No. In addition the organic acid derived from the ester, commonly used in medicinal chemistry to improve stability, is active but is included in the related substances. Thus, it depends of the API and its degradation pathway.
I had gone through the literature and found that the ratio of actives to in-actives in a test set validation must be 1:1 for a statistically significant model. I don't know how you have made the above statement and in-fact it is not clear to me. Could you please send me some references regarding the same?
No reference. But an example would be Vitamin A Acetate (Retinol Acetate) as the API. Therefore, the primary related substance (impurity) is the reaction intermediate used in the manufacture of the ester, which is Vitamin A Alcohol (Retinol). Both are active physiologically, but Retinol degrades rapidly (especially exposure to Oxygen and light). BTW most information is proprietary and confidential to medicinal chemists.