Process Validation Protocol for Parenteral

TABLE OF CONTENTS
  1. Protocol Approval
  2. Purpose
  3. Responsibilities
  4. Requirements
  5. Personnel Responsibilities
  6. Validation parameters
  7. Limits
  8. 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

 

 

 

 

 

 

 

 

 

 

 

 


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 house

Sr. 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.

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