VAL-230 Procedure for Cleaning Validation Coverage Testing

1. Purpose

This Standard Operating Procedure will define the procedure to be used to test the spray coverage of Clean-in-Place (CIP) Systems or Cleaning systems procedures designed for stainless steel vessels.

2. Scope

The test outlined in this procedure will demonstrate that all areas requiring cleaning are contacted by the cleaning solution during the cleaning cycle. This procedure will be utilised throughout the manufacturing area and will typically be conducted during OQ/PQ testing. Riboflavin or Methylene Blue solution can be used for the coverage testing.

3. Definitions

Clean In Place (CIP): Refers to systems utilizing either built-in self-cleaning capabilities or those that can be readily reconfigured for self-cleaning. CIP is usually accomplished through the use of pumps, spray balls/nozzles, and assorted accessory tanks for detergents and waste

Riboflavin (Vitamin B12) – an orange/yellow crystalline compound (C17H20N406). When prepared as a 0.001% w/v solution; riboflavin exhibits an intense yellowish green fluorescence.

UV Light – Ultraviolet Light.

Methylene Blue – At room temperature, this dye appears as a solid, odorless, dark green powder, that yields a blue solution when dissolved in water C16H18N3SCl.

4. Responsibilities

4.1 It is the responsibility of validation team to organize the coverage testing.

4.2 It is the responsibility of the Validation Supervisor/Manager or designee to ensure that validation personnel are properly trained on this SOP.

5. Procedure using Riboflavin

5.1 Obtain a general work permit form using the procedure described in SOP EHS-065 Hot Work Permit Procedure. Due to the necessity of tank entry, a confined space entry permit may also required. Ensure that electrical and service supplies to the process vessels are isolated using the procedure described in SOP MAN-050 – Equipment tag out procedure.

5.2 Prepare a 0.001% w/v solution of Riboflavin in Water for Injection (WFI) and place into an appropriate spray bottle. Cover container with aluminum foil to protect from light, label with name, preparation and expiry date. Use the prepared solution within one month from the preparation date.

5.3 Enter the tank as per procedure and inspect the tank with the UV light and illustrate the hard to clean areas on the Tank diagram (Appendix A). At the end of the coverage testing particular attention must be paid to the hard to clean locations.

5.4 Using the spray bottle, cover all the product contact surfaces with the Riboflavin solution. Ensure that the surfaces are well covered by using a UV light. Particular attention must be paid to the hard to clean areas.

Note: Product contact surfaces are: Upper part of the tank, side walls, bottom surface, shaft, stirrer, blades, baffles, lid etc.

5.5 Exit the tank. Ensure that electrical and service supplies to the process vessels are restored using the procedure described in MAN-050 – Equipment tag out procedure and complete a single 500L Potable water rinse cycle of the CIP system.

5.6 After the rinse cycle is complete, ensure that electrical and service supplies to the process vessels are isolated using the procedure described in SOP MAN-050 – Equipment tag out procedure.

5.7 Re-enter the tank and inspect the product contact surfaces with the UV light. Particular attention must be paid to the hard to clean areas illustrated in the form Appendix A.

5.8 Exit the tank. Return the work permit(s) to EHS and ensure that the electrical and service supplies to the process vessels are no longer isolated using the tag out procedure.

5.9 Document the test details and observation in the form in Appendix A. If there is no fluorescence remaining then the CIP system is functioning effectively showing complete cleaning coverage. Any area showing visible fluorescence on the surface indicates hard to clean locations and that the vessel was not adequately cleaned. In this occasion contact the Validation Supervisor/Manager and raise deviation to investigate into the failure of the event.

6. Acceptance Criteria

6.1 To demonstrate complete coverage, yellow-green fluorescence must be present on all surfaces prior the rinse cycle has been initiated.

6.2 To demonstrate effective CIP system, absence of yellow-green fluorescence must be observed after the rinse cycle has been completed.

7. Procedure using Methylene Blue

7.1 Obtain a general work permit form using the procedure described in SOP EHS-065 Hot Work Permit Procedure. Due to the necessity of tank entry, a confined space entry permit may be required. Ensure that electrical and service supplies to the process vessels are isolated using the procedure MAN-050 – Equipment tag out procedure.

7.2 Weight 200g of Methylene Blue and dilute it in 1L of purified water.

7.3 Pump 199L of purified water inside the tank. Add the Methylene Blue concentrate solution in the tank to obtain a solution at 0.1% w/v. Recirculating the water mixed with Methylene Blue through the spray balls for 15 minutes.

7.4 At the end of the recirculation, drain off the solution of Methylene Blue to the appropriate waste stream.

7.5 Ensure that electrical and service supplies to the process vessels are isolated using the procedure described in SOP MAN-050 – Equipment tag out. Inspect the tank with a telescopic mirror containing a light or a camera.

7.6 All surfaces should be covered by a blue layer. Particular attention must be paid to the hard to clean locations where the solution is not visible. Illustrate these hard to clean areas on the Tank diagram of form Appendix B.

7.7 Ensure that electrical and service supplies to the process vessels are restored using the procedure described in SOP MAN-050 – Equipment tag out.

7.8 Complete water rinse cycles until the dye is completely removed from the tank.

7.9 Ensure that the electrical and service supplies to the process vessels are no longer isolated using the procedure described in SOP MAN-050 – Equipment tag out. Inspect the product contact surfaces with a telescopic mirror containing a light or a camera. The full tank should be absolutely free of dye.

7.10 Return the work permit(s) to EHS and ensure that electrical and service supplies to the process vessels are restored using the procedure described in SOP MAN-050 – Equipment tag out.

7.11 Document the test details and observation in the form Appendix B. If there is no blue color visible then the CIP system is functioning effectively showing complete cleaning coverage. Any area showing visible traces of blue color on the surface indicates hard to clean locations and that the vessel was not adequately cleaned. In this occasion contact the Validation Supervisor/Manager and raise deviation to investigate into the failure of the event.

8. Acceptance Criteria

8.1 To demonstrate complete coverage, blue colour must be present on all surfaces prior the rinse cycle has been initiated.

8.2 To demonstrate effective CIP system, no trace of Methylene blue should be present after the rinse cycle has been completed.

9. Related Documents

VAL-080: Validation Master Plan
VAL-205: Management of Validation Protocols and Reports
MAN-050: Equipment tag out Procedure
EHS-065: Hot Work Permit Procedure
Appendix A: Cleaning Validation Coverage Testing Form
Appendix B: Cleaning Validation Coverage Testing using Methylene Blue Form

Appendix A: Cleaning Validation Coverage Testing – using Riboflavin Solution