Preparation of Validation and Qualification Protocols and Reports

1.0 OBJECTIVE:
To lay down a Procedure for Preparation of Validation and Qualification Protocols and Reports.
2.0 SCOPE:
This SOP is applicable for Preparation of Validation and Qualification Protocols and Reports at ………..
3.0 RESPONSIBILITY:
QA (Officer/ Designee): Preparation, Distribution (to Respective Department), Revision, Retrieval and Destruction of this SOP. Review, Approval, Training and effective implementation of this SOP. Review of Protocols and Reports.
Respective Departments: Preparation and Review of Protocols and Reports.
4.0 ACCOUNTABILITY:
Head QA: Ensure Training and Implementation of this SOP. Custodian of soft copy and hard copy of Master copy of this SOP. To ensure distribution to concerned Departments, Training and Effective Implementation of this SOP. Approved of all Qualification Protocol & Report. Custodian of soft copy and hard copy of Validation / Qualification Protocols and Reports.
Respective Departments Heads: Ensure the Review of contents of Protocols and Reports. Approval of all Qualification Protocol & Report.
5.0 PROCEDURE:
5.1 GENERAL GUIDELINES FOR PREPARATION, APPROVAL OF QUALIFICATION AND VALIDATION PROTOCOL AND REPORTS:
5.1.1 Protocols and Reports shall be written in English Language by using Microsoft Word.
5.1.2 The person performing the Process or activity of respective department / QA Department shall prepare the Protocols and Reports.
5.1.3 Initiator shall have adequate knowledge, Training and experience in the related Areas of activity.
5.1.4 All the points in the Protocol / Report shall be numbered sequentially and sub paragraph of the Protocol / Report be also numbered sequentially with an incremental number derived from the heading number. Bullets may be use for sub paragraph of Protocol / Report.

5.1.5 Initiator shall check the completeness of draft Protocols and Reports and send to the Head of the Department for review.
5.1.6 Protocols and Reports shall have reference of related document such as Pharmacopoeia and Guidelines published by various Regulatory Authorities. Wherever necessary illustrations and drawing shall be indicated to provide better clarity and understanding of the Process / System.

5.1.7 The reviewer shall check the adequacy, accuracy, correctness and completeness of draft Protocols and Reports.
5.1.8 Upon receipt of the comments (if any), same shall be reviewed and incorporated in the Protocols and Reports.
5.1.9 Final draft soft copy of protocol & report shall be provided to QA and the soft copy in other Departments shall be deleted in presence of QA person.
5.1.10 QA shall take the printout of protocol & report for signature.
5.1.11 Print out of protocol & report shall be provided to Respective Departments for signature.
5.1.12 All Protocols and Reports shall be prepared by Operating Officer / Executive of concerned Department, Checked by Operating Manager of concerned Department/ Head of related activity.
5.1.13 Upon signature of Respective Department, signed off copy of Protocol & Report shall be sent back to Department Head for Approved by and Final approved by Head QA
5.1.14 Soft Copy of protocol and report prepared by the User Department and transferred to Head QA and shall be deleted in presence of QA person.

5.2 PREPARATION OF QUALIFICATION PROTOCOL CUM REPORTS:
5.2.1 Qualification Protocol shall be separate for DQ, IQ, OQ and PQ for each activity and report also separate.
5.2.2 The activity flow for Qualification and Validation process is as:

5.2.3 The Responsibility and activity flow for Qualification and Validation process is as

Preparation of Protocol shall be initiated after receipt of approved Specification and Design.
User Requirement Specification (URS) ( Where ever applicable):
Design Qualification:
- Design Qualification shall be provided by the vendor.
Operational Qualification:
- Operational Qualification shall be provided by the vendor

NOTE: If there is no Define of department on Approval page. Concerned and cross functional Department review the data and final approval of Head Quality assurance Department.

Performance Qualification (PQ):
- Performance Qualification Protocol:
- Performance Qualification Protocol shall be prepared as per format shown in Annexure-I.
- Content of Header:

The Header of Performance Qualification Protocol shall have the “Logo” and Name of Organization in Left corner on Top and Title “Performance Qualification Protocol for———–” in center written in Bold and Capital letter of font size 12, format shown in Annexure-I.

Protocol No.: Shall be written as per current version of respective SOP.

Effective Date: Effective Date shall be written in the form of DD/MM/YY in respective column (Effective date 🙂

Page No.: Shall be written in Bold and Normal of Font Size 12. The Page Number shall be mentioned in ‘X of Y’ format. For Example: If a Protocol contains 60 pages then the first page of the Protocol shall be 1 of 60 and the second page shall be 2 of 60 respectively. Shall be Pre-printed.

Content of Footer:

Format No.: 09 Normal and Capital font size printed on the left corner of the page after Footer, out of page border and shall be printed as per Annexure-I with revision no. on all pages of the Protocol.

Content of Body Part:

The format of Performance Qualification Protocol shall contain the following information but not limited to:

Equipment/ Instrument / Utility Qualification:

Protocol Approval
Objective
Scope
Responsibility
Equipment Details
System Description
Reason for Requalification
Site of Study
Frequency of Requalification
Pre-Qualification Requirements
(Procedure) Tests and Checks
Checklist of all Tests & Checks
References
Documents to be Attached
Non Compliance, If Any
Deviation From Pre–Defined Specification, If Any
Change Control, If Any
Abbreviations
Revision History
- Performance Qualification Report:

On the basis of Qualification Protocol, Qualification Report shall be prepared as per Annexure-II.

Content of Header:

The Header of Performance Qualification Report shall have the “Logo” and Name of Organization in Left corner on Top and Title “Performance Qualification Report for———–” in center written in Bold and Capital letter of font size 12, format shown in Annexure-II.

Report No.: Shall be written as per current version of respective SOP and shall be Pre-printed.

Protocol No.: Respective Protocol No. shall be provided. Protocol no. shall be Pre-printed.

Effective Date: Effective Date shall be written in the form of DD/MM/YY in respective column (Effective date 🙂

Content of Footer:

Format No.: 09 Normal and Capital font size printed on the left corner of the page after Footer, out of page border and shall be printed as per Annexure-II with revision no. on All pages of the Report.

Content of Body Part:

The format of Performance Qualification Report shall contain the following information but not limited to:

Equipment / Instrument / Utility Qualification Report:

Report pre-approval
Objective
Scope
Responsibility
Equipment details
Pre-qualification requirements
Tests & checks (result and observation)
Checklist of all tests & checks
Documents to be attached
Non compliance, if any
Deviation from pre–defined specification, if any
Change control, if any
Review (inclusive of follow up action, if any )
Conclusion
Recommendation
Abbreviations
Revision history

Report post approval

The Qualification Report shall be reviewed by Head of User Department, QC / Engineering / Production Head (as applicable) and approved by Head QA. The approval of Qualification Report is considered as handover of the system to user Department for its intended purpose.

Preparation of Validation / Re-Validation Protocols:

All Validation / Re-Validation Protocols shall be prepared as per format “Validation Protocol (Specimen)” as shown in Annexure-III. The format of Validation / Re-validation Protocol shall contain the following information.

Process Validation Protocol:

Process Validation Protocol shall contain the following Headings but not limited to:

Protocol Approval
Objective
Scope
Responsibility
Training Record
Reason for Validation
Process Validation Methodology
Master Document Verification
Process Validation Pre requisite
Product Information
Manufacturing Formula
Specifications and Standard Test Procedure
Equipment Qualification Verification
Process Flow Diagram
Methodology and Sampling Procedure
Process Steps and Critical Process Variables for Validation
Sampling and Analysis Plan
Sampling Locations
Acceptance Criteria
Revalidation

Deviations
Validation Stability Plan
Validation Report
Conclusion
Reference Documents
List of Attachments
Abbreviations
Revision History
- Analytical Method Validation Protocol:

Analytical Method Validation Protocol shall contain the following Heads but not limited to:

Protocol Approval
Objective
Scope
Responsibility
Training Details
Instrument Calibration Verification
Procedure
Materials and Instruments Used
Study Design
Procedure for Method Validation
Validation Acceptance Criteria
References
Summary Report
Deviation (if any)
Abbreviations
Revision History
- Process Simulation Study (Media Fill) Protocol:

Process Simulation Protocol shall contain the following Heads but not limited to:

Protocol pre Approval

Objective
Scope
Responsibility
Re-qualification Criteria
Frequency of Validation
Number of Runs
Duration of Runs
Size of Run
Selection of Media
Interventions (Worse Case Study)
Incubation and Examination of Media-Filled Units
Interpretation of Data and Acceptance Criteria
Analytical Support
Environmental Monitoring
Training Details
Equipment Qualification / Instrument Calibration Verification
Description of Process Simulation Study Methodology
Post Media Fill Cleaning
Media fill process for three piece filling machine
Procedure
Monitoring of Process Parameters
Critical Parameters and Acceptance Criteria
Sampling Plan
Deviations
Definitions
References
Abbreviations
Revision History

Stability Study Protocol:

Stability Protocol shall contain the following Heads but not limited to:

Protocol Approval
Objective
Scope
Responsibility
Reason for Stability Studies
Training Details
Types of Studies
Specification and Test Methodology Information
Test results Acceptance Criteria
Reference to Analytical Validation [Stability Indicating]
Study Design and Condition
Stability Testing Matrix
Data Analysis Details
Stability Study Report
Out of Specifications
Deviations
Change Control
Conclusion
Reference Documents
List of Attachments
Abbreviations

Hold Time Study Protocol (For Product):

Hold Time Study Protocol shall contain the following Heads but not limited to:

Protocol Approval
Objective

3. Scope
4. Responsibility
5. Reason for Validation
6. Site of Study
7. Training Details
8. Methodology
9. Master Document Verification
10. Product Details
11. Manufacturing Formula
12. Manufacturing Procedure
13. Hold Time Study Procedure
14. Sampling and Analysis Plan
15. Acceptance Criteria
16. Revalidation Criteria
17. Frequency of Validation
18. Change Control and Deviation
19. Conclusion
20. References
21. Documents to be Attached
22. Revision History
23. Abbreviations

5.2.10.6 Cleaning Validation Protocol:
Cleaning Validation Protocol shall contain the following Heads but not limited to:
1. Protocol pre approval
2. Objective
3. Scope
4. Responsibility
5. Execution team
6. Training record

7. Introduction of cleaning validation
8. Equipment description and cleaning process description
9. Calculation of maximum allowable carryover (maco)
10. Equipment chain matrix
11. Selection of worst case product for cleaning validation study
12. Methodology of cleaning process validation
13. Acceptance criteria
14. Sampling technique
15. Sampling plan
16. Failure investigation and corrective action
17. Documentation
18. Revalidation criteria
19. Conclusion
20. Reference
21. Abbreviations
22. Revision history
5.2.10.7 System / Utility / other Validation Protocol:
System / Utility / Thermal Mapping / BET Validation / Sterility Test Validation/General Validation Protocols and any Others Validation Protocol shall contain the following Heads but not limited to:
1. Protocol Approval
2. Objective
3. Scope
4. Responsibility
5. Reason for Validation
6. Site of Study
7. Training Details
8. Methodology
9. Master Document Verification

10. Acceptance Criteria
11. Validation / Re-Validation Criteria
12. Frequency of Validation
13. Change Control and Deviation
14. Conclusion
15. Recommendation
16. References
17. Documents to be Attached
18. Deviation From Pre-Defined Specification, If any
19. Change Control, If any
20. Abbreviations
21. Revision History
5.3.8 PREPARATION OF VALIDATION REPORT:
5.2.11.1 All Validation Reports shall be prepared as per format “Validation Report (Specimen)” as shown in Annexure-IV. The format of Validation / Re-Validation Report shall contain the following information.
5.2.11.2 Process Validation Report:
Process Validation Report shall contain the following Heads but not limited to:
1. Report Pre-Approval
2. Objective
3. Scope
4. Responsibility
5. Training Records
6. Master Document Verification
7. Equipment Details
8. Raw Materials and Primary Packing Materials
9. Dispensing Verification
10. Critical Process Variables
11. Environmental Monitoring of Manufacturing Area

12. Semi-Finished Product Analysis
13. Finished Product Analysis
14. Packing
15. Yield Statement
16. Attachments
17. Deviation (if any)
18. Conclusion
19. Recommendation
20. Abbreviations
21. Revision History
22. Report Post Approval
5.2.11.3 Analytical Method Validation Report:
Analytical Method Validation Report shall contain the following Heads but not limited to:
1. Report Pre-Approval
2. Objective
3. Scope
4. Responsibility
5. Training Records
6. Instrument Calibration Verification
7. Materials & Instruments Details
8. Table for System Suitability Study
9. Table for Specificity
10. Table for Accuracy
11. Table for System Precision
12. Table for Method Precision
13. Table for Solution Stability Study
14. Table for Linearity and Range
15. Linearity Curve
16. Range Curve

17. Table for Method Intermediate Precision
18. Table for Robustness
19. Table for Filter Paper Interference
20. Table for Summarized Validation Report
21. Attachments
22. Deviation (if any)
23. Conclusion
24. Recommendation
25. Abbreviations
26. Revision History
27. Report Post Approval
5.2.11.4 Process Simulation Study (Media Fill) Report:
Process Simulation Study (Media Fill) Report shall contain the following heads but not limited to:
1. Report Pre-Approval
2. Objective
3. Scope
4. Responsibility
5. Training Attendance Record
6. Master Document Verification
7. Detail of Media and Primary Packaging Materials used
8. Growth Promotion Test of Media (SCDM)
9. Equipments Details
10. Air Handling Unit (AHU) Qualification Verification
11. Utility Qualification Verification
12. Instrument Calibration Verification
13. Machine Parts and Accessories Sterilization
14. Three Piece Filling Machine
15. Environmental Monitoring of Three Piece Filling and Sealing
16. Container Closer Integrity (Leak Test & Clarity) Test

17. Microbiological Analysis Results
18. Interventions During Filling and Sealing (worst case condition)
19. Inspection of Filled and Sealed Containers
20. Environmental Monitoring Record of Incubation Room / Chamber
21. Observation of Media Filled Containers after Incubation
22. Post GPT of Deactivated Containers
23. Destruction of Incubated Containers after Inspection
24. Batch Yield
25. References
26. Documents to be Attached
27. Non compliance
28. Deviation from Pre-defined Parameters, if any
29. Change Control, if any
30. Review (inclusive of follow up action, if any)
31. Conclusion
32. Recommendation
33. Abbreviations
34. Revision History
35. Report Post Approval
5.2.11.5 Stability Study Report:
Stability Study Report shall contain the following heads but not limited to:
1. Report Pre-Approval
2. Objective
3. Scope
4. Responsibility
5. Training Records
6. Product Details
7. Active Ingredient Details
8. Excipients Details

9. Container Closure System Details
10. Stability Study test Conditions Results
11. Attachments
12. Deviation (if any)
13. Change Control
14. Out of Specification
15. Conclusion
16. Recommendation
17. Abbreviations
18. Revision History
19. Report Post Approval
5.2.11.6 Hold Time Study Report (For Product) :
Hold Time Study Report shall contain the following heads but not limited to:
1. Report Pre-Approval
2. Objective
3. Scope
4. Responsibility
5. Training Record
6. Master Documents Verification
7. Environmental Monitoring Record
8. Hold Time Study Results
9. Change control and Deviation
10. References
11. Documents to be Attached
12. Review (Inclusive of Follow Up Action, If any)
13. Conclusion
14. Recommendation
15. Abbreviations
16. Revision History

17. Report Post Approval
5.2.11.7 Cleaning Validation Report:
Cleaning Validation Report shall contain the following heads but not limited to:
1. Report pre approval
2. Objective
3. Scope
4. Responsibility
5. Training record
6. List of instruments (calibration status)
7. Hold time study of un-cleaned & cleaned equipment
8. Observation and results
9. Deviation (if any)
10. Change control (if any)
11. Document attachment
12. Summary
13. Recommendation
14. Abbreviations
15. Revision history
16. Report post approval
5.2.11.8 System / Utility / General Validation Reports / other Validation Report:
System / Utility / Thermal Mapping / BET Validation / Sterility Validation and any Others Validation Report shall contain the following heads but not limited to:
1. Report Pre-Approval
2. Objective
3. Scope
4. Responsibility
5. Training Records
6. Master Document Verification
7. Equipment / Utility Details

8. Critical Parameters / other Required Heads
9. References
10. Documents to be Attached
11. Deviation from Pre-defined Parameters, if any
12. Change Control, if any
13. Review (inclusive of follow up action, if any)
14. Conclusion
15. Recommendation
16. Abbreviations
17. Revision History
18. Report Post Approval

5.3.9 Font Size of Header, Footer and Body Contents:

NAME OF CONTENT	FONT SIZE
HEADER:
Logo (On Left Hand Side Corner of the Page)	Height-0.75’’and Width-0.63’’
Name of the Organization, Location, Title of URS, Protocol and Report, URS / Protocol / Report No., Page No. (In the form of X of Y),	12 Bold and Capital
FOOTER:
Format No.	09 Capital Normal
BODY:
Main Heading and Table Heading	12 Bold and Capital
Sub Heading	12 Normal and Bold
Table Contents Except Headings	12 Normal
FIRST PAGE CONTENT:
Title of Protocol and Report	28 Bold and Capital with Double Line Space
Table Content	12 Bold and Capital
Space between lines	1.15
Margin of page	Margin top 1.27” Left 1.27” Right 1.27” and Bottom Margin 1.27”

5.3.10 Storage of Protocols and Reports:
5.2.13.1 All Master Copy / Soft Copy of Approved Protocols and Reports shall be stored in QA Department.
5.2.13.2 If Protocol is revised, previous version of Protocol shall be made Obsolete and shall be archived for Historical purpose.
6.0 ABBREVIATIONS

Sr. No.	Abbreviation used	Full form of abbreviation used
1.	QA	Quality Assurance
2.	SOP	Standard Operating Procedure
3.	URS	User Requirement Specification
4.	HVAC	Heating Ventilation & Air Conditioning
5.	DQ	Design Qualification
6.	IQ	Installation Qualification
7.	OQ	Operational Qualification
8.	PQ	Performance Qualification
9.	API	Active Pharmaceutical Ingredients
10.	DS	Design Specification
11.	GPT	Growth Promotion Test
12.	HPLC	High Performance Liquid Chromatography
13.	ID No.	Identification Number
14.	PDF	Portable Document Format
15.	SCDM	Soybean Casein Digest Agar Medium
16.	SS	Stainless Steel
17.	VMP	Validation Master Plan