Regulatory Open Forum

As per EMA and US FDA all APIs manufactured through synthetic process should be subjected to a risk assessment for presence of Nitrosamine impurities. Is there any exemption for this for an API exclusively to be used for topical purposes (say cream and ointments)? I cant get any reference to this and will appreciate your kind opinion.

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Anamitra Chatterjee


Munich
Germany
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This message was posted by a user wishing to remain anonymous

If the topical is non-systemic perhaps you may present an argument for exemption! No exemptions so far!!!
Original Message:
Sent: 04-Aug-2021 12:02
From: Anamitra Chatterjee
Subject: Nitrosamine/ API

As per EMA and US FDA all APIs manufactured through synthetic process should be subjected to a risk assessment for presence of Nitrosamine impurities. Is there any exemption for this for an API exclusively to be used for topical purposes (say cream and ointments)? I cant get any reference to this and will appreciate your kind opinion.

---------------------------------
Anamitra Chatterjee


Munich
Germany
---------------------------------

I think it is not necessary provided that there is no significant systemic absorption. you may need give a scientific justification based on the route of administration.

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SAKENI HADEBE
Pharmacist
LUSAKA
Zambia
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Original Message:
Sent: 04-Aug-2021 12:02
From: Anamitra Chatterjee
Subject: Nitrosamine/ API

As per EMA and US FDA all APIs manufactured through synthetic process should be subjected to a risk assessment for presence of Nitrosamine impurities. Is there any exemption for this for an API exclusively to be used for topical purposes (say cream and ointments)? I cant get any reference to this and will appreciate your kind opinion.

---------------------------------
Anamitra Chatterjee


Munich
Germany
---------------------------------

You may be asked to do nonclinical studies to demonstrate non-systemic absorption, if the FDA agrees with your argument for topical dosage form.

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GRSAOnline
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Original Message:
Sent: 04-Aug-2021 12:02
From: Anamitra Chatterjee
Subject: Nitrosamine/ API

As per EMA and US FDA all APIs manufactured through synthetic process should be subjected to a risk assessment for presence of Nitrosamine impurities. Is there any exemption for this for an API exclusively to be used for topical purposes (say cream and ointments)? I cant get any reference to this and will appreciate your kind opinion.

---------------------------------
Anamitra Chatterjee


Munich
Germany
---------------------------------

Attached is the USFDA guidance for your ready reference.

Risk Assessment is MUST. Based on the API, it may or may not require confirmatory testing. A "Risk Assessment Report" needs to be prepared and kept at the manufacturing facility.

Finished Product manufacturer will sure come to API manufacturer for this risk assessment report to prove that, their finished product`s evaluation for the risk of Nitrosamine.

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Gaurang Bhavsar, MS, RAC
Associate Director - Regulatory Affairs
Micro Labs USA, Inc.
Somerset, NJ 08873
USA
------------------------------

Original Message:
Sent: 04-Aug-2021 12:02
From: Anamitra Chatterjee
Subject: Nitrosamine/ API

As per EMA and US FDA all APIs manufactured through synthetic process should be subjected to a risk assessment for presence of Nitrosamine impurities. Is there any exemption for this for an API exclusively to be used for topical purposes (say cream and ointments)? I cant get any reference to this and will appreciate your kind opinion.

---------------------------------
Anamitra Chatterjee


Munich
Germany
---------------------------------