CLEANING VALIDATION PROTOCOL

Product : Protocol No. :

Revision No. : Page No….of …..

1. Introduction
One equipment used at one stage, manufacturing of different products is very common in
pharmaceuticals manufacturing. After use, the equipment is cleaned to prevent cross-
contamination of drug products.
The efficacy of cleaning procedure should be such that it effectively removes traces of the
previous product and detergent used.
2. Purpose
To validate the cleaning procedure for equipments used for manufacturing is effective to
remove the ingredients of previous product and detergent used to reduce the microbial
contaminants.
3. Objective
• To establish a documented evidence of the cleaning effectiveness of the cleaning procedure
to a predetermined residue level.
• To verify that the cleaning procedure is able to clean the defined equipment consistently
and reliably.
4. Responsibilities
I. Production Supervisor
• To ensure that the various pieces of equipment are cleaned according to the relevant SOP.
(SOP no :…….)
• To train and monitor the operator for collecting sample by final rinse/swab of the various
parts of the equipment.
II. Head of Q.C Department
• Responsible for validating analytical method used to analyze traces of active ingredients of
the previous product and traces of detergent used.
• To test sample according to validated analytical method
III. Head of Microbiology Department
• Responsible for validating analytical used to analyze and count the microbial
contamination
IV. Head of Q.A Department
• Responsible for writing of the protocol and final report
• To supervise the operation to ensure everything is done according to the protocol
V. Production Manager
• Responsible for checking of the protocol and final report
VI. Engineering foreman
• Responsible for supporting production personnel during cleaning validation.
5. Procedure
A. After completion of manufacturing of drug product, cleaning will be carried out by
production personnel according to the relevant SOP. (SOP No.: …..)
B. The production supervisor inspects the equipment visually to assure that it is clean, and
fill the inspection form.
C. For determining the active residue, the sample are taken according to the following steps:
• Wipe off the cleaned equipment with swab test kit saturated with purified water or
methanol (according to the solubility of the API of the previous product) on the critical areas.
• Put the cotton swab into the vial and close the vial with plastic pilfer proof cap. Collected
swabs should not be hold more than 24 hours under refrigeration.
• Then send the collected sample to the Q.C department for analysis (method of analysis
should be validated).
D. For determining detergent residue, the sample are taken according to the following
procedure:
• Rinse the clean equipment with purified water
• Collect approx. 500 ml from the final rinse into a clean amber glass bottle and close the
bottle with the lid.
• Then send the collected sample to the Q.C department for analysis (method of analysis
should be validated).
E. For determining microbial contaminants, the sample is taken according to the following
procedure:
• Open the lid of the RODAC plate.
• Put the nutrient agar surface on the cleaned equipment at the critical area.
• Close the RODAC plate with the lid immediately.
• Then send the RODAC plate to the Microbiological Lab for incubation.

Related: SOP for Environmental Monitoring of Parenteral Processing Area by RODAC Plate
and Swab

6. Acceptance criteria
The following criteria are established:
• Visual examination should not reveal any evidence of contamination. The equipment will
be checked for this and will be recorded.
• Active ingredient of the previous product: Not more than 10 ppm.
• Samples from final rinse have purified water.
• Conductivity of the samples: Not more than 1.3µS.
• Microbial contaminants of the sample: Not more than 25 CFU/25 cm2
7. Corrective action (If required)
• If the cleaning validation results show that the equipments are below the acceptance limits
or not more than the maximum detectable limit, the cleaning SOP is adequately validated.
• A failure to meet this equipment would necessitate a review of the cleaning procedure of
the residual limits. Modification in the procedure to make it more effective, or a change to
more realistic limits would again necessitate three successful cleaning of the equipment
before the procedure can be considered acceptable.
8. Attachments
• SOP for cleaning of the equipments
• Visual inspection form
• Surface sampling form
• Final rinse sampling form
• Monitoring form
9. Protocol Prepared By:

S. No Name Department Signature Date

1. Quality Assurance

10. Protocol Reviewed By:

S. No Name Department Signature Date

1. Quality Control

2. Microbiology

3. Production

4. Engineering

11. Protocol Approved By:

SI. No Name Department Signature Date

1. Head of Quality
Assurance
Attachments:

Cleaning validation visual inspection form:

Product cleaned Batch No.
Cleaned by Date
Cleaning SOP No. Date of revision
Protocol No.

No. Equipment Result Inspected by Date

inspected
Clean Not clean

Remarks:
…………………………………………………………………………………………………
…………………………………………………………………………………………………
…………………………………………………………………………………………………
……………………………

Reviewed
By: ……………………… Date……………………………..
 Cleaning validation surface sampling form:
Product cleaned Batch No.
Cleaned by Date
Cleaning SOP No. Date of revision
Name of the equipment Equipment No.
Protocol No.

No. Sample type Sample Sample Area (cm2) Sampled Date

location code By
1. Microbiological
2. Microbiological
3. Chemical
4. Chemical

Remarks:
…………………………………………………………………………………………………
…………………………………………………………………………………………………
…………………………………………………………………………………………………
……………………………

Reviewed
By: ……………………… Date……………………………..
Cleaning validation final rinse sampling form:
Product cleaned Batch No.
Cleaned by Date
Cleaning SOP No. Date of revision
Name of the equipment Equipment No.
Protocol No.

No. Sample type Which Part of the Sample Quantity Sampled Date
equipment to be code By
use for sampling

Remarks:
…………………………………………………………………………………………………
…………………………………………………………………………………………………
…………………………………………………………………………………………………
……………………………
 Reviewed
By: ……………………… Date……………………………..

Cleaning validation monitoring form:

Product cleaned Batch No.
Cleaned by Date
Cleaning SOP No. Date of revision
Name of the equipment Equipment No.
Protocol No.

No. Parameter monitored Sample Result Monitored Date

location By
1. Detergent
2. Rinsing
3. Final rinsing
4. Mop
5. drying
Remarks:
…………………………………………………………………………………………………
…………………………………………………………………………………………………
…………………………………………………………………………………………………
……………………………

Reviewed
By: ……………………… Date……………………………..