1.0 OBJECTIVE:
The aim of this cleaning validation protocol is to provide documented evidence that the cleaning procedure designated for each equipment used & unused for products manufactured in manufacturing area are capable of removing residues of active to level at or below the predetermined acceptance limit.
1.0 SCOPE:
3.0 RESPONSIBILITY:
3.1 Quality Assurance: Preparation, review & approval of cleaning validation protocol & report
3.2 Production: Cleaning of equipment as per the SOP & review of protocol & report.
3.3 IPQA,QC, Microbiologist: Swab sampling for residue and for Microbial analysis and testing.
4.0 PRODUCT DETAILS:
5.0 VALIDATION DESIGN/PLAN:
5.1 Identification of equipments:
5.1.1 Equipment used to manufacture the product for which cleaning validation to be performed is to be identified.
5.1.2 Cleaning SOP for each equipment is also to be identified.
5.2 Establishment of maximum allowable carry over:
5.2.1 Establish the acceptance criteria for the cleanliness:
5.2.1.1 Dose criteria: the acceptance limit for any of the residue is 1/1000th of the lowest strength label claim in a maximum daily dose of the subsequent product.
5.2.1.2 10 ppm: Not more than 10 ppm of any product will appear in another product.
5.2.1.3 Visual criteria: Equipment’s should be visually cleaned and no traces of product residue appear on surface of equipment.
5.2.2 Calculation of dose criteria:
5.2.3 Calculation of 10 ppm criteria:
Calculation of maximum allowable residue cannot be done based on dose criteria when subsequent product to manufacture is not known, Hence calculation of maximum allowable carry over shall be done based on 10 ppm criteria. In case dose criteria calculation maximum allowable residue found more than 10 ppm, calculation of maximum allowable carry over will be done based on 10 ppm criteria.
5.2.4 Calculation for Rinse water:
5.3 Procedure For Sampling:
5.3.1 Sampling shall be done as per SOP for cleaning validation.
5.3.2 Clean the each equipment as per the respective SOPs.
5.3.3 Inspect the equipment’s and ensure that it is visually clean.
5.3.4 Record the observations in the visual inspection record.
5.3.5 Sampling shall be done by swabbing 10 x 10 cm2 area in each sampling point using the template.
5.3.6 Swab shall be collected as per the following figures (a, b, c & d) from each sampling point.
5.3.7 Collect the swab using swab stick at the predefined location.
5.3.8 Collect the swab covering 10 x 10 cm2 area from the floor, walls and glass panes of doors.
5.3.9 First rinse the swabs with purified water for a minimum of three to four times then dip the swab in purified water. Squeeze the swab against the walls of the test tube and take the swab in respective area.
5.3.10 Then transfer the swab sample to test tube, containing about 10 ml of diluent.
5.3.11 Analyse the swab samples for active residue content using respective analytical method and record the results.
5.3.12 Rinse water shall be collected for the equipment’s where swab sampling cannot be collected.
5.3.13 Rinse the equipment / part of the equipment with 1 litre purified water.
5.3.14 Collect 10ml of the rinse from the above and send the sample to quality control for analysis.
5.3.15 For microbial swab collect swab samples covering 25 cm2 using sterile swab of 150 mm length at the predefined locations.
5.3.16 First dip the swab bud in sterile water and take the swab. Transfer the swab samples to test tube, containing 10 ml of 0.9% sterile saline.
6.0 REPORT PREPARATION:
6.1 Compile the data and compare the results with the acceptance criteria.
6.2 Validate the cleaning procedure for three consecutive batches/cleaning cycles and summary report shall be prepared.
7.0 REVALIDATION CRITERIA:
7.1 Revalidation shall be carried out in the following cases:
7.1.1 Change the cleaning process.
7.1.2 Introduction of new product/ worst case marker product.
7.1.3 Change the manufacturing formula
7.1.4 Change the equipment
8.0 ABBREVIATION:
SOP : Standard operating procedure
IPQA : In-process quality assurance
QC : Quality control
Cm2 : Centimeter square
Also read: SOP for cleaning validation
Also read: SOP for process validation of pharmaceutical products