TABLE OF CONTENTS
- Protocol Approval
- Purpose
- Responsibilities
- Requirements
- Personnel Responsibilities
- Validation parameters
- Limits
- Conclusion Report
PROTOCOL APPROVAL
This document is prepared by the validation and the GMP compliance (QA) team. Hence this document before being effective shall be approved by QA Head.
Designation | Name | Signature | Date |
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PURPOSE
Process validation is establishing documented evidence which provides a high degree of assurance that a specific process (such as manufacturer of pharmaceutical dosages forms) will consistently produce a product meeting its predetermined specifications and quantity characteristics.
RESPONSIBILITIES
Sr. No. | Activity | Responsibility |
1. | Preparation of protocol | |
2. | Chemical analysis and sampling | |
3. | Microbial analysis & sampling | |
4. | Preparation of Validation Report | |
5. | Review of validation protocol & report | |
6. | Approval of protocol & Report | |
REQUIREMENTS
Nil
PERSONNEL RESPONSIBILITIES
The perfect validation program necessitates various department's involvement mainly to balance the total system functioning for its effective utilization for success criteria compliance on regular basis. Quality assurance department initiates validation program with protocol, specified procedure and success criteria. Quality control personnel are responsible for the validation run as per the protocol and during validation maintenance departments have to cooperate to the quality control personnel.
VALIDATION PARAMETERS
Formulation: Product’s Name: Reason for Performing the Validity Study:
Department
Number of batches studied: First Three Batches
Batch numbers: 1. __________ 2. __________ 3. __________
Validation activity Approved by: __________ Date: __________
General
Introduction
The process validation will be performed as prospective validation. The complete documentation for the validation comprises several independent documents; references to relevant documents will be given as part of this protocol, (find below). The results of the validation activities will be summarized in the validation report.
List of Documents for Validation:
Validation protocol
Batch Manufacturing Records
Detailed manufacturing instructions for the production of the validation batches.
Process Description / Flow Sheet
The information given below provides a general description of the process. Detailed information for the manufacturing will be supplied separately in the Batch Processing Record. Prepare production order and according to that issue the BPR Manufacturing/ Batch preparation
Flow Sheet
Formulation
Batch Size:Sr. No | Ingredients | Unit / ml | Quantity in Kgs | Overages | Quantity with Overages | Dispensed Quantity | Function |
1 | | | | | | | |
2 | | | | | | | |
3 | | | | | | | |
4 | | | | | | | |
5 | | | | | | | |
6 | | | | | | | |
7 | | | | | | | |
8 | | | | | | | |
9 | | | | | | | |
10 | | | | | | | |
Equipments/Factory
A detailed list of equipment used for validation together with the cleaning status will be provided in the manufacturing documents.
List of SOP’s, and Validation & Qualification reports used as references.
Sr. No. | Equipment | Equipment No. | SOP No |
1 | | | |
2 | | | |
3 | | | |
4 | | | |
5 | | | |
6 | | | |
7 | | | |
8 | | | |
9 | | | |
10 | | | |
Details of Equipment to be Used
Equipment | Details |
S.S. Manufacturing Tank | Make/Model: | |
ID. No. | |
Capacity: | |
Tag No. | |
RPM | |
M.O.C. | |
Rubber stopper washing machine | Model: | |
ID. No. | |
Capacity: | |
Tag No. | |
M.O.C. | |
Vials washing machine | Make/Model: | |
ID. No. | |
Capacity: | |
Speed | |
Tag No. | |
M.O.C. | |
DHS | Make/Model: | |
ID. No. | |
Capacity: | |
Tag No. | |
M.O.C. | |
Autoclave | Make/Model: | |
ID. No. | |
Capacity: | |
Tag No. | |
M.O.C. | |
Membrane filter | Make/Model: | |
Capacity: | |
Tag No. | |
M.O.C. | |
Filling Machine | Make/Model: | |
ID. No. | |
Capacity: | |
Tag No. | |
Speed | |
M.O.C. | |
Lyophilizer | Make/Model: | |
ID. No. | |
Capacity: | |
Tag No. | |
M.O.C. | |
Sealing Machine | ID. No. | |
Capacity: | |
Speed | |
Tag No. | |
M.O.C. | |
Labeling Machine | Make/Model: | |
ID. No. | |
Capacity: | |
Speed | |
Tag No. | |
M.O.C. | |
Cold storage | Make/Model: | |
ID. No. | |
Capacity: | |
Tag No. | |
M.O.C. | |
Remarks:____________________________________________________________________________________________________
Identification of Critical Process Variables Parameter
Probable causes that may affect final product:
Critical Process Parameters: Batch Mixing time
Sampling, Test Parameters, Acceptance criteria
Sampling site: Use bottom valve for Sampling
Sampling Qty.: As per testing requirements.
Sampling Time: minutes | minutes | minutes |
Total samples: |
Sampling
pH
Note: Leak test and its methodology must be properly understood as per the equipment used.
Recording of Data and Data Treatment
Data Recording
The data obtained from the various analysis & observations shall be recorded in the Data recording sheet for the first three commercial batches.
Data Recording Sheet No. |
Sheet No 1 | For recording batch preparation & results |
Sheet No 2 | For recording of vial washing and sterilization results |
Sheet No 3 | For recording of Rubber stopper washing and sterilization results |
Sheet No 4 | For recording Filtration Details |
Sheet No 5 | For recording of vial filling |
Sheet No 6 | For recording of lyophilization |
Sheet No 7 | For recording of vial sealing |
Sheet No 8 | For recording of labeling and packing |
Sheet No 9 | For recording of analysis report |
Sheet No 10 | For recording general utilities /equipment. |
Sheet No 11 | For recording analytical method validation. |
Data Recording Sheet - 1
Batch Preparation:
Equipment name: ______________________
Identification no: _______________________
Date:____________________
Capacity : ______________________ltrs / gms.
Ingredients and sequence of material addition: ___________
Total Volume of ingredients: _______________ ltrs/gms.
Mixing time: _______ minutes
Stirrer: _______rpm
Procedure: As outlined in the batch manufacturing record.
Plan: Samples to be drawn at _______ minutes, _______ minutes, &______ minutes of mixing from the sampling point
For Batch Preparation Result:
Assay after mixing Time | pH | Weight per ml | Assay |
| | |
Minutes | | | |
Minutes | | | |
Minutes | | | |
Mean | | | |
Note: pH meter calibration is essential.
Data Recording Sheet - 2
Equipment Name: vial washing Machine
Identification no : ________________
Date: __________
Capacity: ______________________ (vials per minutes)
Method reference: Visual inspection.
Observation: Washed vials shall be inspected for particulate matter.
Stage | Inspected by | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
Beginning of washing | | | | | | | | | | | |
Middle of washing | | | | | | | | | | | |
End of washing | | | | | | | | | | | |
Conclusion:____________________________________________________________________________________________________
Note: If you have a procedure or methodology to remove the vials as per non-conformity attach a table how many vials were fed and how many were removed. This is a key point to track the quality of the vials and report to your vendor. More than 0.3% of rejections are considered very high.
Data Recording Sheet - 3
Equipment Name: Rubber stopper washing Machine
Identification no : __________________
Date: ___________
Capacity : ______________________
Method reference: Visual inspection.
Observation: Washed Rubber stoppers shall be inspected for particulate matter.
Stage | Inspected by | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
After washing | | | | | | | | | | | |
Conclusion:____________________________________________________________________________________________________
Data Recording Sheet - 4
Filtration Parameters:
Type of Filter used and Its manufacturer:________________
Membrane filter holder or Cartridge housing number:________
Nitrogen gas or a Pump :________________
Details about sanitization of Pump if it is used:_____________
Integrity check details of Nitrogen filter:_____________
Capacity of Pressure vessel used:_________
Details of pressure vessel :____________
Pressure at which the Filtration is Performed:____________
Results of Pre and Post Integrity tests:_______ & ___________.
Filtration is Pass/ Fail.
Note: Always use a validated and calibrated integrity testing apparatus.
Data Recording Sheet - 5
Equipment Name: Filling machine
Identification no: ___________________
Machine Speed: ___________________
Standard volume: __________________
Procedure: As per In-process check procedure for volume check.
Observation: Volume shall be as per the limit.
Plan: Samples to be drawn from the beginning of filling, middle of filling and end of filling (Depending upon batch size)
Stage | Volume measured in measuring Cylinder | Inspected by |
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | |
Beginning of filling | | | | | | | | | |
Middle of filling | | | | | | | | | |
End of filling | | | | | | | | | |
Conclusion:____________________________________________________________________________________________________
Checked by: ______________ Date______________
Data Recording Sheet - 6
Equipment Name: Lyophilization
Identification no: ____________________
Machine Capacity: ___________________
Procedure: Filled vials send to the lyophilizer for the lyophilization process.
SAMPLING: Sampling should be done after the competition of the lyophilization cycle and check all Parameters mentioned in BPR.
Data Recording Sheet - 7
Equipment Name: Sealing machine
Identification no: ___________________
Machine Speed: ___________________
Procedure: As per In-process check procedure for sealing checkObservation: Sealing should be proper.
Plan: Samples to be drawn from beginning of filling, middle of filling and end of filling (Depends upon batch size)
Stage | Leak test | Remarks
| Inspected by |
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | | |
Beginning of Sealing | | | | | | | | | | |
Middle of sealing | | | | | | | | | | |
End of sealing | | | | | | | | | | |
Conclusion:
Checked by: ________________ Date_____________
Data Recording Sheet - 8
Equipment Name: vial labeling machine
Identification no: _________________
Machine Speed: __________________
Procedure: Labeling should be as per the specifications.
Method reference: Leak test procedure for Sealed vials.
Stage | No of vials tested | Position of label |
After machine Setting | | |
Beginning of Setting | | |
Middle of Setting | | |
At the end of Setting | | |
Data Recording Sheet - 9
Analysis Report
Product Name:Batch No.:
Batch size:
Mfg. Date:
Exp. Date:
Composition:
Test method reference: In houseSr. No. | Test | Specification | Results | Remark |
01 | Description | | | |
02 | pH | | | |
03 | Specific Gravity | | | |
04 | Uniformity Of volume | | | |
05 | Assay | | | |
5.1 | | % Labeled amount: 90 % - 110 % | | |
| | Quantity Found: | | |
5.2 | | % Labeled amount: 90 % - 110 % | | |
| | Quantity Found: | | |
5.3 | | % Labeled amount: 90 % - 110 % | | |
| | Quantity Found: | | |
5.4 | | % Labeled amount: 90 % - 110 % | | |
| | Quantity Found: | | |
Remark:
Result: The sample referred to above complies/does not comply with the standard prescribed as per In house Specification.
Data Recording Sheet - 10
Sr No | Name of critical equipment / Utilities | Qualification / Validation file reference No | Date of Qualification / Validation |
1 | S.S. Manufacturing tank | | |
3 | Membrane Filter | | |
4 | Filtration tank | | |
5 | Washing Machine | | |
6 | Filling Machine | | |
7 | Lyophilization | | |
8 | Sealing Machine | | |
9 | Labeling Machine | | |
Utilities: |
1 | AHU System | | |
2 | Water System | | |
3 | Compressed Air | | |
4 | Steam | | |
5 | Lightning | | |
6 | Drain | | |
Data Recording Sheet - 11
Remark:
Attach Analytical Method Validation protocol
Conclusion
Sr. No. | Stage | Acceptance criteria | Observation |
1. | Manufacturing | Complies as per BPR | |
2. | Vial Washing | Complies as per BPR | |
3. | Rubber stopper washing | Complies as per BPR | |
4. | Filling | Complies as per BPR | |
5. | Lyophilization | Complies as per BPR | |
6. | Sealing | Leak test | |
7. | Labeling and packing | Complies as per BPR | |
Product _______________________manufactured as per B.M.R. No _____________ meets predefined acceptance criteria.
Analysis By | Approved By |
Date | Date |
LIMIT
Based on respective Standard Testing Procedures.
CONCLUSION REPORT
The summary report will contain a discussion and conclusion, which clearly states the successful achievement of the objective of validation studies and recommended concentrations required for sanitization, disinfections, and equipment sanitization.