Validation Protocol PDF

Annex A ERCROS 02/12 Validation Protocol Rev.
1
Pag. 1 / 16
Performance Qualification (PQ)

Purified Water System Validation Protocol
Multipurpose Synthesis Plant (PMS)
TABLE OF CONTENTS
0- DOCUMENT HYSTORY
1- OBJECTIVE
2- DOCUMETATION
2.1 Related Documentation
2.2 Applicable Documentation
3- VALIDATION TEAM
4- SCOPE
5- METHODOLOGY
5.1 System Validation
5.2 Description of purified water system
5.3 Quality Critical Attributes for purified water
5.4 Qualification strategy
5.5 Performance Qualification tests
5.5.1 Assessment of compliance with Standard Operating Procedures
5.5.2 Testing of purified water quality
6- ACCEPTANCE CRITERIA
6.1 Acceptance criteria for compliance with SOPs
6.2 Acceptance criteria for purified water quality
6.3 Deviations and conclusions
7- PROTOCOL APPROVAL
Appendix I Site general plan 90-A3-1624 Rev. 12

Appendix II Sampling plan
Appendix III Purifying plant and loop sampling points plans
Annex A ERCROS 02/12 Validation Protocol Rev. 1

Pag. 2 / 16
0. DOCUMENT HYSTORY
Previous document edition:
Annex A ERCROS 02/12 Validation Protocol February 2012
Changes involved:
Following FDA recommendations this document is reviewed and updated in order to complete the
validation study. The main considerations included are:
-
Identification and evaluation of the critical elements for the purified water system.
Evaluation of the quality of the water at each step in the purification process
Evaluation of the quality of the water at each point of use
Complete microbial and endotoxin concentration analysis of purified water.

Pag. 3 / 16
1. OBJECT
The aim of this study is to demonstrate the consistent and reliable performance of the purified
water production system located in Multipurpose Synthesis Plant (PMS) Building 54, which
ensures that the system produces water appropriate for its intended use in a repetitive manner.
This validation study is carried out after Operational Qualification step and is part of the
Performance Qualification study. It should be evaluated together with initial study ERCROS PQ
013/10.
In addition, this validation study is intended to assess the suitability of production, control and
maintenance of the system in the quality management system.
2. DOCUMENTATION
2.1 Related Documentation
Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients (ICH Q7)
USP 35 monograph Purified Water
European Pharmacopoeia 7.0 monograph Purified Water
2.2 Applicable Documentation
Operating and maintenance handbook Volume IV. (Afarvi)

ERCROS-1697 Purified Water Specification Sheet
ERCROS-4104 Process water sampling SOP
ERCROS-4111 Process water general testing SOP
ERCROS-4303 Process water microbiological testing SOP
3. VALIDATION TEAM
Validation team responsible of carried out this qualification step is consisted of responsible
persons of each involved department. They are shown in following table as well as their
responsibility:

Pag. 4 / 16
Department
PMS Production
Quality Control
Quality Assurance
Responsible / Position
Responsibilities
Assistant of Synthesis Area

Production
Process data recording; defining of

process critical parameters and their
acceptance criteria; defining of
SOPs, equipment and other critical
information; protocol drafting.
Quality Control Assistant
Analytical data recording; defining of

critical quality attributes and their
acceptance criteria; defining of
SOPs, specifications and other
critical information; collaboration in
protocol drafting.
Quality Assurance Assistant
Coordinator; supervision of protocol

and recorded data; statistical
analysis; ensuring of compliance of
documentation with current legal
requirements; protocol approval and
writing of reports.
4. SCOPE
Purified water production plant which supplies water to Multipurpose Synthesis Plant (PMS)
located in Building 54. Refer to site general plan 90-A3-1624 Rev. 12 provided as Appendix I.
This validation protocol considers the performance qualification of production, storage and
distribution of the purified water produced in this plant.
5. METHODOLOGY
5.1 System Validation
Performance Qualification (PQ) step is performed after the qualification of Design (DQ); Installation
(IQ) and Operation of the purified water production plant.
These qualification steps have been properly performed and the supported documentation is
codified as described below:
-
Design qualification:
Installation qualification:
Operational qualification:
Initial Performance Qualification:
DQ 040/04 and DQ 041/04

IQ 040/04 and OQ 041/04
OQ 040/04 and PQ 041/04
PQ 013/10
For performance requalification purposes, two different steps should be considered:

-
First step: during this phase it is demonstrated that the system consistently produces the
desired water quality without failure or performance deviation when operates in
conformance with the stated SOPs.

Pag. 5 / 16
During this period the system is intensively monitored. The sampling is daily after each
step of purification process and at each point of use for three weeks (15 working days).
The validation approach includes:
-
Undertaking of chemical and microbiological testing.

Sampling the incoming feed-water daily to verify its quality.
Sampling after each step in the purification process daily.
Sampling at each point of use and at other defined sample points daily.
Demonstrate consistent production and delivery of water of the required quality
and quantity when the system is operated in accordance with SOPs.
Use and refine the SOPs for operation, maintenance and sanitization.
Verify and confirm stated alert and action levels.
Refine test-failure procedure.
After this initial step critical sampling points are confirmed as it.
After this initial study and whenever no critical deviation or failure of the system occurs, the
second step can address.
-
Second step: during this phase it is demonstrated that when the water system is operated
in accordance with stated SOPs over a long period of time.
The sampling is daily from a minimum of two critical points, with at least all points of use
tested weekly, for a full year worth of data. The validation approach includes:
- Demonstrate extended reliable performance.
- Ensure that seasonal variations are evaluated.
- The sample locations, sampling frequencies and routine monitoring.
After this validation step, final routine water monitoring program will be stated.
As appendix II is included a spreadsheet in which it is shown the samples to be taken in
both steps as well as it frequency.
5.2 Description of purified water system

The facility consists of a purified water production plant (pretreatment; reverse osmosis and water
purifying systems); a storage tank and a loop that supply purified water to the points of use.
Steps of water purifying and distribution are described as follows. In addition cleaning and
sanitization of the system is described too:
WATER PURIFYING PLANT
Pretreatment
This step is considered as critical since the objective is to treat in the first instance the incoming
potable feed water in order to avoid fluctuations of physic-chemical characteristics of water that
could affect the reverse osmosis system. Consist of the following steps:
a) Silex / anthracite filter
In this step particles in suspension larger than 30 microns are retained and colloidal matter is
minimized.
b) Duplex decalcification unit
In this step calcium and magnesium ions are retained in ion-exchange resins.
c) Microfiltration 10 microns
This additional filtration ensures the protection of reverse osmosis membranes.

Pag. 6 / 16
d) Addition of bisulphite
By means of bisulphite addition, chlorine from the water system is neutralized, which prevents
reverse osmosis membranes with polyamide composition can be damaged.
Bisulphite remove other oxidants dissolved in water by means of its reduction power and has a
bacteriostatic effect since oxygen dissolved is minimized.
This process is automatically controlled and performed.
In addition, this production plant is provided with a sanitization and cleavage tank and additional
microfiltration system that ensures the suitable flow conditioning and pressure and supports the
cleaning and sanitization procedures.
Sanitization and cleavage tank
After previous microfiltration, water is storage in the cleavage tank. From this tank water is
pumping to the reverse osmosis membranes. In addition, the tank fulfils the following functions:
-
Feeding tank: whenever the water after electrodesionization system has not the desired
quality, it is returned to this tank. The system automatically makes the feeding of
subsequent equipment independent of flow and pressure.
Cleaning of membranes: periodically, in order to avoid the potential blockage of

membranes, the tank pumps water at low pressure when the production has stopped.
Sanitization: the tank is provided with an element that can heat the water at 80 C for
sanitization purposes.
The loop is provided with a heat exchanger that heats the water to more than 80 C in
order to sanitize the complete system.
Chemical cleaning: cleaning products are dissolved in this tank.
Microfiltration 1.5 microns

This additional filtration ensures the remove of particles in suspension and the additional protection
of reverse osmosis membranes.
The system is controlled by means of a redox-meter that checks the level of chlorine in water and
sends the corresponding signals to the system in order to allow water recirculation again in case of
its presence is too higher.
The potential influence of this treatment on membranes and final quality of water justifies that
system Performance Qualification includes sampling before and after this pre-treatment in order to
verify the correct operation.
-
Reverse osmosis
By means of this treatment, water is subjected to pressure and forced to pass through a
semipermeable membranes across which salts or impurities cannot pass.
These membranes remove 90 98 % of inorganic ions, non-ionic contaminants and organic
molecules with a weight more than 200 (colloidal matter, bacteria, pyrogens), which makes that
this step is considered critical.
The system is provided with a high pressure pump that forces the water to flow through the
membrane surface.
Two different and complementary steps with two membranes per step compose the system.

Pag. 7 / 16
The potential influence of this treatment on membranes and final quality of water justifies that
system Performance Qualification includes sampling before and after reverse osmosis in order to
verify the correct operation.
-
Purifying system
This step is considered as critic since by means of this treatment, water is subjected to an electrodes-ionization E-cell system in order to perform a chemical polishing of osmotic water.
The application of electric power in the system removes salts dissolved in water by means of
conventional ionic exchange resins.
In addition, the bactericidal action is carried out by a UV lamp which treats the water after E-cell
system.
In order to verify the correct performance of the purifying system and final quality of water
Performance Qualification includes sampling before and after electro-des-ionization E-cell system
and UV-lamp.
STORAGE AND DISTRIBUTION
Alter purifying system, water is storage in a storage tank and distributed to every point of use in the
PMS manufacturing plant by means of a loop.
3
Purified water is maintained in the loop under constant flow at 1m /h which avoids point of
stagnant water. In addition and in order to ensure and avoid the microorganism presence the
system is provided with a UV lamp which treats the water after storage tank and prior to its
distribution to the points of use.
In order to verify the correct control of microorganism presence and the potential contamination of
storage tank, Performance Qualification includes sampling after storage tank and before and after
UV-lamp.
-
Points of use
The loop feeds every point of use in the manufacturing plant.

In order to verify the correct distribution of the purified water and identify potential sources of
contamination, Performance Qualification includes sampling in every point of use.
In addition, to ensure the correct recirculation of water and no influence of the loop in water quality,
sampling at return hose is performed too.
WATER PURIFYING PLANT
Sanitization
For sanitization purposes the system is provided with a heat exchanger that allows raising the loop
temperature to 80 85 C.
The procedure is automatically controlled once it is starting. The frequency converter that controls
the feeding pump (SW-P-001) as well as opening and closing of the other valves is automatically
controlled.
Osmotic water is storage in the sanitization and cleavage tank and heated to 80 85 C. Once the
temperature is reached (controlled by means of a TT-001 probe) it is distributed though the

Pag. 8 / 16
purifying system and the loop and maintained under recirculation. During this procedure all the
points of use should be open in order to ensure that opening valves are sanitized too.
The whole sanitization procedure takes approximately 90 120 minutes.
Once the recirculation has finished, water is cooled by means of a default cooling gradient. Once
the water is at operation temperature, it is drained and the usual production cycle starts.
This procedure should be performed after a planned long stoppage (holiday period), after a break
whenever the repairs takes more than 24 hours and/or whenever an analytical parameter is out of
specifications. In addition as part of preventive maintenance program, this procedure could be
performed quarterly.
-
Chemical Cleaning
The aim of this procedure is to remove the damaging substances and materials that cold be
accumulated in the reverse osmosis membranes (colloids, metals, organic matter, biological
compounds) in order to avoid an irreversible damage.
Some evidences that could appear as it or together with other/s show that membranes should be
cleaned, these are for instance:
-
Loosing of load (10 - 15%)

Water conductivity is increased in 15%
Nominal flow decrease (at standard T 20C) in 15%
Accumulation of salts
Accumulation of organic and inorganic materials
Biological contamination in equipments or pipes
Cleaning procedure is performed in the usual operating and acid or base solution could be used.
The procedure takes the following steps:
1.
2.
3.
4.
5.
6.
Preparation of Cleaning solution

Pumping at low pressure
Recirculation of cleaning solution
Draining
Pumping at high flow
Removing of cleaning solution
Once the cleaning has finished, the rejected water and treated water is removed until conductivity
parameter decrease and operating parameters are as usual operating.
5.3 Critical Quality Attributes (CQAs) for Purified Water

According to ICH Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients,
water used in the manufacture of APIs should be demonstrated to be suitable for its intended use.
In this context and in our specific case, water should comply with requirements as laid down in
current edition of official USP and European Pharmacopoeia monographs for purified water. The
parameters established in the monograph are considered as Critical Quality Attributes.
In addition, and taking into account that the product can be used in the production of sterile drug
products, microbial and endotoxin content should be assessed and considered as Critical Quality
Attributes.
In following table are summarized the CQAs and their limits. Reference to internal code for
methods of analysis is included too:

Pag. 9 / 16
PURIFIED WATER
TEST
1
Appearance
Nitrates
UNITS
SPECIFICATIONS*
INTERNAL SOP
Clean liquid, transparent,

colorless and odorless
ERCROS-4111
NMT 0.2
ERCROS-4111
S cm
NMT 1.3 (at 25 C)
ERCROS-4111
mg / l
NMT 0.5
ERCROS-4260
mg / l
-1
Conductivity
TOC
Total Germs Viable
Germs / ml
NMT 100
ERCROS-4303
Bacterial Endotoxin
IU/ml
NMT 0.25
ERCROS-4047
NMT: No more than

* According to official USP / European Pharmacopoeia monographs.
5.4 Qualification Strategy

The qualification strategy is based on the system validation described in section 5.1. The main
objective is to check and verify that the critical production steps identified in section 5.2 for purified
water system fulfill their functions correctly.
In a first instance, it should be ensured that incoming water is suitable for the system feeding and
from this point, the following topics should be considered for assessing:
-
Correct using of SOPs for operation, maintenance and sanitization.

Performance of pretreatment step.
Performance of reverse osmosis step.
Performance of storage and distribution steps.
Quality of water in points of use and return hose.
5.5 Performance Qualification Tests

Two different approaches should be taken into account for qualification purposes:
1- Assessment of compliance with Standard Operating Procedures
2- Testing of purified water quality
5.5.1 Assessment of compliance with Standard Operating Procedures

5.5.1.1 Objective
The aim of this test is to ensure by writing evidences that the Operating and Maintenance SOP
described properly the production and distribution of purified water.
In addition alarm system will be verified. In this context, whenever al alarm is detected and informed
by the system, it should be recorded in appropriate section of Annex B. The cause of every alarm
should be properly investigated according to ERCROS 4008 Investigation of Deviation internal SOP.
The SOPs will be checked by means of verification of every item described in the corresponding
check-list.
Every check-list has been drawn up on the basis of the procedures and steps described in internal
SOPs and taking into account the worst-case in every situation.

Pag. 10 / 16
Worst-case:
-
Production step: starting the production after a stoppage which involves a cleaning of
membranes and sanitization treatment.
Storage and distribution step: starting the system after a stoppage which involves a
sanitization treatment.
The tests should be performed by PMS Plant staff since they are usually who operates in the Water
Purifying Plant and supervised by PMS Manager.
5.5.1.3 Records
The following check-list should be fulfilled:
-
Annex B Water Purifying; Distribution and Sanitization of the system data check-list
5.5.2 Testing of Purified Water Quality

5.5.2.1 Objective
The aim of this test is to ensure by writing evidences that the purified production system produces
in a consistent and repetitive way purified water of the desired quality and only this water is
distributed to the loop.
In addition, it will be verified that the loop has no influence in water quality and bacteriostatic level
in maintained.
5.5.2.2 Methodology
Taking into account the critical production steps considered in section 5.2 Description of Purified
Water System, water quality will be tested as follows.
The first step of this performance qualification study should be considered all the sampling point
described below. After this step, critical point (defined below and remarked in bold with *) will be
sampled during the second step during a whole year of worth data.
As Appendix III is provided a sketch of the purifying plant and loop which includes sampling points and
the desired quality of water in each one.
A Purifying plant:
a) Water pretreatment checking:
1. Sampling of incoming feed water. (VHB 001)
2. Sampling at the end of pretreatment (VHD 003)
b) Reverse osmosis checking:
1. Sampling at the end of pretreatment (VHD 003). This sampling point is the same
mentioned above.
2. Sampling at the end of reverse osmosis treatment (VHD 007)
c) Purifying system checking.
1. Sampling at the end of reverse osmosis treatment (VHD 007). This sampling point is the
same mentioned above.
2. Sampling after electrodeionization treatment (VHD 010)
3. Sampling after UV lamp (VHD 011)

Pag. 11 / 16
B Storage and distribution

a) Storage tank checking:
1. Sampling before storage tank (VHD 011). This sampling point is the same mentioned
above.
2. Sampling after storage tank (SV 541 001)
b) UV lamp checking:
1. Sampling after storage tank (SV 541 001). This sampling point is the same mentioned
above.
2. Sampling after UV lamp (SV 541 002)
c) Points of use checking:
1. Sampling at every point of use (refer to table below)*
d) Water recirculation checking:
1. Sampling at return hose*.
In table below is summarized all considered sampling points; their location their identification and
the water quality desired in each one.
Sampling points marked with * are those considered as critical and they should be sampled in the
second step of this performance qualification during a whole year of worth data.

Pag. 12 / 16
Sampling sketch
Sampling point
Identification
Location
Quality
a1) VHB 001
VHB 001
Incoming feed water
Potable water
a2) VHD 003
VHD 003
After 1.5 mc microfiltration unit
Potable water
b2) VHD 007
VHD 007
After reverse osmosis system
Osmotic water
c2) VHD 010
VHD 010
After electrodesionization
system
Purified water
c3) VHD 011
VHD 011
After UV lamp UVA
Purified water
Purifying Plant (A)
Storage and Distribution (B)

a2) SV 541 001
SV 541 001
After storage tank and before

UV lamp
Purified water
b2) SV 541 002
SV 541 002
After UV lamp
Purified water
d1) SV 541 003
SV 541 002
At return hose
Purified water
c1) Points of use

DC-0502-00
Reactor
PU-5
DC-0501-00
Reactor
PU-4
DC-0504-00
Reactor
PU-3
DC-0507-00
Reactor
PU-2
DC-0508-00
Reactor
PU-1
DF-0532-02
DF-0532-03
Dissolution Tanks
DF-0532-00
DF-0532-01
Dissolution Tanks
PU-8
PU-9
JL-0512-00
Centrifuge
PU-6
Laboratory
PU-11
DF-0531-00
DF-0531-01
Dissolution Tanks
PU-10
JL-0511-00
Centrifuge
PU-7
EI-0521-00
Drier
PU-12
Level 2.
Intake drainage valve at
DC-0502-00 reactor
Level 2.
DC-0501-00 reactor
Level 2.
DC-0504-00 reactor
Level 2.
DC-0507-00 reactor
Level 2.
DC-0508-00 reactor
Level 2.
Intake common drainage valve
at auxiliary tanks
Level 2.
at auxiliary tanks
Level 1.
JL-0512-00 centrifuge
Level 1.
Laboratory
Level 0.
at auxiliary tanks
Level 0.
Level 0.
Drier room
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water

Pag. 13 / 16
5.5.2.2.1 Analytical test and methods

In following tables are summarized the tests performed for every quality of water and reference to
internal SOPs.
PURIFIED WATER
TEST
1
Appearance
Nitrates
UNITS
SPECIFICATIONS*
INTERNAL SOP
Clean, transparent, colorless

and odorless liquid
ERCROS-4111
NMT 0.2
ERCROS-4111
S cm
NMT 1.3 (at 25 C)
ERCROS-4111
mg / l
NMT 0.5
ERCROS-4260
mg / l
-1
Conductivity
TOC
Total Germs Viable
Germs / ml
NMT 100
ERCROS-4303
Bacterial Endotoxin
IU/ml
NMT 0.25
ERCROS-4047
NMT: No more than

* According to official USP / European Pharmacopoeia monographs.
OSMOTIC WATER
TEST
1
Appearance
Nitrates
UNITS
SPECIFICATIONS*
INTERNAL SOP

and odorless liquid
ERCROS-4111
NMT 5
ERCROS-4111
S cm
NMT 200 (at 25 C)
ERCROS-4111
mg / l
NMT 3
ERCROS-4260
mg / l
-1
Conductivity
TOC
Total Germs Viable
Germs / ml
NMT 100
ERCROS-4303
Bacterial Endotoxin
IU/ml
**
ERCROS-4047
NMT: No more than

* According to internal established specifications.
** No specification is established for endotoxins in osmotic water. Obtained result is only for
information and it should be taken into account for checking the capacity of purified water
system for endotoxins removing.

Pag. 14 / 16
POTABLE WATER
TEST
UNITS
SPECIFICATIONS*
INTERNAL SOP

and odorless liquid
ERCROS-4111
Appearance
Calcium
mg / l
NMT 500
ERCROS-4111
Chlorides
mg / l
NMT 250
ERCROS-4111
Sulfates
mg / ml
NMT 250
ERCROS-4111
Nitrates
mg / l
NMT 50
ERCROS-4111
Ammonium
mg / l
NMT 0.5
ERCROS-4111
pH
pH
6.5 9.5
ERCROS-4111
Total Solids
mg / l
NMT 1000
ERCROS-4111
Heavy metals (Pb)
g / l
NMT 0.25
ERCROS-4111
mg / l
NMT 1.3
ERCROS-4111
S cm-1
NMT 2500
ERCROS-4111
mg / l
NMT 5
ERCROS-4260
Germs / ml
NMT 100
ERCROS-4303
Absence
ERCROS-4303
IU/ml
**
ERCROS-4047
10 Organic matter
11 Conductivity
12 TOC
13 Total Germs Viable
14 Escherichia coli
15 Bacterial endotoxins
NMT: No more than

* According to internal established specifications.
** This test will be performed only at point identified as VHB 001 with the aim of knowing the
endotoxin burden of incoming water.
Endotoxins test at point VHD 003 has not been considered since any treatment to remove or
minimize endotoxins content has been performed at this point.
No specification is established for endotoxins in potable water. Obtained result is only for
information and it should be taken into account for checking the capacity of purified water
system for endotoxins removing.
Detailed description of method of analysis to be performed for each sample is described in the
corresponding internal SOPs. (Refer to section 2.2. Applicable Documentation).
5.5.2.2.2 Sampling method
Sampling should be performed once the purified plant and loop are normally working.
Sampling during this validation step will be daily for 15 working days. It should be recorded date
and time (in sample label) of sampling in every sample.
Sampling date should be recorded as follows:
Sampling point / day / month (two digits) / year (two digits)
Example: sample taken at VHD 007 on July 14th, 2012, should be identified as follows:
VHD 007 / 14 / 07 /12
Two different labels are available depending on the test. Label model is as follows:

Pag. 15 / 16
Chemical Tests
Purified Water
Microbiological
Control
Purified Water
Sampling Point / Date
Sampling Point / Date
Analyst
Analyst
Initials / Signature
Initials / Signature
The label should be fulfilled just before sampling and stick to the bottle immediately.
The sampling should be performed according to the instructions given in ERCROS-4104 Process
water sampling internal SOP. A brief summary of this procedure is provided below:
Process water sampling should be carried out by Quality Control Laboratory staff.
It should be taken into account the test to be performed and prepare the material needed for
sampling and testing according to this.
In this context, sampling material for endotoxins test should be prepared in non-pyrogenic
conditions by Quality Control staff and material for microbiological analysis should be
prepared and maintained in sterile conditions.
For other chemical analysis is enough that the material is properly clean.
The general operating procedure is as follows:
1. Check that the drain or faucet is clean. Otherwise, clean them.
2. Open the drain or the faucet and let the water run a few minutes (5 minutes).
3. Open the bottle where it will take the sample and rinse with the same water
to be taken. Pull the water.
Sample for TOC and conductivity should be approximately 500 mL in non-sterile bottle
and sample for total viable germ should be approximately 200 mL in sterile bottle.
4. Fill the bottle completely and cover it perfectly. Label the form unequivocally dated,
internal code and plant.
5. Transfer the sample to the laboratory as soon as possible.
5.5.2.3 Records
Analytical data should be recorded in Annex C of this validation study and in ERCROS 4111
Process water general testing record data sheet.
6.
ACCEPTANCE CRITERIA
6.1 Acceptance criteria for compliance with SOPs

Acceptance criteria for this test is that check lists provided as Annex B and Annex C are fulfilled
following the tested SOP and every item is recorded as positive.
The procedure is considered valid if quality water meets established specifications after tests
described in section 5.5.2.

Pag. 16 / 16
6.2 Acceptance criteria for purified water quality

Acceptance criteria for this test is that every sample taken and tested as described in section 5.5.2
meets established specifications for its quality.
6.3 Deviations and conclusions

Deviations occur during validation should be recorded in the deviation sheet provided at the end of
the corresponding annex.
Results and conclusions will be summarized in the Validation Report.
7.
PROTOCOL APPROVAL

Appendix II
APPENDIX II

Appendix II
First Step
Frequency
Sampling Point
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
VHB 001
VHD 003
VHD 007
VHD 010
VHD 011
SV 541 001
SV 541 002
SV 541 002
PU-5
PU-4
PU-3
PU-2
PU-1
PU-8
PU-9
PU-6
PU-10
PU-7
PU-11
PU-12

Appendix II
Second Step
Even-numbered weeks:
Day 1
Sampling
Point
Chemical
SV 541 002
PU-5
PU-4
PU-3
Day 2
Microbiological
Chemical
Day 3
Microbiological
Chemical
Day 4
Microbiological
Day 5
Chemical
Microbiological
PU-6
PU-10
PU-7
Chemical
Microbiological
PU-2
PU-1
PU-8
PU-9
PU-11
PU-12

Appendix II
Odd-numbered weeks:
Sampling
Point
SV 541 002
PU-5
PU-4
PU-3
PU-2
PU-1
PU-8
PU-9
PU-6
PU-10
PU-7
PU-11
PU-12
Day 1
Day 2
Chemical
Microbiological
Day 3
Chemical
Microbiological
Day 4
Chemical
Microbiological
Chemical
Day 5
Microbiological
Chemical
Microbiological
x
x
x
x
x

Appendix III
APPENDIX III

Appendix III
Water Purifying System

Appendix III
Points of use

Appendix III

Appendix III
Annex B ERCROS 02/12 Validation Protocol Rev. 1

Pag. 1 / 8
Compliance with Standard Operating Procedures Check-list
TABLE OF CONTENTS
1- TABLE 1 Purifying step

2- TABLE 2 Distribution and sanitization steps
PREPARED BY:
Date and signature
SUPERVISED BY:
Date and signature
APPROVED BY:
Date and signature

Pag. 2 / 8
TABLE 1
Starting and operating of purifying system after stoppage
Step
Operation
Results
Bisulphite
removing
Press button:
Proceso despus de
parada de larga
duracin
Manual
Bisulphite
removing
Send Bisulphite
Solution to sewage
Manual
Bisulphite
removing
PLC shows:
CONECTAR LAS
CONEXIONES DE
LIMPIEZA DE
PERMEADO Y
RECHAZO CON
DRENAJE.
Automatic
Bisulphite
removing
Connect and press

ACCEPT
Manual
Bisulphite
removing
Decalcified water
loading starts
Automatic
Bisulphite
removing
High and low

pressure pumping
start
Automatic
Bisulphite
removing
Stop pumps
Automatic
Bisulphite
removing
Bisulphite
removing
E-cell system
regeneration
E-cell system
regeneration
E-cell system
regeneration
E-cell system
regeneration
E-cell system
regeneration
PLC shows:
VOLVER A
CONECTAR
CLAMP CIEGO EN
LAS
CONEXIONES DE
LIMPIEZA.
Connect the Clamp
and press ACCEPT
Opening of valves:
VHB-010, VHB-011,
VHD-012 and
VHD-008.
Close VPD-008 and
open VPD-009
Starting the preosmosis and
reverse osmosis for
this valve
Stabilize the inlet
flow
Starting the
concentrate
recirculation pump
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Manual
Yes
No
Manual
Yes
No
Yes
No
Manual
Manual
Manual
Manual
Supervised by
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Yes
No
Automatic
Performed by:
Yes
No
Yes
No

Pag. 3 / 8
Step
Operation
E-cell system
regeneration
Stabilize the flow of

concentrate:
Inlet Pressure from
0.3 to 0.6 bars
Outlet Pressure
from 0.3 to 0.6 bars
Manual
E-cell system
regeneration
Adjust the flow of

purge concentrate
Manual
E-cell system
regeneration
Verification of
suitability of flow
rates and pressures
E-cell system
regeneration
E-cell system
regeneration
Normal Start
Normal Start
Normal Start
Normal Start
Normal Start
Normal Start
Normal Start
Normal Start
Normal Start
Starting the rectifier

Water quality and
flow (parameters
shown at PLC) are
suitable
Press button:
NORMAL
OPERATION
Enter Password
Confirm the
password for the
computer and the
screen
Message appears:
NORMAL
OPERATION
Operation of UV
Lamp
Correct
Pretreatment Cycle
Correct
Osmosis Cycle
Correct Water Cycle
of Refinement
Correct water return
to sanitization and
cleavage tank
Results
Yes
No
Yes
No
Manual
Yes
No
Manual
Yes
No
Manual
Manual
Automatic
Yes
No
Yes
No
Yes
No
Automatic
Yes
No
Manual
Yes
No
Automatic
Yes
No
Automatic
Automatic
Yes
No
Yes
No
Yes
No
Automatic
Supervised by
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Date / Sign.
Yes
No
Manual
Performed by:

Pag. 4 / 8
Alarms Detected:
Date / Signature:
Remarks:
Date / Signature:
Results and conclusion:

Number of Positive responses:
Number of Negative responses:
Conclusion*:
*The test is considered valid only if all the questions are positive.
Performed by:
Date / Signature
Supervised by:
Date / Signature

Pag. 5 / 8
TABLE 2
Starting and operating of distribution and sanitization after stoppage

Step
Starting
Starting
Starting
Operation
Verify that all the
points of use are
closed.
Verified that storage
tank valve is closed.
Verify that all the
pumping and
intaking valves are
closed.
Starting
Verify that purifying

system is operation.
Starting
Verify the availability

of comprised air.
Starting
Verify the availability

of electric power.
Starting
Starting
Starting
Starting
Starting
Starting
Turn off the general

switch in the electric
frame.
Release emergency
stop.
Connect all the
switches and fuses
in electric frame.
Verify screen is on.
Press button:
CONSIGNAS.
Verify that operating
parameters shown in
the screen are
correct and no
alarms are shown.
Starting
Press button:
AUTOMATICO.
Starting
Press button:
MARCHA LOOP.
Starting
Verify that water is

entering in storage
tank.
Results
Manual
Manual
Manual
Manual
Manual
Manual
Manual
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Yes
No
Manual
Yes
No
Manual
Manual
Yes
No
Yes
No
Manual
Yes
No
Manual
Manual
Automatic
Supervised by
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Yes
No
Manual
Performed by:
Yes
No
Yes
No
Yes
No

Pag. 6 / 8
Step
Starting
Operation
Verify the correct
level of water for
pumping starts.
Starting
Pumping system
starts.
Starting
Speed of water
return is regulated.
Starting
Starting
Starting
Sanitization
Sanitization
Sanitization
Sanitization
Sanitization
Sanitization
Sanitization
Sanitization
Sanitization
UV lamp starts.
Valves at points of
use operate
correctly.
Valves at sampling
points operate
correctly.
Verify the operating
program is:
AUTOMATICO
Verify the system is
operating.
Verify that no
consume is any
point of use.
Verify availability of
cool water and
steam.
Verify valves at
steam entrance;
condenser returns;
cool water entrance
and cool water
return are open.
Start sanitization
program.
Confirmation.
Storage tank
draining.
Valve in storage
tank is in draining
position.
UV lamp starts.
Results
Automatic
Yes
No
Automatic
Yes
No
Automatic
Yes
No
Automatic
Yes
No
Automatic
Manual
Manual
Manual
Manual
Manual
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Yes
No
Yes
No
Yes
No
Date
Yes
No
Supervised by
Yes
No
Automatic
Performed by:
Yes
No
Yes
No
Manual
Yes
No
Automatic
Yes
No
Automatic
Yes
No
Automatic
Yes
No

Pag. 7 / 8
ETAPA
Sanitization
Sanitization
Sanitization
Sanitization
Sanitization
Sanitization
Normal
operation
ACCIN
Purge
Heating
Water is maintained
hot during
sanitization.
Purge.
Cooling.
Water is at operating
temperature.
Water is available at
every point of use.
CONFORMIDAD
Automatic
Automatic
Yes
No
Yes
No
Automatic
Yes
No
Automatic
Automatic
Yes
No
Yes
No
Automatic
Yes
No
Yes
No
Automatic
REALIZADO
VERIFICADO
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date
Date

Pag. 8 / 8
Alarms Detected:
Date / Signature:
Remarks:
Date / Signature:
Results and conclusion:

Number of Positive responses:
Number of Negative responses:
Conclusion*:
*The test is considered valid only if all the questions are positive.
Performed by:
Date / Signature
Supervised by:
Date / Signature
Annex C ERCROS 02/12 Validation Protocol Rev. 1

Pag. 1 / 29
Sampling Control and Data Record
TABLE OF CONTENTS
1. Introduction
2. Sampling record template
3. Analytical data record template
PREPARED BY:
Date and signature
SUPERVISED BY:
Date and signature
APPROVED BY:
Date and signature

Pag. 2 / 29
1.
INTRODUCTION
A very important part of Performance Qualification step of this purifying water system involves
sampling and testing of water along the whole production and distribution.
This annex covers and compiles sampling, codification of samples, acceptance criteria and
obtained results.
In table below is summarized considered sampling points; their location their identification and
the quality desired in each one.
During the first step of this qualification study, every point listed below should be sampled
during 20 days. After this step and whenever no critical deviation or failure of the system occurs,
only critical points (marked in bold) will be tested during a whole year of worth data.

Pag. 3 / 29
Sampling sketch
Sampling point
Identification
Location
Quality
VHB 001
VHB 001
Incoming feed water
Potable water
VHD 003
VHD 003
After 1.5 mc microfiltration unit
Potable water
VHD 007
VHD 007
After reverse osmosis system
Osmotic water
VHD 010
VHD 010
After electrodesionization
system
Purified water
VHD 011
VHD 011
After UV lamp UVA
Purified water
SV 541 001
SV 541 001
After storage tank and before

UV lamp
Purified water
SV 541 002
SV 541 002
After UV lamp
Purified water
SV 541 003
SV 541 002
At return hose
Purified water
Purifying Plant
Storage and Distribution
Points of use
DC-0502-00
Reactor
PU-5
DC-0501-00
Reactor
PU-4
DC-0504-00
Reactor
PU-3
DC-0507-00
Reactor
PU-2
DC-0508-00
Reactor
PU-1
DF-0532-02
DF-0532-03
Dissolution Tanks
DF-0532-00
DF-0532-01
Dissolution Tanks
PU-8
PU-9
JL-0512-00
Centrifuge
PU-6
Laboratory
PU-11
DF-0531-00
DF-0531-01
Dissolution Tanks
PU-10
JL-0511-00
Centrifuge
PU-7
EI-0521-00
Drier
PU-12
Level 2.
DC-0502-00 reactor
Level 2.
DC-0501-00 reactor
Level 2.
DC-0504-00 reactor
Level 2.
DC-0507-00 reactor
Level 2.
DC-0508-00 reactor
Level 2.
at auxiliary tanks
Level 2.
at auxiliary tanks
Level 1.
Level 1.
Laboratory
Level 0.
at auxiliary tanks
Level 0.
Level 0.
Drier room
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water
Purified water

Pag. 4 / 29
2.
SAMPLING RECORD TEMPLATE
Purifying Plant
Sampling Point:
Sampling Date
VHB 001
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 5 / 29
Sampling Point:
Sampling Date
VHD 003
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 6 / 29
Sampling Point:
Sampling Date
VHD 007
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 7 / 29
Sampling Point:
Sampling Date
VHD 010
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 8 / 29
Sampling Point:
Sampling Date
VHD 011
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 9 / 29
Storage and Distribution
Sampling Point:
Sampling Date
SV 541 001
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 10 / 29
Sampling Point:
Sampling Date
SV 541 002
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 11 / 29
Sampling Point:
Sampling Date
SV 541 003
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 12 / 29
Points of use
Sampling Point:
Sampling Date
PU-5
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 13 / 29
Sampling Point:
Sampling Date
PU-4
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 14 / 29
Sampling Point:
Sampling Date
PU-3
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 15 / 29
Sampling Point:
Sampling Date
PU-2
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 16 / 29
Sampling Point:
Sampling Date
PU-1
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 17 / 29
Sampling Point:
Sampling Date
PU-8
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 18 / 29
Sampling Point:
Sampling Date
PU-9
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 19 / 29
Sampling Point:
Sampling Date
PU-6
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 20 / 29
Sampling Point:
Sampling Date
PU-11
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 21 / 29
Sampling Point:
Sampling Date
PU-10
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 22 / 29
Sampling Point:
Sampling Date
PU-7
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 23 / 29
Sampling Point:
Sampling Date
PU-12
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
Day 9
Day 10
Day 11
Day 12
Day 13
Day 14
Day 15
Day 16
Day 17
Day 18
Day 19
Day 20
Sample taken by:

(Initials and
signature)
Verify by:
(Initials and
signature)

Pag. 24 / 29
Deviations
Description
Affect the
validation study:
Date / Sign.
Yes
No
Remarks
Conforms
Non conforms
Final result:
Performed by:
Signature:
Date:
Verify by:
Signature:
Date:

Pag. 25 / 29
3.
ANALYTICAL DATA RECORD TEMPLATE
Complete the following record data sheet per taken sample and enclose copy of raw data
record:

Pag. 26 / 29
POTABLE WATER
Sampling Point:
Sampling date:
Test
Specification
Appearance
Clean, transparent,
liquid
Calcium
NMT 500 mg / l
Chlorides
NMT 250 mg / l
Sulfates
NMT 250 mg / ml
Nitrates
NMT 50 mg / l
Ammonium
NMT 0.5 mg / l
pH
6.5 9.5 pH
Total Solids
NMT 1000 mg / l
Heavy metals (Pb)
NMT 0.25 g / l
Organic matter
NMT 1.3 mg / l
Conductivity
NMT 2500S cm-1
TOC
NMT 5 mg / l
Total Germs Viable
NMT 100 Germs / ml
Escherichia coli
Absence
Bacterial
endotoxins*
(informative)
IU/ml
Result
* Only to be tested at point identified as VHB 001

Remarks
Analysis Date
Analyzed
by:
Verify by:

Pag. 27 / 29
OSMOTIC WATER
Sampling Point:
Sampling date:
Test
Specification
Appearance
Clean, transparent,
liquid
Nitrates
NMT 5 mg / l
Conductivity
NMT 200 (at 25 C)

S cm-1
TOC
NMT 3 mg / l
Total Germs Viable
NMT 100 Germs / ml
Bacterial Endotoxin
(informative)
IU/ml
Remarks
Result
Analysis Date
Analyzed
by:
Verify by:

Pag. 28 / 29
PURIFIED WATER
Sampling Point:
Sampling date:
Test
Specification
Appearance
Clean, transparent,
liquid
Nitrates
NMT 0.2 mg / l
Conductivity
NMT 1.3 (at 25 C)

S cm-1
TOC
NMT 0.5 mg / l
Total Germs Viable
NMT 100 Germs / ml
Bacterial Endotoxin
NMT 0.25 IU/ml
Remarks
Result
Analysis Date
Analyzed
by:
Verify by:

Pag. 29 / 29
Deviations
Description
Affect the
validation study:
Date / Sign.
Yes
No
Remarks
Conforms
Non conforms
Final result:
Performed by:
Signature:
Date:
Verify by:
Signature:
Date:

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Annex A ERCROS 02/12 Validation Protocol Rev.

Performance Qualification (PQ)

Appendix I Site general plan 90-A3-1624 Rev. 12

Annex A ERCROS 02/12 Validation Protocol Rev. 1

Annex A ERCROS 02/12 Validation Protocol Rev. 1

2.2 Applicable Documentation

Operating and maintenance handbook Volume IV. (Afarvi)

Annex A ERCROS 02/12 Validation Protocol Rev. 1

Assistant of Synthesis Area

Process data recording; defining of

Quality Control Assistant

Analytical data recording; defining of

Quality Assurance Assistant

Coordinator; supervision of protocol

DQ 040/04 and DQ 041/04

For performance requalification purposes, two different steps should be considered:

Annex A ERCROS 02/12 Validation Protocol Rev. 1

Undertaking of chemical and microbiological testing.

5.2 Description of purified water system

WATER PURIFYING PLANT

Annex A ERCROS 02/12 Validation Protocol Rev. 1

Cleaning of membranes: periodically, in order to avoid the potential blockage of

Chemical cleaning: cleaning products are dissolved in this tank.

Microfiltration 1.5 microns

Annex A ERCROS 02/12 Validation Protocol Rev. 1

STORAGE AND DISTRIBUTION

The loop feeds every point of use in the manufacturing plant.

WATER PURIFYING PLANT

Annex A ERCROS 02/12 Validation Protocol Rev. 1

Loosing of load (10 - 15%)

Preparation of Cleaning solution

5.3 Critical Quality Attributes (CQAs) for Purified Water

Annex A ERCROS 02/12 Validation Protocol Rev. 1

Clean liquid, transparent,

NMT 1.3 (at 25 C)

Total Germs Viable

NMT: No more than

5.4 Qualification Strategy

Correct using of SOPs for operation, maintenance and sanitization.

5.5 Performance Qualification Tests

5.5.1 Assessment of compliance with Standard Operating Procedures

Annex A ERCROS 02/12 Validation Protocol Rev. 1

5.5.2 Testing of Purified Water Quality

Annex A ERCROS 02/12 Validation Protocol Rev. 1

B Storage and distribution

Annex A ERCROS 02/12 Validation Protocol Rev. 1

a1) VHB 001

Incoming feed water

a2) VHD 003

After 1.5 mc microfiltration unit

b2) VHD 007

After reverse osmosis system

c2) VHD 010

c3) VHD 011

After UV lamp UVA

Purifying Plant (A)

Storage and Distribution (B)

After storage tank and before

b2) SV 541 002

d1) SV 541 003

c1) Points of use

Annex A ERCROS 02/12 Validation Protocol Rev. 1

5.5.2.2.1 Analytical test and methods