TDD in the context of cleaning validation refers to Total Daily Dose of the Next Product, used in calculating Maximum Allowable Carryover (MACO).
In cleaning validation, determining the acceptable residue limits of a previous product is critical to prevent cross-contamination. The MACO calculation helps establish these limits, and the TDD of the next product to be manufactured on the same equipment is a crucial factor in this calculation.
How TDD is used in MACO Calculation:
The TDD represents the maximum amount of the next product a patient could potentially be exposed to in a single day. This information is used to ensure that any residual contamination from the previous product is at a safe level, even if the patient receives the maximum daily dose.
Example:
Let's say the Total Daily Dose (TDD) of the next product is 500 mg, and the batch size is 400 kg. The MACO can be part of the calculation for determining the acceptable residue limit (ARL) and is often represented by the following simplified formula (more complex formulas are commonly used):
MACO ≈ (TDD x Minimum Safe Dose Factor) / (Batch Size of Next Product)
- TDD: 500 mg
- Minimum Safe Dose Factor: A safety factor (e.g., 1/1000 or 0.001) often applied to provide an extra margin of safety.
- Batch Size of Next Product: 400 kg = 400,000,000 mg
MACO would then be part of a calculation to determine the acceptable residue limit (ARL):
ARL (ppm) = MACO (mg) / Surface Area (cm²)
The MACO value, derived using the TDD, directly impacts the acceptable residue limits set for the cleaning process. A higher TDD generally allows for a higher MACO (and thus higher ARLs), while a lower TDD necessitates stricter cleaning to achieve lower residue levels. This ensures the safety of the patients receiving the next product.
