SOP for Operational Qualification for RO Water System

Objective

This SOP intends to provide documented evidence that the newly installed Reverse Osmosis Water Purification System is capable to consistently producing purified water that meets the pre-defined requirement throughout all anticipated operating ranges.

Scope

This protocol applies to the Reverse Osmosis water purification system located in the Purified Water Room of PharmaInfo Ltd.

Responsibility

Quality Assurance Department

• To prepare protocol and record.
• To review protocol and record.
• To execute related data collection.
• To interpret operational qualification data.
• To prepare Operational Qualification report.

Maintenance Department

• To review protocol and record.
• To execute related Operational Qualifications as per protocol.
• To execute related data collection

Management

• To review the Operational Qualification protocol and report.
• To approve execution of Operational Qualification protocol.
• To approve the Operational Qualification Report.

System Design Details

The water system design has the following major stages pretreatment, purification, distribution, and control.

• Pre-treatment stage: Multimedia Filtration, Carbon Filtration, and Production of Soft Water.
• Purification stage: generation of reverse-osmosis water
• Storage and Distribution System for normal and hot purified water
• Control Panel for generation and distribution system for normal and hot purified water.

Operational Qualification (OQ) Process

Validation activity shall be carried out by filling the required data into the Operational Qualification Checklist.

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Test Program

• The Operational Qualification of the water system shall be carried out in four phases: 

1. Phase 1 - sampling for 4 weeks
2. Phase 2 - sampling for 4 weeks
3. Phase 3 - sampling for 12 weeks
4. Phase 4 - sampling for 6 months

• During the 4 phases of operational qualification activities, all maintenance records shall be documented. Any deficiency in the systems equipment shall be investigated and rectified. The result data of the purified water system shall be tabulated periodically and the data summary shall be reviewed.

The detailed methodology of the 4 phases of validation is as stated below:

Phase 1: For 4 weeks

• The operational qualification of the water system shall be started when all the equipment and piping of the water system have been verified to be installed properly and are operating correctly.
• Phase 1 of the operational qualification of the water system shall include the sampling of water, from all usage points for a period of 8 weeks. Sampling and testing of water for microbiological analysis shall be carried out as stated in the Testing Method. During this phase water samples from the usage, points shall be analyzed and monitored for compliance with the predetermined specifications. During this phase, the purified water is not allowed to be used in bulk product preparation except for all cleaning activities.
• Once the purified water complies with the predefined specification, the QC department shall advise the Research and Development department to initiate a laboratory trial of bulk product preparation based water based on product types i.e shampoo, shower cream, lotion and etc. The product stability record shall be documented accordingly.
• At the end of four weeks, the standard operation procedure of the water system shall be developed.

Phase 2: For 4 weeks

• Phase-2 of the operational qualification shall commence, after the successful completion of Phase-1. The second phase of the system validation will demonstrate that the system will consistently produce the desired water quality when operated in conformance with the SOPs. The sampling is performed as in the initial stage and for the same time period.
• During this phase, the purified water is not allowed to be used in bulk product preparation except for all cleaning activities and laboratory trials.
• After successful completion of Phase-2 of the operational qualification, the data should demonstrate that the system will consistently produce the desired quality of water.

Phase 3: For 4 months

• Phase 3 of the operational qualification shall commence, after the successful completion of Phase-2. The objective of Phase-3 is to demonstrate that when the water system is operated in accordance with the SOP over a long period it will consistently produce water of the desired quality. Any variation in the quality of the feedwater that could affect the operation and ultimately the water quality will be picked up during this phase of validation. 
• Sampling is to be performed according to the routine procedures and frequencies. The validation of water systems will be completed within a full year's worth of data.
• After four weeks of this phase, if the system is capable of delivering chemical and microbiological controlled-purified water, provided that the product types showed stability under laboratory trial, the water will be allowed to be used for bulk product preparation.

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• After completion of Phase 3, Alert and Action limits of testing parameters will be calculated as per the given equation and these alert and action limits will be followed for further qualification of a water system.
• Alert levels are levels or ranges that when exceeded; indicate that a process may have drifted from its normal operating condition. Alert levels constitute a warning and do not necessarily require corrective action.

Alert Level = (Average + 2) x Standard Deviation

• Action levels are levels or ranges that, when exceeded, indicate that a process has drifted from its normal operating range. Exceeding an Action level indicates that corrective action should be taken to bring the process back into its normal operating range).

Action Level = (Average + 3) x Standard Deviation

• For parameters that the alert and activity level are not suitable to be calculated based on the above formula, recommended alert and action level from a certified regulatory body will be used.

Phase 4: For 6 months

• Phase 4 shall commence immediately after completion of Phase 3. When the third phase is completed data shall be collected and the routine monitoring schedule shall be frozen. Samples shall be collected from selected sampling points once a week and shall randomly cover all user points in a week.

The objective of Phase 4 is to demonstrate that the water system is capable of producing pre-determined specification quality of water, by taking care of all possible seasonal variations when operated under the established SOP over a long time. The sampling shall be done as per the routine sampling procedures.

References

• FDA’s Office of Regulatory Affairs: Guide to Inspection of High Purity Water System.
• Design Qualification for RO Water Purification System.

Acceptance Criteria

Operational qualification shall be considered acceptable when the specifications listed in the below table are met and all the components of the purified water generation, storage, and distribution system are performed as per design specification and as per manufacturer recommendation.

Parameter	Specification
Conductivity	< 5.1 µS/cm at 25°C
Bacteria Count	< 100cfu/ml
pH	5 – 7
Total Dissolved Solid	< 50ppm
Distribution flow rate (FM05)	> 6.0 m3/hour
Feed water hardness (mg/L)	< 20 ppm
Coliform	Absence

Revision History

Nil

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