Identification
of Worst Case in Cleaning Validation
It is not
possible to carry out cleaning validation of all products manufactured in the
facility. Therefore, products are selected on the basis of the worst case.
Worst case is the condition when it is difficult to clean the residues of the
manufactured product from the equipment surface.
Different
parameters are considered during the worst case identification in
pharmaceutical cleaning validation.
1. Solubility
of API in Water
2. Potency of
Product
3. Maximum
Allowable Carryover (MACO)
3. Toxicity of
API
4.
Concentration of API
6. Color of
Product
7. Contact
Surface Area
8. Microbial
Growth
9.
Manufacturing Process
1. Solubility of API in Water
The solubility
of the API in water plays an important role in the cleaning of the equipment.
Insoluble API shall be hard to clean comparing the freely soluble one.
Therefore, the solubility of API is an important factor in cleaning validation.
A product containing less soluble or insoluble API shall be considered as worst
case and shall be selected for cleaning validation. If two products have the
same solubility in water then other factors are considered to select the worst
case.
2. Potency of Product
Products having
a low quantity of API are highly potent while the products with a low quantity
of the API are low potent products. Highly potent products are more active and
a low amount of those can cause an effect on the user. Therefore, the highly
potent product is considered as the worst case in cleaning validation.
3. Maximum Allowable Carryover (MACO)
MACO is another
parameter that helps to identify the worst case in cleaning validation. Lowest
MACO value is considered the worst case for cleaning validation. The product
containing higher MACO value will have higher LD50 value hence the product will
be less toxic than the product having lower MACO value.
4. Toxicity of API
Toxicity of the
API is determined by the LD50 value. The API with higher LD50 is less toxic
than the API having lower LD50 value because a very low quantity of it is toxic
than the other one. Therefore, the product with API containing lower LD50 is
considered the worst case in cleaning validation.
5. Concentration of API
Percentage of
API concentration is another parameter for worst-case identification. The
residues of product on equipment having more concentration of API will
contaminate the next product more than the product with low API concentration.
The product having higher API concentration is considered as the worst case.
6. Color of Product
Some product
colors are difficult to clean. Some coating colors are insoluble in water.
Products containing colors are considered the worst case compared to products
without color formulation.
7. Contact Surface Area
Contact surface
area is also a parameter to identify the worst case. If two products are
manufactured in different size of equipment then the total quantity of the
product will be more on the big equipment than the quantity of product on the
small equipment. In this situation, the product manufactured on big equipment
shall be considered as the worst case.
8. Microbial Growth
Products having
excipients those support the microbial growth as starch, lactose, sucrose,
gelatin, lactose etc. are considered as the worst case because microbial growth
may occur on equipment surface having residues of these products.
9. Manufacturing Process
Products that
are manufactured by aqueous granulation method or any other activity that can
increase microbial load in the product have possibilities to develop microbial
growth on the equipment surface. These products are considered as the worst
case in cleaning validation.
Every new
product added in manufacturing must be compared with the existing worst-case
product and assessed for the above parameters. If the new product qualifies for
the worst case assessment then cleaning validation of the new product must be
done.