ISPE NORDIC COP CLEAN UTILITIES SEPTEMBER 7 2016 TUUSULA … · Connecting Pharmaceutical Knowledge ispe.org Introduction-Conductivity monitoring is normal practice in all water stills

ISPE NORDIC COP CLEAN UTILITIESSEPTEMBER 7 2016 TUUSULA FINLAND

Mika PärkkäSTERIS [email protected]

WFI AND STEAMQUALITY TESTINGCONSIDERATIONS ATFACTORY ACCEPTANCETESTING

Connecting Pharmaceutical Knowledge ispe.org

Contents

1. Introduction2. FAT and leveraging the FAT results3. What to measure4. Methods for monitoring the quality in FAT5. Gas removal6. Quality considerations for feed water7. Discussion


Introduction-Conductivity monitoring is normal practice in allwater stills and most pure steam generators (PSGs)-It is a very good way to monitor the quality: fast,reliable and sensitive-However, there are also many other qualityattributes for WFI, which should be measured-Same quality attributes and methods can be appliedalso for pure steam


FAT and leveraging

-Traditional approach in FATs has been approval of the unitfor shipping and getting to know it-When the unit has been started on site, almost all FATtests have been repeated as part of SAT

– If something goes wrong, at least the user knows it worked in the FAT

-It is getting more common that users will not repeateverything in SAT anymore-Instead, they use the FAT results for their qualification-This is called leveraging


FAT and leveraging

-This shortens the time needed for site testing and can savemoney-On the other hand, it also sets stricter requirements for theFAT testing and can make FATs longer-Static tests are typically used for leveraging-Generally speaking, dynamic tests and quality tests haveto be repeated on site but well performed FAT may assistsimplifying also them


What to measure

-It can be said pharmacopeias set the minimumrequirements for chemical impurities in WFI

– These are conductivity, TOC, pH, nitrates, heavy metals, endotoxinsand microbial contamination

-There are no requirements for chemical quality of puresteam in the pharmacopeias

– However, a commonly accepted approach is that condensed puresteam equals WFI

– This terminology is a little vague; clean steam can mean pure steam orsteam the quality of which is between plant steam and pure steam


What to measure

-Requirements for physical quality apply only to steam-These can be found in European standard EN285, which isstrongly based on superseded British standard HTM2010-EN285 is used also outside the EU-There are three physical quality attributes: non-condensable gases (NCG), dryness and superheat


Methods for measuring quality inthe FAT

-Offline sampling is always possible but the results areavailable only afterwards-All stills and most PSGs are equipped with onlineconductivity monitoring

– Conductivity monitoring of feed water is also fairly common

-Online TOC analyzer is possible to install on both, MWSand PSG. However, they are generally expensive andinstallation of one to a PSG is not fully straightforward



-The FAT test bay can be equipped with an online TOCanalyzer and it can be used for every equipment-Online measurement of pH is simple but is not donenormally-Nitrates, heavy metals, endotoxins and microbialcontamination are measured offline



-EN285 is a standard for steam sterilization but steamquality measurement can be applied also for steamgenerators

– This does not eliminate the need to do the measurements at point ofuse but helps troubleshooting and proves the PSG works properly

-The methods are simple but they are not very robust;apparatus and person doing the mesurements can affectthe results quite a lot-It is important to follow the instructions given in EN285exactly. Particularly the sampling point for dryness test iscritical


Non-condensable gas test


-The idea is to condense steam and lead it through a burettefilled with water-Condensate will continue to a graduate and NCGs will lower thewater level in the burette-NCG content can be calculated based on these-Acceptance criteria is max. 3,5 % v/v

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Non-condensable gas test


Dryness test


Dryness test

-Steam is introduced to a Dewar flask with a known amountof water at a known temperature-The amount of steam and temperature increase arerecorded-Dryness can be calculated using a formula shown on nextslide-The result is a dimensionless figure-Acceptance criteria is min. 0,90 generally and 0,95 formetal loads-Dryness value 1,00 equals fully saturated steam


Calculation formula for dryness

Me = mass of the empty flask (kg)Ms = mass of the flask and water (kg)Mf = mass of the flask, water and condensate (kg)T1 = initial temperature of the water in the flask (°C)T2 = final temperature of the water in the flask (°C)T3 = temperature of the steam in the pure steam line (°C)L = latent heat of steam at temperature T3 (kJ/kg)0,24 = heat capacity of the test equipment


Superheat test


Superheat test

-Steam is allowed to expand to ambient pressure-Temperatures of expanded steam and steam in the line isrecorded-Acceptance criteria for this temperature difference is max.25 K


Gas removal

-There are mainly three gases present in feed water:oxygen, nitrogen and carbon dioxide-CO2 is the most difficult to remove because it has thehighest solubility-O2 and N2 are present in greater quantities but since theirsolubilities are lower, they are present mostly as free O2and N2 and are thus easier to remove


Gas removal

-Gases can be removed before the still / PSG using aseparate gas removal apparatus which is based on vacuum-Another possibility is to remove them in the equipment

– Condenser is the traditional location for water stills

– 1st column is a good place for gas removal in stills and PSGs

– In stills, an additional gas vent can be added to the outlet of preheaters


Gas removal


Quality considerations for feedwater

-Theoretically it is possible to do WFI / pure steam directlyfrom potable water

– In practice, this does not work. Content of impurities is too high, soscaling and corrosion issues arise

-Using softened water is also possible but not verycommon-The most common approach is the use of RO/DI water, PWin practice-Sometimes pure steam generators are fed with hot WFI


Quality considerations for feedwater

-The impurities are removed with blowdown in stills andPSGs-When lower quality feed water is used, a higher blowdownrate has to be used to ensure adequate product quality-This evens out overall cost differences between differentWFI / pure steam production methods


Questions?

Thank you!

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ISPE NORDIC COP CLEAN UTILITIES SEPTEMBER 7 2016 TUUSULA … · Connecting Pharmaceutical Knowledge ispe.org Introduction-Conductivity monitoring is normal practice in all water stills