I would like to raise a question/discussion about the proper way to establish limits in drug products. From my understanding the correct way is to divide the AI (ng/day) by the MDD (mg/day). But what do we mean by MDD mg/day, is it only for the amount of active or we also take into account the product weight that corresponds to the maximum mg per day of active?
From my point of view the risk for an NDSRI comes from the active, therefore by calculating the tablet weigh we calculate placebo as a risk which is not true.
Further to that if we accept that tablet weight should be taken into account for the limit calculation. How do we further calculate the test solution concentration, do we also include the actual average weight? Does that mean that we calculate twice the tablet weight therefore results will be higher than expected?
Please let me know your thoughts and share your knowledge for the above.
You are right. The limit is established by dividing the AI by the MDD, since the authorities require that limits be set with respect to the API. As you mentioned, the risk comes from the active, and the authorities do not want to have many limits that might result from considering the total weight of the formulation which, in fact, corresponds to the MDI (Maximum Daily Intake) since the MDI considers the total weight of the formulation; a product with 100 mg of API may weigh differently depending on the manufacturer, but the actual risk comes from those 100 mg. Another issue is that many laboratories and companies report results in terms of both the MDI and the MDD, but many of them report only the MDI and this is not fully accepted by health agencies.