water part2

Water | Slide 1 of 19 January 2006

Water for Pharmaceutical Use

Part 2: Water purification and

engineering

Supplementary Training Modules on Good Manufacturing Practice

WHO Technical Report Series No 929, 2005. Annex 3


Objectives

To examine the basic technology and requirements for:

Water treatment systems

Storage and distribution requirements

Sampling and testing

Sanitization


6.


General

Part 1 – reviewed types of water and water purification systems

Water can be used directly, or stored in a storage vessel for subsequent distribution to points of use

Design appropriately to prevent recontamination after treatment

Combination of on-line and off-line monitoring to ensure compliance with water specification


6.1


WPU system contact materials

Contact materials include:– Pipes– Valves and fittings– Seals– Diaphragms and instruments– Tanks– Pumps, etc.

Proper selection to ensure these are suitable


6.2


WPU system contact materials (2)

Factors to consider (including components)

– Compatibility and leaching effect

– Corrosion resistance

– Smooth internal finishing, ease of jointing

– Hygienic / sanitary design

– Documentation

– Materials of construction (MOC) - (including original/certified copies of material certificates


6.2



Compatibility– With temperature and chemicals used in the system

Leaching effect– Non-leaching at temperature range

Corrosion resistance– PW, HPW, WFI highly corrosive– Stainless steel Grade 316L to be used– System passivated after installation and modification

according to SOP


6.2



Smooth internal finish

– Biofilms and microbial contamination

– Crevices and roughness result in problem areas associated with contamination and corrosion

– Internal finish to have arithmetical average surface roughness not greater than 0.8 micrometer arithmetical mean roughness (Ra)

– Mechanical and electropolishing needed when stainless steel is used


6.2



Joints– System materials easily jointed, e.g. by welding– Process controlled including requirements such as:

• Qualification of operator • documentation of welder set up • work session test pieces • weld logs • visual inspection of defined proportions of welds


6.2



Suitable materials include:– Stainless steel Grade 315 L (low carbon)– Polypropylene (PP)– Polyvinylidenedifluoride (PVDF)– Perfluoroalkoxy (PFA)

Unplasticized polyvinylchloride (uPVC) used for non-hygienic designed water treatment equipment such as ion exchangers and softeners


6.2


System sanitization and bioburden control

Systems in place to control proliferation of microbes

Techniques for sanitizing or sterilization

Consideration already during design stage – then validated

Special precautions if water not kept in the range of 70 to 80 degrees Celsius


6.3


Storage and distribution - Storage vessels

Design and size important– Serves as buffer between generation and use– Avoid inefficiencies and equipment stress during frequent on-

off cycles– Short-term reserve in case of failure

Contamination control consideration– Headspace (kept wet with spray ball / distributor device)– Nozzles (no dead zone design)– Vent filters (type, testing, use of heat)– Pressure relief valves and burst discs (sanitary design)


6.4


Storage and distribution – Pipes and heat exchangers

Continuous circulating loop needed

Filtration not recommended in loop and take-off point

Heat exchangers:– Double tube plate or double plate and frame type– Designed to ensure no stasis of water

Where water is cooled before use, done in minimum time, and validated process


6.5, 6.5.1


Storage and distribution – Circulation pumps

Sanitary design with appropriate seals

Standby pumps– Can be used– Configured or managed in a way to avoid trapped dead

zones


6.5.2


Typical water storage and distribution schematicTypical water storage and distribution schematic

Water must be kept

circulating

Spray ball

Cartridgefilter 1 µm

Air breakto drain

Outlets

Hygienic pump

Optionalin-line filter

0,2 µm

UV light

Feed Water from

DI or RO

Heat Exchanger

Ozone Generator

Hydrophobic air filter& burst disc



Biocontamination control techniques

Continuous turbulent flow circulation– Specified velocity proven (qualification), and monitored

Avoid dead legs

Hygienic pattern diaphragm valves

Shortest possible length of pipe work

Pipe work of ambient temperature systems, isolated from hot pipes


6.5.3


Biocontamination control techniques (2)

There should be no dead legs

Water scours dead leg

If D=25mm & distance X isgreater than 50mm, we havea dead leg that is too long

Dead leg section

>1.5D

Flow direction arrows on pipes are important

Sanitary Valve

D

X



3. The water is contaminated as it passes through the valve

2. Bacteria can grow when the valve is closed


1. Ball valves are unacceptable

Stagnant water

inside valve




Pressure gauges separated from system membranes

Pipe work laid to fall (slope) – allows drainage

Maintain system at high temperature (above 70 degrees Celsius)

Use UV radiation– Flow rate, life-cycle of the lamp

Suitable construction material


6.5.3



Periodic sanitization with hot water

Periodic sanitization with super-heated hot water or clean steam– Reliable– Monitoring temperature during cycle

Routine chemical sanitization using, e.g. ozone– Removal of agent before use of water important


6.5.3

water part2

Documents

water specification6

stasis of water

water treatment systemsstorage

reviewed types of water

pharmaceutical use storage

pharmaceutical use wpu

use design

mspray ball water mustoptional