Objective for URS of Pre treatment, Generation & Distribution of Water System:
This document is generating for the purpose of specifying the URS of Pre treatment, Generation & Distribution of Water System. The objective of this document is to provide the requirement and appropriate design to support the prospective supplier to identify company needs, price quote for the Purified Water storage & Distribution system and performance requirements for procurement of Purified Water storage & Distribution system including major ancillary component or fabrication of the area so as to meet the in-house requirements as well as compliance with cGMP. The URS of Pre treatment, Generation & Distribution of Water System is also provided to the Supplier to provide a price quote for the supply for Purified Water storage & Distribution system including the design, Performance and manufacture of the equipment.
To ensure that the system consistently distributes water to a pre-determined standard and if it does not, that there are sufficient warnings and procedures so that the final product is not adulterated
TABLE OF CONTENT
| Description |
| Objective |
| Table of contents |
| Approval of Documents |
| Scope |
| Location of equipment |
| Communication |
| Applicable codes and standard |
| System/equipment/instruments details |
| Scope of supply |
| Brief system description |
| Technical specification |
| Safety features |
| List of Abbreviations |
Approval of Documents for URS of Pre treatment, Generation & Distribution of Water System:
Prepared by:-
| Name | Designation/Department | Signature | Date |
Reviewed by:-
| Name | Designation/Department | Signature | Date |
Approved by:-
| Name | Designation/Department | Signature | Date |
Scope:
The scope of this document is to define the requirements of the Purified Water storage & Distribution system in company.
Location of equipment:
Purified Water storage & Distribution system will be installed in service area
References
The supplier shall use the following references in all communications: –
Applicable Codes and Standards: –
The entire Supplier’s work shall comply with all relevant Indian and International Standards and Codes of Practice.
The Supplier shall confirm all the Standards which have been used for the design and manufacture of the equipment.
System/equipment/Instruments details:
| Name of the equipment | Purified Water storage & Distribution system |
| Model/Type | As per cGMP model |
| Capacity | As per requirement |
Scope of Supply:
| Type of Device | Purified Water storage & Distribution system |
| Machine Standard | The current state of the art GMP Compliance. European medicine agency (EMA) and WHO, Regulations compliance. |
| Machine design standard & Refrences | The European machinery Directive 2006/42/EC. The European low voltage Directive 2014/35/EUISO/TR 12100:1992 safety machinery (Basic Concepts, general Principle of design), part 1&2.ISO 15534:2000 Ergonomic design for the safety of machine WHO TRS 929 39 report WHO TRS 970 Annex 2WHO TRS 1033 Annex 3 |
| Features | Design conforming to cGMP standards Simple and Convenient operation, Cleanliness, Operator protection and Ease to maintenance. Easy cleaning designed AC Frequency drive for motor |
| Document & Certificate | Manuals and Maintenance Instructions Operator manual Installation and assembly instructions for all devices. User’s manuals for all components. Trouble shooting guide. Maintenance Manual. Safety instruction. Training documentation. Electrical and Control diagrams Single line drawing for electrical distribution. Circuit diagrams Cable list. P & ID |
| Qualification Protocols | DQ Protocols and reports. FAT protocol and report. SAT protocol and report IQ protocol and report OQ Protocol and report Vendor should organize for Execution of IQ/OQ and support for PQ |
| Training | Vendor should impart necessary Operational training to user department and maintenance training to maintenance department. |
| TEST, CALIBRATION, MOC Certification | All test certificate for brought items will be provides during FAT with FAT Documents MOC Certificate will be providing during FAT with FAT documents Calibration certificate provides for gauges during FAT. |
Brief system description:
- Purified water is crucial in pharmaceutical manufacturing as both a solvent and an essential ingredient in various formulations, directly impacting the efficacy and safety of pharmaceutical products. Its pivotal role is underscored by its use in a multitude of pharmaceutical processes. For instance, purified water acts as a medium that aids in the synthesis of active pharmaceutical ingredients, and its purity directly influences the chemical reactions and stability of the formulations. The purified water includes the formulation of drugs and the rinsing of equipment. It also serves as a medium for compounded medications, necessitating strict adherence to purity standards to prevent contamination that could compromise product safety. Consequently, maintaining high standards of water purity is not just advantageous but essential for ensuring the production of safe and effective pharmaceuticals.
- Purifying water for pharmaceutical use begins with essential initial treatment methods. Techniques such as sedimentation, filtration, and disinfection are employed to prepare raw water for further purification. Sedimentation helps in removing large particulates, filtration aids in eliminating smaller impurities, and disinfection kills microorganisms, thereby ensuring the water is prepped for advanced purification stages. Advanced purification techniques play a crucial role in enhancing water quality by targeting impurities at a molecular level. Reverse osmosis is prominently used in this phase, capable of removing up to 99% of contaminants. Distillation is another method that ensures high purity by separating impurities through heat, while ultraviolet (UV) light treatment helps in further sterilizing the water, neutralizing any remaining pathogens. The effectiveness of these advanced methods is crucial in complying with standards set by regulatory bodies. For instance, reverse osmosis systems greatly reduce dissolved solids and contaminants, aligning with the stringent purity requirements necessary for pharmaceutical manufacturing. By utilizing such advanced purification techniques, the industry ensures that the water used in production processes meets the necessary health and safety standards, safeguarding both product efficacy and consumer health.
- Reverse osmosis filtration is a widely adopted purification method due to its efficiency in producing high-quality purified water. This system is often considered the cornerstone in pharmaceutical water treatment due to its effectiveness in removing impurities such as salts, microorganisms, and other organic substances. The utilization of semi-permeable membranes ensures that only water molecules pass through, leaving behind a significant portion of contaminants.Electrodeionization, or EDI, complements reverse osmosis by focusing on the removal of ions to produce ultra purified water.
- The pharmaceutical industry operates under strict regulatory guidelines to ensure the safety and quality of purified water used in production. Regulatory bodies such as the FDA and the European Pharmacopoeia set stringent standards that manufacturers must adhere to. These standards are crucial in ensuring that water used in pharmaceuticals is not only safe but also suitable for its intended use. They address various quality attributes, including but not limited to microbial counts, endotoxins, and chemical residues.
- Purified water plays a crucial role in pharmaceutical production by minimizing the risk of contamination, thereby ensuring higher quality formulations and safeguarding patient safety. Contaminants in water can compromise the integrity of pharmaceutical products, potentially leading to harmful consequences for consumers. By eliminating impurities such as bacteria, viruses, and dissolved minerals, purified water helps maintain the purity and efficacy of medications.
Main Components for URS of Pre treatment, Generation & Distribution of Water System
Pre-treatment system shall consist of following main components:
Dosing for disinfection of feed water
In order to maintain the required level of free chlorine in raw water tank and chlorine circulation loop should be provided in raw water tank.
Hydro-pneumatic System
HPS system should be provided for soft water generation and at inlet of UF for maintaining constant pressure in the line.
Multi Grade Filter (MGF)
A Multi-Grade Filter (MGF) is used as a pre-treatment step to remove suspended solids, dust, and dirt from raw water before it undergoes further purification processes. and backwash procedure to be provided
Softener System
Softening system should be provided to reduce the total hardness content due to presence ofcalcium & magnesium ions and charging procedure to be provided.
Ultra filtration System (UF)
Ultra filtration System (UF) shall be provided to remove SDI causing particles in the process and also to reduce microbial load.
Transfer pump
To transfer water from UF product tank to the potable water tank, Potable water feed pump should be provided.
Chemical Sanitizable Reverse Osmosis System
Antiscalant dosing unit should be provided for silica and hardness treatment. Water should then pass through SMBS which removes chlorine traces after which the water should be dosed with suitable chemical for sanitization of RO. RO should be provided to reduce high content of dissolved ions, organic matters from incoming raw water before water enters in to Ozone system.
CIP System for UF and RO
CIP system is used for cleaning of Ultra filtration membranes and RO membranes when there is fouling of membranes due choking and scaling & Differential pressure (Δ P).
Following are the main components of Purified water generation system:
UV System
The ultraviolet lights (UV) have two major functions; acts as the surface disinfectant and removal of ozone, which results from an ozone, process water system. The absorbed ultraviolet quantity must be enough to kill all the microorganisms
Process water distribution:
Product water after UV purifier shall be used for process
PW Generation Systems
The water from ozone destructive UV will enter the PW Generation system and will pass through RO and EDI system to produce Purified water. PW Generation system shall consist of the following main components:
Dosing system for conditioning of PW Generation system feed water
Hot water sanitizable Reverse Osmosis System for removal of dissolved solids
EDI (Electrode ionization) Module to control Endotoxins limit
Purified Water Storage & Distribution System
The storage and distribution system shall be configured to prevent recontamination of the water after treatment and be subjected to a combination of online and offline monitoring to ensure that the appropriate water specification is maintained.
PW storage & distribution system shall consist of following main components:
PW Storage Tank & Accessories
PW Distribution Skid with damping valve
Distribution Loop Piping
Finishing and Line Balancing:
Purified Water Scheme:
This option is expressed with the intent of each purification step without any controls etc. This is to give our brief on expectation and vendor is free to suggest any changes, if necessary, based on water analysis report and with scientific rationale & impact on cost/operation/maintenance etc.
The Water system should be a pre-validated, Pre-tested RO + EDI+ UV skid mounted. DS rejection up to 98% by RO and further polishing by hot sanitizable EDI system assuring conductivity less than 1µS/ cm. R.O. system with sanitary pressurized SS316L tube with drain manifold for pretreatment, softener, and R.O.-EDI system. According to PID and raw water analysis.
Operating Panel MOC should be SS 304, PLC based with HMI.
System should be suitable for HDPE raw water tank; raw water tank should have level switch to maintain the tank level.
Multi grade filter should be made-up of Fibre-reinforced plastic shell.
System should have a suitable capacity activated Carbon filter.
Softener should be suitable capacity made-up of Fibre-reinforced plastic shell with valve, air vent, Brine tank with stirrer and sampling wall.
Passing of soft water through 10.0 µ cartridge filter to reduce load on UF system.
Ultra filtered water storage tank should have level control, inlet, outlet, overflow controller and drain facility.
Dosing of SMBS in filtered water to remove any excess chlorine. Dosing of NaOH to control pH dosing of antiscalent to avoid scaling on RO membrane.
PH corrective system with tank level control PH indicator and sampling valve.
Anti scaling dosing system with tank and level control.
SMBS dosing system with tank and level control, ORP indicator and sampling valve.
Passing of water through 5.0 µ cartridge filter to reduce load on RO system.
Buffer tank made up of SS 316 with heat, temperature and level control with CIP system.
Reverse osmosis unit to remove ionic/microbial contamination to an Acceptable level for feed to EDI.
EDI as a polishing unit to remove ionic load to assure conductivity less than 1.3 µs/cm (at 25°C) consistently.
Conductivity meter should be displaying the R.O feed, R.O out and EDI out.
Purified water then stores in PW Storage tank & distributed through the loop piping by Distribution pump.
And for detail Refer purified water system Given Below: –
Specific Requirement for :
RO & EDI units will be Hot Water Sanitizable and chemical sanitizable.
During non-consumption period, the system should run in “Flushing mode” to save power/energy/water. In this mode system should operate for fixed time after a fix interval of time frame. Vendor to ensure necessary controls/functions to ensure that system does not allow microbial growth. Velocity of water in the return loop should be not less than 2.0 m/s.
Control Scheme:
This section includes details of automation required for purified water generation scheme and distribution system.
Vendor should note the following points should be considered for designing of PLC for Generation and distribution, the specific requirement given below is not exhaustive, any other necessary specific requirement not stated below can be incorporated in the offer.
Vendor to include necessary controls & interlocks in the design to ensure safe working of System& to ensure the consistent output quality.
P & ID for both Generation and Distribution system should be stored in MMI.
Vendor to furnish following details to be considered for PLC.
Technical Specification for URS of Pre treatment, Generation & Distribution of Water System:
Scope of work:
The purified water distribution package should include design, engineering, manufacture, testing at works, packaging and forwarding, transportation, unloading at site, storage, start up, installation and commissioning.
The package unit shall comprise of the following & generally as per the P& I diagram for purified water system:
Purified water storage tanks.
Purified water circulation pumps.
All piping from storage tank to circulation pump.
All piping should be as shown on the P& I diagram from circulation pump toindividual equipment in process & return loop.
It should also include all accessories and control instrumentation such as but not restricted to the following:
- Instrumentation.
- Conductivity meter with high alarm level indication.
- Level controller for purified water tank.
- Hydrophobic vent filters mounted on the purified water storage tanks.
- All connections shall be tri-clamp type.
- Complete piping shall be of welded construction type and all welding shall be orbital welding.
- Start up and commissioning spares required shall be specified clearly in your offer.
- Inspection shall be as per specification.
- Documentation shall be as per specification.
In case of any deviation of scope of supplies and services as specified in the offer, contractor to clearly highlight the same.
Contractor to follow legend P& ID and adhere to the equipment and line numbering system for maintaining consistency.
Material of Construction for URS of Pre treatment, Generation & Distribution of Water System:
All parts in contact with the purified water, except gaskets and membrane of valves, must be in SS316L Electro polished.
Surface Finish:
Inside surface (contact part with purified water) of the material should be Electro polished the internal finish should have an arithmetical average surface roughness of not greater than 0.8 micrometer arithmetical mean roughness (Ra).
Tubing Specification:
All tubes to be provided should be with original heat marks.
All tubing is to be supplied with material certification sheet for material of construction. All tubing used to be pre-cleaned and capped. Material (tubing, valves etc.) has to be handled insuch a way as to prevent introduction of contamination in the piping system.
Tolerances:
Minimum tolerances to assure proper alignment for Automatic Welding.
Outside diameter: ½” to 2” (excluded): + 0.002 over to 0.008 under 2 & 3 inch: 0.002 over to 0.001 under inch.
Wall thickness: + 0.0065 inch
Plane angularity: 0.005 degrees
Angle angularity: + 0.005 degrees
Square ness: + 0.005 inch
Valves:
All the valves in contact with water must be diaphragm valves.
Weir type 316 Stainless Steel body.
All valves shall be self-draining type.
Valve ends shall be suitable for Tri clamps.
Tolerances: inside dimensions as specified for tubing.
Fittings:
Material, wall thickness and finishing of all fittings shall be same as tubing specification
Connections:
The largest possible number of connections should be automatic TIG orbital welding without external filler wire (butt welded). Manual welding or Tri clamps connections are authorized case by case, but have to be minimized and agreed by the Consultant in writing.
Ferrules:
Material, tolerances, wall thickness and finishing of all the ferrules shall be same as that specified for tubing.
For Orbital welding: 15 mm long weldable ferrule.
For TIG welding: 5 mm long ferrule.
Clamps:
The material of construction shall be SS 304 in 2 segments design with wing nut.
Gasket:
Material of gasket should be Food grade Silicon or Teflon (PVDF). Must be steam resistant, inside diameters shall be same as tubing.
Purified Water Distribution Pump:
Centrifugal type, single stage with one standby pump.
Pump casing, back plate, impeller pin, back shrouded impeller and shaft shall be SS 316, 240 grit finish.
Suction and discharge shall be suitable for sanitary clamps fabricated from bar stock.
Pump to be provided with seal flush kit including valves, tubing and gauges. Pump must be fully drainable.
Purified water transfer pump should be with Mech. Seal.
Storage Tank:
The tank should be jacketed vertical tank. The material of construction for storage tank should be SS 316L and for non-contact parts it should be SS 304. All internals and fittings on tanks shall be electro-polished to surface roughness of 0.4µm. Tank must be totally drainable type. Storage tank must be equipped with a cleaning rotary type spray ball to be put on circulation return path to assure that the tank interior surfaces above the water level are continuously flushed.
Tank to be equipped with a hydrophobic type vent filter of 0.2µ. It is to be installed in such a way that condensate should be prevented from being trapped. The model selected for the vent filter to be approved by client.
The sterile vent filter must be electrical traced to avoid condensation of moisture in filter.
All nozzles should be flushed with surface & grounded off.
Sensors:
All required sensors (temperature, pressure, pH, ORP, conductivity, flow meter, level indicator) in contact with the process water must be, sanitary type connected by Tri clover.
The length of the electrical connection must be long enough to allow the calibration of the sensor.
Piping Installation Criteria:
Adequate slope in distribution system to be provided to enable complete drain ability of distribution system (Normally acceptable slope is 1:100, preferably to be kept 1:50).
To avoid bio film formation flow of water through distribution should be maintained turbulent (Normally velocities through distribution systems are to be kept minimum 2.0 m / sec).
If any dead leg is unavoidable effort should be taken to keep it less than or equal to 3 X D, where D is the diameter of branch & distance 3 D is measured from center of main header.
According to WHO TRS 929 (Page 54), dead-led should not be more than 1.5 times of internal diameter (ID) of the pipe.
As far as possible avoid double mechanical seal on Purified Water Loop Pump.
The entire skid producing Purified water should have clearance of minimum 350 mm from ground for ease of cleaning.
The skid producing Purified water should be designed in such a way to have sufficient space for maintenance of plant & components.
There has to be Sampling Point provided before & after each treatment component to draw water samples. These sampling points should be properly located & placed to have proper access for sampling.
The entire skid to be provided with clear / visible & legible signage for all components, flow direction, In case of indicators their maximum & minimum range with LC. The identifications provided should match with the identification numbers given in finally approved P & ID.
Execution:
The pre-fabricated parts must be stocked, cleaned and capped to prevent introduction of contamination into the piping system. Tubes, which get bent during storage or at a time of handling, should not be used.
Drainage:
Purified Water Loop Pump should be provided with an arrangement for complete drain ability of Pump Casing.
The skid should be provided with minimum 75 NB drain all around with adequate slope & out let. This drainpipe should be provided with properly located drain cups to avoid water spillage on ground.
The low points must be fitted with diaphragm valve for drainage.
Supports:
All supports in contact with the tubing must be stainless Steel 304.
Do not rigidly anchor tubing.
The distance between two supports must be:
- 1 meter for horizontal tubing (dia. 1/2”)
- 1.5 meter for horizontal tubing (dia. 3/4” to 1”)
- 2 meters for vertical tubing (dia. 1”)
- 3 meters for tubing (dia.>1”)
Also Support to be fixed at every change of direction.
Slope determination:
Slope of 1:100 should be maintained to enable complete drain ability.
Welded Stainless Steel Connection (At site and workshop):
Orbital welding to be carried out at site should follow following procedure: –
Vendor to furnish welding procedure to be carried out on weld joints.
Approval of procedure.
Carry out Weld as per approved procedure on pieces as required for testing and documenting the parameters.
Send the sample pieces for analysis.
After receiving analysis report and final approval of weld, prepare final procedure for weld approved with all prints out documents and weld analysis reports.
Carry out further welding exactly with same parameters and keep printouts with weld identification number.
Weld identification no. to be marked on isometrics also.
Every day one sample piece of weld each at the start and end of welding with printout of parameters to be preserved as reference welds for the day.
Upon completion of all welds as specified above minimum 10% of weld joints to be checked with boroscopy. Also 1% of total joints to be opened by cutting for visual inspection.
Purging:
Use 99.996% minimum purity Argon gas for the backup purge and the torch gas.
Provide Certificates for purity of Gas.
Alignment and Tacking:
Accomplish tack welding in a manner that will not cause any deleterious effect on completed welds.
Make tack welding as light as possible to reduce excessive heat that may cause structural changes to the granular composition of the system components.
Do not allow tack to penetrate the inner surface of components. Use backs up purge’s gas for tack welding.
Provide three tacks at 1200 per weld (maximum Four tacks allowed in case of any defect in Tacks)
While welding center the electrodes over the butt weld joint by using a setting gauge.
Inspection:
Examine each external weld visually to ensure that there are no surface defects and record.
Document and log each weld as follows:
Provide the “as built” isometric view with the number, location and type of welds (manual, automatic).
Engrave each weld with the number.
Location and number of weld and parameter print for the same.
Name of welder.
Name of Inspector.
After completion of inspection the joints should be cleaned by using proper material.
Weld Defects:
Welds will be rejected and removed including the heat affected zone under the following conditions:
Internal concavity of the weld: Not allowed
External concavity of the weld: < 25% of the thickness
Full penetration of the entire weld joint periphery: Required
Lack of fusion: Not allowed
Crevices: Not allowed
Slag or inclusions: Not allowed
Cracks: Not allowed
Burn through: Not allowed
Re-welding of defective weld is not permitted.
Pressure Test:
The pressure test must be done before each cleaning and passivation.
The test must be hydraulic with purified water or soft water. During testing there should be no loss of initial pressure for 6 hours. The test pressure must be 1.5 times the design pressure.
Cleaning and Passivation:
Cleaning:
Cleaning medium shall be compatible with 0.3µ surface finishes. Cleaning is mandatory. Submit written procedure for approval of Consultant/Client and operate according to the pre-approved procedure. Record and log cleaning dates and steps.
Passivation:
Circulation of HNO3 solution in water for 1 hour to remove weld particles.
Use 3.5% by weight nitric acid solution in water.
Circulate for at least 2 hours. Drain the system completely.
Operate according to a written pre-approved procedure.
Do not use hydrofluoric acid for passivation.
Record and log passivation dates and steps.
Rinsing:
Fill the system with purified water, circulate for 15 minutes and flush each use point outlet and equipment connection until the pH of discharge water is balanced with the inlet pH.
Record and log cleaning dates and steps.
Operational Requirement URS of Pre treatment, Generation & Distribution of Water System:
The water system should be suitable to produce the water with desired specifications:
- Process Requirements:
- Total Operation per day: 24 Hours
- Operating temperature for Process Water: NLT 55 oC
- Operating temperature for Purified Water: NMT 25 oC
- Type of Operation: Discontinuous.
- The system should be capable of producing treated water of Clear, Odourless, tasteless
Quality and Process Instruments:
Suitable instruments should be provided in the system with respect to safety of plant and quality point of view such as pH sensor, Ozone sensor, ORP sensor, Conductivity sensor etc.
Based on site condition vendor should accommodate as built drawing foot prints of the water system
Vendor should provide the elevation drawing of the water system.
Safety Features for URS of Pre treatment, Generation & Distribution of Water System:
| Critical Variables | Acceptance Criteria | Reference |
| MCB | MCB is provided so that when there is an overload in current or any short circuit then the MCB trips. | Safety Requirement |
| Metal Parts | All the metal parts should be properly grounded without any sharp Edges. | Safety Requirement |
| Installation | Allthe Installation must be in accordance with the cGMP. | Safety Requirement |
| Alarm system | Alarm should be provided. | Safety Requirement |
| Electrical Wiring and Earthing | Electrical wiring should be as per approved drawings. Double external Earthing to control machine (panel and motors) and operator should be provided. | Safety Requirement |
| Noise Level | Below 80 db. | Safety Requirement |
| Emergency/Safety Switch | Provided easy access position | Safety Requirement |
Spare parts / Change parts
Vendor should provide Preventive Maintenance SOP, List of recommended critical spare parts with code no. considering 2 years of satisfactory working of machine. After Sale Service/ AMC for the machine should be provided after warranty period
List of Abbreviations.
| URS | User Requirement Specification |
| ENG | Engineering |
| QA | Quality Assurance |
| cGMP | Current Good manufacturing |
| WHO | World Health Organization |
| TRS | Technical Report Series |
| AC | Alternate Current |
| P & ID | Piping & Instrumentation Diagrams |
| DQ | Design Qualification |
| FAT | Factory Acceptance Test |
| SAT | Site Acceptance Test |
| IQ | Installation Qualification |
| OQ | Operational Qualification |
| PQ | Performance Qualification |
| MOC | Material of construction |
| UV | Ultra violet |
| EDI | Electro deionization |
| FDA | Food & Drugs Administration |
| UF | Ultra Filtration |
| SDI | Silt Density Index |
| RO | Reverse Osmosis |
| CIP | Clean in Place |
| PW | Purified Water |
| SS | Stainless Steel |
| HPDE | High-Density Polyethylene |
| PLC | Programmable Logic Controller |
| HMI | Human machine interface |
| SMBS | Sodium Meta bi Sulphate |
| NaOH | Sodium Hydroxide |
| pH | Potential of Hydrogen |
| ORP | Oxidation reduction potential |
| NaOCl | Sodium Hypochlorite |
| ROH | Reverse Osmosis housing |
| HIUV | High Density Ultra violet |
| m/s | Meter per second |
| MMI | Man, Machine Interface |
| TIG | Tungsten Inert gas |
| PVDF | Polyvinylidene fluoride, |
| NB | Nominal Bore |
| HNO3 | Nitric Acid |
| MCB | Miniature Circuit Board |
| DB | Decibel |
| SOP | Standard Operating Procedure |
| AMC | Annual maintenance Contract |
| TOC | Total organic carbon |
| PPB | Parts per billion |