Know what is cleaning validation, maximum allowable carryover ( MACO), acceptance criteria and recovery factor in cleaning validation.
The Cleaning validation is performed to demonstrate the effectiveness of procedures for cleaning to remove the residue of the previous product.
After the process, the equipment used for manufacturing of the product shall be cleaned as mentioned in
respective SOPs
for cleaning.
All procedures for cleaning of process equipment 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 forthe existing products, however, if acceptance criteria become stringent or maximum rinse volume is changed after addition of new products, theacceptance criteria and maximum rinse volume is communicated to the concerned department. The stringent acceptance criteria are added in thespecifications during the scheduled periodic review of the specifications.
A specification shall minimally contain the following
Sampling quantity
Shall provide sampling quantity for chemical and
microbiological testing
or as applicable.
Sampling procedure
Shall explain briefly the procedure for sample collection.
Analytical specification
Shall provide specifications for the applicable tests.
Method of analysis
Shall provide analytical method for the applicable tests
All 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 verification
Study of monitoring the cleaning activity before completion of the three cleaning cycles on commercial batches of the product shall be considered ascleaning verification.
Cleaning verification / validation Acceptance Criteria:
Where,
Product A – Product manufactured before cleaning
Product B – Next Product after cleaning
For 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 samples
Active Ingredient Residue (For Non-dedicated equipment): Acceptance criteria based on the following rationale for swab samples :
Calculation [Applicable to all items of common equipment in product train].
V – Volume of solvent used to dispense swab.
1000 – Multiplication factor to convert the value in mcg from mg.
D – Swabbed Surface Area in cm2
.
Calculation of acceptance criteria for Rinse samples
Active Ingredient Residue (For Non-dedicated equipment): Acceptance criteria based on the following rationale for rinse samples:
Calculation [Applicable to all items of common equipment in product train].
Calculation of recovery factor :
% Recovery shall not
be
less than 75% unless otherwise specified and justified in the individual protocol of
analytical method validation
.
Recovery factor
shall be calculated as follows:
Recovery factor = -100 / % Recovery
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 isused for different products.
After addition of new product, the acceptance criteria and maximum rinse volume shall be recalculated in the matrix. If the acceptance criteria arestringent than as specified.
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 minimumof three cleaning cycles.
Modification of cleaning procedure / Surface area of product cocontact parts of the equipment or any modification to the equipment which has got adirect bearing on product contact parts.
Change in cleaning procedure.
Change in the 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.
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