Performance Qualification of Purified Water System

In a pharmaceutical company, we often need to conduct Performance Qualification. While performing Performance Qualification, we have to pay attention to many aspects, such as following and implementing each step of the process according to the protocol. Therefore, you can review each process and its steps listed below, which should be included in a protocol. Performance Qualification of Purified Water System describes the following content.

Performance Qualification of Purified Water System Contents:

SERIAL NO.	ITEM DESCRIPTION
1.0	PROTOCOL APPROVAL
2.0	OVERVIEW
2.1	Objective
2.2	Purpose
2.3	Scope
2.4	Responsibility
2.5	Execution Team
3.0	GENERAL CONSIDERATION/PREREQUISITE
4.0	REVALIDATION CRITERIA:
5.0	PERFORMANCE QUALIFICATION PROCEDURE
6.0	SAMPLING FREQUENCY
7.0	SPECIFICATION OF PURIFIED WATER
8.0	PERFORMANCE QUALIFICATION OF FIRST PHASE
9.0	DEFICIENCY AND CORRECTIVE ACTION(S) REPORTS(S)
10.0	PERFORMANCE QUALIFICATION REPORT (PHASE-I)
10.1	SUMMARY
10.2	CONCLUSION
10.3	FINAL REPORT APPROVAL (FIRST PHASE)

SERIAL NO.	ITEM DESCRIPTION
11.0	PERFORMANCE QUALIFICATION OF FIRST PHASE
12.0	DEFICIENCY AND CORRECTIVE ACTION(S) REPORTS(S)
13.0	PERFORMANCE QUALIFICATION REPORT (PHASE-II)
13.1	SUMMARY
13.2	CONCLUSION
13.3	FINAL REPORT APPROVAL (SECOND PHASE)
14.0	PERFORMANCE QUALIFICATION REPORT (PHASE-III)
15.0	ABBREVIATIONS
16.0	ANNEXURES
17.0	DEFICIENCY AND CORRECTIVE ACTION(S) REPORTS(S)
18.0	PERFORMANCE QUALIFICATION FINAL REPORT
18.1	SUMMARY
18.2	CONCLUSION
18.3	FINAL REPORT APPROVAL (SECOND PHASE)

1.0	PROTOCOL APPROVAL :

This Protocol for Performance Qualification of Purified Water System to be used for producing Purified Water.

FUNCTION	NAME	DEPARTMENT	SIGNATURE	DATE
PREPARED BY		QUALITY ASSURANCE
REVIEWED BY		PROJECTS / ENGINEERING
REVIEWED BY		QUALITY CONTROL
REVIEWED BY		PRODUCTION
APPROVED BY		QUALITY ASSURANCE

2.0	OVERVIEW :

As an important Regulatory requirement, Performance Qualification becomes an important integral part of the qualification process.

2.1 OBJECTIVE:

The objective of the performance qualification of the water system is to establish and confirm that the generation and distribution system will operate within specified operating ranges. To develop and evaluate the system operation, sanitization, and maintenance procedures. To verify that the water produced and delivered to the points of use consistently meets the required quality specifications and acceptance criteria.

2.2 PURPOSE:

The purpose of this protocol is to establish documentary evidence to ensure that the Purified water system received gives pre-determined quality of water consistently.

2.3 SCOPE:

The scope of this protocol is to verify the Purified water system for the following boundaries and establish the operating ranges and procedures. -To ensure that purified water meets the requirements of the USP and European Pharmacopoeia. -To confirm the appropriateness of critical parameters and the operating ranges. -To establish the reproducibility and reliability of the systems to establish Alert and Action levels. -To validate and establish sanitization and regeneration procedures> -To Evaluate the effects of seasonal changes.

2.4 RESPONSIBILITY:

Write the persons along with the department’s name included in protocols along with their Responsibilities.

2.5 EXECUTION TEAM:

The execution team is responsible for the execution of this report. The execution team comprises of:

DEPARTMENT	DESIGNATION	NAME	SIGNATURE	DATE
PROJECTS
PRODUCTION
QUALITY CONTROL
QUALITY ASSURANCE

3.0	GENERAL CONSIDERATION/PREREQUISITE
3.1	Approved Standard operating procedure of the equipment shall be available
3.2	Approved analytical methods for testing the samples collected during the processing
3.3	The installation and operational qualification of the equipment shall be successfully completed before the execution of the performance qualification.
3.4	All the deficiencies and discrepancies related to the system that affect the product quality and corrective action taken shall be recorded in the appropriate section of the protocol.
3.5	The analytical test results and other reports related to the system shall be attached to the performance qualification of the equipment and finally verified.

4.0	REVALIDATION CRITERIA:
	The system shall be revalidated if
	There are any major changes that affect the performance of the equipment. After major changes in the components of the system

5.0	PERFORMANCE QUALIFICATION PROCEDURE :

The performance Qualification of the purified water system shall be done in three phases. The purpose and sampling plan are described as below:

The initial phase (phase-one) typically begins only after the successful completion of operational qualification. The water generated during the various phases will be used for manufacturing as long as the water meets the specifications.

PHASE- I

During this phase, appropriate operating ranges will be established. Sampling should be done after each step in the treatment process and from each point of use. The incoming feed water will also be tested to verify compliance with the specifications. The detailed sampling plan is mentioned in section 07.0. At the end of this phase alert and action limits will be established. This alert and action limit will be used during phase two and beyond.

PHASE- II

This phase is to demonstrate that the system consistently operates within predetermined operating ranges and delivers water of the required quality (as specified) when operated in accordance with the SOPs. The sampling plan will be the same as phase-I.

PHASE- III

This phase will be continued for one year to verify the extended performance of system procedures, quantity, and quality of water despite possible seasonal variations of feed water.

At the end of this phase, the performance qualification is considered as completed and ongoing monitoring will be established as a continuous record of water quality.

PHASE	PRIMARY OBJECTIVES	TYPICAL DURATION
1	Develop appropriate operating rangesDevelop and finalize operating, cleaning, and maintenance procedures. Demonstrate production and delivery of water of the required quality.	4 weeks
2	Demonstrate consistent operation within established ranges. Demonstrate consistent production and delivery of water of the required quality.	4 weeks
3	Demonstrate extended performance Ensure that potential seasonal variations are evaluated and treated	One year

6.0	SAMPLING FREQUENCY :

The sampling points indicating sampling point number and their sampling frequencies are mentioned as below.

Sampling points	Sampling point No	Frequency
		Phase -1	Phase -2	Phase -3

During the First phase and Second phase, samples shall be collected and tested daily for four weeks from all Sampling points. During the Third phase, feed water samples shall be collected and tested on a weekly basis, and purified water samples shall be collected and tested for every alternative user point so that all user points shall covered in two days (i.e. all odd no. points shall be collected one day and even no. points on next day).

7.0	SPECIFICATION OF PURIFIED WATER :

Test	Limits
	Ph. Eur.	USP	In-house
Description	A Clear, colorless, odorless, and tasteless liquid	A Clear, colorless, and odorless liquid	A Clear, colorless, and odorless liquid
pH	—	5.0  –  7.0	5.0  –  7.0
Conductivity at 25°c	Not More Than 1.3 ms/cm	Not More Than 1.3 ms/cm	Not More Than 1.3 ms/cm
Total Organic Carbon	NMT 500 ppb	NMT 500 ppb	NMT 500 ppb
Nitrates	0.2 ppm	—	0.2 ppm
Heavy Metals	0.1 ppm	—	0.1 ppm
Total Aerobic Microbial count	100 CFU /ml	100 CFU /ml	100 CFU /ml
Pathogens: Escherichia coli Salmonella Species Pseudomonas-aruginosa Staphylococcus aureus	Should be Absent Should be Absent Should be Absent Should be Absent	Should be Absent Should be Absent Should be Absent Should be Absent	Should be Absent Should be Absent Should be Absent Should be Absent

During the first phase, the operational parameters and the cleaning/sanitization procedures and

frequency will be developed. Sampling should be done daily after each step of the purification process

and at each point of use for four weeks.  The second phase of the system validation is to demonstrate that the system will consistently produce the desired water quality when operated in confirmation with the SOPs. The third phase of validation is to demonstrate the seasonal variation.

8.0	: PERFORMANCE QUALIFICATION OF FIRST PHASE

8.1 Objective

The objective of this phase is to establish appropriate operating ranges and provide data for the development of cleaning and sanitization procedures, regeneration procedures, and frequencies.

8.2 Procedure

• The Phase One Qualification will be carried out for 30 days.
• The Purified Water system will be Operated/Regenerated/Sanitized as per respective Standard Operating Procedures.
• A sample shall be collected from all the specified points (refer to sampling points schematic diagram as shown in annexure-1) at a specified frequency as shown in section 06.0
•  Water samples shall be analyzed for the tests specified in section 07.0 as per the respective test procedures. 
• Record the results of each sampling point in respective data sheets. 

8.3 Acceptance criteria

Water, which is collected from different locations in the generation system, shall meet the specified acceptance limits mentioned in section 7.0 Water, which is collected from a purified water storage tank and all user points, shall meet the specification mentioned in section 7.0.

In case of any failure investigation shall be carried out and rectification or modification shall be done if required.  In such case, the sampling and test period of Phase I study shall be extended for a further 2 weeks. During this period no production activity shall be carried out.

*Stress Operating Condition

a. Power failure test:

Verify the system performance in terms of water quality after power failure (5 minutes).

Collect water samples from all the sampling points from SP 01 to SP 10 before and after power failure and analyze for the tests specified in section 07.0.

b. Continuous circulation Loop testing

Keep water in continuous circulation in a loop and collect water samples from different sampling points preferably 2 user points and one from storage tank at frequent intervals of 12 hours, 24 hours, 48 hours, and 72 hours, and analyze for tests specified for respective points.

9.0	DEFICIENCY AND CORRECTIVE ACTION(S) REPORT(S)
The following deficiency was identified and corrective actions taken in consultation with the validation team.
Description of deficiency :
Corrective action(s) taken :

Reviewed By:

Date

10.0	PERFORMANCE QUALIFICATION REPORT (PHASE-I):

10.1	SUMMARY :
10.2	CONCLUSION  :

10.3 FINAL REPORT APPROVAL(FIRST PHASE):

Verified that all test cases required for phase one studies, and results data attached to this protocol or included in the qualification summary report are completed.

Signatures in the block below indicate that all tests in this phase of the Qualification Protocol have been reviewed and found to be acceptable and qualified for phase two studies.

NAME	DESIGNATION	DEPARTMENT	SIGNATURE	DATE
		PROJECTS / ENGINEERING
		PRODUCTION
		QUALITY  CONTROL
		QUALITY ASSURANCE

11.0	PERFORMANCE QUALIFICATION OF SECOND PHASE :

11.1 Objective

The objective of this phase is to demonstrate that the system consistently operates within pre-determined operating ranges and produces water of the specified quality when operated in accordance with the SOPs.

11.2 Procedure

• The phase two qualification will be carried out for 30 days.
•  The Purified Water system will be Operated/Regenerated/Sanitized as per respective Standard Operating Procedures.
• Sample shall be collected from all the specified points (refer to sampling points schematic diagram as shown in annexure-1) at a specified frequency as shown in section 06.0
•  Water samples shall be analyzed for the tests specified in section 07.0 as per the respective test procedures. 
•  Record the results of each sampling point in respective data sheets.

11.3 Acceptance criteria:

Water shall meet the specified acceptance limits established at the end of the First Phase Qualification.

In case of any failure w.r.t. CFU counts and Chemical test failure, sanitization, and regeneration frequency have to be reviewed. Any leakage or stagnancy of distribution system due to mis-operation or sampling error may result in microbial failure.  Hence an extensive investigation is required before revision for the requirement of frequency of sanitization.  Any microbial count, (though within limit), shall be identified and action shall be decided on the basis of type of organism and re-occurrence of the organism in the next sample(s) (if any).

12.0	DEFICIENCY AND CORRECTIVE ACTION(S) REPORT(S)
The following deficiency was identified and corrective actions taken in consultation with the validation team.
Description of deficiency :
Corrective action(s) taken :

Reviewed By:

Date

13.0	PERFORMANCE QUALIFICATION FINAL REPORT:

13.1	SUMMARY :
13.2	CONCLUSION  :

13.3 FINAL REPORT APPROVAL(SECOND PHASE):

 Verified that all test cases required for phase two studies, and results data attached to this protocol or included in the qualification summary report are completed.

Signatures in the block below indicate that all tests in this phase of Qualification Protocol have been reviewed and found to be acceptable and qualified for phase three studies.

NAME	DESIGNATION	DEPARTMENT	SIGNATURE	DATE
		PROJECTS / ENGINEERING
		PRODUCTION
		QUALITY  CONTROL
		QUALITY ASSURANCE

14.0	PERFORMANCE QUALIFICATION OF THIRD PHASE :

14.1 Objective

The objective of this phase is to demonstrate that when operated for an extended time period, the system produces and delivers water of the required quality, despite possible seasonal variations of the feed water.

14.2 Procedure

• The third phase of qualification will be carried out for one year.
• The Purified Water system will be Operated/Regenerated/Sanitized as per respective Standard Operating Procedures.
• A sample shall be collected from all the specified points (refer to sampling points schematic diagram as shown in annexure-1) at a specified frequency as shown in section 06.0
• Water samples shall be analyzed for the tests specified in section 07.0 as per the respective test procedures. 
• Record the results of each sampling point in respective data sheets.

14.3 Acceptance criteria

Water shall meet the specified acceptance limits established at the end of the Second Phase Qualification.

15.0	Abbreviation:
	PWS: Purified water system PW: Purified water RW: Raw water UV: Ultraviolet SOP: Stander operating procedure SAC: Strong acidic  cation SBC: Strong basic cation CFU: Colony Forming Unit

16.0  Annexure(s):

Sr.No.	Annexure No.	Title of Annexure

17.0	DEFICIENCY AND CORRECTIVE ACTION(S) REPORT(S)
The following deficiency was identified and corrective actions taken in consultation with the validation team.
Description of deficiency :
Corrective action(s) taken :

Reviewed By:

Date

18.0	PERFORMANCE QUALIFICATION FINAL REPORT:

18.1	SUMMARY :
18.2	CONCLUSION  :

18.3 FINAL REPORT APPROVAL(THIRD PHASE):

Verified that all test cases required for performance qualification studies, and results data attached to this protocol or included in the qualification summary report are completed.

Signatures in the block below indicate that all tests in this performance Qualification Protocol have been reviewed and found to be acceptable, considered to be safe, and qualified for regular use

NAME	DESIGNATION	DEPARTMENT	SIGNATURE	DATE
		PROJECTS / ENGINEERING
		PRODUCTION
		QUALITY  CONTROL
		QUALITY ASSURANCE