You can find this detail as API ICH guideline .

CHECK APIC Cleaning guideline .

I thing these two links may help you.

https://www.youtube.com/watch?v=sWyC1T0KnxM

http://www.ema.europa.eu/docs/en_GB/document_library/Overview_of_comments/2015/10/WC500195205.pdf

Thank you

In regards to your statement "There will not be any adverse effects caused by an API." All APIs, at some dose, will have an adverse effect. It goes back to the basic concept of toxicology, 'The Dose Makes the Poison." If the API has any therapeutic effect, then that is considered an effect.

Hi,

Sir,

please share the article

The "dose makes the poison" is a fundamental toxicology principle, not a specific journal article. https://en.wikipedia.org/wiki/The_dose_makes_the_poison

There is a toxicology textbook by the same name, but the book would be of little value for specifically determining PDEs. In order to calculate PDEs, the author should have a deep knowledge of toxicology principles, education, and experience. Otherwise, there is a high degree of probability that the value will be incorrect.

PDE can be calculated for API in this case by review or performing studies like:

Acute toxicity,

Repeated dose toxicity

Gentoxicity,

Reproductive toxicity

and carcinogenicity also some product related or exposure route related toxicity.

Take NOAEL values and MTD fo considerations, take lowest NOAEL and calculate by using formula for PDE.

PDE Formula-= Avg wieght of Human X NOAEL divide this by F1 x F2 x F3 x F4 x F5

reference number 2 will help you. Anyone can calculate PDE, just deep learning by self is required.

Best Luck!!

Ref:

1. https://www.pmda.go.jp/files/000215510.pdf

2. https://www.lhasalimited.org/Public/Library/2018/Adjustment%20Factors%20-%20Joel%20Bercu.pdf

PDE=NOEL.Weight adjustment/f1.f2.f3.f4.f5