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Cleaning is a crucial step in the manufacturing of pharmaceutical products, and it is essential to validate that the equipment is cleaned thoroughly. In identifying products for cleaning validation, worst-case identification is essential as well.
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 worst case. Worst case in condition when it is difficult to clean the residues of the manufactured product from the surface.
Different parameters are considered during the worst case identification in pharmaceutical cleaning validation.
- Solubility of API in Water
- Potency of Product
- Maximum Allowable Carryover (MACO)
- Toxicity of API
- Concentration of API
- Color of Product
- Contact Surface Area
- Microbial Growth
- Manufacturing Process
· Solubility of API in Water
The solubility of the API in water is crucial for cleaning equipment. In comparison to freely soluble API, insoluble API will be more difficult to clean. The API’s solubility is crucial for cleaning validation because of this. A product with a lower or insoluble API content will be chosen for cleaning validation as the worst-case scenario. When choosing the worst-case scenario, other parameters are taken into consideration if two products have the same solubility in water.
· Potency of Product
Products with a low amount of API are low potent whereas those with a large amount of API are very potent. A small amount of highly potent products might affect the consumer since they are more active. For example, the fact that a product containing 1 mg of API is more potent than one containing 10 mg of API shows that even a small amount of API can have an impact. So, in terms of cleaning validation, the very potent product is regarded as the worst scenario.
· Maximum Allowable Carryover (MACO)
Another parameter that helps in cleaning validation to find the worst case is MACO. The worst case for cleaning validation is considered to have the lowest MACO value. A product with a higher MACO value will have a higher LD50 value and be less harmful to humans as a result than one with a lower MACO value.
· Toxicity of API – Worst Case in Cleaning Validation
The LD50 number establishes the API’s toxicity. A far lesser quantity of the API with a higher LD50 value is more harmful than the API with a lower LD50 value, hence it is less toxic than the other one. The worst case in cleaning validation is therefore the product with API containing lower LD50.
· Concentration of API
A further parameter for worst-case identification is the percentage of API concentration. The next product will be more contaminated by product residues on equipment with higher API concentrations than by product residues with lower API concentrations. The worst-case scenario is a product with a greater API concentration.
· Color of Product
Certain product colors are difficult to clean. Water cannot dissolve some coating colors. When compared to products without color formulation, products with colors are considered to be the worst-case scenario.
· Contact Surface Area – Worst Case in Cleaning Validation
To determine the worst case, an additional parameter is contact surface area. If the two products are manufactured on different-sized equipment, the total quantity produced will be greater on the larger equipment than on the smaller equipment. The item produced with huge equipment is to be considered the worst scenario in this particular case.
· Microbial Growth
Products with excipients like starch, lactose, sucrose, gelatin, or lactose that promote microbial growth are considered the worst scenario because microbial growth might happen on surfaces of equipment that have residue from these products.
· Manufacturing Process
There is a possibility that products produced through the aqueous granulation method or any other process that may increase the product’s microbial load may produce microbial growth on the equipment surface.
These items are regarded as the worst possibilities for cleaning validation. Every new product that is added throughout production must be compared to the current worst-case product and evaluated for all of the above.
