Cleaning Validation Protocol

Cleaning Validation Protocol

1.1Background

After product Y or group of products^# equipment X is cleaned in accordance with the procedure XYZ...

^# for group of products rationale should be described for strategy in grouping of products

• Equipment, cleaning method and cleaning agents should be described.

1.2Purpose

The study should demonstrate that product residues remaining in a piece of equipment should always be within acceptance criteria if the equipment is cleaned by using defined cleaning method.

1.3Scope

To ensure that no product residues (active pharmaceutical ingredients, intermediates or excipients) and cleaning agent residues (solvents) remain after cleaning a visual test and chemical evaluation of the equipment should be performed. They have to be removed to levels within the range of acceptance criteria.

Generally after three consecutive cleans the equipment cleanliness has to be proved by testing and evaluation of samples in accordance with the protocol.

Visual revision of the working areas should be performed to reduce cross contamination which results from contamination of surface of process room.

To ensure that cleaning procedure is valid all data produced during the study should be within the acceptance criteria. From the data generated a report is prepared thus determining the validity of cleaning procedure.

The equipment should not be used to process another product until the equipment is adequately cleaned and clearance is given by the department of validation.

1.4Responsibility

The responsibility of the cleaning procedure should be as follows:

Scheduling                                                            Manufacturing, Engineering, QC, QA.

Cleaning of equipment                              Manufacturing

Removal of samples                                  QA

Testing of samples                                    QC

Review of data and approval of study     Validation or QC or Manufacturing

1.5Sampling procedure

Swab and rinse samples should be removed from the equipment

1.5.1Swab Samples

Based on the risk assessment sampling locations should be defined. According to the swabbing procedure swab samples should be removed. The swab sampling locations are as follows:

Product residue samples – list of number of swabs to be removed and sample locations

Cleaning agent samples – list of number of swabs to be removed and sample locations

• Samples that are removed from the locations on the equipment are meant to be the “worst case” which are difficult to clean and thereby creating a chance for the product to reside if not cleaned properly.

1.5.2Rinse Samples

Rinse samples should be removed as per the SOP describing the sampling technique for the QA sampler. The volume of the liquid for rinsing the equipment should be in detail and this should also be mentioned in protocol.

1.6Microbiological Testing

Microbiological testing should be done in accordance with the procedure as given in the SOP detailing the procedure of sampling technique.

Microbiological testing location                List of sample locations and number of                                                                                        microbiological test samples to be removed

All sampling details whether microbiological or rinse or swab should be referenced in Table samples and then sent to QC department for analysis.

1.7Testing Procedure

• Rinse samples and swab samples should be tested for product and cleaning agent residues according to analytical protocol.
• Microbiological test samples should be tested for total germ number.
• The limits of detection and quantitation and recovery% should be noted.

All data produced during this study should be given to validation department where adherence and calculations to acceptance criteria is determined.

1.8Acceptance criteria

After cleaning is done according to the procedure detailed in the SOP, equipment should be checked for Visual Cleanliness.

Equipment is visually clean:          Signed (Manufacturing):________ Date: ______

                                                      Verified (QA):_______ Date: ______

The swab and rinse sample acceptance criteria for product and cleaning agent residues and microbiological test acceptance criteria should be given along with proper rationale.

1.9Deviation

Any deviations that occur during the completion of validation protocol should be indicated. The effectiveness of the cleaning procedures along with any corrective or preventive actions should be indicated.

1.10Revalidation

The revalidation strategy for the cleaning process should be defined.

Signed: _________ Verified: ________

Table 1: Sample reference table

Format for cleaning validation protocol

Prepared by (Dept.): ________________      Date: _________

Reviewed by (Dept.): ________________    Date: _________

Approved by (Dept.): ________________    Date: _________

Approved by (Dept.): ________________    Date: _________

Approved by (Dept.): ________________    Date: _________

Title:

Protocol Number: ________________

Protocol Issue date: ________________

Cleaning SOP Reference and Issue number: _____________

Validation, sampling, microbiological testing, protocol

• guidance on aspects of cleaning validation in active pharmaceutical ingredient plants. active pharmaceutical ingredients committee (apic). http://apic.cefic.org/pub/apic_cleaning_validation_2014.pdf. published may 2014. accessed june 2016.