Water is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms. It is vital for all known forms of life, even though it provides no calories or organic nutrients. Density: 997 kg/m³ Boiling point: 100 °C Formula: H2O Melting point: 0 °C Molar mass: 18.01528 g/mol Water travels throughout your body carrying nutrients, oxygen, and wastes to and from your cells and organs. Water keeps your body cool as part of your body's temperature regulating system. Water cushions your joints, and protects your tissues and organs from shock and damage. Some waterborne pathogenic microorganisms spread by water can cause severe, life-threatening diseases. Examples are typhoid fever, cholera and Hepatitis A or E. Other microorganisms induce less dangerous diseases. Water is one of the major commodities used by the pharmaceutical industry. It is widely used as a raw material, ingredient, and solvent in the processing, formulation, and manufacture of pharmaceutical products, active pharmaceutical ingredients (APIs) and intermediates, and analytical reagents.

1. PHARMACEUTICAL
WATER

2. Speaker Profile
MD.ASLAM ALI
In-Charge of Microbiology
Microbiology department
Biopharma Ltd.

3. Water is an inorganic, transparent, tasteless,
odorless, and nearly colorless chemical
substance, which is the main constituent of
Earth's hydrosphere and the fluids of all known
living organisms. It is vital for all known forms of
life, even though it provides no calories or organic
nutrients.
Density: 997 kg/m³
Boiling point: 100 °C
Formula: H2O
Melting point: 0 °C
Molar mass: 18.01528 g/mol

4. Water travels throughout your body
carrying nutrients, oxygen, and wastes
to and from your cells and organs. Water
keeps your body cool as part of your
body's temperature regulating system.
Water cushions your joints, and protects
your tissues and organs from shock and
damage.
IMPORTANT OF WATER FOR BODY

5. The main sources of water are—
surface water, groundwater and rainwater.
SOURCE OF WATER

6. Waterborne diseases are illnesses caused by
microscopic organisms, like viruses and bacteria, that
are ingested through contaminated water or by coming
in contact with feces.
Some waterborne pathogenic microorganisms spread by
water can cause severe, life-threatening diseases. Examples
are typhoid fever, cholera and Hepatitis A or E. Other
microorganisms induce less dangerous diseases.
Diarrhea. The most common of all water-borne diseases,
diarrhea, mainly affects children below five years of age. The
symptoms include dizziness, dehydration, pale skin, and loss
of consciousness in severe cases

12. Water is one of the major commodities
used by the pharmaceutical industry. It is
widely used as a raw material, ingredient, and
solvent in the processing, formulation, and
manufacture of pharmaceutical products,
active pharmaceutical ingredients (APIs) and
intermediates, and analytical reagents.
PHARMACEUTICAL WATER

13. TYPES OF WATER
 Different grades of Water for Pharmaceutical
Purposes- each type has its on characteristic for all
parameters.
 Potable water
 Purified water
 Water for injection(WFI)
 Sterile water for injection, inhalation, irrigation
 Sterile bacteriostatic water for injection

14. Impuritie
s
 TDS (Total Dissolved Solids) : Na, Ca, Mg, Cl,
etc..
 Silica : Colloidal, Reactive.
 TSS (Total Suspended Solids): Suspended
particles, Heavy metals etc..
 Micros : Total Bacterial Count, Pathogens,
etc……

15. Purified Water is used as an
excipient in the production of non-
parenteral preparations and in
other pharmaceutical applications,
such as cleaning of certain
equipment's and non-parenteral
product-contact components
Water for injection has the highest purity
possible and it is sterile. ... WFI is condensed
and is generally kept at 80 - 90 ºC to maintain its
properties. The main difference between a PW
and a WFI loop is that the purified water is held at
room temperature while the WFI is kept at 80-90ºC.

16.  High-quality water is essential for the manufacturing of
pharmaceuticals. Water is the most commonly used raw
material in pharmaceutical manufacturing.
 water is directly or indirectly used in the pharmaceutical
manufacturing such as a major component in injectable
products and in cleaning of manufacturing equipment.
 It is one of the raw material that is usually processed by the
pharmaceutical manufacturer prior to use because it cannot be
supplied by the vendor.
 Water is thus an important raw material in GMP and in
validating the manufacturing process.

17. Why purification?
o Although tap water is reasonably pure, it is
always variable due to seasonal variations,
regional variation in quality.
o One must remove impurities and control microbes
to avoid contamination of products.
o Pretreatment depends on quality of feed water.

18. Quality of water should be specific for product
quality.
Water contains,
 Organic and inorganic impurities
 Microbial contamination
 Endotoxin
 Particulate contamination
Low quality of water can lead to
 product degradation
 product contamination
 loss of product and profit

19. Potable Water
 Potable water normally we are using for
drinking purpose.
 For Purified water Generation, we required
Potable water as feed water. Required
Parameter for Potable water are as below.
- TDS < 500 ppm
- Turbidity < 1NTU
- TBC < 500 cfu/ml

20. Purified Water Quality
 As per USP Purified water should be:
- Conductivity : <1.3 μs/cm2
- pH : 5.0 to 7.0
- TOC : <500 ppb(0.5ppm)
- TBC : <100 cfu/ml
- Pseudomonas: Absent
- E.coli : Absent
- Coli form : Absent
- Salmonella : Absent

21. WFI (Water For Injection)
 As per USP WFI should be:
- Conductivity : <1.3 μs/cm2
- pH : 5.0 to 7.0
- TOC : <500 ppb(0.5ppm)
- TBC : <10 cfu/100ml
- Pseudomonas: Absent
- E.coli : Absent
- Coli form : Absent
- Salmonella : Absent

22. Chlorination
 Chlorination consists of Chemical tank,
Dosing Pump.
 Location : Online at the inlet of Raw water
storage tank.
 Chemical : Sodium Hypo Chloride (NaOCl)
 Dosage Requirement : 3 to 5 ppm (Depend
up on Microbial Problem)
 Purpose : To control Microbial growth.

23. PURIFIED WATER SYSTEM PLANT OF BIOPHARMA

24. DIFFERENT TECHNIQUES USED FOR
WATER TREATMENT
De-chlorination (Sodium Bisulphite,
Carbon Filter)
Filtration
Ultra Filtration
Softening
Demineralization
Reverse Osmosis
UV Treatment
Deionization
Ozonization

25. DIFFERENT EQUIPMENTS AND
COMPONENTS FOR WATER SYSTEM
 Piping
 Valves
 Pumps
 Pressure gauges
 Heat exchangers
 Distillation unit
 Filters
 Deionizers
 Sensors
 Auxiliary equipment

26. Conti….
 Design of the following should be appropriate to
prevent recontamination after treatment-
Vent filter
Sanitary overflow
Tank UV light
Conical Bottom
Steam sterilization
 Combination of on-line (TOC, Conductivity meter etc.)
and off-line monitoring (lab testing by proper sampling)
to ensure compliance with water specification

27. Dosing System
 pH Correction
 SMBS (Sodium Mete Bi Sulfite)
 Consist : Dosing tank, Dosing Pump
 Purpose : To decrease rate of Scaling and
precipitation of Silica pH.
 Chemical : Silica Antiscalent
 Location : Before Micron Cartridge Filter

28. Reverse Osmosis
 Filters : RO Membranes
 Purpose : To reduce TDS
(Conductivity)
 Heat Sanitization Membrane.
RO Membrane

29. MCF OUTLET
H.P.P
FI
FI
FI
REVERSE OSMOSIS (RO) IN SERVICE
FEED PG
AUTO
DUMP
VALVE
REJ PG
REJ
VALVE
FEED
PRODUCT
RECYCLE
PROD. PG
MEMBRANE MEMBRANE
MEMBRANE MEMBRANE

30. EDI (Electro Deionization)
 Electro-Deionization, or EDI, is a process that evolved from
conventional ion exchange technology. EDI provides continuous
demineralization at recovery rates of 90% or more. In EDI, just as in
conventional ion exchange, cations and anions in the feed water
are exchanged for hydrogen and hydroxyl ions in the ion exchange
resins, producing demineralized water.
 Continuous regeneration in EDI is achieved electrochemically, by
means of ion conducting membranes and an imposed electric
current.
EDI Structure

31. UF System
 Hollow Fiber Membrane.
 Heat Sanitizable
 Very Effective in Micro reduction
 Operating Cycles
- Service.
- Fast Flush
- Back wash
 SS Storage Tank of ----- ltr.
 Distribution Pump VFD controlled
 Ultra Violation
 Heat Exchanger
Storage & Distribution System

33. VALIDATION
Water system validation is mandatory in order to
study the reproducibility, consistency &
effectiveness of water system.
Water Validation different Steps :
Pharmaceutical water treatment system validation
consists of some steps which are:
DQ (Design Qualification)
IQ (Installation Qualification)
OQ (Operational Qualification) &
PQ (Performance Qualification)

34. SYSTEM QUALIFICATION
Validation Master Plan
User Requirement Specification
Design Qualification
Installation Qualification
Operation Qualification
Performance Qualification
Re- Qualification.

35. STEPS OF VALIDATION
 Establishing standards for quality attributes
 Defining system and subsystem
 Designing equipment, control, & monitoring
technologies
 Establishing standards for operating parameters
 Developing an IQ stage & OQ stage
 Establishing alert and action levels
 Developing a prospective PQ stage
 Completing protocols and documenting each
steps

36. PERFORMANCE QUALIFICATION
 The purpose of PQ is to verify and document that
water supply system provides acceptable control
under ‘ Full Operational ‘ conditions.
 PQ should follow successful completion of IQ
and OQ.
 PQ verifies that over time, the critical
parameters, as defined in the DQ are being
achieved.

37. Water system validation (generation and distribution) should
contain three phases:
Phase I: investigation phase;
Phase II: short-term control; and
Phase III: long-term control.
When water system has operationally verified,
performance qualification step comes.

38. Phase I Validation :
1. This is preliminary phase and requires a 2 – 4
weeks (14 days minimum) testing period in
order to monitor the system deeply.
Chemical and microbiological testing should
include in accordance with a defined plan
Phase II Validation :
1.This phase is continuity of previous
phase i-e phase I, it carries the sampling
plan same as previous phase plan & it also
facilitates the monitoring of system for 2 –
4 weeks (30 days) period.

39. Phase III Validation :
1.In this phase sampling locations and frequency reduced as
compared to previous phases.
2. Phase III represents that the water system shows reliable
under control attainment over such a long time period & Phase III
typically runs for one year after the satisfactory completion of
phase II.
3. Manufacturing can be done during phase III & Feed water
seasonal variations also evaluated & monitored in this Phase.
4. Complete microbiological and chemical analysis must be
carried out in phase III
5. Whole validation report should be compiled, written, reviewed
and approved as per company’s standard procedure.

40. MAINTENANCE
A controlled, documented maintenance covering :
 Defined frequency with plan and instructions
 Calibration programme
 SOPs for tasks
 Control of approved spares
 Record and review of problems and faults during
maintenance

41. MAINTENANCE
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

42. REVALIDATION & CHANGE CONTROL
 Once the validation is completed, the standard operating
procedures (SOPs) are formalized.
 Routine operation should be performed according to the
established SOP.
 If any deviation from SOP observed, determine the change
and their impact on whole system
 Revalidation and evaluation should be performed
depending upon the impact of the change on system.

43. VALIDATION REPORT
 Written at the conclusion of the equipment IQ, OQ
and at completion of process validation.
 Will serve as primary documentation for FDA
regulatory inspection
 Will serve as reference document when changes to
the system are occurred and revalidation is needed.

44. Complete Documentation
 Verification of design documentation, including
◦ Description of installation and functions
◦ Specification of the requirements
 Instructions for performance control
 Operating procedures
 Maintenance instructions
 Maintenance records
 Training of personnel (program and records)
 Environmental records
 Inspection of plant
Finally certification (Sign Off) by Engineering,
User (Production) and QA Heads.

46. THANK YOU ALL
FOR
YOUR KIND PRESENCE