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

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.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

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

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

In case there is any deviation followed during any stage of validation, corrective action shall be taken after proper investigation. Deviations shall be recorded in Annexure-4

  • QUALIFICATION/ VALIDATION REPORT PREPARATION

After completion of validation, a report based on all phase-wise evaluations shall be prepared by the validation team members supported with tabulated data and statistical analysis (trending and graphical presentation of data). Water System Validation Report shall include various components compiled in following sequence:

  • Validation Report cover page (Annexure-1)
  • Index page for Validation Report
  • Approval Sheet (Annexure-2)
  • Conclusion/ Summary (Report format:Annexure-3) on validation detailed with trending and graphical presentation of data along with and phase-wise sampling & testing plan followed as per protocol.
  • Deviations and Investigations, if any (Annexure-4)
  • Tabulated data (Annexure-5), Analytical Testing-Raw Data Sheet (Annexure-6) & Parametric Recording (Annexure-9)
  • Phase-wise Validation Reports (Annexure-7)
  • Name of validation team members (Annexure-8)
  • Certification of completion of validation (Annexure-10)
  • P & I Diagram for Generation and P.W. Storage & Distribution System (Annexure-11)
  • RE-VALIDATION/ RE-QUALIFICATION OF WATER SYSTEM

After completion of three-phase validation study, frequency of re-qualification or re-validation of purified water system shall be fixed. Moreover the water system shall invite revalidation as and when any major modification(s) is/ are done. Any change in water system shall be executed through change control procedure as per SOP titled ‘Change Control’

  • REFERENCES
    • SOP ‘Sampling and Analysis of Ground Water and Drinking Water
    • User Requirement Specifications
    • Design Qualification
    • Installation Qualification ,Operational Qualification

About Pharmaceutical Guidanace

Ms. Abha Maurya is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 18 years of rich experience in pharmaceutical field. During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube

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