About APIC Cleaning validation

GOOD VALIDATION PRACTICE (cGVP) CLEANING VALIDATION
1

Hi all,
I wont to speak about GUIDANCE ON ASPECTS OF CLEANING VALIDATION IN ACTIVE PHARMACEUTICAL INGREDIENT PLANTS.

  1. I can’t understand how I can derive ADE data from OEL or LD50 data?? In some scientific publication I find that ADI = 10 mcg/m3 *OEL, but ADI it’s Acceptable Daily Intakes. And how I can calculate ADE (acceptable daily exposure) it’s the same? (see chapter 4.2.1 in page Nr. 8.)
  2. If I understand correctly, when we calculate MACO from ADE we don’t use safaty factor, but why in example Nr. 3 (in page Nr. 17.) in equation we use 0,002 mg ADE , but in exercise write that the product has an ADE of 2 mg??? It’s mistake???
2

[quote=Dimitrij]Hi all,
I wont to speak about GUIDANCE ON ASPECTS OF CLEANING VALIDATION IN ACTIVE PHARMACEUTICAL INGREDIENT PLANTS.

  1. I can’t understand how I can derive ADE data from OEL or LD50 data?? In some scientific publication I find that ADI = 10 mcg/m3 *OEL, but ADI it’s Acceptable Daily Intakes. And how I can calculate ADE (acceptable daily exposure) it’s the same? (see chapter 4.2.1 in page Nr. 8.)
  2. If I understand correctly, when we calculate MACO from ADE we don’t use safaty factor, but why in example Nr. 3 (in page Nr. 17.) in equation we use 0,002 mg ADE , but in exercise write that the product has an ADE of 2 mg??? It’s mistake???[/quote]

I could be wrong, and I would love if someone else can confirm. It seems the ADE should be 2mcg and that would translate into .002mg

3

[quote=Dimitrij]Hi all,
I wont to speak about GUIDANCE ON ASPECTS OF CLEANING VALIDATION IN ACTIVE PHARMACEUTICAL INGREDIENT PLANTS.

  1. I can’t understand how I can derive ADE data from OEL or LD50 data?? In some scientific publication I find that ADI = 10 mcg/m3 *OEL, but ADI it’s Acceptable Daily Intakes. And how I can calculate ADE (acceptable daily exposure) it’s the same? (see chapter 4.2.1 in page Nr. 8.)
  2. If I understand correctly, when we calculate MACO from ADE we don’t use safaty factor, but why in example Nr. 3 (in page Nr. 17.) in equation we use 0,002 mg ADE , but in exercise write that the product has an ADE of 2 mg??? It’s mistake???[/quote]

It is not so easy to explain, especially considering the novel guidelines about toxicological data.
The ADE is calculated from the NOEL (no observed effect level) of the API/worst-case, corrected from human body weight and a safety factor (depending on the cavia used to find out the value). If NOEL is not available (it is common, if the active substance is relatively “young”), guidelines allow to extrapolate the value from other ones (OEL, NOAEL, DL50 and so on…) correcting them by a further safety factor.
The final “real” or “extrapolated” value you obtain is used in the “standard” formula for MACO calculation, using ADE instead of 1/1000 active dosage.

I hope to have been at least a bit useful to you :wink:

Marco