Regulatory Open Forum

Dear distinguished members,

I would humbly request for your kind help for the following.

API contains methansulfonamide (i.e. -CH₃SO₂NH) group in it's structure (e.g. Dronedarone).

However as a result of chlorination of methane sulphonamide group (-CH₃SO₂NH) during reaction; an impurity Chloro-methanesulfonamide (ClCH₂SO₂NH-) forms in API.

For better understanding Below is the representation of API structure and Chloro-Impurity structure;

API: CH₃SO₂NH-X

Impurity: ClCH₂SO₂NH-X

(X= Cyclic rings of API structure)

Since all the structure of API & Impurity is identical except the chlorination of Methanesulfonamide functional group of API to form Chloro-methanesulfonamide as an Impurity as represented above.

I would request your kind help for following options,

a) Can we call it Chloro-analogous impurity of API ?? And control as an ordinary impurity in line with ICH Q3A qualification threshold???

b) Deriving impurity limit based on Chloro-methane (-CH₂-) structure alert:  

Considering the Alkyl halide (i.e. Chloro-methane) substructure , solely responsible for susceptible mutagenic potential of ClCH₂SO₂NH Impurity. Can we use ICH M7 (addendum) prescribed PDE value (I.e.1360 mcg/day) of chloro methane to derive the limit of Chloro impurity and fix it in the API specs??

Many-many thanks in advance for your kind support and help!!!

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Best personal regards,
Sushil Sharma
Visakhapatnam
India
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