Potency adjustment, Overages and Excess

Hi, Can anyone explain on the different between three topics above & legit reference

Please note the differences as follows,

Potency adjustment -
This means adding an extra quantity of API (active ingredient) into the formulation when manufacturing the drug product. This is done to compensate when the potency is less than 100%. This extra quantity of API is added in the formulation so that in the final product the assay/potency is obtained 100% or as per the label claim for that drug product. Sometimes, when the API is available as dihydrate (2 molecules of water), OR Trihydrate (with 3 molecules of water) the extra quantity of API is added to the formulation to compensate for water content so that the assay of that drug product can meet the label claim as 100% on anhydrous basis. For example, Amoxicillin trihydrate API (with 3 molecules of water) is added in the formulation of the drug product as capsules or suspension so that the assay for Amoxicillin in the capsule meets the label claim as 500 mg of anhydrous Amoxicillin. Therefore the amount of Amoxicillin trihydarate added in the formulation of the drug product is equivalent to 500 mg anhydrous Amoxicillin. The extra amount accounts for water content (3 H2O per molecule) and potency difference (100 - actual potency or assay obtained of that API).

Overages -
Overages mean an extra quantity of the API added in the formulation of drug products to compensate for its losses during the shelf life or storage period because of the instability of that API in the formulation (Drug product). Therefore, to ensure that at least 100% of the amount of API as per label claim remains in the formulation/drug product till the expiry date (shelf life), the overages are added in the drug product formulation during its manufacturing. The extra quantities are decided based on stability studies of that drug product. For example, vitamins and antibiotics are most unstable at higher temperatures and high humidity storage conditions. Therefore there is a provision in the drug laws to add overages of such APIs in the drug product formulations based on its stability profile in the specific packaging (container closure system).

Excess -
This means using an extra quantity of API or excipients in the drug product formulation during its manufacturing to compensate for handling losses or production losses, such as loss of materials during the sifting or drying of powders, and granules or during coating of tablets (for example, tablet coating solutions), so that at least required amount of that material (API or excipients) remains in the formulated batch of that drug product.