Cleaning Validation of Equipments
OBJECTIVE: To describe the procedure for Cleaning Validation.SCOPE: Demonstrate and validate that current standard operating procedure for Cleaning can consistently clean the equipment to a pre-determined level of cleanliness.Demonstrate that no cross contamination will be observed on shared equipment between drug product to be cleaned and next drug product to be manufactured.RESPONSIBILITY: Pharmacist, Executive- QA, Executive- QC, Head – Production, Head – QA & QC.PROCEDURE: The Cleaning validation is performed to demonstrate the effectiveness of procedures for Cleaning to remove residue of previous product.After the process, equipments used for manufacturing of the product, shall be cleaned as mentioned in respective SOPs for cleaning.All procedures of cleaning of process equipments used to manufacture more than one product shall be validated.If the product contains more than one active substance, the active substance least soluble in water and/or highly potent is tested, unless otherwise specified in the individual specification.Before initiating any cleaning validation, a product specific specification shall be prepared. The specification shall mention the acceptance criteria for the existing products, however if acceptance criteria becomes stringent or maximum rinse volume is changed after addition of new products, the acceptance criteria and maximum rinse volume is communicated to concerned department. The stringent acceptance criteria is added in the specifications during the scheduled periodic review of the specifications. A specification shall minimally contain the followingSampling quantityShall provide sampling quantity for chemical and microbiological testing or as applicable.Sampling procedureShall explain briefly the procedure for sample collection.Analytical specificationShall provide specifications of the applicable tests.Method of analysisShall provide analytical method for the applicable testsAll the applicable tests shall be incorporated in the specification itself.Minimally three cleaning cycles shall be monitored and validated to establish the effectiveness of cleaning procedure. Cleaning verificationStudy of monitoring the cleaning activity before completion of the three cleaning cycles on commercial batches of the product shall be considered as cleaning verification.Cleaning verification / validation Acceptance Criteria:Calculation of the maximum Allowable carryover ( MACO) For the calculation by considering 0.1 % Safety factor
Daily therapeutic dose Min. Batch Size of Product B of product A in mg (in mg) Limit (mg) = ----------------------------------- x ------------------------------------------------ 1000 Max. daily therapeutic dose of product B in (mg) Where,Product A – Product manufactured before cleaningProduct B – Next Product after cleaningFor Considering 10 ppm as acceptance criteria.The quantity equivalent to 10 mg/L of the batch size is considered as the acceptance criteria for the acceptance criteria as 10 ppm. Calculation of acceptance criteria Calculation of acceptance criteria for swab samplesActive Ingredient Residue (For Non-dedicated equipments): Acceptance criteria based on the following rationale for swab samples :Calculation [Applicable to all items of common equipment in product train]. 1000 DLimit (PPM) = MACO x ---------- x ----------- C V
Where, C – Cumulative surface area of the equipments used (in cm2). V – Volume of solvent used to dispense swab. 1000 – Multiplication factor to convert value in mcg from mg. D – Swabbed Surface Area in cm 2 .Calculation of acceptance criteria for Rinse samplesActive Ingredient Residue (For Non-dedicated equipments): Acceptance criteria based on the following rationale for rinse samples:Calculation [Applicable to all items of common equipment in product train]. 1000 1
Limit (PPM) = MACO X ---------- x ------ C V
Where, C – Cumulative surface area of the equipments used (in cm2). V – Volume of solvent used for rinse of the same in mL per cm2 of Equipment. 1000 – Multiplication factor to convert value in mcg from mg.
Calculation of recovery factor :% Recovery shall be not less than 75% unless otherwise specified and justified in individual protocol of analytical method validation. Recovery factor shall be calculated as follows:Recovery factor shall be calculated as follows:
% Recovery
Recovery factor = --------------------
100
Microbiological
Quality: a) A Total count limit, is Not more than 10 cfu/100 ml by rinse method.b) Not more than 5 cfu / 25 cm 2 Cleaning validation shall be performed on all the products. The matrix for acceptance criteria shall be prepared when the same set of equipment is used for different products.After addition of new product the acceptance criteria and maximum rinse volume shall be recalculated in matrix. If the acceptance criteria is stringent than as specified in the
Revalidation of cleaning procedure:Revalidation of cleaning procedure is required if any of the following occur and revalidation of cleaning procedure shall be performed on a minimum of three cleaning cycles.Modification of cleaning procedure / Surface area of product contact parts of the equipment or any modification to the equipment which has got direct bearing on product contact parts.
Change in cleaning procedure.
Change in analytical method for determination of residue.Major non-traceable contamination occurrence.Failure during cleaning verification / validation.Monitor the validation status for cleaning during new product introduction.In case of microbial analysis results of swab samples or rinse samples, no need to wait for the release of results.
The specification shall mention the acceptance criteria for the existing products, however if acceptance criteria becomes stringent or maximum rinse volume is changed after addition of new products, the acceptance criteria and maximum rinse volume is communicated to concerned department.more information
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