Monitoring of water system

Monitoring of water system in Pharmaceutical Manufacturing plants.

1. October 2018
Sreenath Sasidharan
Welcome
Monitoring of water
System

2. Water is widely used in pharmaceutical
manufacturing –either as a raw material, as
an ingredient, or as a final product. Water is
also used for rinsing equipment or for the
preparation of disinfectants and detergents…

3. These applications require pharmaceutical-grade
water to be used, which is water that has been
through a chemical purification step. Purification
is undertaken so that the water is free of
substances that might cause interaction with
drug substances, as well as to obtain water of an
appropriate microbiological standard.

4. Microbiological risks are ever present with water systems. Risks
can arise through poorly maintained water generation systems,
through badly designed distribution networks (such as the
presence of dead legs), or at user outlets (where ineffective
tubing management can lead to contamination). Weaknesses in
water systems are exacerbated by microorganisms being
ubiquitous and varied in their ability to survive and grow under
different conditions. Therefore, monitoring pharmaceutical-grade
water systems for bioburden is important.

5. Types of water at Geltec facility
1.RawWater(3Points)-S1toS3
2.Potable&Softwater(7Points)S4toS10
3.Purifiedwater–(27Points)S11toS37
Testing Frequency (Routine Analysis)
1.RawWater(3Points)-Monthly
2.Potable&Softwater(7Points)Monthly
3.Purifiedwater–(27Points)Monthlyexcept
S14,S11,S34
S14-Return loop (Daily)
S11-EDI outlet (Weekly)
S34 (Upon Production Demand/Monthly)

6. Critical Parameters-Purified water
Parameter Alert Limit Action Limit Standard Limit
pH 6.0 6.5 5.0 to 7.0
Conductivity (µS/cm) Maximum 3.0 at 20˚C Maximum 3.5 at 20˚C Maximum 4.3 at 20˚C
Total Viable Aerobic Count
(CFU/ml)
NMT 50 NMT 75 NMT 100

7. Critical Parameters-Potable & Soft water
Parameter Alert Limit Action Limit Standard Limit
pH 9.0 9.3 6.5 to 9.5
TDS (ppm) NMT 300 NMT 400 NMT500
Hardness (ppm) NMT 100 NMT 110 NMT120
Chlorides (ppm) NMT 150 NMT 200 NMT250
Total Viable Aerobic Count (CFU/ml)NMT 200 NMT 300 NMT 500

8. Critical Parameters-Raw water
Parameter Alert Limit Action Limit Standard Limit
pH 9.0 9.3 6.5 to 9.5
TDS (ppm) NMT 300 NMT 400 NMT 500
Hardness (ppm) NMT 200 NMT 250 NMT 300
Chlorides (ppm) NMT 150 NMT 200 NMT 250
Total Viable Aerobic Count (CFU/ml) NMT 200 NMT 300 NMT 500

9. Enumeration Methods (MLT)
Membrane Filtration Method, (Purified water)
Plate Count Method (Raw & potable)
MPN method (Not using in our facility)

10. Sample Size
Purified Water–100 mL for MF & 20mL for Pathogens
Potable & Raw Water–2 mL for Plate count & 20mL for Pathogens
Membrane Filtration (MF)
-100mLsample
-SterileMembraneFilters(0.45µ)

11. Raw & Potable water (Pour Plate method )
•1 ml of water sample in to 90mm sterile petri plates
in duplicates
•Pour R2A agar Media at 45°C and swirl the plates
to solidify
•Incubate at 30 to 35°C
Purified water (MF method )
•Membrane filter shall be placed carefully in to
90mm sterile petri plates with R2A agar Media in it.
•Incubate the plates at 30 to 35°C

12. Tests for Specified Microorganisms
(Pathogens)
Bile-Tolerant Gram-Negative Bacteria
E .Coli
Salmonella sp
Pseudomonas aeruginosa
Staphylococcus aureus
•10 ml of sample into 90mL SCDM in duplicates
•1
st
sample prep for Salmonella Sp. and the 2
nd
sample
preparation for other specified pathogens.

13. Tests for Specified Microorganisms(Pathogens)
BT G-ve Bacteria:
From Sample prep.
(after 2 hrs (to NMT 5 hrs) of incubation in RT/20-25°C)
Transfer 10mL to 100mL EEBM
(Incubate at 30-35ºC/ 24-48 Hrs)
Subculture
onVRBGA
(30-35ºC/ 18-24 Hrs)
EEBM & VRBGA-Only Boiling

14. Tests for Specified Microorganisms(Pathogens)
E.coli
After 18-24 Hrs, From Sample prep. (SCDM)
Transfer 1 mLto 100mL MCB
(Incubate at 42-44ºC/ 24-48 Hrs)
Subculture
onMCA
(30-35ºC/18-72 Hrs)

15. Tests for Specified Microorganisms(Pathogens)
Salmonella.sps
After 18-24 Hrs, From Sample prep. (SCDM)
Transfer 0.1 mLto 10 mL RVSEM
(Incubate at 30-35ºC/ 18-24 Hrs)
Subculture
onXLDA
(30-35ºC/18-48 Hrs)
XLDA-Only Boiling

16. Tests for Specified Microorganisms
(Pathogens)
Pseudomonas.aeruginosa
After 18-24 Hrs, From Sample prep. (SCDM)
Subculture onCA
(Incubate at 30-35ºC/ 18-72 Hrs)

17. Tests for Specified Microorganisms
(Pathogens)
Staphylococcus.aureus
After 18-24 Hrs, From Sample prep. (SCDM)
Subculture onMSA
(Incubate at 30-35ºC/ 18-72 Hrs)

18. OOS
AlertLimit:Incasetheresultsexceedthealertlimits,informtheEngineering
departmenttocheckforanymaintenanceworkoranysuchprobableactivitiesfor
exceedingalertlimits.InformProductionandQAabouttheresult,aninvestigation
shallbeinitiatedtoidentifytheprobablereason.Thewatersystemhastobetaken
forsanitizationincaseofmicrobialalert.
ActionLimit:Iftheresultsexceedactionlimits,informalltheconcerned
departmentsandthewatershallnotbeusedtilltheresultsareinbelowlimits.All
theproductswhicharemanufacturedduringthisperiodshallbetestedformicrobial
countsasperthecurrentSOPonMicrobialLimitTest.Morenumberofsamplesshall
betakenfromacrossthebatchandtestedindividually
TRENDING OF DATA
•EVERY SIX MONTHS

19. Do U Really Wanna Screw UP….????

20. THANKS
FOR YOUR
KIND ATTENTION