MAR/MACO CALCULATION

Based on Therapeutic Daily Dose
This method only applies when the therapeutic daily dose (TDD) is known of the drug substance investigated (Previous product) in the cleaning validation and next drug substance (product to be taken). It is generally used for final product change over API Process “A” to API Process “B”.

Calculation formula for MAR (Maximum Allowable Residue) according the following:
 

                                                                 TDD _{min A} x MBS  x  10⁶

MAR                 =          ------------------------------------

                                                 SF x TDD _{max B}

 
Where,
MAR                 : Maximum Allowable Residue
TDD _{min A}          : Minimum Daily Dose in mg of the previous product A
TDD _{max B}          : Maximum Daily Dose in mg of the next product B
MBS                  : Minimum batch size of the product B
SF                      : Safety factor (normally 1000 is used in calculations based on TDD)

In case of Multipurpose plant, then MAR to be calculate in following ways
 

Sr	Name of Product	Minimum B.Size in kg	Minimum Daily Dose in mg	Maximum Daily Dose in mg	MAR	MAR ppm (B. Size x 10 ppm)
1	Product A (Previous Product)	50	100	500	Not Applicable	-
2	Product B (To be taken)	70	25	100	70000 mg	700 mg
3	Product C (To be taken)	10	500	1000	1000 mg	100 mg

MAR Calculation

MAR of Product A to Product B	=	100 x 70 x 1000000 ---------------------------------- 1000 x 100	= 70000 mg ≈ 70 g
MAR of Product A to Product C	=	100 x 10 x 1000000 ---------------------------------- 1000 x 1000	= 1000 mg ≈ 1 g

Based on above calculation, least MAR (1000 mg) shall be considered for cleaning validation of Product A (previous product / product to be cleaned) for all train of equipments of Product A, which to be shared with Product B, Product C,.....Product n

In case of least Maximum Allowable Residue (MAR) value shall be obtained greater than 10 ppm (General Limit), then MAR _ppm shall be calculated as following:
                               10           
MAR _ppm      = -------------- x MBS of next product B, C, .....n
                           1000000
Hence MAR _ppm of above example is respectively 700 mg and 100 mg. If the calculated MAR ppm is higher than General limit (10 ppm), then General limit shall be considered for cleaning validation and shall be applicable for individual equipment. However total carry over for train of equipment should not be more than calculated MAR or MAR _ppm