Suez Total Organic Carbon - March 2020 - 9

reference values in developing
acceptance criteria
MAC calculations start by identifying clinical reference values for
each product. These may include, but are not limited to, Therapeutic
Daily Dose (TDD), Acceptable Daily Intake (ADI), Lethal Dose for 50%
of population (LD50), or Permitted Daily Exposure (PDE). Clinical
reference values may be found in literature or online, including
PubChem DSSTox FDA Maximum Daily Dose Database (DSSTox
FDAMDD).2 Regardless of the citation source for starting reference
values, they must be scientifically defensible. Starting reference
values in this application brief originate from DSSTox FDAMDD.

product limit (in ppm). The product limit accounts for the sampling
method with the MAC value.
Two common sampling methods are:
1. collecting a swab sample from inside the tank
2. collecting a rinse grab sample

Product Limit from Swabbing
If sampling involves swabbing a specified area in the tank, the target
value may be calculated using the MAC value, assuming an even,
homogenous API deposition throughout the active surface area.

MAC from TDD
When determining MAC from TDD, the current product in the tank
(Product A) and the next product in the tank (Product B) must be known
(see Figure 1). The known identity of both products allows identification
of a defensible starting clinical reference value. Depending on what
types of compounds Product A and B are, a different Safety Factor
(SF) in the calculation is used based on the risk assessment of those
compounds.3 A typical safety factor value is 1000.3

MAC from LD50
As with TDD, when determining MAC from LD50, the current product
in the tank (Product A) and the next product in the tank (Product
B) must be known (see Figure 1). Next, calculate the No Observed
Effect Limit (NOEL) using the LD50 reference value for Product A.
Then, calculate MAC from the derived NOEL value. Please note that
the denominator value of 2000 in the NOEL equation is an empirical
constant referenced in literature.3

Product Limit from Rinse
If sampling involves collecting a final rinsate from the tank, the
MAC value is converted into a concentration (mg/L) based on final
rinse volume.

product limit to TOC limit
Specific product limits are not directly transferrable to a TOC method.
The specific product limit, depending on the sampling method, can be
converted to a TOC limit by multiplying by relative mass percentage of
carbon from the chemical formula of the product.
When a specific method limit has been previously calculated,
converting from the specific cleaning validation method, such as
HPLC, to a nonspecific method, such as TOC, can be achieved using
the percentage carbon in the chemical formula. For example, if a
specific API limit for HPLC is established at 10 ppm and the percentage
carbon is 50%, the TOC limit would be 5 ppm.

example using TDD
In this example, Product A is Epinephrine and Product B is Diazepam.
The clinical reference values are as follows2:

MAC to product limit
A MAC value alone is not sufficient to release equipment for use. Once
MAC has been determined, the value must be converted into an actual

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