in change control.
    • After Head QA approval Change control shall be shared (if applicable) to the customer, MA holder/PL/QP for review, and final approval before implementation of the proposed change.
  • Assigning of Activity / Task for Implementation:

    • Designated QA personnel shall list out the activities to be completed with the target completion date, name of the responsible person/department for assigning activity/action plan (Annexure-II) based on the overall assessment.
    • Upon completion of the activity, the impacted department shall inform QA with supporting/changed documents for review.
    • The initiator shall inform QA about the implementation of change/completion of the activity to close the change control.
  • Tracking and Reporting by QA:

    • A monthly review shall be conducted to evaluate, track activity completion, and implementation.
    • QA shall write the details like change effective date, first effective product (if any) / or first effective batch (if any), and verify.
    • If the change control could not be implemented fully within the stipulated period of three months, Concerned Person/Department responsible for the completion of activity shall request for period extension (Annexure-IV) through their head of department, who shall review the extension request and put their comment/justification for the delay in implementation.

Note: If the proposed changes are with respect to the introduction of a new product in the facility/Modification of facility then the TCD can be taken up to 1 year. Further, if the activity is not completed within 1 year, a Request for period extension (Annexure-IV) shall be initiated by the concerned person/department.

    • QA shall assess the impact of delay in the committed action plan, and may approve or reject the “Period Extension Request” as applicable.
    • Accordingly, a decision on change request shall be taken by Head QA in consultation with the relevant department head.
  • Post-implementation effectiveness checks:

    • After the implementation of change, the QA designee shall carry “Post effective evaluation” of the change implemented by suitable means which may include but not limited to evaluation of the results of studies/activities carried out during change implementation.
    • Post-effective evaluation needs to be done to check whether the objective of the change has been achieved and to verify that the quality parameters are not affected.
    • After satisfactory post-effective evaluation and availability of all enclosures/attachments, Head QA shall finally approve the change for regularization (closure of change)
    • After final approval (closure of change), respective stakeholders like QP / MA Holder / Customer shall be intimated, where applicable.
    • A copy of evidence (intimation) shall be attached with closed change control.

    • A change control shall be preferably closed within three (3) months after approval. If a change is related to the manufacturing processes, the impact of change shall be evaluated periodically (more frequently) to ensure that the stability results are under control, in case of any insignificant effect of change, the change implemented shall be immediately reversed and such information shall be floated to all concerned (QP / MA holder / Regulatory Authority/customer as applicable).
    • If a change control is processed for change in premises, equipment, or any such matter, where it is not feasible to complete all activities within three months,
    • Exceptionally the change request may be kept open with remark/justification and shall be monitored through appropriate manner under the supervision of Head – QA / Designee.

Note: This provision is made considering those changes, where “prior approval” is needed from concerned regulatory agency / civil construction department, the change control shall be closed after receipt of consents/orders from concerned regulatory agency / civil construction department.

    • Details of change control shall be recorded in the “Change Control Log” (Annexure-III) at the respective locations where the change control is logged.
    • Head – QA shall ensure the implementation of the change control system at the location.
  • Trending of Change control:

    • Continuous trending of the change control shall be carried out.
    • QA shall carry out the trend analysis for all the whole year change control, at the beginning of the next year.
    • A copy of the trend analysis shall be forwarded to Head QA.
    • The trending shall be carried out for the changes to be done as minor, major, and critical changes.
    • However, the trending of the major and critical changes shall be done, like facility-related, document related, product related, Machine related, etc.

5.0   Reference (S)

    • The Rules Governing Medicinal Products in the European Union: Volume 4, EUGMP
      Medicinal Products for Human and Veterinary Use. Chapter 4: Documentation.
    • The Rules Governing Medicinal Products in the European Union: Volume 4, EUGMP
      Medicinal Products for Human and Veterinary Use. Chapter 1: Pharmaceutical Quality System.
    • Schedule M.
    • WHO TRS/908, Annexure -4.

6.0   Glossary

Change : A change is an improvement, extension, modification, relocation, the introduction of discontinuation of facility, equipment, utilities, system, material, product, process, and related documents
SOP : Standard Operating Procedure.
IAT : Impact assessment team
QP : Qualified Person
CAPA : Corrective Action and Preventive Action
IT : Information technology
QA : Quality Assurance
QC : Quality Control
HR : Human Resource

7.0   Annexure (S)

Annexure – I: Change Control Form.

Change Control No:  CC /                                                                   Issuance  Date:………………..

(To be filled by QA Department)

Originating Department :
Originator :
(Name) Sign Date
Title of Change :
Description of Activity:

1. Existing Activity   :

2. Proposed Activity  :

3. Reference (s) :

4. Risk Analysis (attach approved risk analysis, if any)

Outcome:

The action of Risk Assessment (if any):

5. Reason for Change :

                                                                                                                            (Originated By)

6. Approval / Rejection

Comments:

                                                                                                               (Originating Dept. Head)                                                                                                                      

7. Evaluation of proposed changes (To be filled by QA):

A. Review of proposed changes:

                                                                                                                                         (QA) Sign/Date

B. Impact Assessment: Check impact on the following:

Check impact on Following Yes/No/NA Comments
Equipment/Utilities/Instrument /facility
Manufacturing process/Formula / Batch size
MFR/BMR/BPR/BOM
Artwork / Item codes
Standard Operating Procedure / Formats (list the other impacted procedures)
Raw Material / Packing Material
VMP / Calibration master plan
Process Validation / Cleaning validation
Qualification (DQ/IQ/OQ/PQ)

Check impact on Following

Yes/No/NA Comments
Stability Study
Drawings / Layouts
Technical agreement with customers/suppliers
Specification / STP
Training Requirement
Area/step/document needs to be evaluated
Assessment of risk in connection to the proposed change
Analytical Method Validation
License
Any other (Specify)
8. QA Comments :

Sign. & Date

9. QA shall forward the change control to the following concerned department (wherever applicable):

QA/QC/Production/Engineering/HR/Store/IT/DRA/Purchase/Others______

Impact Assessment Team:

S. No.             Name                                                              Department

  1. Comments and Impact analysis of IAT (if required attach the separate sheet)
Sr. No. Department Impact Analysis / Comments

Responsibility

11. Action Items

(attach separate sheet if required)

Name of activity / Document Person Name / Department Target Completion Date
13. Head QA:  Approval / Rejection.

Classify the change control:          Critical         Major         Minor

Assessment Checks Tick where applicable Remarks:

( Specify in details)

Co-ordination with QP, DRA & Marketing Authorization for notification to Regulatory Authorities
Stability to be charged
Relevant documents (MFR / BMR / BPR / Specification) to be changed
Validation Required
Qualification Required
Training to be given
Issuance of revised Document
Others
Comments:
  1. Tracking & Reporting:
Details Tick (Ö) wherever applicable Remark (if any)

Periodic review for checking change control

 

1)
2)
3)
Change Effective From:
Effective Product Name (if any):
Effective Batch No. (if any):
Verified By QA:

16. Action Plan Verification:

Sr. No. Name of activity/Document Target Completion date Actual Completion date Verified By Enclosure

(Attached/Not Attached)

  1. Post effective evaluation:
Results (if applicable) Comments
Results of Validation study/exhibit batch/commercial batch
Results of stability study
Modification of BMR/BPR / Specification
Results of trail carried out by production
Coordination with RA & Marketing for notification to regulatory authorities
Results of qualification
Issuance of new documents
Any other (specify)
18. Final Change Control Approval for Regularization (closing):

Head QA

Sign. & Date

19. Information to Stakeholders by QA: Tick (Ö) wherever applicable:

Annexure-II: Responsibilities of Impact Assessment Team and impact over Documentation/activity/system.

Nature of change Impact over the Documentation / Activity / System

Change in manufacturing Process/Formula/ parameters

1.    BMR

2.    Stability study

3.    BOM

4.    Filling update (market specific)

5.    Process Validation

6.    Cleaning Process

7.    Cleaning agents

8.    Site Change

9.    Waste handling

10.  Artwork (If the change in composition, addition/deletion of any ingredient printed as in label claim)

Change in Packing Process/parameters

1.    BPR

2.    Labeling

3.    Container Closure

4.    Component preparation

5.    Process control

6.    Process parameters

7.    Cleaning process

8.    Cleaning agents

9.    Site change

10.  Waste handling

11.  Stability study

12.  Filling (Market  Specific)

13.  Packing Validation

Change in Materials (Raw / Packing)

1.    Specification

2.    Material Code (New or Revised)

3. Supplier/vendor

4.    Source

5.    Manufacturing site

6.    Manufacturing process

7.    Shipping and Storage conditions

8.    Name and address of suppliers

9.    Stability study of first 3 batches

10.  Material Equivalency

11.  Vendor suitability reports

Change/modification in Facility

1. Design/layouts

2.    Security Changes

3.    Flow of Man, Material, Machine, process

4.    Designs of HVAC / AHU’s and area classifications.

5.    Environmental Controls

6.    Cleaning process/validations

7.    Area Qualification

Change in laboratories

1.    Analytical methods

2.    Analytical Hardware and Software

3.    Specifications of Raw / KSM packing / intermediate / in-process / finished product.

4.    Stability protocols

5.    Alert and action levels.

6.   Site/facility Change

7.    Qualification and Calibrations (Analyst/equipment/methods)

8.    Other procedures i.e. OOS, Lab, Incidents, OOT, etc.

Change in Equipment / Instruments

1.    Design / URS

2.    Layouts.

3.    Qualification and calibrations

4.    Locations for non-portable equipment.

5.    Operating procedures

6.    Preventive maintenance Schedules

Change in Warehouse / Shipping / Distribution centers

1.    Storage Conditions

2.    Environmental Monitoring

3.    Re-packing and labeling activity and control

4.    Shipping conditions and control

5.    Temperature and Humidity mapping.

6.    Procedural control over receipt, verification, storage, and distribution.

7.    Sampling and cleaning facility for equipment.

8.    Balances and its operational management.

Change in the computer system (hardware and software)

1.    Hardware and Software affecting GMP activities.

2.    Standalone system affecting GMP activities.

3.    Process control, laboratory control, desktop, Laptop

4.    Data Flow and data loss

5.    Cabling integrity and data security, resistance fluctuations.

6.    Earthing controls.

7.    Computer System Validation (GAMP)

Change in Utility, services, and support system

DI water, Purified Water, Compressed gas, Steam, Electrical, Emergency power, Security system

1.    Layouts and designs

2.    Qualification and validation

3.    Periodical calibration and validation

4.    Specification and system monitoring

5.    Operating Procedures

6.    SCADA / Software validations.

7.    Preventive maintenance

Change in vendors

1.    Vendor suitability reports

2.    Vendor Qualifications

3.    Material equivalency report (for alternative vendors)

4.    Item codes and descriptions

5.    BOM

6.    Stability study

7.    Process Validation

8.    Method Validations/verifications.

9. Working/impurity standards.

10.  Material de-activation / cleaning procedure

Change in Artwork

1.    Packing BOM

2.    Material code

3.    Specification

4.    Physical dimension and machine suitability

5.    Shade cards, Print proofs.

6.    BPR

Change in Market/product extension to another market/customer

1.  Specifications (RM/PM/FP/SFG)

2.  Stability protocols and reports

3.  Packing material codes, Artwork, BOM, Shade Cards

4.  Regulatory Filing & Approval

5.  Specific requirement in APQR

6.  Technical Agreement (commercial and Quality)

 

Change in SOP / Formats

1.    Training

2.    Impact on other SOPs.

Change in shelf life

1.    Stability data

2.    Control sample analysis report at proposed expiry and additional one year / six months (as per market-specific requirement.

3.    Update in SAP, BOM, BMR, BPR, Specifications, Stability protocols.

4.    Shelf life extension protocol and report.

Change in specifications / STP

1.    Material compliance report with the proposed specification. (3 batches for RM, 1 batch for PM, 3 batches for FP).

2.    Stability report compliance report with the proposed specification.

3.    Change in Specifications / STP.

4.    Filing requirement (for specific market)

5.    Method Validation/verification

6.    Impurities and working standards.

7.    Equipment, Instrument, Column, Chemicals, Reagent availability

Pharmacopeial Changes

In addition to Change in Specification and STP, the following requirements to be assessed.

1.    MFR, BMR, BOM

2.    BPR, Artwork, PM-BOM

3.    Item Code

4.    License renewal.

Remark: The above-mentioned checklist for impact assessment is for reference/guidance only impact on other aspects can be extended based on the nature of change.

Annexure – III: Change Control Log.

Sr.

No.

Initiation

Date

Change control No. Initiating Dept. Proposed Change Classification of Change Approval Date Expected date of completion The actual date of completion Status

Annexure-IV: Request for the period extension for the closing of change control

From : Date :
Change Control No.                            :

Title of Change Control                       :

Proposed date of implementation       :

Extension required                              :

Justification / Comments                    :

Head of Department

Sig. & Date

Extension Approved / Rejected

Comments:

Head QA

Sig. & Date

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