This SOP is introducing what is change control system, what is the change control board, what is the procedure of change control management/ process, what is the content of the change control form, why change control required in the pharmaceutical industry, in which condition change control will raise with examples.

 

SOP on Change Control Procedure and Role of Change Control Board

 

1.0 PURPOSE

The purpose of this procedure is to describe the change control system which ensures that proposed changes with the potential impact on products are properly reviewed, documented, evaluated, approved, and implemented in conformance with regulatory requirements and maintain traceability of changes throughout the Product lifecycle.

2.0 SCOPE

2.1 Applicable to all over unit/ plant/ facility/ manufacturing site this change includes below but not limited to:

2.1.1 Change in existing products, product design, vendors, existing process, process parameters, batch size, raw materials, packaging components, shelf life, storage condition, additional processing, analytical method, intended use, distribution of the products etc.

2.1.2 Artwork of primary or secondary packaging material (including leaflet, label)

2.1.3 Changes in the documents like Standard Operating Procedures (SOP), Specifications, Validation documents, Master Batch Records, Batch Packing Record, etc.

2.1.4 Facility or System-related changes. 

3.0 RESPONSIBILITY

3.1 User / Concern Department:  

3.1.1 User or concern department is any department that is responsible for initiating the change.

3.1.2 The User Department is responsible for the initiation of change by providing details of the changes with reasons, a procedure for implementation, providing comparison criteria between existing and proposed change for evaluation,  carrying out an impact assessment of the change, documents etc., providing a tentative closeout date, set an action plan for impacted areas, post-approval implementation of changes, and carrying out comparison as per the criteria proposed for evaluation, completion of the change control form with all details, provide training to the concern area person where change is impacted and necessary attachments and implementation and execution of the same.

 3.2 User / Concern Department Head (HOD):

3.2.1 Responsible for review the change control form and provide justification on the proposed change, ensuring that the change control procedure followed for all the changes and evaluate the area of impact of change.

3.3 Quality Assurance:

3.3.1 Issuance of change control form.

3.3.2 Assign change control number in the change control form and in respective change control logbook/register.

3.3.3 Review the details of proposed change which includes a description of the change, the reason for change and justification of user/concern department HOD.

3.3.4 Categorized change and type of change in the change control form.

3.3.5 Assign a tentative change closure date as provided by the user/concern department.

3.3.6 Verification of evaluation strategy of change, a methodology for implementation, and impact assessment for the proposed change.

3.3.7 Review of change control after implementation, monitoring the change control till closure.

3.3.8 Ensuring for completion of training (if required).

3.4 Quality Assurance Head (HOD):

3.4.1 Evaluation, approval, or rejection of proposed change, monitoring the change control closure.

3.4.2 Ensuring that the change control procedure followed as mentioned for all the changes.

3.5 Regulatory Affairs

3.5.1   Evaluation of the impact of change on any regulatory requirement.

3.5.2 Inform regulatory bodies or customer regarding the change (if any).

3.5.3 Follow up on the change-related activity.

3.6 Change Control Board (CCB)

3.6.1 Members involved in the Change Control Board should have suitable levels of site management skills. Functional Head of Quality Should be a Change Control Board members and will act as the Change Control Board.

3.6.2 Change Control Board has responsibility for:

3.6.2.1 Review the impact elements of a proposed change and based on this decide to proceed or not. The change plan should be approved or rejected by the Change Control Board before raising change control. 

3.6.2.2 Define priorities and ensuring the availability of resources.

3.6.2.3 Review proposed changes to ensure that the changes are not repeated, reproduce or do not harmful impact on other changes.

3.6.2.4 Consult with user department to define a method for proceeding with changes.

3.6.2.5 Resolve issues and conflicts related to the change.

4.0 DEFINITION:

4.1 Change:

Any addition, modification, or removal of product, document, process, equipment, instrument, the system, facility, etc.

4.2 Change Control:

The procedure in which initiate, reviews, evaluates, manages, implement, approve and controls the changes made to the existing operating system/facility/process/procedure / document / product.

4.3 Closure Date:

The date on the proposed changes are implemented and evaluated is the closure date of Change Control.

4.4 Major Change:

Change that directly impacts on the quality of the product includes identity, quality, purity, strength, stability, safety, efficacy or the accuracy of the product.

Example –

1. Change in the manufacturing process
2. Change in starting raw material (API)
3. Change in starting raw material (API) vendor
4. Change in batch size (more than 10 folds)
5. Change in a critical reagent that could alter impurity profile
6. Change in the shelf life of the product
7. Change in manufacturing formula
8. Change in critical processing equipment
9. Major change part of the equipment
10. Modification in an existing facility
11. Change in the type of primary packing material

4.5 Minor Change:

Change which does not directly impact on the quality of product includes the identity, quality, purity, strength, stability, safety, efficacy, or accuracy of the product.

Example –

1. Change in similar equipment
2. Correction of a typographical error in documents
3. Addition of equipment having the same principle, make, model
4. Minor change part of the equipment

 5.0 PROCEDURE:

5.1 Change control board (CCB) should decide the change plan and CCB should be authorized for approval and rejection of the change plan. After change plan approval by the change control board. The User/concern department should become issued a change control form from Quality Assurance (QA).

5.2 Change control is divided into 5 phases.

Phase -I: Initiation of change

Phase -II: Change Evaluation (Assessment)

Phase -III: Approval of change control

Phase -IV: Implementation of change

Phase -V: Closure

5.3   Phase I (Initiation of change)

5.3.1 Quality Assurance should select an appropriate option where change is applicable. Below are the options.

Product/ Document / System / Facility / Equipment / Instrument.

5.3.2 Assign the change control number as per the below change control numbering system:

CC/YY/ZZZ                   where,

CC – Change Control

YY – last two digits of a calendar year

ZZZ – serial number.

E.g. CC/20/001 where,

CC – Change Control

20 – for the year 2020,

001 – for the serial number.

5.3.3 Never allot the same change control number whether the change is approved or rejected.

5.3.4 After receiving the form from the QA department. User department should fill the details in the form as per below:

5.3.4.1 Name of the change initiating Department.

5.3.4.2 User The department should provide the details of the proposed change as per the selected option by Quality Assurance.

Document / Product / System / Facility / Equipment / Instrument.

Documents: mention document number along with version number.

Product: mention product name and code

Instrument/Equipment: mention code no. of instrument/equipment

Facility: mentioned the area details and area code.

System: mentioned the system code and details

5.3.4.3 If there is new products / instrument / equipment / document, a change control should be filled to evaluate the impact on available existing products/facility / documents.

5.3.4.4 Change control should also be filled in case of discontinuation of the instrument / equipment / Document / System / Product / Facility.

5.3.4.5 If there is same change in different SOPs then a single change control should be raised.

E.g. addition or deletion of the same Pictogram in the different SOP.

5.3.4.6 The ” Change Description ” should be given in enough detail with reasons for the change.

5.3.4.7 If the space provided for writing ” Change Description ” and the reason for the change is not enough then attach annexure for better clarification.

5.4 Phase -II: Change Evaluation (Assessment)

5.4.1 Phase –II should be performed by the User Department and Quality Assurance.

5.4.2 Evaluate the possibility of the impacted area, document, process, etc.

5.4.3 Select the below options for the evaluation:

Impact of change on product  name and code, Manufacturing area code,   Process validation, Method validation, Cleaning validation, Stability, Qualification (Equipment/Instrument, area   and   system), Hold   time  the study, Specification (RM, FP, PM, Stability), SOP, Layouts, Site Master File (SMF), Master Manufacturing Formula (MMF), Master Batch Manufacturing Record (BMR), Master Batch Packing Record, Process Flow Sheet, List of  equipment/instruments, Preventive Maintenance, Calibration  schedule, Validation Master Plan (VMP), List of Products etc. should be evaluated.

5.4.4 Details of the impacted area should be mentioned by the User Department and QA.

5.4.5 If a change of one procedure impacts other procedures or systems, all impacted documents/procedures should be revised on time before the closure of change control.

5.4.6 User Department   should   specify   the   proposed   stepwise methodology for implementation of change.

5.4.7 As per evaluation QA person should categorize as Minor or Major change as per evaluation, definition, and consultation with the user department.

5.4.8 Change should be three types New / Upgradation / Deletion

5.4.8.1 New — Any replacement or addition of the new process, equipment, method, facility, a system for improvement of quality.

5.4.8.2 Upgradation – Modification/ revision in the existing process, equipment, method, facility, a system for improvement of quality.

5.4.8.3 Deletion – Removal of the new process, equipment, method, facility, a system for improvement of quality.

5.4.9 Criteria for evaluation should be established by the user department and Quality Assurance.

5.4.10 Quality Assurance evaluate impacting department and intimate other departments about change control.

5.4.11 Other departments evaluate the impact of the change in their department and write a comment on the change. Other department includes Production, Quality Control, Stores, Engineering, EHS (if applicable), R&D, Regulatory Affairs, Administration, Corporate Quality Assurance etc.

5.4.12 Based on the evaluation and impact assessment, a tentative closure date should be mentioned by Quality Assurance in consultation with the user department in the change control form and change control logbook or register.

5.5 Phase -III: Approval of change control

5.5.1 All proposed changes should be rejected or approved by Quality Assurance Head based on the evaluation.

5.5.2 Other department approvals required then, same should be decided by Quality Assurance and forward the Change Control Form to the concerned departments like R&D, Regulatory affair, Marketing, Corporate Quality Assurance and customers.

5.5.3 In case major change control is required to approved by the customer then intimate to customer.

5.5.4 Any major change in facility, systems, process, equipment, process or the formula, changes related to regulated market such changes required other department approval.

5.5.5  If the change does not require any other approvals as mentioned above, proceed change control to Phase-IV for implementation of change.

5.5.6 In case of changes impacting the dossier, then updated the dossier should be provided by Regulatory Affairs to QA before the implementation of change.

5.5.7 If the change control proposal is rejected at any stage during review and approval, then remarks / reason for rejection should be recorded at the appropriate stage and the person rejected the change control should sign with the date. A further approval procedure is not required for such change control and it should be closed by Quality Assurance. The log should have a remark of rejection in the close-out date column.

5.6    Phase- IV (Implementation of Change)

5.6.1  Quality Assurance  should verify the implementation of change.

5.6.2 Quality Assurance should verify all impacted documents and for the current status of that documents and verify the completion of the proposed action plan.

5.6.3 QA verify below points prior to closure of the Change control but not limited:

1. Training completion on changes to concerned parsons (if applicable)
2. New/ Revised document number
3. If a change in existing documents (consider old documents) then existing documents should withdrawn and Stamped “OBSOLETE” and check the availability of new documents.
4. Effective Date of the documents
5. Others, if any

5.6.4 After verifying the implementation status of change control if all are good then Quality Assurance should sign along with the date on Change Control Form.

5.6.5 In case the impacted actions in change control are partially completed and equipment /system is to be given over for use then the impact analysis should be done for uncompleted actions.

5.6.6 Customer approval is pending for change control and if the change is required to be implemented and will not have an impact on product quality then raise a planned deviation and implement the same change on the basis of planned deviation.

5.7     Phase -V: Closure

5.7.1 Quality Assurance should ensure and confirm that the changes do not have quality risks and expected results are achieved.

5.7.2 Verify any supporting documents should be attached along with the change control form and the same should be recorded in the change control form.

Example- (but not limited and depends on the nature of change)

1. Rationale of change
2. Layouts
3. P&ID Diagrams
4. Flow Charts
5. Comparison Data of Batches on existing and proposed changes
6. Validation report
7. Standard Operating Procedures
8. Equipment Equivalency (for same equipment)
9. Specification
10. Stability Data
11. Any further changes or deviations with respect to change
12. Quality Attributes of the produced batches
13. Obtained results after changes implementation etc.

5.7.3 After complete evaluation by Quality Assurance, the Change Control form should be sent for evaluation and approval to other departments (If required).

5.7.4 If the change control does not require any other approvals, then change control form should be reviewed for appropriateness and closure of the impacted changes and finally change control should be closed.

5.8 Timeline for change closure

5.8.1 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.

5.8.2 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.

5.8.3 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.

5.8.4 Reason for the extension should be reviewed and approved by Head QA after consulting the User Department.

5.8.5   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.

6.0   ABBREVIATIONS:

QA- Quality Assurance

HOD – Head of department

API – Active Pharmaceutical Ingredients

SOP – Standard Operating Procedure

RM – Raw Material

FP – Finished product

PM – Packing Material

R & D – Research and Development

 7.0 REFERENCES

7.1 Schedule Mof Drugs and Cosmetics Act. 1940

7.2 FDA 21 CFRPart 10 and Part 211.22

7.3 PIC/SGuideline Annex 15 of “Qualification and Validation”

7.4 ICH Pharmaceutical Quality Systems Q10, Current Step 4 Version, Dated 4 June 2008.Sec. 3.2.3.

7.5 EudralexVolume 4 – Annex 15

7.6 ICH Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients, Point No. 13

7.7 WHO good manufacturing practices for pharmaceutical products

8.0 HISTORY

Not Applicable

9.0 ANNEXURES

9.1 Change Control Board Meeting

9.2 Change Control Form

9.2 Extension of change control

FAQ: