For clinically relevant tolerances, perhaps the most important consideration is that the tolerance should reflect consistent and reproducible delivery of the patient’s expected dose (amount of the drug). Commonly, the dosage or strength of a tablet/capsule reflects the expected amount of drug to be released or delivered. Therefore, the amount of drug to be released is fixed for clinical relevance, i.e. 100% (at least on average). The only variable which needs to be determined is the time, i.e., how long would it take for the drug to be released. For IR products, this duration of drug release is usually an hour or less. However, based on experimental evidence, this time duration may be adjusted as required in exceptional cases.
Therefore, the setting of tolerances should be based on the duration of time required for the release of all drug present in the product.
At present, tolerances are set (e.g. see USP) based on two parameters (values), i.e., the amount of drug released at a certain time.
The amount (%age of drug) released is often referred to as the Q-value. Although the Q-value is set based on the product behavior at the product development stage, it is still chosen arbitrarily rather than based on any scientific/clinical relevance. It is not clear why this Q-value is chosen arbitrarily and set at less than 100%, usually 80% or lower when it should be 100%. The practice of setting tolerances at 80% or less may not be clinically relevant and require reconsideration.
In short, clinically relevant tolerances should only be based on the time duration, i.e., how long would it take for 100% of the drug to be released from a product.