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Maximum daily dose and Total dialy Intake
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MDD is the maximum daily dose calculated based on the therapeutic dose. (Therapeutic dose mg * 60 kg average body weight per day).
TDI is the total daily intake what you have taken. TDI should be less than the MDD.
TDI for Impurities is calculated based on toxicity data
Dear Mr. Prashant,
To make it more clear on this subject I have given below an example.
A drug "D1" with a therapeutic dose of 1 mg having an impurity "Impurity A" with the specification level 1%.
The maximum daily dose (MDD) of the drug "D1" is 60 mg.
The total daily intake (TDI) of "Impurity A" when it is present at specification level and when the drug is administrated at MDD is 0.6 mg.
The toxicity studies has to reveal that there is no adverse effects of "Impurity A" at TDI of 0.6 mg, otherwise the revision of specification of "Impurity A" has to be considered.
The TDI is also used to denote the degradation products. The impurities does't have any therapeutic value and its intake is based on the dosage of the drug. So it is denoted by the term TDI.
Could you please give clarity on Assay limit.
Ex: In synthetic products it has been gven as 98 to 102 by HPLC at the same case in Titrimetry given as 99-102. Actually most of the limit range fixed like this. But some times this range may be changed.
In semisynthetic products this range has been given in relaxed.
The semi synthetic products are prepared by chemical synthesis from natural materials and it contains mixture of natural and synthetic substances. (Partial altration by chemical manupulation). Most of the cases the semi synthetic products involve complex structures. The semisynthetic producess is normally adopted when the starting material is structurally complex or the syntetic process is difficult or costly. Because of this reason there may be flexibility in assay limit for semi synthetic products. But there are examples with assay limits equal to synthetic process.
The HPLC method and titrimetry are two different methods and the principle is different. Although the equivalancy of both the methods have to be estabilished there is always minor variations.
Normally the Titrimetry methods will be little higher assay than the HPLC methods. The HPLC method is more specific where as in the titrimetry methods the assay depends on other factors.
For example in acid base titration the presence of free acid and in iodometry the presence of oxidising impurities will make the assay slightly higher.
In cleaning validation study campaign batches study to be done (batches can run up to complete) but as per the cleaning of equipment validity will be fixed 5 days or 7 days. Here my query is if campaign batches can take more than 7 days how to justify
Please give clarity on this
As you are said that cleaning of equipment validity will be fixed 5days or 7 days, but it is applicable for when equipment is not in use or after it was cleaned, but for campaign batches you can fixed the limit, like max 15 continuous batches can be taken or 30 days which ever is earlier................and this study you can proved based on swab analysis of different types of equipments ( any one SS and GL reactor of max and min capacity of plant.....same allow for every equipments also) at different regular interval (like after 7,10,15,20,25 and 30 days etc............)
It's not like that only 15 days or 30 days. It can be fixed based on your established periodical equipment cleaning data. It can be longer if your data supports. If not it could be lesser also.