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.
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
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:
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 4 / 16

Department Responsible / Position Responsibilities

Process data recording; defining of

process critical parameters and their
Assistant of Synthesis Area
PMS Production acceptance criteria; defining of
Production
SOPs, equipment and other critical
information; protocol drafting.

Analytical data recording; defining of

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

Coordinator; supervision of protocol

and recorded data; statistical
analysis; ensuring of compliance of
Quality Assurance Quality Assurance Assistant
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: DQ – 040/04 and DQ – 041/04

- Installation qualification: IQ – 040/04 and OQ – 041/04
- Operational qualification: OQ – 040/04 and PQ – 041/04
- Initial Performance Qualification: 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.
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
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.
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
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 ºC for
sanitization purposes.
The loop is provided with a heat exchanger that heats the water to more than 80 ºC 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.
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
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 electro-
des-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 ºC.

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 ºC. Once the
temperature is reached (controlled by means of a TT-001 probe) it is distributed though the
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
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 Tª 20ºC) 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. Preparation of Cleaning solution

2. Pumping at low pressure
3. Recirculation of cleaning solution
4. Draining
5. Pumping at high flow
6. 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:
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 9 / 16

PURIFIED WATER
TEST UNITS SPECIFICATIONS* INTERNAL SOP
Clean liquid, transparent,
1 Appearance - ERCROS-4111
colorless and odorless
2 Nitrates mg / l NMT 0.2 ERCROS-4111
-1
3 Conductivity S – cm NMT 1.3 (at 25 ºC) ERCROS-4111
4 TOC mg / l NMT 0.5 ERCROS-4260
5 Total Germs Viable Germs / ml NMT 100 ERCROS-4303
6 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.
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
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)
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
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.
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 12 / 16

Sampling sketch

Sampling point Identification Location Quality

Purifying Plant (A)

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 Purified water
system
c3) VHD 011 VHD 011 After UV lamp UVA Purified water
Storage and Distribution (B)
a2) SV 541 001 SV 541 001 After storage tank and before Purified water
UV lamp
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
Level 2.
DC-0502-00
PU-5 Intake drainage valve at Purified water
Reactor
DC-0502-00 reactor
Level 2.
DC-0501-00
PU-4 Intake drainage valve at Purified water
Reactor
DC-0501-00 reactor
Level 2.
DC-0504-00
PU-3 Intake drainage valve at Purified water
Reactor
DC-0504-00 reactor
Level 2.
DC-0507-00
PU-2 Intake drainage valve at Purified water
Reactor
DC-0507-00 reactor
Level 2.
DC-0508-00
PU-1 Intake drainage valve at Purified water
Reactor
DC-0508-00 reactor
DF-0532-02 Level 2.
DF-0532-03 PU-8 Intake common drainage valve Purified water
Dissolution Tanks at auxiliary tanks
DF-0532-00 Level 2.
DF-0532-01 PU-9 Intake common drainage valve Purified water
Dissolution Tanks at auxiliary tanks
Level 1.
JL-0512-00
PU-6 Intake drainage valve at Purified water
Centrifuge
JL-0512-00 centrifuge
Level 1.
Laboratory PU-11 Purified water
Laboratory
DF-0531-00 Level 0.
DF-0531-01 PU-10 Intake common drainage valve Purified water
Dissolution Tanks at auxiliary tanks
Level 0.
JL-0511-00
PU-7 Intake drainage valve at Purified water
Centrifuge
JL-0511-00 centrifuge
EI-0521-00 Level 0.
PU-12 Purified water
Drier Drier room
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
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 UNITS SPECIFICATIONS* INTERNAL SOP
Clean, transparent, colorless
1 Appearance - ERCROS-4111
and odorless liquid
2 Nitrates mg / l NMT 0.2 ERCROS-4111
-1
3 Conductivity S – cm NMT 1.3 (at 25 ºC) ERCROS-4111
4 TOC mg / l NMT 0.5 ERCROS-4260
5 Total Germs Viable Germs / ml NMT 100 ERCROS-4303
6 Bacterial Endotoxin IU/ml NMT 0.25 ERCROS-4047

NMT: No more than

* According to official USP / European Pharmacopoeia monographs.

OSMOTIC WATER
TEST UNITS SPECIFICATIONS* INTERNAL SOP
Clean, transparent, colorless
1 Appearance - ERCROS-4111
and odorless liquid
2 Nitrates mg / l NMT 5 ERCROS-4111
-1
3 Conductivity S – cm NMT 200 (at 25 ºC) ERCROS-4111
4 TOC mg / l NMT 3 ERCROS-4260
5 Total Germs Viable Germs / ml NMT 100 ERCROS-4303
6 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.
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 14 / 16

POTABLE WATER
TEST UNITS SPECIFICATIONS* INTERNAL SOP
Clean, transparent, colorless
1 Appearance - ERCROS-4111
and odorless liquid
2 Calcium mg / l NMT 500 ERCROS-4111
3 Chlorides mg / l NMT 250 ERCROS-4111
4 Sulfates mg / ml NMT 250 ERCROS-4111
5 Nitrates mg / l NMT 50 ERCROS-4111
6 Ammonium mg / l NMT 0.5 ERCROS-4111
7 pH pH 6.5 – 9.5 ERCROS-4111
8 Total Solids mg / l NMT 1000 ERCROS-4111
9 Heavy metals (Pb) μg / l NMT 0.25 ERCROS-4111
10 Organic matter mg / l NMT 1.3 ERCROS-4111
11 Conductivity S – cm-1 NMT 2500 ERCROS-4111
12 TOC mg / l NMT 5 ERCROS-4260
13 Total Germs Viable Germs / ml NMT 100 ERCROS-4303
14 Escherichia coli - Absence ERCROS-4303
15 Bacterial endotoxins IU/ml - ** ERCROS-4047

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:
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 15 / 16

Microbiological
Chemical Tests Control
Purified Water 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.
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
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
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
Appendix II
 
 

APPENDIX II
 

 
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
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 x x x x x x x x x x x x x x x

VHD 003 x x x x x x x x x x x x x x x

VHD 007 x x x x x x x x x x x x x x x

VHD 010 x x x x x x x x x x x x x x x

VHD 011 x x x x x x x x x x x x x x x

SV 541 001 x x x x x x x x x x x x x x x

SV 541 002 x x x x x x x x x x x x x x x

SV 541 002 x x x x x x x x x x x x x x x

PU-5 x x x x x x x x x x x x x x x

PU-4 x x x x x x x x x x x x x x x

PU-3 x x x x x x x x x x x x x x x

PU-2 x x x x x x x x x x x x x x x

PU-1 x x x x x x x x x x x x x x x

PU-8 x x x x x x x x x x x x x x x

PU-9 x x x x x x x x x x x x x x x

PU-6 x x x x x x x x x x x x x x x

PU-10 x x x x x x x x x x x x x x x

PU-7 x x x x x x x x x x x x x x x

PU-11 x x x x x x x x x x x x x x x

PU-12 x x x x x x x x x x x x x x x

 
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
Appendix II
 
- Second Step

 Even-numbered weeks:

Sampling Day 1 Day 2 Day 3 Day 4 Day 5

Point Chemical Microbiological Chemical Microbiological Chemical Microbiological Chemical Microbiological Chemical Microbiological

SV 541 002 x

PU-5 x x

PU-4 x

PU-3 x x

PU-2 x

PU-1 x x

PU-8 x

PU-9 x x

PU-6 x x

PU-10 x

PU-7 x x

PU-11 x

PU-12 x x
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
Appendix II
 

 Odd-numbered weeks:

Sampling Day 1 Day 2 Day 3 Day 4 Day 5

Point Chemical Microbiological Chemical Microbiological Chemical Microbiological Chemical Microbiological Chemical Microbiological

SV 541 002
x x

PU-5
x

PU-4
x x

PU-3
x

PU-2
x x

PU-1
x

PU-8
x x

PU-9
x

PU-6
x

PU-10
x x

PU-7
x

PU-11
x x

PU-12
x
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
Appendix III
 
 

APPENDIX III
 

 
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
Appendix III
 
 Water Purifying System

 
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
Appendix III
 
 Points of use

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

 
 Annex A ERCROS 02/12 Validation Protocol – Rev. 1
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: SUPERVISED BY: APPROVED BY:

Date and signature Date and signature Date and signature

 Annex B ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 2 / 8

TABLE 1

Starting and operating of purifying system after stoppage

Step Operation Results Performed by: Supervised by

Press button:
Bisulphite Proceso después de  Yes
Manual
removing parada de larga  No
duración Date / Sign. Date / Sign.
Bisulphite Send Bisulphite  Yes
Manual
removing Solution to sewage  No
Date / Sign. Date / Sign.
PLC shows:
CONECTAR LAS
CONEXIONES DE
Bisulphite Automatic  Yes
LIMPIEZA DE
removing  No
PERMEADO Y
RECHAZO CON
DRENAJE. Date / Sign. Date / Sign.
Bisulphite Connect and press  Yes
Manual
removing ACCEPT  No
Date / Sign. Date / Sign.
Bisulphite Decalcified water Automatic  Yes
removing loading starts  No
Date / Sign. Date / Sign.
High and low
Bisulphite Automatic  Yes
pressure pumping
removing  No
start Date / Sign. Date / Sign.
Bisulphite Automatic  Yes
Stop pumps
removing  No
Date / Sign. Date / Sign.
PLC shows:
VOLVER A
CONECTAR
Bisulphite CLAMP CIEGO EN Automatic  Yes
removing LAS  No
CONEXIONES DE
LIMPIEZA.
Date / Sign. Date / Sign.
Bisulphite Connect the Clamp  Yes
Manual
removing and press ACCEPT  No Date / Sign. Date / Sign.
Opening of valves:
E-cell system VHB-010, VHB-011, Manual  Yes
regeneration VHD-012 and  No
VHD-008. Date / Sign. Date / Sign.
E-cell system Close VPD-008 and Manual  Yes
regeneration open VPD-009  No Date / Sign. Date / Sign.
Starting the pre-
E-cell system osmosis and  Yes
Manual
regeneration reverse osmosis for  No
this valve Date / Sign. Date / Sign.
E-cell system  Yes
Stabilize the inlet Manual
regeneration  No
flow Date / Sign. Date / Sign.
Starting the
E-cell system concentrate Manual  Yes
regeneration recirculation pump  No
Date / Sign. Date / Sign.
 Annex B ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 3 / 8

Step Operation Results Performed by: Supervised by

Stabilize the flow of
concentrate:
E-cell system Inlet Pressure from  Yes
Manual
regeneration 0.3 to 0.6 bars  No
Outlet Pressure
from 0.3 to 0.6 bars Date / Sign. Date / Sign.
E-cell system Adjust the flow of  Yes
Manual
regeneration purge concentrate  No
Date / Sign. Date / Sign.
Verification of
E-cell system Manual  Yes
suitability of flow
regeneration  No
rates and pressures Date / Sign. Date / Sign.
E-cell system  Yes
Starting the rectifier Manual
regeneration  No Date / Sign. Date / Sign.
Water quality and
E-cell system flow (parameters  Yes
Manual
regeneration shown at PLC) are  No
suitable Date / Sign. Date / Sign.
Press button:
 Yes
Normal Start NORMAL Manual
 No
OPERATION Date / Sign. Date / Sign.
 Yes
Normal Start Enter Password
Manual  No Date / Sign. Date / Sign.
Confirm the
password for the Automatic  Yes
Normal Start
computer and the  No
screen Date / Sign. Date / Sign.
Message appears:
Automatic  Yes
Normal Start NORMAL
 No
OPERATION Date / Sign. Date / Sign.
Operation of UV  Yes
Normal Start Manual
Lamp  No Date / Sign. Date / Sign.
Correct Automatic  Yes
Normal Start
Pretreatment Cycle  No
Date / Sign. Date / Sign.
Correct  Yes
Normal Start
Osmosis Cycle Automatic  No Date / Sign. Date / Sign.
Correct Water Cycle  Yes
Normal Start
of Refinement Automatic  No Date / Sign. Date / Sign.
Correct water return
 Yes
Normal Start to sanitization and Automatic
 No
cleavage tank Date / Sign. Date / Sign.
 Annex B ERCROS 02/12 Validation Protocol – Rev. 1
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
 Annex B ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 5 / 8

TABLE 2

Starting and operating of distribution and sanitization after stoppage

Step Operation Results Performed by: Supervised by

Verify that all the
points of use are  Yes
Starting Manual
closed.  No
Date Date
Verified that storage
 Yes
Starting tank valve is closed. Manual
 No
Date Date
Verify that all the
pumping and
 Yes
Starting intaking valves are Manual
 No
closed.
Date Date
Verify that purifying
 Yes
Starting system is operation. Manual
 No
Date Date
Verify the availability
 Yes
Starting of comprised air. Manual
 No
Date Date
Verify the availability
 Yes
Starting of electric power. Manual
 No
Date Date
Turn off the general
switch in the electric  Yes
Starting Manual
frame.  No
Date Date
Release emergency
 Yes
Starting stop. Manual
 No
Date Date
Connect all the
switches and fuses  Yes
Starting Manual
in electric frame.  No
Date Date
Verify screen is on.  Yes
Starting Manual
 No Date Date
Press button:  Yes
Starting Manual
CONSIGNAS.  No Date Date
Verify that operating
parameters shown in
the screen are  Yes
Starting Manual
correct and no  No
alarms are shown.
Date Date
Press button:
 Yes
Starting AUTOMATICO. Manual
 No
Date Date
Press button:
 Yes
Starting MARCHA LOOP. Manual
 No
Date Date
Verify that water is
entering in storage  Yes
Starting Automatic
tank.  No
Date Date
 Annex B ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 6 / 8

Step Operation Results Performed by: Supervised by

Verify the correct
level of water for  Yes
Starting Automatic
pumping starts.  No
Date Date
Pumping system
 Yes
Starting starts. Automatic
 No
Date Date
Speed of water
 Yes
Starting return is regulated. Automatic
 No
Date Date
UV lamp starts.  Yes
Starting Automatic
 No Date Date
Valves at points of
use operate  Yes
Starting Automatic
correctly.  No
Date Date
Valves at sampling
points operate  Yes
Starting Automatic
correctly.  No
Date Date
Verify the operating
program is:  Yes
Sanitization Manual
AUTOMATICO  No
Date Date
Verify the system is
 Yes
Sanitization operating. Manual
 No
Date Date
Verify that no
consume is any  Yes
Sanitization Manual
point of use.  No
Date Date
Verify availability of
cool water and  Yes
Sanitization Manual
steam.  No
Date Date
Verify valves at
steam entrance;
condenser returns;
 Yes
Sanitization cool water entrance Manual
 No
and cool water
return are open.
Date Date
Start sanitization
 Yes
Sanitization program. Manual
 No
Date Date
Confirmation.  Yes
Sanitization Automatic
 No Date Date
Storage tank
draining.
Valve in storage  Yes
Sanitization Automatic
tank is in draining  No
position.
Date Date
UV lamp starts.  Yes
Sanitization Automatic
 No Date Date
 Annex B ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 7 / 8

ETAPA ACCIÓN CONFORMIDAD REALIZADO VERIFICADO

Purge  Yes
Sanitization Automatic
 No Date Date
Heating  Yes
Sanitization Automatic
 No Date Date
Water is maintained
hot during  Yes
Sanitization Automatic
sanitization.  No
Date Date
Purge.  Yes
Sanitization Automatic
 No Date Date
Cooling.  Yes
Sanitization Automatic
 No Date Date
Water is at operating
 Yes
Sanitization temperature. Automatic
 No
Date Date
Water is available at
Normal  Yes
every point of use. Automatic
operation  No
Date Date
 Annex B ERCROS 02/12 Validation Protocol – Rev. 1
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: SUPERVISED BY: APPROVED BY:

Date and signature Date and signature Date and signature

 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
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.
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 3 / 29

Sampling sketch

Sampling point Identification Location Quality

Purifying Plant
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 Purified water
system
VHD 011 VHD 011 After UV lamp UVA Purified water
Storage and Distribution
SV 541 001 SV 541 001 After storage tank and before Purified water
UV lamp
SV 541 002 SV 541 002 After UV lamp Purified water
SV 541 003 SV 541 002 At return hose Purified water
Points of use
Level 2.
DC-0502-00
PU-5 Intake drainage valve at Purified water
Reactor
DC-0502-00 reactor
Level 2.
DC-0501-00
PU-4 Intake drainage valve at Purified water
Reactor
DC-0501-00 reactor
Level 2.
DC-0504-00
PU-3 Intake drainage valve at Purified water
Reactor
DC-0504-00 reactor
Level 2.
DC-0507-00
PU-2 Intake drainage valve at Purified water
Reactor
DC-0507-00 reactor
Level 2.
DC-0508-00
PU-1 Intake drainage valve at Purified water
Reactor
DC-0508-00 reactor
DF-0532-02 Level 2.
DF-0532-03 PU-8 Intake common drainage valve Purified water
Dissolution Tanks at auxiliary tanks
DF-0532-00 Level 2.
DF-0532-01 PU-9 Intake common drainage valve Purified water
Dissolution Tanks at auxiliary tanks
Level 1.
JL-0512-00
PU-6 Intake drainage valve at Purified water
Centrifuge
JL-0512-00 centrifuge
Level 1.
Laboratory PU-11 Purified water
Laboratory
DF-0531-00 Level 0.
DF-0531-01 PU-10 Intake common drainage valve Purified water
Dissolution Tanks at auxiliary tanks
Level 0.
JL-0511-00
PU-7 Intake drainage valve at Purified water
Centrifuge
JL-0511-00 centrifuge
EI-0521-00 Level 0.
PU-12 Purified water
Drier Drier room
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 4 / 29

2. SAMPLING RECORD TEMPLATE

 Purifying Plant

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
VHB 001 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 5 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
VHD 003 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 6 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
VHD 007 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 7 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
VHD 010 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 8 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
VHD 011 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 9 / 29

 Storage and Distribution

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
SV 541 001 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 10 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
SV 541 002 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 11 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
SV 541 003 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 12 / 29

 Points of use

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
PU-5 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 13 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
PU-4 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 14 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
PU-3 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 15 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
PU-2 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 16 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
PU-1 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 17 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
PU-8 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 18 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
PU-9 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 19 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
PU-6 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 20 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
PU-11 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 21 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
PU-10 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 22 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
PU-7 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 23 / 29

Sampling Point: Sample taken by: Verify by:

Sampling Date (Initials and (Initials and
PU-12 signature) signature)
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
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 24 / 29

Deviations

Affect the
Description Date / Sign.
validation study:

□Yes

□ No

Remarks

Final result:  Conforms  Non conforms

Performed by: Signature: Date:

Verify by: Signature: Date:

 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 25 / 29

3. ANALYTICAL DATA RECORD TEMPLATE

Complete the following record data sheet per taken sample and enclose copy of raw data
record:
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 26 / 29

POTABLE WATER

Sampling Point: Sampling date:

Analyzed Verify by:

Test Specification Result Analysis Date
by:
Clean, transparent,
Appearance colorless and odorless
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 μg / l

Organic matter NMT 1.3 mg / l

Conductivity NMT 2500S – cm-1

TOC NMT 5 mg / l

Total Germs Viable NMT 100 Germs / ml

Escherichia coli Absence

Bacterial (informative)
endotoxins* IU/ml

* Only to be tested at point identified as VHB 001

Remarks
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 27 / 29

OSMOTIC WATER

Sampling Point: Sampling date:

Analyzed Verify by:

Test Specification Result Analysis Date
by:
Clean, transparent,
Appearance colorless and odorless
liquid

Nitrates NMT 5 mg / l

NMT 200 (at 25 ºC)

Conductivity
S – cm-1
TOC NMT 3 mg / l

Total Germs Viable NMT 100 Germs / ml

(informative)
Bacterial Endotoxin
IU/ml

Remarks
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 28 / 29

PURIFIED WATER

Sampling Point: Sampling date:

Analyzed Verify by:

Test Specification Result Analysis Date
by:
Clean, transparent,
Appearance colorless and odorless
liquid

Nitrates NMT 0.2 mg / l

NMT 1.3 (at 25 ºC)

Conductivity
S – cm-1

TOC NMT 0.5 mg / l

Total Germs Viable NMT 100 Germs / ml

Bacterial Endotoxin NMT 0.25 IU/ml

Remarks
 Annex C ERCROS 02/12 Validation Protocol – Rev. 1
Pag. 29 / 29

Deviations

Affect the
Description Date / Sign.
validation study:

□Yes

□ No

Remarks

Final result:  Conforms  Non conforms

Performed by: Signature: Date:

Verify by: Signature: Date: