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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:

Installation (IQ) and Operation of the purified water production plant. defining of SOPs. equipment and other critical information. protocol approval and writing of reports. specifications and other critical information. 12 provided as Appendix I. This validation protocol considers the performance qualification of production. defining of process critical parameters and their acceptance criteria. defining of SOPs. SCOPE Purified water production plant which supplies water to Multipurpose Synthesis Plant (PMS) located in Building 54. collaboration in protocol drafting. storage and distribution of the purified water produced in this plant. 4 / 16 Department Responsible / Position Responsibilities Process data recording. ensuring of compliance of documentation with current legal requirements. 1 Pag. statistical analysis. Coordinator. Analytical data recording. . supervision of protocol and recorded data. defining of critical quality attributes and their acceptance criteria.1 System Validation Performance Qualification (PQ) step is performed after the qualification of Design (DQ). 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. 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. METHODOLOGY 5. 5. PMS Production Assistant of Synthesis Area Production Quality Control Quality Control Assistant Quality Assurance Quality Assurance Assistant 4.Annex A ERCROS 02/12 Validation Protocol – Rev. Refer to site general plan 90-A3-1624 Rev. protocol drafting.

The sampling is daily after each step of purification process and at each point of use for three weeks (15 working days). maintenance and sanitization.Annex A ERCROS 02/12 Validation Protocol – Rev.2 Description of purified water system The facility consists of a purified water production plant (pretreatment. 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. 1 Pag. Use and refine the SOPs for operation. The sampling is daily from a minimum of two critical points. a storage tank and a loop that supply purified water to the points of use.Ensure that seasonal variations are evaluated. . After this validation step. sampling frequencies and routine monitoring. b) Duplex decalcification unit In this step calcium and magnesium ions are retained in ion-exchange resins.Demonstrate extended reliable performance. 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. 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 validation approach includes: Undertaking of chemical and microbiological testing. 5 / 16 During this period the system is intensively monitored. Steps of water purifying and distribution are described as follows. Sampling after each step in the purification process daily. The validation approach includes: . c) Microfiltration 10 microns This additional filtration ensures the protection of reverse osmosis membranes. Sampling the incoming feed-water daily to verify its quality. . with at least all points of use tested weekly. 5. After this initial study and whenever no critical deviation or failure of the system occurs.The sample locations. 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. Verify and confirm stated alert and action levels. Demonstrate consistent production and delivery of water of the required quality and quantity when the system is operated in accordance with SOPs. reverse osmosis and water purifying systems). Sampling at each point of use and at other defined sample points daily. Refine test-failure procedure. After this initial step critical sampling points are confirmed as it. . for a full year worth of data. the second step can address.

5 microns This additional filtration ensures the remove of particles in suspension and the additional protection of reverse osmosis membranes. it is returned to this tank. In addition.Annex A ERCROS 02/12 Validation Protocol – Rev. the tank pumps water at low pressure when the production has stopped. chlorine from the water system is neutralized. The system automatically makes the feeding of subsequent equipment independent of flow and pressure. - Reverse osmosis By means of this treatment. non-ionic contaminants and organic molecules with a weight more than 200 (colloidal matter. - - Microfiltration 1. water is subjected to pressure and forced to pass through a semipermeable membranes across which salts or impurities cannot pass. which makes that this step is considered critical. 6 / 16 d) Addition of bisulphite By means of bisulphite addition. bacteria. This process is automatically controlled and performed. Two different and complementary steps with two membranes per step compose the system. From this tank water is pumping to the reverse osmosis membranes. in order to avoid the potential blockage of membranes. Sanitization and cleavage tank After previous microfiltration. The loop is provided with a heat exchanger that heats the water to more than 80 ºC in order to sanitize the complete system. water is storage in the cleavage tank. Bisulphite remove other oxidants dissolved in water by means of its reduction power and has a bacteriostatic effect since oxygen dissolved is minimized. Chemical cleaning: cleaning products are dissolved in this tank. . the tank fulfils the following functions: Feeding tank: whenever the water after electrodesionization system has not the desired quality. These membranes remove 90 – 98 % of inorganic ions. Sanitization: the tank is provided with an element that can heat the water at 80 ºC for sanitization purposes. 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. 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. 1 Pag. Cleaning of membranes: periodically. 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. The system is provided with a high pressure pump that forces the water to flow through the membrane surface. In addition. pyrogens…). which prevents reverse osmosis membranes with polyamide composition can be damaged.

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 addition. to ensure the correct recirculation of water and no influence of the loop in water quality. The frequency converter that controls the feeding pump (SW-P-001) as well as opening and closing of the other valves is automatically controlled.  STORAGE AND DISTRIBUTION Alter purifying system. water is subjected to an electrodes-ionization E-cell system in order to perform a chemical polishing of osmotic water. 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. In addition. the bactericidal action is carried out by a UV lamp which treats the water after E-cell system. The procedure is automatically controlled once it is starting. Performance Qualification includes sampling after storage tank and before and after UV-lamp.  - 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. In order to verify the correct control of microorganism presence and the potential contamination of storage tank. Performance Qualification includes sampling in every point of use. 1 Pag. 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. Once the temperature is reached (controlled by means of a TT-001 probe) it is distributed though the . In order to verify the correct distribution of the purified water and identify potential sources of contamination. Osmotic water is storage in the sanitization and cleavage tank and heated to 80 – 85 ºC. The application of electric power in the system removes salts dissolved in water by means of conventional ionic exchange resins. - Purifying system This step is considered as critic since by means of this treatment. sampling at return hose is performed too.Annex A ERCROS 02/12 Validation Protocol – Rev. - Points of use The loop feeds every point of use in the manufacturing plant. 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.

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. During this procedure all the points of use should be open in order to ensure that opening valves are sanitized too. 2. This procedure should be performed after a planned long stoppage (holiday period). 6. 5. The parameters established in the monograph are considered as Critical Quality Attributes. The whole sanitization procedure takes approximately 90 – 120 minutes. water is cooled by means of a default cooling gradient. - 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. 1 Pag. microbial and endotoxin content should be assessed and considered as Critical Quality Attributes. 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. water used in the manufacture of APIs should be demonstrated to be suitable for its intended use.3 Critical Quality Attributes (CQAs) for Purified Water According to ICH Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients. 8 / 16 purifying system and the loop and maintained under recirculation. water should comply with requirements as laid down in current edition of official USP and European Pharmacopoeia monographs for purified water. this procedure could be performed quarterly. after a break whenever the repairs takes more than 24 hours and/or whenever an analytical parameter is out of specifications. organic matter. Once the recirculation has finished. 3. the rejected water and treated water is removed until conductivity parameter decrease and operating parameters are as usual operating. it is drained and the usual production cycle starts. Once the water is at operation temperature. Reference to internal code for methods of analysis is included too: . Some evidences that could appear as it or together with other/s show that membranes should be cleaned. In addition.Annex A ERCROS 02/12 Validation Protocol – Rev. 5. In this context and in our specific case. In addition as part of preventive maintenance program. In following table are summarized the CQAs and their limits. these are for instance: Loosing of load (10 . and taking into account that the product can be used in the production of sterile drug products. 4. biological compounds…) in order to avoid an irreversible damage. The procedure takes the following steps: 1.

Annex A ERCROS 02/12 Validation Protocol – Rev. 9 / 16 PURIFIED WATER TEST 1 2 3 4 5 6 Appearance Nitrates Conductivity TOC Total Germs Viable Bacterial Endotoxin UNITS mg / l S – cm mg / l Germs / ml IU/ml -1 SPECIFICATIONS* Clean liquid. whenever al alarm is detected and informed by the system.1. colorless and odorless NMT 0.25 INTERNAL SOP ERCROS-4111 ERCROS-4111 ERCROS-4111 ERCROS-4260 ERCROS-4303 ERCROS-4047 NMT: No more than * According to official USP / European Pharmacopoeia monographs.5.3 (at 25 ºC) NMT 0.5 NMT 100 NMT 0.5. .1 Assessment of compliance with Standard Operating Procedures 5.2 for purified water system fulfill their functions correctly. maintenance and sanitization. Performance of reverse osmosis step. it should be recorded in appropriate section of Annex B. Performance of pretreatment step. The main objective is to check and verify that the critical production steps identified in section 5.Assessment of compliance with Standard Operating Procedures 2. The cause of every alarm should be properly investigated according to ERCROS 4008 Investigation of Deviation internal SOP. 5. In addition alarm system will be verified. In a first instance. In this context.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. transparent.2 NMT 1. The SOPs will be checked by means of verification of every item described in the corresponding check-list. 5.Testing of purified water quality 5. Performance of storage and distribution steps. 1 Pag.5 Performance Qualification Tests Two different approaches should be taken into account for qualification purposes: 1. 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. Quality of water in points of use and return hose. 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.4 Qualification Strategy The qualification strategy is based on the system validation described in section 5.

Distribution and Sanitization of the system data check-list 5.5. Sampling after UV lamp (VHD 011) .1. - 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. This sampling point is the same mentioned above. 2. Storage and distribution step: starting the system after a stoppage which involves a sanitization treatment. Sampling at the end of pretreatment (VHD 003). Sampling of incoming feed water.5.5. This sampling point is the same mentioned above. 1. (VHB 001) 2.2. Sampling at the end of reverse osmosis treatment (VHD 007) c) Purifying system checking.Annex A ERCROS 02/12 Validation Protocol – Rev. 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.2 Methodology Taking into account the critical production steps considered in section 5.2 Testing of Purified Water Quality 5.5. 5. In addition. 10 / 16  Worst-case: Production step: starting the production after a stoppage which involves a cleaning of membranes and sanitization treatment. water quality will be tested as follows. After this step.2. 5. The first step of this performance qualification study should be considered all the sampling point described below.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. Sampling at the end of pretreatment (VHD 003) b) Reverse osmosis checking: 1.2 Description of Purified Water System. Sampling after electrodeionization treatment (VHD 010) 3. 2. it will be verified that the loop has no influence in water quality and bacteriostatic level in maintained. A – Purifying plant: a) Water pretreatment checking: 1.3 Records The following check-list should be fulfilled: Annex B Water Purifying. 1 Pag. Sampling at the end of reverse osmosis treatment (VHD 007). critical point (defined below and remarked in bold with “*”) will be sampled during the second step during a whole year of worth data.

Sampling after storage tank (SV 541 001). . Sampling after storage tank (SV 541 001) b) UV lamp checking: 1. 1 Pag. Sampling before storage tank (VHD 011). their location their identification and the water quality desired in each one. 2. In table below is summarized all considered sampling points.Annex A ERCROS 02/12 Validation Protocol – Rev. 2. Sampling at every point of use (refer to table below)* d) Water recirculation checking: 1. 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. This sampling point is the same mentioned above. 11 / 16 B – Storage and distribution a) Storage tank checking: 1. This sampling point is the same mentioned above. Sampling after UV lamp (SV 541 002) c) Points of use checking: 1. Sampling at return hose*.

Intake drainage valve at DC-0507-00 reactor Level 2. Intake drainage valve at DC-0501-00 reactor Level 2. Intake drainage valve at DC-0504-00 reactor Level 2.5 mc microfiltration unit After reverse osmosis system After electrodesionization system After UV lamp UVA After storage tank and before UV lamp After UV lamp At return hose Level 2. 1 Pag. Intake drainage valve at JL-0511-00 centrifuge Level 0. Drier room Potable water Potable water Osmotic water Purified water Purified water Purified water Purified water Purified water Storage and Distribution (B) PU-5 PU-4 PU-3 PU-2 PU-1 PU-8 PU-9 PU-6 PU-11 PU-10 PU-7 PU-12 Purified water Purified water Purified water Purified water Purified water Purified water Purified water Purified water Purified water Purified water Purified water Purified water . Intake drainage valve at JL-0512-00 centrifuge Level 1. 12 / 16 Sampling sketch Sampling point Purifying Plant (A) a1) VHB 001 a2) VHD 003 b2) VHD 007 c2) VHD 010 c3) VHD 011 a2) SV 541 001 b2) SV 541 002 d1) SV 541 003 c1) Points of use DC-0502-00 Reactor DC-0501-00 Reactor DC-0504-00 Reactor DC-0507-00 Reactor DC-0508-00 Reactor DF-0532-02 DF-0532-03 Dissolution Tanks DF-0532-00 DF-0532-01 Dissolution Tanks JL-0512-00 Centrifuge Laboratory DF-0531-00 DF-0531-01 Dissolution Tanks JL-0511-00 Centrifuge EI-0521-00 Drier Identification Location Quality VHB 001 VHD 003 VHD 007 VHD 010 VHD 011 SV 541 001 SV 541 002 SV 541 002 Incoming feed water After 1. Intake common drainage valve at auxiliary tanks Level 2. Intake common drainage valve at auxiliary tanks Level 1. Intake drainage valve at DC-0508-00 reactor Level 2. Intake drainage valve at DC-0502-00 reactor Level 2. Intake common drainage valve at auxiliary tanks Level 0. Laboratory Level 0.Annex A ERCROS 02/12 Validation Protocol – Rev.

Annex A ERCROS 02/12 Validation Protocol – Rev.2 NMT 1. 1 Pag. PURIFIED WATER TEST 1 2 3 4 5 6 Appearance Nitrates Conductivity TOC Total Germs Viable Bacterial Endotoxin UNITS mg / l S – cm mg / l Germs / ml IU/ml -1 SPECIFICATIONS* Clean. Obtained result is only for information and it should be taken into account for checking the capacity of purified water system for endotoxins removing.3 (at 25 ºC) NMT 0.2.2. 13 / 16 5.25 INTERNAL SOP ERCROS-4111 ERCROS-4111 ERCROS-4111 ERCROS-4260 ERCROS-4303 ERCROS-4047 NMT: No more than * According to official USP / European Pharmacopoeia monographs. . transparent. transparent. colorless and odorless liquid NMT 5 NMT 200 (at 25 ºC) NMT 3 NMT 100 ** INTERNAL SOP ERCROS-4111 ERCROS-4111 ERCROS-4111 ERCROS-4260 ERCROS-4303 ERCROS-4047 NMT: No more than * According to internal established specifications.5 NMT 100 NMT 0. ** No specification is established for endotoxins in osmotic water.5. OSMOTIC WATER TEST 1 2 3 4 5 6 Appearance Nitrates Conductivity TOC Total Germs Viable Bacterial Endotoxin UNITS mg / l S – cm mg / l Germs / ml IU/ml -1 SPECIFICATIONS* Clean.1 Analytical test and methods In following tables are summarized the tests performed for every quality of water and reference to internal SOPs. colorless and odorless liquid NMT 0.

5 6.Annex A ERCROS 02/12 Validation Protocol – Rev. (Refer to section 2. 14 / 16 POTABLE WATER TEST 1 2 3 4 5 6 7 8 9 Appearance Calcium Chlorides Sulfates Nitrates Ammonium pH Total Solids Heavy metals (Pb) UNITS mg / l mg / l mg / ml mg / l mg / l pH mg / l μg / l mg / l S – cm-1 mg / l Germs / ml IU/ml SPECIFICATIONS* Clean.2. No specification is established for endotoxins in potable water. Applicable Documentation). 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. Detailed description of method of analysis to be performed for each sample is described in the corresponding internal SOPs. transparent.5 – 9. 5. Label model is as follows: .5 NMT 1000 NMT 0.2.25 NMT 1. Obtained result is only for information and it should be taken into account for checking the capacity of purified water system for endotoxins removing. 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. 1 Pag.3 NMT 2500 NMT 5 NMT 100 Absence ** INTERNAL SOP ERCROS-4111 ERCROS-4111 ERCROS-4111 ERCROS-4111 ERCROS-4111 ERCROS-4111 ERCROS-4111 ERCROS-4111 ERCROS-4111 ERCROS-4111 ERCROS-4111 ERCROS-4260 ERCROS-4303 ERCROS-4303 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. 2012. ** This test will be performed only at point identified as VHB 001 with the aim of knowing the endotoxin burden of incoming water. colorless and odorless liquid NMT 500 NMT 250 NMT 250 NMT 50 NMT 0.5.2 Sampling method Sampling should be performed once the purified plant and loop are normally working.2. It should be recorded date and time (in sample label) of sampling in every sample. Sampling during this validation step will be daily for 15 working days. should be identified as follows: VHD 007 / 14 / 07 /12 Two different labels are available depending on the test.

1 Pag. In this context. Pull the water. clean them.2. . It should be taken into account the test to be performed and prepare the material needed for sampling and testing according to this. Transfer the sample to the laboratory as soon as possible. 2. 4. 5. Check that the drain or faucet is clean.Annex A ERCROS 02/12 Validation Protocol – Rev. Open the drain or the faucet and let the water run a few minutes (5 minutes). Open the bottle where it will take the sample and rinse with the same water to be taken. 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.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. 15 / 16 Chemical Tests Purified Water Sampling Point / Date Analyst Initials / Signature Microbiological Control Purified Water Sampling Point / Date Analyst Initials / Signature The label should be fulfilled just before sampling and stick to the bottle immediately. Label the form unequivocally dated. Fill the bottle completely and cover it perfectly. 6.5. 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. The general operating procedure is as follows: 1. Otherwise.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. 5. A brief summary of this procedure is provided below: Process water sampling should be carried out by Quality Control Laboratory staff. The procedure is considered valid if quality water meets established specifications after tests described in section 5. internal code and plant. The sampling should be performed according to the instructions given in ERCROS-4104 Process water sampling internal SOP.2. ACCEPTANCE CRITERIA 6. 3.5.

Annex A ERCROS 02/12 Validation Protocol – Rev.2 Acceptance criteria for purified water quality Acceptance criteria for this test is that every sample taken and tested as described in section 5.3 Deviations and conclusions Deviations occur during validation should be recorded in the deviation sheet provided at the end of the corresponding annex. 16 / 16 6. 7.2 meets established specifications for its quality. 6. PROTOCOL APPROVAL . 1 Pag.5. Results and conclusions will be summarized in the Validation Report.

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

1 Appendix II   First Step Frequency Sampling Point Day 1 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 x x x x x x x x x x x x x x x x x x x x Day 2 x x x x x x x x x x x x x x x x x x x x Day 3 x x x x x x x x x x x x x x x x x x x x Day 4 x x x x x x x x x x x x x x x x x x x x Day 5 x x x x x x x x x x x x x x x x x x x x Day 6 x x x x x x x x x x x x x x x x x x x x Day 7 x x x x x x x x x x x x x x x x x x x x Day 8 x x x x x x x x x x x x x x x x x x x x Day 9 x x x x x x x x x x x x x x x x x x x x Day 10 x x x x x x x x x x x x x x x x x x x x Day 11 x x x x x x x x x x x x x x x x x x x x Day 12 x x x x x x x x x x x x x x x x x x x x Day 13 x x x x x x x x x x x x x x x x x x x x Day 14 x x x x x x x x x x x x x x x x x x x x Day 15 x x x x x 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 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 Chemical x x x x x x x x Microbiological Chemical Day 2 Microbiological Chemical Day 3 Microbiological Chemical Day 4 Microbiological Chemical Day 5 Microbiological x x x x x x x x x x x x .Annex A ERCROS 02/12 Validation Protocol – Rev.

Annex A ERCROS 02/12 Validation Protocol – Rev. 1 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 Chemical Microbiological Chemical Day 2 Microbiological Chemical Day 3 Microbiological Chemical Day 4 Microbiological Chemical Day 5 Microbiological x x x x 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 III                         APPENDIX III     .

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

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

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

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

1 Pag.Annex B ERCROS 02/12 Validation Protocol – Rev.TABLE 2 – Distribution and sanitization steps PREPARED BY: SUPERVISED BY: APPROVED BY: Date and signature Date and signature Date and signature .TABLE 1 – Purifying step 2. 1 / 8 Compliance with Standard Operating Procedures Check-list TABLE OF CONTENTS 1.

. Supervised by Date / Sign. VHB-011. Date / Sign. Date / Sign. Date / Sign. Bisulphite removing E-cell system regeneration E-cell system regeneration E-cell system regeneration E-cell system regeneration E-cell system regeneration Manual Manual         Date / Sign. Date / Sign. 1 Pag. Bisulphite removing Automatic   Yes No Date / Sign. Bisulphite removing Bisulphite removing Bisulphite removing Bisulphite removing Manual         Yes No Yes No Yes No Yes No Date / Sign. Manual Date / Sign. Date / Sign. 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 Results Manual   Performed by: Yes No Date / Sign. Bisulphite removing Automatic   Yes No Date / Sign. Date / Sign. Date / Sign.Annex B ERCROS 02/12 Validation Protocol – Rev. Manual   Yes No Date / Sign. Manual   Date / Sign. Manual Yes No Yes No Date / Sign. VHD-012 and VHD-008. Manual   Date / Sign. Yes No Yes No Date / Sign. Yes No Yes No Date / Sign. Automatic Date / Sign. Date / Sign. 2 / 8 TABLE 1 Starting and operating of purifying system after stoppage Step Bisulphite removing Bisulphite removing Operation Press button: Proceso después de parada de larga duración Send Bisulphite Solution to sewage PLC shows: CONECTAR LAS CONEXIONES DE LIMPIEZA DE PERMEADO Y RECHAZO CON DRENAJE. Date / Sign. Date / Sign. Connect and press ACCEPT Decalcified water loading starts High and low pressure pumping start Stop pumps PLC shows: VOLVER A CONECTAR CLAMP CIEGO EN LAS CONEXIONES DE LIMPIEZA. Automatic Date / Sign. Connect the Clamp and press ACCEPT Opening of valves: VHB-010. Date / Sign. Date / Sign. Automatic Date / Sign.

Automatic Manual Automatic             Date / Sign. Date / Sign. Date / Sign. Date / Sign. 3 / 8 Step Operation Stabilize the flow of concentrate: Inlet Pressure from 0.6 bars Outlet Pressure from 0. . Date / Sign. Date / Sign. Date / Sign.3 to 0. Date / Sign. Normal Start Normal Start Yes No Yes No Yes No Date / Sign. Date / Sign.Annex B ERCROS 02/12 Validation Protocol – Rev. Date / Sign. Manual Manual Date / Sign. Date / Sign.3 to 0. Manual Automatic Normal Start Date / Sign. Automatic Automatic Automatic Date / Sign. E-cell system regeneration E-cell system regeneration E-cell system regeneration E-cell system regeneration Manual Manual         Yes No Yes No Yes No Yes No Date / Sign. Date / Sign. Date / Sign. Date / Sign. Normal Start Normal Start Normal Start Normal Start Normal Start Normal Start Yes No Yes No Yes No Yes No Yes No Yes No Date / Sign. Date / Sign.6 bars Adjust the flow of purge concentrate Verification of suitability of flow rates and pressures 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 Performed by: Supervised by E-cell system regeneration Manual   Yes No Date / Sign. Date / Sign. Date / Sign. Manual       Date / Sign. Date / Sign. Date / Sign. Date / Sign. 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.

Connect all the switches and fuses in electric frame. 5 / 8 TABLE 2 Starting and operating of distribution and sanitization after stoppage Step Starting Operation Verify that all the points of use are closed. Verify that all the pumping and intaking valves are closed. Press button: MARCHA LOOP. Press button: AUTOMATICO. Release emergency stop. Verify that purifying system is operation. Press button: CONSIGNAS. Verified that storage tank valve is closed. Verify that operating parameters shown in the screen are correct and no alarms are shown. Verify the availability of electric power. 1 Pag. Verify the availability of comprised air. Verify that water is entering in storage tank. Turn off the general switch in the electric frame. Verify screen is on.Annex B ERCROS 02/12 Validation Protocol – Rev. Results Manual   Performed by: Yes No Date Supervised by Date Starting Manual   Yes No Date Date Starting Manual   Yes No Date Date Starting Manual       Yes No Yes No Yes No Yes No Date Date Starting Manual Date Date Starting Manual Date Date Starting Manual   Date Starting Manual   Date Yes No Yes No Date Date Starting Manual       Date Starting Starting Manual Manual Yes No Yes No Date Date Date Date Date Starting Manual   Yes No Date Date Starting Manual     Yes No Yes No Yes No Date Date Starting Manual Date Date Starting Automatic   Date Date .

condenser returns. Pumping system starts. Valve in storage tank is in draining position. Verify valves at steam entrance. Confirmation. 6 / 8 Step Operation Verify the correct level of water for pumping starts. 1 Pag. Verify that no consume is any point of use. UV lamp starts. Verify the operating program is: AUTOMATICO Verify the system is operating. Storage tank draining. Valves at points of use operate correctly. Results   Performed by: Yes No Date Supervised by Starting Automatic Date Starting Automatic         Yes No Yes No Yes No Yes No Date Date Starting Starting Automatic Automatic Date Date Date Date Starting Automatic Date Starting Automatic   Date Yes No Date Date Sanitization Manual   Yes No Date Date Yes No Yes No Date Date Sanitization Manual   Date Date Sanitization Manual   Sanitization Manual   Yes No Date Date Sanitization Manual   Yes No Date Date Sanitization Sanitization Manual Automatic     Yes No Yes No Date Date Date Date Sanitization Automatic   Yes No Date Date Date Sanitization Automatic   Yes No Date . Speed of water return is regulated. UV lamp starts.Annex B ERCROS 02/12 Validation Protocol – Rev. Valves at sampling points operate correctly. Verify availability of cool water and steam. Start sanitization program. cool water entrance and cool water return are open.

Water is at operating temperature.Annex B ERCROS 02/12 Validation Protocol – Rev. 7 / 8 ETAPA Sanitization Sanitization ACCIÓN Purge Heating Water is maintained hot during sanitization. Water is available at every point of use. Cooling. Purge. 1 Pag. CONFORMIDAD Automatic Automatic               REALIZADO Date Date VERIFICADO Date Date Yes No Yes No Yes No Sanitization Automatic Date Sanitization Sanitization Sanitization Normal operation Automatic Automatic Automatic Yes No Yes No Yes No Yes No Date Date Date Date Date Date Date Automatic Date Date .

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 B ERCROS 02/12 Validation Protocol – Rev.

Analytical data record template PREPARED BY: SUPERVISED BY: APPROVED BY: Date and signature Date and signature Date and signature . Sampling record template 3. 1 Pag. 1 / 29 Sampling Control and Data Record TABLE OF CONTENTS 1. Introduction 2.Annex C ERCROS 02/12 Validation Protocol – Rev.

only critical points (marked in bold) will be tested during a whole year of worth data.Annex C ERCROS 02/12 Validation Protocol – Rev. 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. In table below is summarized considered sampling points. acceptance criteria and obtained results. their location their identification and the quality desired in each one. After this step and whenever no critical deviation or failure of the system occurs. codification of samples. . This annex covers and compiles sampling. 1 Pag. every point listed below should be sampled during 20 days. During the first step of this qualification study. 2 / 29 1.

Intake drainage valve at JL-0512-00 centrifuge Level 1. Intake drainage valve at DC-0507-00 reactor Level 2. Intake drainage valve at DC-0502-00 reactor Level 2. Laboratory Level 0.Annex C ERCROS 02/12 Validation Protocol – Rev. Intake drainage valve at DC-0504-00 reactor Level 2.5 mc microfiltration unit After reverse osmosis system After electrodesionization system After UV lamp UVA After storage tank and before UV lamp After UV lamp At return hose Level 2. Intake drainage valve at DC-0501-00 reactor Level 2. 1 Pag. Drier room Potable water Potable water Osmotic water Purified water Purified water Purified water Purified water Purified water Storage and Distribution SV 541 001 SV 541 002 SV 541 003 Points of use DC-0502-00 Reactor DC-0501-00 Reactor DC-0504-00 Reactor DC-0507-00 Reactor DC-0508-00 Reactor DF-0532-02 DF-0532-03 Dissolution Tanks DF-0532-00 DF-0532-01 Dissolution Tanks JL-0512-00 Centrifuge Laboratory DF-0531-00 DF-0531-01 Dissolution Tanks JL-0511-00 Centrifuge EI-0521-00 Drier PU-5 PU-4 PU-3 PU-2 PU-1 PU-8 PU-9 PU-6 PU-11 PU-10 PU-7 PU-12 Purified water Purified water Purified water Purified water Purified water Purified water Purified water Purified water Purified water Purified water Purified water Purified water . Intake drainage valve at JL-0511-00 centrifuge Level 0. Intake drainage valve at DC-0508-00 reactor Level 2. Intake common drainage valve at auxiliary tanks Level 2. Intake common drainage valve at auxiliary tanks Level 0. Intake common drainage valve at auxiliary tanks Level 1. 3 / 29 Sampling sketch Sampling point Purifying Plant VHB 001 VHD 003 VHD 007 VHD 010 VHD 011 Identification Location Quality VHB 001 VHD 003 VHD 007 VHD 010 VHD 011 SV 541 001 SV 541 002 SV 541 002 Incoming feed water After 1.

1 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) .Annex C ERCROS 02/12 Validation Protocol – Rev.

Annex C ERCROS 02/12 Validation Protocol – Rev. 1 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) .

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

1 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) .Annex C ERCROS 02/12 Validation Protocol – Rev.

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

1 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) .Annex C ERCROS 02/12 Validation Protocol – Rev.

1 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) .Annex C ERCROS 02/12 Validation Protocol – Rev.

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

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

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

Annex C ERCROS 02/12 Validation Protocol – Rev. 1 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)

Annex C ERCROS 02/12 Validation Protocol – Rev. 1 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)

Annex C ERCROS 02/12 Validation Protocol – Rev. 1 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)

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

Annex C ERCROS 02/12 Validation Protocol – Rev. 1 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) .

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

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

1 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) .Annex C ERCROS 02/12 Validation Protocol – Rev.

1 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) .Annex C ERCROS 02/12 Validation Protocol – Rev.

Annex C ERCROS 02/12 Validation Protocol – Rev. 1 Pag. 24 / 29 Deviations Description Affect the validation study: Date / Sign. □Yes □ No Remarks Final result: Performed by: Verify by:  Conforms  Non conforms Signature: Signature: Date: Date: .

1 Pag. 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. 25 / 29 3.

colorless and odorless liquid NMT 500 mg / l NMT 250 mg / l NMT 250 mg / ml NMT 50 mg / l NMT 0.5 pH NMT 1000 mg / l NMT 0.3 mg / l NMT 2500S – cm-1 NMT 5 mg / l NMT 100 Germs / ml Absence (informative) IU/ml Result Analysis Date Appearance Calcium Chlorides Sulfates Nitrates Ammonium pH Total Solids Heavy metals (Pb) Organic matter Conductivity TOC Total Germs Viable Escherichia coli Bacterial endotoxins* * Only to be tested at point identified as VHB 001 Remarks .Annex C ERCROS 02/12 Validation Protocol – Rev.5 – 9. transparent.25 μg / l NMT 1. 26 / 29 POTABLE WATER Sampling Point: Sampling date: Analyzed by: Verify by: Test Specification Clean.5 mg / l 6. 1 Pag.

1 Pag. colorless and odorless liquid NMT 5 mg / l NMT 200 (at 25 ºC) S – cm-1 NMT 3 mg / l NMT 100 Germs / ml (informative) IU/ml Result Analysis Date Appearance Nitrates Conductivity TOC Total Germs Viable Bacterial Endotoxin Remarks . transparent.Annex C ERCROS 02/12 Validation Protocol – Rev. 27 / 29 OSMOTIC WATER Sampling Point: Sampling date: Analyzed by: Verify by: Test Specification Clean.

25 IU/ml Result Analysis Date Appearance Nitrates Conductivity TOC Total Germs Viable Bacterial Endotoxin Remarks .Annex C ERCROS 02/12 Validation Protocol – Rev.3 (at 25 ºC) S – cm-1 NMT 0. transparent.2 mg / l NMT 1. 1 Pag. 28 / 29 PURIFIED WATER Sampling Point: Sampling date: Analyzed by: Verify by: Test Specification Clean.5 mg / l NMT 100 Germs / ml NMT 0. colorless and odorless liquid NMT 0.

□Yes □ No Remarks Final result: Performed by: Verify by:  Conforms  Non conforms Signature: Signature: Date: Date: .Annex C ERCROS 02/12 Validation Protocol – Rev. 29 / 29 Deviations Description Affect the validation study: Date / Sign. 1 Pag.

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