Cleaning Validation - Calculations of Residue Limits For Drug Products for Equipment Cleaning

Cleaning Validation - Calculations of Residue Limits for Drug Product Therapeutic and
Non-therapeutic Materials for Equipment Cleaning
Introduction
This guideline provides equations and examples for calculating the Maximum Allowable Residue (MAR),
and Residue Acceptability Limits (RAL) for Drug Products and Non-Therapeutics.
Examples are provided for determining the acceptable equipment cleaning residue limits for
therapeutic drug products (MART and RALT) and for non-therapeutic ingredients (MARN and
RALN). For the therapeutic drug products both single product combination (Product A to B)
and multiple products combination examples are given.
Recommendations & Rationale
The attached Appendices give equations and example calculations for therapeutic drug
product cleaning limits for a solid oral dosage form (tablet), creams/ointment and ophthalmic
product. In Case-1 therapeutic example it is included the calculation of Maximum Allowable
Residue (MAR) limits using two formulas; dose MART and toxicity MAR. It also includes an
example for determining the worst case limit for shared equipment using multiple products.
Example for residue limits calculation of CIP® 100 detergent, a non-therapeutic ingredient is
also given.
Background Information and Equations:
The Maximum Allowable Residue for Therapeutics (MART) and Residue Acceptability Limit for
Therapeutic Dose (RALT) should be calculated based on each product that is to be processed in a specific
equipment train and determined by the formulas and equations provided in Appendix A. A common
default MART is not more than ten (10) ppm.
The calculated MART and the default MART should be compared and the lower of the two (2)
used. A Toxicity limit may also be calculated and compared to the default MART and the
NMT 10 ppm, and the lower of the three limits chosen.
The Maximum Allowable Residue for Non-Therapeutics (MARN) and Residue Acceptability Limit for
Non-Therapeutic Materials (RALN), such as materials used for equipment cleaning,
is a function of toxicity, and should be determined by use of the formulas and equations provided in
Appendix B. A default MARN is not more than one hundred (100) ppm. The calculated MARN and the
default MARN should be compared and the lower of the two (2) used. Residue