PERFORMANCE QUALIFICATION PROTOCOL PURIFIED WATER SYSTEM
OBJECTIVE
To describe the Performance Qualification procedure to be used during validation of purified water system in order to:
a) ensure the system reproducibility over an appropriate time period as per user requirement specifications.
b) ensure that the system is showing consistency in producing water of pre-established specifications.
SCOPE
This procedure applies to the Performance Qualification or Validation of Purified Water System.
RESPONSIBILITY
Validation team shall be responsible for the preparation and checking of the Performance Qualification/ Validation protocol.
Plant Head, Head-Quality Control & Head-Quality Assurance shall be responsible for the approval of Performance Qualification/ Validation protocol.
Head -Quality Control shall be responsible for facilitating analysis of water samples, evaluations of the test results and compilation of validation data.
Head -Quality Assurance shall be responsible for approval of the Performance Qualification / Validation Report and certification after successful validation of purified water system
ABBREVIATIONS AND DEFINITIONS
PQ: Performance Qualification; documented verification that the integrated system or subsystem functions as intended, in its normal operating environment.
DQ: Design Qualification.
IQ: Installation Qualification.
OQ: Operational Qualification
Validation Team: Trained representatives from Quality Assurance, Quality Control,Engineering and Production departments participating in validation. For water system validation, the validation team members shall enlist their names & signatures as per Annexure-8
HVAC: Heating, Ventilation and Air-Conditioning
USP: United States Pharmacopoeia
BP: British Pharmacopoeia
IP: Indian Pharmacopoeia
Ph.Eur.: European Pharmacopoeia
UV: Ultra Violet
TOC: Total Organic Carbon
EDI: Electrodeionization
SS: Stainless Steal
SDI: Silt Density Index
HDPE: High Density Polyethylene
BRIEF DESCRIPTION OF WATER SYSTEM
Raw Water sourced from Bore well is converted into purified water complying with current USP/ BP/ IP/ Ph.Eur. This water is chlorinated by Sodium Hypochlorite Solution (NaOCl) so as to maintain residual free chlorine. Dosing is done using electronic metering pump. Chlorinated water is stored in an under ground tank and from the tank it is pumped to pass through a Multi Grade Filter (MGF) for removal of suspended solids. Sodium meta-bisulphite (SMBS) dosing system is provided on the outlet discharge pipe of MGF to remove the residual chlorine. Water after de-chlorination is stored in 10 Kiloliter HDPE storage tank. Water from this tank is pumped to distribute in two loops:
- Feed to soft water plant
- Treated water distribution
Filtered water then is passed through softener to reduce Hardness. Softened water is further treated to generate high purity water as per current USP/ BP/ IP/ Ph. Eur. standards for purified water.
Soft water from the softener is stored in a HDPE storage tank of capacity 10 KL. Soft water from this tank is supplied to different utilities such as Boilers, Cooling towers; Chillers and hot water make up tank of HVAC and Purified water generation plant. Soft water will be stored in the feed water tank to the RO.
Soft water from softener may form scaling in Reverse Osmosis (RO) membranes, to avoid that special anti-scalant is added to the soft water. pH of the water is maintained at 7.5-8.5 at the inlet of the Reverse Osmosis unit through pH correction dosing system
Soft water is further passed through single stage SDI filtration (with filter of 5µ) before pumping into Purified Water Generation System (consisting of RO and EDI units). For protecting the RO membrane incase of accidental entry of free chlorine water ORP meter is installed in the RO feed water. As soon as ORP meter senses the free chlorine it will trip the system and open the flow divert valve to avoid damage to RO membrane.
Purified water is stored in an SS Storage Tank Assembly and is distributed through loop system to various sections. Before final distribution the purified water is passed through UF/UV purifiers.
PRE-REQUISITES
Before validating the Water system following should be ensured:
Successful completion of Operational Qualification of Water System as per Protocol
Availability of Test Protocols for testing of water produced at different stages
Availability of following Draft SOP(s)
Operation and Regeneration of MGF & soft water plant, etc
Operation of the purified water system
Sanitization (purified water generation system & Distribution system)
Water Sampling (also describing sampling micro testing)
Availability of all the relevant Log books of water system
QUALIFICATION/ VALIDATION PROCEDURE
Qualification/ Validation Strategy
This Validation Study shall be executed in three phases:
- Phase- 1
- Phase – 2
- Phase – 3
Phase- 1
Phase-1 shall last for minimum two (2) weeks or unless water of every stage meets the specifications during which preliminary sampling of water shall be done to assure that the system is ready to go into Phase- 2, the prospective phase of validation. (refer sampling and testing plan for Phase-1 & Phase-2)
During this phase operating, regeneration and sanitization procedures shall be verified & frequencies for sanitization shall be established and fixed.
On completion of Phase-1, report (Annexure-7) shall be prepared and it shall be checked and approved for further proceeding to Phase-2.
In case there is any deviation in Phase-1, corrective action shall be taken and after corrective action (recording shall be done as per Annexure-4), validation activity shall be continued. On the basis of Phase-1 data Alert and Action levels for key quality attributes like TOC, Conductivity and Microbial Count shall be established. Criteria for taking alert limit and action limit shall be as follows:
Alert limit = Average Value + 2σ
Action limit = Average Value + 3σ
After Phase-1, sampling shall be continued till the approval of Phase-1 report as per Phase-1 schedule and their respective data shall be incorporated in the Phase-2 report.
Phase-2
Phase-2 shall last for Four (4) weeks with sampling frequency similar to Phase-1. (refer sampling and testing plan for Phase-1 & Phase-2)
This phase shall demonstrate the system consistency with respect to desired water quality when operated after sanitization in conformance with SOP(s). During this phase Alert and Action levels for key quality attributes like TOC, Conductivity and Microbial Count shall be verified.
In case there is any deviation in Phase-2, corrective action shall be taken and after correction action (recording shall be done as per Annexure-4)
Purified water system shall be cleared for the production after successful completion of Phase-2
A report (Annexure-7) shall be prepared after completion of Phase-2 study
Phase-3
Phase-3 shall last for about eleven (11) months with each sampling point being covered every week (refer sampling and testing plan for Phase-3)
In this concurrent phase of validation routine monitoring shall be conducted and seasonal variation shall be studied.
Scheduled preventive maintenance shall be finalized at this phase of water system validation.
A schedule for periodic review of the system performance and re-qualification or revalidation shall also be instituted after the completion of this phase.
A report (Annexure-7) shall be prepared after completion of Phase-3 study. Trending of data shall be done.
Water system shall be evaluated at following stages through various sampling points and user points:
- Raw water (Stage-1)
- Raw Water after Chlorination (Stage-2)
- Dechlorinated Water after MGF treatment (Stage-3)
- Soft Water after Softener (Stage-4)
- Soft Water after 5 micron filter [Feed water to Purified Water Generation System consisting of Reverse Osmosis (RO) and Electrodeionization (EDI) units] (Stage-5)
- Water after RO treatment (Stage-6 & 7)
- Water after EDI treatment (Stage-8)
- Water after Ultra filtration (Stage-9)
- Purified Water from Purified Water Storage Tank (Stage-10)
- Purified water Return from Distribution loop/UV lamp (Stage-11)
- Purified water from all user points (Stage-11)
Description of Sampling Points
The following sampling points shall be defined for validation and monitoring the purified water system and its distribution during validation through three phases
| S.No | Sampling Point Description | Code |
| 1 | Raw Water (Bore well) | S-1 |
| 2 | MGF-001 Inlet (Multi grade filter) | S-2 |
| 3 | Dechlorinated Water Storage Tank | S-3 |
| 4 | ISFD-001 Outlet (Softener) | S-4 |
| 5 | MCF-001 Outlet (5Micron Filter) | S-5 |
| 6 | RO-001 Outlet (Reverse Osmosis) | S-6 |
| 7 | RO-002 Outlet (Reverse Osmosis) | S-7 |
| 8 | EDI-001 Outlet (Electro De-Ionizer) | S-8 |
| 9 | UF-001 Outlet (Ultra filter) | S-9 |
| 10 | T-2101 (Purified water storage tank) | S-10 |
| 11 | UV-2101 outlet | S-11 |
| 12 | Purified water return from distribution | S-12 |
| 13 | Fabrication-1 | S-13 |
| 14 | Fabrication-2 | S-14 |
| 15 | Fabrication-3 | S-15 |
| 16 | Coating-1 | S-16 |
| 17 | Coating-2 | S-17 |
| 18 | Coating-3 | S-18 |
| 19 | Product development lab (PDL) | S-19 |
| 20 | Bin wash area | S-20 |
| 21 | Bin wash machine | S-21 |
| 22 | Ointment wash | S-22 |
| 23 | Ware house | S-23 |
| 24 | Drain point-1 | S-24 |
| 25 | Drain point-2 | S-25 |
| 26 | Drain point-3 | S-26 |
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List of Tests and Acceptance Criteria
Raw Water (Stage-1)
Chemical analysis (C1; refer Table-1) of Raw water
Table-1
| Test | Acceptance Criteria |
| Description | Clear, Colourless and Odourless liquid |
| pH | 6.0 to 8.5 at 25ºC |
| Total Hardness | NMT 1000 ppm |
| Total Dissolved Solids | NMT 800 ppm |
| Total Suspended Solids | NMT 1000 ppm |
| Total Alkalinity | NMT 400 ppm |
| Chloride | NMT 250 ppm |
| Sulphates | NMT 500 ppm |
| Heavy Metals | NMT 0.5 ppm |
| Microbiological analysis (M1) of Raw water | |
| Total Aerobic Microbial Count | Informative |
| Yeast and Moulds | Informative |
| Escherichia coli | Informative |
| Salmonella species | Informative |
| Pseudomonas aeruginosa | Informative |
| Staphylococcus aureus | Informative |
After Chlorination (Stage-2)
Free chlorine content (FC1) of Raw water after chlorination should range from 0.5-1 ppm
Dechlorinated Water (after MGF treatment; Stage-3)
Chemical analysis (C2; refer Table-2) of dechlorinated water storage tank
Table-2
| Test | Acceptance Criteria |
| Description | Clear, Colourless and Odourless liquid |
| Taste | Agreeable |
| pH | 6.0 to 8.5 at 25ºC |
| Total Hardness | NMT 800 ppm |
| Total Suspended Solids | NMT 500 ppm |
| Residual Free Chlorine | NMT 0.2 ppm (on-line measurement) |
| Microbiological analysis (M2) of dechlorinated water from dechlorinated water storage tank | |
| Total aerobic microbial count | Not More Than 500 CFU/ml |
| Yeast and Mould | Not More Than 10 CFU/ ml |
| Escherichia coli | Should be absent |
| Salmonella species | Should be absent |
| Pseudomonas aeruginosa | Should be absent |
| Staphylococcus aureus | Should be absent |
Soft Water (Stage-4)
Chemical analysis (C3; refer Table-3) of Softened water in the ISFD-001 (sampling point) Outlet (Softener)
Table-3
| Test | Acceptance Criteria |
| Description | Clear, Colourless and Odourless liquid |
| pH | 6.0 to 8.5 at 25ºC |
| Total Hardness (as CaCO3) | NMT 10 ppm |
| Total Dissolved Solids | NMT 500 ppm |
Soft Water after 5 µM filter (Stage-5)
Chemical analysis (C4; refer Table-4) of Softened water in the MCF -001 Outlet (5 micron filter)
Table-4
| Test | Acceptance Criteria |
| Description | Clear, Colourless and Odourless liquid |
| pH | 7.5 to 8.5 at 25ºC |
| Residual Free Chlorine | NMT 0.02 ppm (on line measurement) |
RO Water (Stage-6)
Chemical analysis (C5; refer Table-5) of RO-001 Outlet water
Table-5
| Test | Acceptance Criteria |
| Description | Clear, Colourless and Odourless liquid |
| pH | Informative |
| Total Dissolved Solids | Informative |
| Conductivity in µS.cm-1 at 25ºC | Informative (on-line measurement) |
RO Water (Stage-7)
Chemical analysis (C6; refer Table-6) of RO-002 Outlet water
Table-6
| Test | Acceptance Criteria |
| Description | Clear, Colourless and Odourless liquid |
| pH | 5.0 to 7.0 at 25ºC |
| Total Hardness | NMT 1 ppm |
| Total Dissolved Solids | Informative |
| Conductivity | NMT 30µS.cm-1 at 25ºC (on-line measurement) |
| Sulfide | NMT 0.01 ppm |
| Silica(SiO2) | NMT 1 ppm |
- EDI Water (Stage-8)
Chemical analysis (C7; refer Table-7) of EDI-001 Outlet water
Table-7
| Test | Acceptance Criteria |
| Conductivity | NMT 1.3 µS.cm-1 at 25ºC (on-line measurement) |
- Water after Ultra Filtration/ (Stage-9)
Chemical analysis (C8; refer Table-8) of Ultra filter(UF-001) Outlet water
Table-8
| Test | Acceptance Criteria |
| Description | Clear, Colourless and Odourless liquid |
| pH | 5.0-7.0 at 25ºC |
| Conductivity | NMT 1.3 µS.cm-1 at 25ºC |
Purified Water from Storage Tank outlet (Stage-10)
Chemical analysis (C9; refer Table-9) of Purified Water from Storage Tank outlet
Table-9
| Test | Acceptance Criteria |
| Description | Clear, Colourless and Odourless liquid |
| pH | 5.0-7.0 at 25ºC |
| Conductivity | NMT 1.3 µS.cm-1 at 25ºC |
| Acidity or Alkalinity | a) Should not produce red colour with 10 ml of sample quantity using 0.5ml methyl red solution.
b) Should not produce blue colour with 10 ml of sample quantity using 0.1ml bromothymol blue solution. |
| Ammonium | NMT 0.2 ppm |
| Calcium and Magnesium | To 100 ml add 2 ml of ammonium chloride buffer solution pH 10.0, 50 mg of mordant black 11 triturate and 0.5 ml of 0.01 M sodium edetate. A pure blue colour is produced. |
| Heave metals | NMT 0.1 ppm |
| Chloride | No change in the appearance of solution up to 15 min |
| Sulphate | No change in the appearance of solution up to 60 min |
| Nitrate | NMT 0.2ppm |
| Oxidisable substances | Pink colour should be retained, for 100 ml of sample + 10 ml of H2SO4 + 0.1 ml of 0.02 M KMnO4 |
| Carbon Dioxide | Should produce clear mixture |
| Residue on Evaporation | NMT 0.001% w/v |
| Microbiological analysis (M3) | |
| Total Aerobic Bacterial Count | NMT 100 CFU /ml |
| Yeast and Moulds | NMT 1.0 CFU /ml |
| Escherichia coli | Should be absent |
| Salmonella species | Should be absent |
| Pseudomonas aeruginosa | Should be absent |
| Staphylococcus aureus | Should be absent |
Purified Water Return from Distribution Loop (Stage-11)
Chemical analysis (C9) of Purified Water return from Distribution Loops, UV Lamp and User Points. Refer Table-9 for specifications and acceptance criteria.
Operational Checks during Validation
Following operating parameters for Purified water system shall be monitored every 1 hour during running condition and shall be summarized along with Phase-wise reports.
Table-10
| Parameter | Acceptance Criteria |
| MGF-001 Inlet water pressure | Not less than 3.5 kg/cm2 |
| ISFD-001 Inlet water pressure | Not less than 3.5 kg/cm2 |
| RO-I Inlet water flow rate | Not less than 5.23 m3/h |
| RO-II .Inlet water flow rate | Not less than 3.66 m3/h |
| RO-I Operating pressure | Not more than 7.7 kg/cm2 |
| RO-II Operating pressure | Not more than 6.8 kg/cm2 |
| EDI Inlet water flow rate | Not less than 2.93m3/h |
| EDI Operating pressure | Not more than 3.0 kg/cm2 |
| UF Inlet water flow rate | Not less than 2.64 m3/h |
| UF Inlet water pressure | 2 to 3 kg/cm2 |
| TOC( In the loop) | NMT 500ppb |
This parametric recording shall be done in the format given as Annexure-9
Other operational parameters like UV light consumption, pressure differential for all the filters, etc shall also be monitored and recorded in respective log books during validation studies
Sampling Plan and Testing Plan
Sampling and testing plan for Phase-1 & Phase-2
Following table indicate the sampling and testing plan for Phase-1 & Phase-2.
Table-11
| Sampling point Description | Sampling Point code | Stage | Week days | ||||||
| Sun | Mon | Tue | Wed | Thu | Fri | Sat | |||
| Raw Water (Bore well) | S-1 | 1 | C1 M1 | C1 M1 | C1 M1 | C1 M1 | C1 M1 | C1 M1 | C1 M1 |
| MGF-001 Inlet (Multi grade filter) | S-2 | 2 | FC1 | FC1 | FC1 | FC1 | FC1 | FC1 | FC1 |
| Dechlorinated Water Storage Tank | S-3 | 3 | C2 M2 | C2 M2 | C2 M2 | C2 M2 | C2 M2 | C2 M2 | C2 M2 |
| ISFD-001 Outlet (Softener) | S-4 | 4 | C3 | C3 | C3 | C3 | C3 | C3 | C3 |
| MCF-001 Outlet (5Micron Filter) | S-5 | 5 | C4 | C4 | C4 | C4 | C4 | C4 | C4 |
| RO-001 Outlet (Reverse Osmosis) | S-6 | 6 | C5 | C5 | C5 | C5 | C5 | C5 | C5 |
| RO-002 Outlet (Reverse Osmosis) | S-7 | 7 | C6 | C6 | C6 | C6 | C6 | C6 | C6 |
| EDI-001 Outlet (Electro De-Ionizer) | S-8 | 8 | C7 | C7 | C7 | C7 | C7 | C7 | C7 |
| UF-001 Outlet (Ultra filter) | S-9 | 9 | C8 | C8 | C8 | C8 | C8 | C8 | C8 |
| T-2101 (Purified water storage tank) | S-10 | 10 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| UV-2101 outlet | S-11 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Purified water return from distribution | S-12 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Fabrication-1 | S-13 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Fabrication-2 | S-14 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Fabrication-3 | S-15 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Coating-1 | S-16 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Coating-2 | S-17 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Coating-3 | S-18 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Product development lab (PDL) | S-19 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Bin wash area | S-20 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Bin wash machine | S-21 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Ointment wash | S-22 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Ware house | S-23 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Drain point-1 | S-24 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Drain point-2 | S-25 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
| Drain point-3 | S-26 | 11 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 |
Sampling and testing plan for Phase-3
Following table indicate the sample plan for Phase-3.
Table-12
| Sampling point Description | Sampling Point code | Stage | Week days | |||||||
| Sun | Mon | Tue | Wed | Thu | Fri | Sat | ||||
| Raw Water (Bore well) | S-1 | 1 | C1 M1 | |||||||
| ISFD-001 Outlet (Softener) | S-4 | 4 | C3 | C3 | C3 | C3 | C3 | C3 | C3 | |
| T-2101 (Purified water storage tank) | S-10 | 10 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | C9 M3 | |
| Fabrication-1 | S-13 | 11 | C9 M3 | C9 M3 | ||||||
| Fabrication-2 | S-14 | 11 | C9 M3 | C9 M3 | ||||||
| Fabrication-3 | S-15 | 11 | C9 M3 | C9 M3 | ||||||
| Coating-1 | S-16 | 11 | C9 M3 | C9 M3 | ||||||
| Coating-2 | S-17 | 11 | C9 M3 | C9 M3 | ||||||
| Coating-3 | S-18 | 11 | C9 M3 | C9 M3 | ||||||
| Product development lab (PDL) | S-19 | 11 | C9 M3 | C9 M3 | ||||||
| Bin wash area | S-20 | 11 | C9 M3 | C9 M3 | ||||||
| Bin wash machine | S-21 | 11 | C9 M3 | C9 M3 | ||||||
| Ointment wash | S-22 | 11 | C9 M3 | C9 M3 | ||||||
RECORDING/ DATA COMPILATION
During validation study the Data from each phase shall be compiled by Validation Team Representative from Quality Control in following formats
- Tabulated Data- Date wise evaluations (Annexure-5)
- Analytical Testing -Raw Data Sheet (Annexure-6)