PERFORMANCE QUALIFICATION PROTOCOL PURIFIED WATER SYSTEM

PERFORMANCE QUALIFICATION PROTOCOL PURIFIED WATER SYSTEM

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

Performance Qualification

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:

  1. Raw water (Stage-1)
  2. Raw Water after Chlorination (Stage-2)
  3. Dechlorinated Water after MGF treatment (Stage-3)
  4. Soft Water after Softener (Stage-4)
  5. Soft Water after 5 micron filter [Feed water to Purified Water Generation System consisting of Reverse Osmosis (RO) and Electrodeionization (EDI) units] (Stage-5)
  6. Water after RO treatment (Stage-6 & 7)
  7. Water after EDI treatment (Stage-8)
  8. Water after Ultra filtration (Stage-9)
  9. Purified Water from Purified Water Storage Tank (Stage-10)
  10. Purified water Return from Distribution loop/UV lamp (Stage-11)
  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.NoSampling Point DescriptionCode
1Raw Water (Bore well)S-1
2MGF-001 Inlet (Multi grade filter)S-2
3Dechlorinated Water Storage TankS-3
4ISFD-001 Outlet (Softener)S-4
5MCF-001  Outlet (5Micron Filter)S-5
6RO-001 Outlet (Reverse Osmosis)S-6
7RO-002 Outlet (Reverse Osmosis)S-7
8EDI-001 Outlet (Electro De-Ionizer)S-8
9UF-001 Outlet (Ultra filter)S-9
10T-2101 (Purified water storage tank)S-10
11UV-2101 outletS-11
12Purified water return from distributionS-12
13Fabrication-1S-13
14Fabrication-2S-14
15Fabrication-3S-15
16Coating-1S-16
17Coating-2S-17
18Coating-3S-18
19Product development lab (PDL)S-19
20Bin wash areaS-20
21Bin wash machineS-21
22Ointment washS-22
23Ware houseS-23
24Drain point-1S-24
25Drain point-2S-25
26Drain point-3S-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

TestAcceptance Criteria
DescriptionClear, Colourless and Odourless liquid
pH6.0 to 8.5 at 25ºC
Total HardnessNMT 1000 ppm
Total Dissolved SolidsNMT 800 ppm
Total Suspended SolidsNMT 1000 ppm
Total AlkalinityNMT 400 ppm
ChlorideNMT 250 ppm
SulphatesNMT 500 ppm
Heavy MetalsNMT 0.5 ppm
Microbiological analysis (M1) of Raw water
Total Aerobic Microbial CountInformative
Yeast and MouldsInformative
Escherichia coliInformative
Salmonella speciesInformative
Pseudomonas aeruginosaInformative
Staphylococcus aureusInformative

 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                    

TestAcceptance Criteria
DescriptionClear, Colourless and Odourless liquid
TasteAgreeable
pH6.0 to 8.5 at 25ºC
Total HardnessNMT 800 ppm
Total Suspended SolidsNMT 500 ppm
Residual Free ChlorineNMT 0.2 ppm

(on-line measurement)

Microbiological analysis (M2) of dechlorinated water from dechlorinated water storage tank
Total aerobic microbial countNot More Than 500 CFU/ml
Yeast and MouldNot More Than 10 CFU/ ml
Escherichia coliShould be absent
Salmonella speciesShould be absent
Pseudomonas aeruginosaShould be absent
Staphylococcus aureusShould 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

TestAcceptance Criteria
DescriptionClear, Colourless and Odourless liquid
pH6.0 to 8.5 at 25ºC
Total Hardness (as CaCO3)NMT 10 ppm
Total Dissolved SolidsNMT 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

TestAcceptance Criteria
DescriptionClear, Colourless and Odourless liquid
pH7.5 to 8.5 at 25ºC
Residual Free ChlorineNMT  0.02 ppm

(on line measurement)

RO Water (Stage-6)

Chemical analysis (C5; refer Table-5) of RO-001 Outlet water

Table-5

TestAcceptance Criteria
Description Clear, Colourless and Odourless liquid
pHInformative
Total Dissolved SolidsInformative
Conductivity in µS.cm-1 at 25ºCInformative

(on-line measurement)

 RO Water (Stage-7)

 Chemical analysis (C6; refer Table-6) of RO-002 Outlet water

 Table-6

TestAcceptance Criteria
DescriptionClear, Colourless and Odourless liquid
pH5.0 to 7.0 at 25ºC
Total HardnessNMT 1 ppm
Total Dissolved SolidsInformative
ConductivityNMT 30µS.cm-1 at 25ºC

(on-line measurement)

SulfideNMT 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

TestAcceptance Criteria
ConductivityNMT 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

TestAcceptance Criteria
Description Clear, Colourless and Odourless liquid
pH5.0-7.0 at 25ºC
ConductivityNMT 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

TestAcceptance Criteria
DescriptionClear, Colourless and Odourless liquid
pH5.0-7.0 at 25ºC
ConductivityNMT 1.3 µS.cm-1 at 25ºC
Acidity or Alkalinitya) 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.

AmmoniumNMT 0.2 ppm
Calcium and MagnesiumTo 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 metalsNMT 0.1 ppm
ChlorideNo change in the appearance of solution up to 15 min
SulphateNo change in the appearance  of solution up to 60 min
NitrateNMT 0.2ppm
Oxidisable substancesPink colour should be retained, for 100 ml of sample + 10 ml of H2SO4 + 0.1 ml of 0.02 M KMnO4
Carbon DioxideShould produce clear mixture
Residue on EvaporationNMT 0.001% w/v
Microbiological analysis (M3)
Total Aerobic Bacterial CountNMT 100 CFU /ml
Yeast and MouldsNMT 1.0 CFU /ml
Escherichia coliShould be absent
Salmonella speciesShould be absent
Pseudomonas aeruginosaShould be absent
Staphylococcus aureusShould 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

ParameterAcceptance Criteria
MGF-001 Inlet water pressureNot less than 3.5 kg/cm2
ISFD-001 Inlet water pressureNot less than 3.5 kg/cm2
RO-I Inlet water flow rateNot less than 5.23 m3/h
RO-II .Inlet water flow rateNot less than 3.66 m3/h
RO-I Operating pressureNot more than 7.7 kg/cm2
RO-II Operating pressureNot more than 6.8 kg/cm2
EDI Inlet water flow rateNot less than 2.93m3/h
EDI Operating pressureNot more than 3.0 kg/cm2
UF Inlet water flow rateNot less than 2.64 m3/h
UF Inlet water pressure2 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 DescriptionSampling Point codeStageWeek days
SunMonTueWedThuFriSat
Raw Water (Bore well)S-11C1

M1

C1

M1

C1

M1

C1

M1

C1

M1

C1

M1

C1

M1

MGF-001 Inlet (Multi grade filter)S-22FC1FC1FC1FC1FC1FC1FC1
Dechlorinated Water Storage TankS-33C2

M2

C2

M2

C2

M2

C2

M2

C2

M2

C2

M2

C2

M2

ISFD-001 Outlet (Softener)S-44C3C3C3C3C3C3C3
MCF-001  Outlet (5Micron Filter)S-55C4C4C4C4C4C4C4
RO-001 Outlet (Reverse Osmosis)S-66C5C5C5C5C5C5C5
RO-002 Outlet (Reverse Osmosis)S-77C6C6C6C6C6C6C6
EDI-001 Outlet (Electro De-Ionizer)S-88C7C7C7C7C7C7C7
UF-001 Outlet (Ultra filter)S-99C8C8C8C8C8C8C8
T-2101 (Purified water storage tank)S-1010C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

UV-2101 outletS-1111C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Purified water return from distributionS-1211C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Fabrication-1S-1311C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Fabrication-2S-1411C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Fabrication-3S-1511C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Coating-1S-1611C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Coating-2S-1711C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Coating-3S-1811C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Product development lab (PDL)S-1911C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Bin wash areaS-2011C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Bin wash machineS-2111C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Ointment washS-2211C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Ware houseS-2311C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Drain point-1S-2411C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Drain point-2S-2511C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Drain point-3S-2611C9

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 DescriptionSampling Point codeStageWeek days
SunMonTueWedThuFriSat
Raw Water (Bore well)S-11C1

M1

ISFD-001 Outlet (Softener)S-44C3C3C3C3C3C3C3
T-2101 (Purified water storage tank)S-1010C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

C9

M3

Fabrication-1S-1311C9

M3

C9

M3

Fabrication-2S-1411C9

M3

C9

M3

Fabrication-3S-1511C9

M3

C9

M3

Coating-1S-1611C9

M3

C9

M3

Coating-2S-1711C9

M3

C9

M3

Coating-3S-1811C9

M3

C9

M3

Product development lab (PDL)S-1911C9

M3

C9

M3

Bin wash areaS-2011C9

M3

C9

M3

Bin wash machineS-2111C9

M3

C9

M3

Ointment washS-2211C9

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

  1. Tabulated Data- Date wise evaluations (Annexure-5)
  2. Analytical Testing -Raw Data Sheet (Annexure-6)

 

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