Worst Case Selection
Worst Case Selection
Worst Case Selection
Cleaning in pharmaceutical manufacturing is a critical process and it validation id important to ensure the proper
cleaning of the equipment. Worst-case identification plays an important role in selection of products for 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
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.
8. Microbial Growth
Products having excipients those support the microbial growth as starch, lactose,
sucrose, gelatine, 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.