PQ of WFI generation, storage and distribution system

January 16, 2024October 27, 2016 by Pharma Editor

PQ of WFI generation, storage, and distribution system

Protocol Approval
This is a specific protocol for Performance Qualification of Water for Injection generation, Storage, Distribution System, which is located in the first floor of the production department.
This protocol has been approved by the following:

	Name	Department	Signature	Date
Prepared By
Checked By
Approved By

Final Approval:
Final approval has been given by the following:

Name

Signature

Date

Approved By

(Plant Head)

Approved By

(Head – QA)

Protocol / Report Preparation: Officer or above QC / QA
Responsibility
Assure the accurate and precise results/observations of the substances being examined are recorded.
Assure that the WFI System performance is adequate to support the method/methods for which the system is intended.
Document the initial performance of the WFI System for future reference.
Demonstrate that WFI System shall perform reproducibly and consistently with in its full dynamic range of operation according to Functional / Manufacturer’s / In house specifications.
The purpose of this Protocol is to establish the performance Qualification of WFI generation, Storage and Distribution system to:
Purpose and Scope
To establish the methodology for the Performance Qualification of WFI Generation, Storage and Distribution system, which produces pyrogen free, water for injection, used as a Sterile products manufacturing facility.
Objective:
Overview
Protocol / Report Checking: Manager QC / Nominee
Execution of Qualification Activity: Officer or above QC / QA
Protocol / Report Approval: Head QA
Final Approval: GM formulation / Head QA
The Production and Engineering Department shall be responsible for checking the operation. The Quality Control shall be collecting the sample from the sampling points according to the sampling plan and Quality Control shall carry out the tests as per the specifications and respective test procedures. The Quality Control shall prepare the data trend for all the three phase of validation study. The summary report of the Performance Qualification shall be prepared by Quality Assurance Department. Separate reports will be prepared for phase-I, phase-II, and phase-III studies respectively.
Qualification Team:
User Department Officer / Executive
Officer / Executive QA
Manager QA / QC
Training Record
Purpose
The purpose of the training is to familiarize the trainees with the principle of working & technical specifications of WFI System as well as overall strategy of Performance Qualification of the WFI Generation, Storage and Distribution System.
Scope

This Training is related to the Water for Injection generation, storage and distribution system and being imparted to the people involved in the WFI water system validation.

The return loop to the WFI tank is having following instrumentation and control
Control of WFI distribution loop and WFI storage tank will be through common PLC panel. Distribution of WFI through various user point provided in the loop system. WFI is generated using Multicolumn and stored in WFI storage tank at 85°C to 90°C. It is pumped into distribution loop using centrifugal pump. One stand by pump is also provided. All piping is having Armaflex insulation with SS 304 cladding below false ceiling and with aluminum foil above false ceiling.
Brief Description of Distribution System
So, WFI produced from each column except first column will be collected at bottom of the column & transferred to cooler. Steam, which is produced in final column, will also be taken to cooler, which will convert into WFI.
System has unique feature of purging which remove water containing pyrogen and other impurities and keep concentration of impurities to minimum level.
Plant operates on PLC system. PLC system ensures efficient working of plant under favorable conditions. In case of violation of any critical condition, plant will automatically stop & give audio-visual signal to operator. When the problem gets solved, plant will start automatically.
Unevaporated water becomes the feed water & this process is repeated in all the remaining effects each working at lower temperature & pressure than the one preceding it. Pure steam condenses as WFI in each effects & WFI along with the pure steam from the last column is taken to the condenser where it is cooled to 95º C by using cooling water.
As the steam moves upwards, the spirals provided on the shell of the evaporator forces the steam to move in a circular path. The resulting centrifugal action forces the remaining microscopic droplets and impurities including the Endotoxins to the outer surface, which then gets blow down through the windows provided on the separator (Third stage separation).
This vapor as it moves outside the tubes is forced to change its direction to a 180º turn. This directional changes induces the separation of large water droplets (secondary separation), which fall into the bottom of the column, where they are collected with excess feed water that has not evaporated.
Feed water is pre heated by waste heat recovery method and enter the first effect from tube side. Specially designed distribution plate ensures the water falls down the tube as a “Thin film”. The falling film is heated with plant steam and causing it to instant flash evaporation. This flash evaporation helps the steam to leave behind the heavier particles or droplets. (First stage of separation). This transformation from water to steam significantly increases the velocity as it approaches the bottom of the column with high pressure.
The unit design to remove microbial contamination by three stage separation. Number of effects is connected in series. Each effect has a innermost evaporator (shell & tube heat exchanger), an intermediate separator and outer column. Source of energy for this effect is boiler steam & the remaining effects use the intrinsic heat to supplement consumption needs of the heating energy.
Water for Injection system works on “Falling Film Evaporator” principle. It employs high temperature which assures constant sterile water.
Water for Injection System produces pyrogen free, sterile water for injection which meets the requirements of the international pharmacopeias including USP, BP, and IP. It operates on the distillation as a unit process. Sterile water generation engross with Liquid-vapor-liquid phase change to produce very high purity water.
Brief Instrument Description:
The Water For Injection System Still is working on the Principle of inters stage heat exchange (Reuse of energy) drastically reduce the consumption of heat energy and cooling water. Thus enable to produce large- scale of Pyrogen free sterile water for injection. The Distillation Column operates at different pressure and temperature making it possible to transfer the energy in process forward column to column.
Working Principle:
Design
Date of Installation :
Purchase Order Number :
Model :
Manufacturer’s Name :
Name of the system/Instrument :
Location :
Equipment Identification Number :
System/Equipment Details
System / Equipment Description
Media
All test solutions.
Bottles for Sampling.
Following reagents/ chemical/standards shall be required for the Performance Qualification of Water for Injection system
Performance Qualification Requirements
Training is given as per SOP Title: SOP on cGMP Training
Note: –
General precautions / guidelines to be followed during qualification.
Overall strategy of Qualification process.
Technical specifications of the system components.
Principle and operating of Water for Injection system.
The following topics to be covered during training:
Topics
Flow Indicator and controller: – It will indicate flow rate in the return line and will control the minimum return flow rate to WFI tank using VFD of circulation pump.
Conductivity sensor and controller: – Conductivity sensor will sense conductivity of WFI coming in return loop and if conductivity is beyond the set point, it will drain all WFI.
Temperature sensor, Transmitter and Indicator: – It will sense temperature of WFI in return line and will indicate same.
Performance Qualification Procedure
The following procedure has been used for performance qualification of Water for Injection generation, storage and distribution system:
Water for Injection System was checked for completion of the operational qualification activity.
The Performance Qualification of water system is proposed to be carried out in three phases:
Performance Qualification Plan & Rationale:
Phase-I – extensive sampling from Generation points & usage points for 1 month
Phase-II – extensive sampling from selective generation & all usage points for 3 months
Phase-III – routine sampling from usage points on rotation basis, for 8 months
The phase-I study shall be done as per procedure mentioned below. After completion of phase-I studies the graphical representation of the data of all the parameters shall be done individually.
Phase – I: (For a period of 1 month)
The performance qualification of Water for Injection System shall be started, when all the equipment and piping of WFI system had been verified to be installed properly and operating correctly.
Phase-I of the performance qualification of Water for Injection System included extensive sampling of WFI, from various points along with all the usage points of the distribution loops . The phase-I sampling shall be carried out for a period of 1 month.
During this phase water samples from all generation / usage points shall be analysed and monitored for compliance to the pre-determined specifications.
After successful completion of Phase-I of the performance qualification, the Water for Injection System should be cleared for usage of WFI water in manufacturing operations. Purpose of Phase-I qualification is to stabilize the operating parameters. Conclusions have been described in a summary form.
The phase-II studies shall be done as per procedure mentioned below. The observations of the study shall be recorded as per the format provided in Exhibit-01. After completion of phase-II studies the graphical representation of the data of all the parameters shall be done individually and shall be attached in Annexure-05.
Phase – II: (For a period of 3 months)
Phase-II of the performance qualification shall be commence, after successful completion of Phase-I. Purpose of Phase-II qualification is to monitor the operating parameters. The objective of Phase-II is also to demonstrate that system is producing desired quality of water, on a consistent basis, when operated in conformance with SOP established at the end of Phase-I. Conclusions shall be mentioned in Summary report.
During Phase-II, WFI water samples shall be collected from various Sampling Points in generation system as mentioned in sampling plan and Usage Points on a Daily basis . Phase-II of the performance qualification of Water for Injection System include extensive sampling of WFI water from all sampling points in the Water for Injection System & usage points of the distribution loops on daily basis. Phase-II sampling carried out for a period of 3 month. Water samples from the all the usage points shall be analysed and monitored daily, for compliance to the pre-determined specifications.
After successful completion of Phase-II of the performance qualification, the Water for Injection shall be cleared for Phase-III.
The phase-III studies shall be done as per procedure mentioned below. The observations of the study shall be recorded. The data sheets should be attached. After completion of phase-III studies the graphical representation of the data of all the parameters shall be done individually and shall be attached.
Phase – III: (For a period of 8 months)
Phase-III of the performance qualification shall be commencing, after successful completion of Phase-II. Purpose of Phase-II qualification is to monitor the operating parameters. The objective of Phase-III is also to demonstrate that system is producing desired quality of water, on a consistent basis, when operated in conformance with established SOP and does not have any seasonal variation through out the Phase-III study to collect the robust data. Conclusions shall be mentioned in Summary report.
During Phase-III, WFI water samples shall be collected from various Sampling Points in Water for Injection System as mentioned in sampling plan and Usage Points on a weekly basis. Phase-III of the performance qualification of Water for Injection System include extensive sampling of water from various points in the WFI water generation system & all the usage points of the distribution loops on weekly basis. Phase-III sampling carried out for a period of 8 months. Water samples from the all the usage points shall be analysed and monitored weekly, for compliance to the pre-determined specifications.

Specifications of Water for Injection:

S. No.	Test Parameter	Specification	STP/ GTP code
A. Chemical Analysis
1.	Description	Clear colourless, odourless and tasteless liquid
2.	pH (at 25°C)	Between 5.0 to 8.0
3.	Conductivity (at 25°C)	NMT 1.3 µS / cm
4.	Ammonium	NMT 0.3 ppm
5.	Calcium	No turbidity observed
6.	Chlorides	NMT 0.50 ppm
7.	Sulphates	No turbidity observed
8.	Total Organic Carbon	NMT 500 ppb
9.	Oxidisable Substance	The solution remain faintly pink
10.	Carbon Dioxide	The solution should remain clear
B. Microbiological Analysis
1.	Total Aerobic Microbial Count (TAMC)	NMT 10 cfu / 100 ml
2.	Bacterial Endotoxin Test	NMT 0.125 EU / ml

Sampling Plan & Frequency

S. N.	Name of the Sampling point	Specification Compliance	Sampling point No.	Room No.	Phase – 1 Sampling frequency	Phase – 2 Sampling frequency	Phase – 3 Sampling frequency / Day
A	WFI sampling points in Generation system
1.	After Column II	As per WFI	WFI – 01	NA	Daily	Daily	Weekly
2.	After Column III	As per WFI	WFI – 02	NA			Weekly
3.	After Column IV	As per WFI	WFI – 03	NA			Weekly
4.	After Column V	As per WFI	WFI – 04	NA			Weekly
5.	After WFI Generation	As per WFI	WFI – 05	NA			Weekly
6.	Storage Tank	As per WFI	WFI – 06	NA			Daily
B	Usage points in WFI Distribution loop system for Dry Powder Injection
7.	Garment Washing Room	As per WFI	WFI – 07		Daily	Daily Daily	Weekly
8.	Equipment Washing and Sterilization Room	As per WFI	WFI – 08				Weekly
9.	Vial Washing Room	As per WFI	WFI – 09				Weekly
10.	Before Bung Processor	As per WFI	WFI – 10				Weekly
11.	Return Loop	As per WFI	WFI – 11				Daily

Evaluation of test results shall be done by comparison against the standard criteria. Alert level and action level shall be established on the basis of Phase-I and Phase-II data. Alert levels are levels or range that, when exceeded; indicate that a process may have drifted from its normal operating condition. Alert levels constitute a warning and do not necessarily require a corrective action. “Alert Level = Max. Count + 2 X Standard Deviation”. Action levels are levels or range that, when exceeded, indicate that a process has drifted from its normal operating range. Exceeding an Action level indicates that corrective action should be taken to bring the process back into its normal operating range). “Action Level = Max. Count + 3 X Standard Deviation”
Deviation observed during the Phase-I, Phase-II & Phase-III of performance qualification shall be noted.
Re – validation Criteria:

Performance Qualification of WFI Water System to be revalidated on:

Any major modification in the existing system including distribution loop since purchase, which potentially could affect flow rates storage, delivery, sampling or water quality, or significant change in the operational parameter.
If the system is found to be malfunctioning after any deviation / after any major breakdown maintenance.
Relocation of the system.
Acceptance Criteria
Performance qualification shall be considered acceptable when requirements of this protocol has been fulfilled and all the parameter is functioning as per the design specifications and as per manufacturer’s recommendations.
Qualification Report
The performance qualification report shall consist of a summary document, in narrative form, which shall briefly describe the activity performed along with the observations recorded in relevant exhibits.
This report shall also include the related documents and attachments / annexure which were completed at the time of qualification activity.
Observed Deviation

Sr. No.	Page No.	Point No.	Observed Deviation	Deviation Reported By	Deviation Approved By	Corrective Action Taken	Justification of Corrective Action	Corrective action taken and justification given by

Report Approved By

Department Head						Quality Head

Reference Documents
Design Qualification .
Installation Qualification.
Operation Qualification.
United States Pharmacopoeia.
Indian Pharamcopoeia.
Exhibit – E01
Data Sheet for PQ Test Results of WFI Water
System Name:
Sampling Point No.: Phase: I/ II/ III

Date (è)
Test Parameters (ê)			Results
Description
pH (at 25°C)
Conductivity (at 25°C)
Ammonium
Calcium
Sulphate
Total Organic Carbon
Oxidisable Substance
Carbon Dioxide
Total Aerobic Microbial Count (TAMC)
Bacterial Endotoxin Test
Sampled By	Chemical Analysis
Sampled By	Microbiological Analysis
Analysed By		Chemical Analysis
Analysed By		Microbiological Analysis
Done By (Sign & Date)
Checked By (Sign & Date)

Approved By:

Date:

PQ of WFI generation, storage, and distribution system

Pharma More Jobs and post Please click here