Instrument Business Group

6060 Spine Road

Boulder, Colorado
80301-3323 USA
Telephone: (303) 444-2009
Main Fax: (303) 444-9543
Fax Orders: (303) 527-1797
www.IonicsInstruments.com

Calculation of Acceptable Residue Limits

This will be a multiple step calculations, and we’ll step through it one calculation at a time.

1) Concentration of Product A (your product of interest) in the next product (we’ll call it Product B here)

(Active dose in Product A)(Number of A per dose)(Minimum # of doses of Product A per day)
(Total dose in Product B)(Number of Product B per dose)(Maximum # of doses of Product B per
day)

• The top line of the equation indicates the minimum dose of active in Product A per day. The
first variable will be defined by the concentration in a single tablet or injection of a product.
For example, the product may be given in 25 mg tablets. A certain percentage of that tablet
will be the active ingredient (or the ingredient of interest). For the second variable, each
time the product is introduced, there will be a specific number of tablets or injections. For
example, there may be two of the 25 mg tablets taken at a time. The final variable in the
numerator indicates how many times per day the product will be taken, once or twice for
example.
• The denominator of the equation indicates the maximum dose of Product B per day. We
need to know that to determine how much of product A can be remain after the cleaning
procedure.
• The result from this equation will be the Concentration of Product A.

2) Absolute Amount Limit

(Concentration of Product A)(Batch size of Product B)(Safety Factor)

• The first variable in this equation will be the result of equation 1, above. The second
variable will be the batch size of the next product, 200 kg for example. The safety factor
will be defined by the means of introduction of Product A. If it is introduced topically, the
factor is 1/100, if it is introduced orally, the factor is 1/1000 and if it is parenteral or
injectable, the factor is 1/10,000.
• The result from this equation will be the Absolute Amount Limit.

3) Limit per Surface Area

(Absolute Amount Limit)

Surface Area

• The first variable will be the result of equation 2, above. The second variable will be the
surface area. Assuming that Product A and Product B will have the same batch size, they
should also have the same shared surface area (200,000 cm2, for example)

4) To calculate the limit per sample, we have two options. The first we will discuss is limit per sample
as determined by sample swabbing.
 a. (Limit per Surface Area)(Swabbed Area)
Desorbed Solvent Amount

o The first variable, Limit per Surface Area will be the result of equation 3, above.
The second variable is the area that is physically swabbed (100 cm2, for example).
The desorbed solvent amount is the amount of solvent (usually water) that the swab
is being placed in for analysis. If you are using an autosampler with the 40 mL
vials, the solvent amount will likely be between 30 and 40 mL (although the exact
amount used is not important, ensuring that the exact volume that is used is
inserted to the formula is important).
o This will give the limit per sample of the active. You will need to convert this to limit
per sample of TOC. For example, the active product may by 65% carbon. You
would need to multiply the results of the above equation by 0.65 to determine the
acceptable limit per sample in terms of TOC.

To calculate the limit per sample for a rinse sample, we will determine that by the following:
b. (Absolute Amount Limit)
Amount of Rinse Solution

o The variable in the top of the equation, absolute amount limit, will be the result of
equation 3. The variable in the bottom of the equation will be equal to the rinse
volume (this will be something equal to or less than the capacity of the preparation
vessel).
o Again, this value will need to be multiplied by the percent of the active that is
carbon (65% was the example used above) to determine the limit in terms of TOC.