CLEANING VALIDATION PROTOCOL

1.0 APPROVAL SHEET Approval Sheet contains particulars about the Names of persons with designations and signature with date and nature of work performed for preparing this document. User of this document should prepare the Table and incorporate in this section. 2.0 Introduction: Medicinal products can be contaminated by other medicinal products, by cleaning agents, by microorganisms or by other material (e.g. Air borne particles, dust, lubricants, raw materials, intermediates, auxiliaries. In many cases, the same equipment may be used for processing different products. To avoid contamination of medicinal products, adequate and validated cleaning procedures are essential. 3.0 Unit Operation: Cleaning of Equipment. 4.0 Objective: To ensure that the Cleaning Procedure as detailed in the SOP is effective and removes all residues up to a predetermined acceptance level, and that there is no possibility of any resultant cross contamination. 5.0 Site of the Study : Production Department. 6.0 Validation Team: Representatives from : Production Quality Assurance Quality Control Engineering Individuals name to be entered in the report. 7.0 Description of the Equipment to be cleaned: All equipments used in the manufacturing of Tablet and Capsule: Details of the machine like Machine name and Code No. of Equipment/s to be entered in the report. 8.0 Standard Operating Procedure (SOP) for Cleaning of Equipment: SOP applicable to the cleaning of equipment: SOP No. To be recorded in the report. 9.0 Control: 9.1 Absence of traces of Active Ingredient and cleaning agent in swab/Rinse by validated analytical method. 9.2 Determination of bioburden (Microbiological Contamination) 9.3 Analytical method validation for cleaning validation shall be done. It should include analytical performance parameters like limit of detection and recovery of swab samples. 9.4 SOP for taking swab: SOP No. to be entered in the report. 10.0 Experimental Details: 10.1 Clean the equipment as per the SOP. 10.2 Collect the Swab / Rinse individually various parts as per the sampling plan.

10.3 Collect the final rinse in potable water. 10.4 Collect final rinse in purified water. 10.5 Swab various parts of the equipment for microbiological analysis. 10.6 Estimate the content of active in Swab / Rinse as per the validated analytical method. 10.7 Find the presence of cleaning agent in all rinse. 10.8 Visual inspection of final rinse. 10.9 Visually inspect the equipment and its parts to ensure that it is clean. 0.10 Based on the above analysis, calculate the amount of residue present in each rinse and swab and estimate probable contamination in the next product. 10.11 Calculate the limits for Acceptance criteria as follows: 10.10.1 DOSE CRITERION FORMULA: I/J x K/L x M = _________mg of previous product / 4sqinch. Where, I = 0.001 of smallest strength of previous product in mg / tablet (or) Capsule. K = No. of dosage units per batch of final mixture of next product. J = Maximum number of dosage units of next product taken / day. L = Surface area of equipment's common for both the products. M = 4 square inch / swab. 10.10.2 10 PPM CRITERION: FORMULA: RxSxU _______________ =________mg of previous product / 4sqinch T Where, R = 10 S = Kilograms per batch of final product of next product. T = Surface area of equipment's common for both the products. U = 4 square inch/swab. The carry over of previous product residue should not be more than the lowest value among the dose criterion & 10 ppm criterion. 10.11 Criteria for microbiological contamination: 10.11.1 Total Bacterial Count: Not More Than (NMT) 100 CFU per 4 square inch / swab 10.11.2 Mold and Yeast: NMT 10 CFU 4 square inch / swab 11.0 Acceptance criteria: 11.1 Equipment should be visually clean. 11.2 Residue of previous product or products in the swabs should be less than the minimum Value determined by dose Criterion and 10 ppm Criterion. 12.0 Type of validation: Concurrent Validation 13.0 Frequency : Three validations exercise per equipment. Three validations exercise per equipment for change in cleaning procedure.

Three validations exercise per equipment for major change in equipment. Re validation every two years.