Purified Water System PQ is a critical validation activity that demonstrates a pharmaceutical water system consistently produces and distributes purified water meeting IP, USP, BP, and GMP requirements. This guide explains the qualification process, sampling strategy, testing requirements, acceptance criteria, and best industry practices.
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Purpose of Purified Water System PQ
To establish that the equipment performance according to specifications and to record all relevant information and data to demonstrate its functions as expected by ensuring the following:
Verification of water quality at various purification stages in the system.
Verification of water produced and delivered to the point of use consistently meets the required quality specifications and acceptance criteria.
Establishing sanitization/Cleaning frequencies.
Studying the seasonal variations.
To provide documented evidence that the system is capable to continuously supply the purified water with the specified quality attributes.
Scope of Purified Water System PQ:
The PQ for the system covers the Purified water Generation and distribution system. The tests will be designed to show that the system is capable of producing water as per IP/USP/BP quality over a sustained period.
Trained personnel shall be responsible for executing the tests in this protocol. This protocol consists of Performance Qualification tests to
Protocol pre approval:
Protocol prepared by:
| Department | Name | Signature | Date |
| Quality Assurance (Officer/ Executive) |
Protocol reviewed by:
| Department | Name | Signature | Date |
| Quality Assurance Manager) | |||
| Production (Executive/ Manager) | |||
| Engineering (Executive/ Manager) | |||
| Quality Control (Executive/ Manager) |
Protocol approved by:
| Department | Name | Signature | Date |
| Quality Assurance (Head QA) |
verify that the Purified Water Generation and Distribution system perform as required.
Responsibilities:
| Department | Name | Designation | Sign | Date | |
| Qualification Team | Quality Assurance | ||||
| Production | |||||
| Engineering | |||||
| Quality Control |
| Department | Responsibilities |
| Quality Assurance | Quality Assurance department shall be responsible for- 1. Preparation, Approval and execution of Performance qualification study. 2. Review of the data documented during equipment qualification & ensures compliance with all specification. 3. Confirmation, verification and approval any change control generated during the qualification study. |
| Production | Production department shall be responsible for- 1. Checking of performance criteria of purified water system. 2. Providing the support as and when required for execution of qualification activity. 3. Approval of performance qualification protocol. |
| Engineering | Engineering department shall be responsible for- 1. Preparation of performance criteria for purified water system. 2. Provide the necessary support during qualification activity. 3. Preparation of critical performance parameters as per requirement. 4. Preparation of drawings required for purified water system design if any. 5. Calibration of all measuring/test instruments and rectification of Breakdown during qualification activity. 6. Approval of final protocol. |
| Quality Control & Microbiology | Quality control department shall be responsible for- Selection of performance criteria. Sampling & Testing of samples. Review of the complied data & qualification report. Preparation of analysis report and submission to quality assurance department. Approval of performance qualification protocol. |
Purified Water Generation and Distribution System Overview: Purified Water System PQ
| Name of the system/ equipment: Purified water Generation and Distribution Department : Engineering Manufactured by : Supplier Name (If any) : Manufacturing Year : Equipment ID Number : Capacity : Equipment Location : System Description : Purified water generation system is designed to generate water to meet IP /USP/BP requirements and this purified water generation system is designed for continuous operation of purified water generation and to provide consistent quality of purified water. This purified water generation system is designed to generate water 3.0m3 /Hr. This water system consists of Sod. Hypochlorite dosing system, Multi grade filter, Softener, SMBS dosing system, pH correction dosing system, Antiscalent dosing system, cartridge filter, RO membrane, EDI system, and distribution system. |
Pre-Requisites for Purified Water System PQ Performance Qualification
Requirements Before Starting PQ
- Completion of Design Qualification, Installation Qualification, and Operational Qualification
- Calibration of critical instruments
- Approval of SOPs and validation protocol
- Availability of trained personnel
- Utility and system readiness
Sampling Plan for Purified Water System PQ
Purpose of the sampling Plan
The sampling plan is to verify the purified water generation and distribution system consistently produce the purified water which complies with the IP, USP and applicable GMP guideline. The overall sampling plan helps to confirm the system’s overall performance.
Sampling points in water generation system
The sampling points for collecting samples of Purified water for chemical and microbiological tests over the entire manufacturing and distribution system will be as per below:-
Raw Water Sampling Points
| Location of sampling point | I.D. No. of Sampling Point | Seasonal Change | Operation | Testing | Comment |
| Bore well | BW-001 | Validation exercise schedule of Purified Water Generation and Distribution System: Phase – III Daily | After Completion of Phase –I & II, Depends up on sampling Plan. | Chemical & Micro | Failure in 15 days basis can reduce the frequency |
| Before Chlorination | RW-001 | ||||
| After chlorination | RW-002 |
Pre treatment sampling points
| Location of sampling point | I.D. No. of Sampling Point | Seasonal Change | Operation | Testing | Comment |
| Before MGF | RW-003 | Validation exercise schedule of Purified Water Generation and Distribution System: Phase – III Daily | After Completion of Phase –I & II, Depends up on sampling Plan. | Chemical & Micro | Failure in 15 days basis can reduce the frequency |
| After MGF | RW-004 | ||||
| After Softener | SW-001 | ||||
| Before Ultra Filtration | SW-002 | ||||
| After Ultra Filtration | SW-003 | ||||
| After PH correction Dosing System | SW-004 | ||||
| After SMBS Dosing System | SW-005 |
Reverse Osmosis (RO) Sampling Points
| Location of sampling point | I.D. No. of Sampling Point | Seasonal Change | Operation | Testing | Comment |
| Before RO Membrane | SW-006 | Validation exercise schedule of Purified Water Generation and Distribution System: Phase – III Daily | After Completion of Phase –I & II, Depends up on sampling Plan. | Chemical & Micro | Failure in 15 days basis can reduce the frequency |
| At RO-1 | RO-001 | ||||
| At RO-1 Permeate | RO-002 | ||||
| At RO-1 | RO-003 | ||||
| At Inlet Line | RO-004 | ||||
| At RO-2 Housing | RO-005 | ||||
| At RO-2 Permeate | RO-006 |
EDI Sampling Points
| Location of sampling point | I.D. No. of Sampling Point | Seasonal Change | Operation | Testing | Comment |
| At EDI dilute Inlet | RO-007 | Validation exercise schedule of Purified Water Generation and Distribution System: Phase – III Daily | After Completion of Phase –I & II, Depends up on sampling Plan. | Chemical & Micro | Failure in 15 days basis can reduce the frequency |
| Permeate line of EDI | PW-001 |
Purified Water Distribution Sampling Points
| Location of sampling point | I.D. No. of Sampling Point | Seasonal Change | Operation | Testing | Comment |
| After Pump | PW-002 | Validation exercise schedule of Purified Water Generation and Distribution System: Phase – III Daily | After Completion of Phase –I & II, Depends up on sampling Plan. | Chemical & Micro | Failure in 15 days basis can reduce the frequency |
| After UV | PW-003 | ||||
| In PW Return line | PW-004 |
Point-of-Use (POU) Sampling Locations- Manufacturing Areas
| Location of sampling point | I.D. No. of Sampling Point | Seasonal Change | Operation | Testing | Comment |
| Binder preparation room | PW-001 | Validation exercise schedule of Purified Water Generation and Distribution System: Phase – III Daily | After Completion of Phase –I & II, Depends up on sampling Plan. | Chemical & Micro | Failure in 15 days basis can reduce the frequency |
| Janitor room | PW-002 | ||||
| Unclean Utensil room | PW-003 | ||||
| Equipment washing room | PW-005 | ||||
| Binder preparation room | PW-008 | ||||
| IPQA room | PW-009 | ||||
| Granulation area | PW-010 | ||||
| Blending room | PW-011 | ||||
| Binder preparation room | PW-014 | ||||
| Capsule IPQA room | PW-015 | ||||
| Sampling tool washing area | PW-016 | ||||
| IPQA room | PW-017 | ||||
| Equipment washing room | PW-018 | ||||
| Coating room | PW-019 | ||||
| Washing area | PW-023 | ||||
| Washing room solution preparation area | PW-024 | ||||
| IPQA room | PW-025 | ||||
| Coating solution preparation room | PW-026 | ||||
| Wet lab | PW-028 | ||||
| Dissolution room | PW-029 | ||||
| Micro Autoclave loading room | PW-030 | ||||
| Garment washing room | PW-031 | ||||
| Glass ware washing & De-pyrogenation room | PW-032 | ||||
| Decontamination room | PW-033 | ||||
| Stability room | PW-037 |
Chemical and Microbiological Analysis During Phase III Purified Water System PQ– Frequency
| S. No. | Name of sampling point | I.D. No. of Sampling Point | Location | Frequency of Analysis |
| Raw Water | BW-001 | Bore well | Weekly | |
| Raw Water | RW-001 | Before Chlorination | Weekly | |
| Raw Water | RW-002 | After chlorination | Weekly | |
| Raw Water | RW-003 | Before MGF | Weekly | |
| Raw Water | RW-004 | After MGF | Weekly | |
| Soft water | SW-001 | After Softener | Weekly | |
| Soft water | SW-002 | Before Ultra Filtration | Weekly | |
| Soft water | SW-003 | After Ultra Filtration | Weekly | |
| Soft water | SW-004 | After PH correction Dosing System | Weekly | |
| Soft water | SW-005 | After SMBS Dosing System | Weekly | |
| Soft water | SW-006 | Before RO Membrane | Weekly | |
| RO water | RO-001 | At RO-1 Housing | Weekly | |
| RO water | RO-002 | At RO-1 Permeate | Weekly | |
| RO water | RO-003 | At RO-1 Housing drain | Weekly | |
| RO water | RO-004 | At Inlet Line of RO2 System | Weekly | |
| RO water | RO-005 | At RO-2 Housing | Weekly | |
| RO water | RO-006 | At RO-2 Permeate | Weekly | |
| RO water | RO-007 | At EDI dilute Inlet | Weekly | |
| Purified water | RO-001 | Permeate line of EDI | Weekly | |
| Purified water | RO-002 | After Pump | Weekly | |
| Purified water | RO-003 | After UV | Weekly | |
| Purified water | RO-004 | In PW Return line before | Daily | |
| Purified water | PW-001 | Binder preparation room | Daily | |
| Purified water | PW-002 | Janitor room | Weekly | |
| Purified water | PW-003 | Unclean Utensil room | Weekly | |
| Purified water | PW-005 | Equipment washing room | Weekly | |
| Purified water | PW-008 | Binder preparation room | Weekly | |
| Purified water | PW-009 | IPQA room | Weekly | |
| Purified water | PW-010 | Granulation area | Weekly | |
| Purified water | PW-011 | Blending room | Weekly | |
| Purified water | PW-014 | Binder preparation room | Weekly | |
| Purified water | PW-015 | Capsule IPQA room | Weekly | |
| Purified water | PW-016 | Sampling tool washing area | Weekly | |
| Purified water | PW-017 | IPQA room | Weekly | |
| Purified water | PW-018 | Equipment washing room | Weekly | |
| Purified water | PW-019 | Coating room | Weekly | |
| Purified water | PW-023 | Washing area | Weekly | |
| Purified water | PW-024 | Washing room solution preparation area | Weekly | |
| Purified water | PW-025 | IPQA room | Weekly | |
| Purified water | PW-026 | Coating solution preparation room | Weekly | |
| Purified water | PW-026 | OSD Processing area | Weekly | |
| Purified water | PW-028 | Wet lab | Weekly | |
| Purified water | PW-029 | Dissolution room | Weekly | |
| Purified water | PW-030 | Micro Autoclave loading room | Weekly | |
| Purified water | PW-031 | Garment washing room | Weekly | |
| Purified water | PW-032 | Glass ware washing & De-pyrogenation room | Weekly | |
| Purified water | PW-033 | Decontamination room | Weekly | |
| Purified water | PW-037 | Media preparation room | Weekly |
Note: After Successful completion of validation Phase – I & II, There may be reduction in sampling frequency of these sampling Points.
Recording of Results and Data Evaluation
Feed water analysis results will be recorded. Where typical values are stated the results will be recorded for information only and trended throughout the Performance Qualification period to ensure control of the water quality.
Chemical testing of purified water as per IP/USP/BP will be performed and recorded in format.
Management of Microbiological samples will be performed as per SOP.
Sampling Frequency After Successful Validation
Reduction in Sampling Frequency
After the successful completion of Phase I and Phase II validation, the sampling frequency may be reduced based on historical performance data, trend analysis, risk assessment, and approved validation procedures. Any reduction in sampling frequency should be scientifically justified, documented, and approved through the company’s quality management system.
Test Methods and Acceptance Criteria for Raw Water
Chemical Test method for Raw Water:
Chemical test methods are described in IP/In-house
Acceptance criteria for Raw Water:
All Raw Water samples collected must meet the chemical requirements listed in the monograph ofIP
| Test Description | Specification |
| Description | Clear, colorless and odorless liquid |
| pH | Between 6.5 to 8.5 |
| Chlorides | Not more than 250ppm |
| Sulphate | Not more than 200ppm |
| Total dissolved solids | Not more than 500ppm |
| Total suspended solids | Not more than 100ppm |
| Total hardness | Not more than 300ppm |
| Nitrates | Not more than 10ppm |
Microbiological Test Method:
All the samples shall be tested for Total Aerobic Microbial Count and Absence of Pathogens namely coliform including E.coli and Pseudomonas aeruginosa. Salmonella, Staphylococcus aureus.
The microbiological tests will be carried out as per the standard operating procedures Action Limits and rejection limits have been set in the testing SOP.
Acceptance Criteria:
| Test | Specification |
| Total Aerobic Microbial Count: | |
| Total aerobic bacterial count | Max 500cfu /ml |
| Total fungal count | Should be absent |
| Test for specified Microorganisms: | |
| Escherichia coli | Should be absent/100 ml |
| Staphylococcus aureus | Should be absent/100 ml |
| Pseudomonas aeruginosa | Should be absent/100 ml |
| Salmonella species | Should be absent/100 ml |
Test Methods And Acceptance Criteria for RO Water:
Chemical Test Method for RO Water:
Chemical test methods are described in IP/USP.
Acceptance Criteria for RO Water:
All Purified Water samples collected must meet the chemical requirements listed in the monograph of Purified Water IP/USP.
| Test Description | Specification |
| Description | Clear, colorless and odorless liquid |
| Acidity / Alkalinity | For acidity, the resulting solution in not red. For alkalinity, the resulting solution is not blue For alkalinity, the resulting solution is not blue For acidity, the resulting solution is not red. For alkalinity, the resulting solution is not blue. |
| Ammonium | Not more than 1ppm |
| Calcium and magnesium | A pure blue color is produced |
| Chlorides | The solution shows no change in appearance for at least 15 minutes. |
| Nitrates | Not more than 0.2 ppm |
| Sulphate | The solution shows no change for at least I hour. |
| Residue on evaporation | Not more than 0.001% |
| pH | Between 5.0 to 7.0 |
| Conductivity at 250 C (µS/cm) | |
| RO-1 | Not more than 100 µS/cm |
| RO-2 | Not more than 30 µS/cm |
| Total Organic Carbon | Not more than 500ppb |
Microbiological Test Method:
All the samples shall be tested for Total Aerobic Microbial Count and Absence of Pathogens namely coliform including E.coli and Pseudomonas aeruginosa. Salmonella, Staphylococcus aureus.
The microbiological tests will be carried out as per the standard operating procedures Action Limits and rejection limits have been set in the testing SOP.
Acceptance Criteria:
| Test | Specification |
| Total Aerobic Microbial Count: | |
| Total aerobic bacterial count | Not more than 100 cfu /ml |
| Total fungal count | Should be absent |
| Test for specified Microorganisms: | |
| Escherichia coli | Should be absent |
| Staphylococcus aureus | Should be absent |
| Pseudomonas aeruginosa | Should be absent |
| Salmonella species | Should be absent |
Test Methods And Acceptance Criteria for Purified Water: Purified Water System PQ
Chemical Test Method:
Chemical test methods are described in IP/USP/BP.
Acceptance Limits:
All Purified Water samples collected must meet the chemical requirements listed in the monograph of Purified Water IP/USP
| Test Description as per IP/USP | Specification |
| Description | Clear, colorless and odorless liquid |
| Acidity / Alkalinity | For acidity, the resulting solution in not red. For alkalinity, the resulting solution is not blue For alkalinity, the resulting solution is not blue For acidity, the resulting solution is not red. For alkalinity, the resulting solution is not blue. |
| Ammonium | Not more than 1ppm |
| Calcium and magnesium | A pure blue color is produced |
| Chlorides | The solution shows no change in appearance for at least 15 minutes. |
| Nitrates | Not more than 0.2 ppm |
| Sulphate | The solution shows no change for at least I hour. |
| Residue on evaporation | Not more than 0.001% |
| pH | Between 5.0 to 7.0 |
| Conductivity at 250 C (µS/cm) | Not more than 1.3 µS/cm |
| Total Organic Carbon | Not more than 500ppb |
| Oxidisable substances | The solution remains faintly pink. |
| Heavy metals | Not more than 0.1 ppm |
Microbiological Test method:
All the samples shall be tested for Total Aerobic Microbial Count and Absence of Pathogens namely coliform including E.coli and Pseudomonas aeruginosa. Salmonella, Staphylococcus aureus.
The microbiological tests will be carried out as per the standard operating procedures Action Limits and rejection limits have been set in the testing SOP.
Acceptance Criteria:
| Test | Specification |
| Total Aerobic Microbial Count: | |
| Total aerobic bacterial count | Not more than 100cfu /ml |
| Total fungal count | Should be absent |
| Test for specified Microorganisms: | |
| Escherichia coli | Should be absent |
| Staphylococcus aureus | Should be absent |
| Pseudomonas aeruginosa | Should be absent |
| Salmonella species | Should be absent |
Deviation, change control and corrective action:
Any deviation or modifications in to the Purified Water Generation and Distribution system should be performed in accordance with the appropriate change control procedure. A separate assessment will be made,
Deviation:
| S. No. | Specification | Deviation | Checked by | Verified by |
Any Deviation or Modification to the Purified Water Generation and Distribution System design shall be recorded:
Change control:
Change control shall be authorized and approved by ___________and manufacturer for taking up the corrective actions. Record the Change Control.
| S. No. | Title of Change Control | Change Control No. | Checked by | Verified by |
Corrective actions:
Corrective actions to be taken up as per approved change control and record the corrective action.
| S. No. | Deviation | Corrective Actions | Action taken by Vendor | Checked by | Verified by |
Requalification Criteria for Water System:
- If any major changes or modification in the system which is affecting the water quality.
- If there is a continuous failure of purified water quality.
Summary, conclusion and recommendation:
After completion of Performance Qualification activity for Purified Water Generation and Distribution System, record the summary, conclusion and recommendation for further action.
Summary:
________________________________________________________________________________________________________________________________________________________________
Conclusion:
________________________________________________________________________________________________________________________________________________________________
Recommendation:
________________________________________________________________________________________________________________________________________________________________
Abbreviations:
| Abbreviation | Full Form |
| PW | Purified Water |
| PWS | Purified Water Generation and Distribution System |
| PQ | Performance Qualification |
| cGMP | Current Good Manufacturing Practices |
| IP | Indian Pharmacopoeia |
| USP | United State Pharmacopoeia |
| BP | British Pharmacopoeia |
| SMBS | Sodium Meta Bisulphite |
| RO | Reverse Osmosis |
| EDI | Electro Deionization |
| I.D. | Identification |
| MGF | Multi Grade Filter |
| UF | Ultra-Filtration |
| UV | Ultra Violet |
| P/W | Purified Water |
| SOP | Standard Operating Procedure |
| FPP | Finished Pharmaceutical Product |
Protocol post approval:
Approved BY:
| Department | Name | Signature | Date |
| Production (Head) | |||
| Engineering (Head) | |||
| Quality Control (Head) | |||
| Quality Assurance (Head) |