What purpose PDE is used in the context of cleaning validation?

PDE is used to determine the acceptable amount of a previous drug that may be allowed in the next drug as carry over cross contaminant. This acceptable level is called MACO (Maximum Allowable Carryover). The MACO is then used for the calculation of the maximum safe surface residue or rinse concentration (the operational cleaning limit), which takes into account the shared equipment surface areas or volumes of the rinse of equipment between products A and B. MACO = PDEPrevious x MBSnext TDDnext Where, MACO (Maximum Allowable Carryover): Acceptable transferred amount from the previous product into your next product (mg). PDE- Permitted daily exposure. MBSnext- Minimum batch size for the next product(s) (where MACO can end up) (mg) TDDnext: Standard therapeutic daily dose for the next product (mg/day). As evident from the equation, larger the PDE value, higher will be MACO. This means more amount of a relatively safe drug may be allowed as a cross-contaminant while highly toxic compound can be allowed only a minute amount in the next product.

What is PDE and why it is needed in the context of cleaning validation?

ISPE-Risk MaPP, ICH Quality guidelines, EU GMP, and EMA guidance recommends a risk-based decision making in the pharmaceutical manufacturing. When different medicinal products are produced in shared facilities, the potential for cross-contamination is a concern. Medicinal products provide a benefit to the intended patient or target animal; however as a cross contaminant, they provide no benefit to the patient or target animal and may even pose a risk. Hence, the presence of such contaminants should be managed according to the risk posed which in turn are related to levels that can be considered safe for all populations. To this end, health based limits through the derivation of a safe threshold value should be employed to identify the risks posed. The derivation of such a threshold value (e.g. permitted daily exposure (PDE) or threshold of toxicological concern (TTC) should be the result of a structured scientific evaluation of all available pharmacological and toxicological data including both non-clinical and clinical data. PDE is a substance-specific dose that is unlikely to cause an adverse effect if an individual is exposed at or below this dose every day for a lifetime. It is synonymous to ADE (Acceptable Daily Exposure). PDE is a reflection of toxic potential of the compound; higher the PDE lower is the toxic potential. PDE is derived by a toxicologist from a structured scientific evaluation of relevant data.

What is cleaning validation?

Cleaning validation is documented evidence that an approved cleaning procedure will reproducibly remove the previous product used in the equipment below the scientifically set maximum allowable carryover level in a shared manufacturing facility.