Spring Intro 2023

03/03/2023

• Characterisation (Elucidation of Structure/other Characteristics, Impurities) • Drug Substance Common Deficiencies – 3.2.S.3

• Polymorphic form not discussed or confirmed, for example what happens to the form when the active is formulated, e.g. into a cream? • Impurities • Absence of discussion on the carry-over of impurities/by-products from key materials in the process • Impurities structures not provided • Genotoxic impurities – no discussion

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Common Deficiencies – 3.2.S.3

• Nitrosamines • Nitrosamines are chemical compounds classified as probable human carcinogens on the basis of animal studies. • Marketing authorisation holders should review their manufacturing processes for all products containing chemically synthesised or biological active substances to identify and, if necessary, mitigate the risk of presence of nitrosamine impurities. • Failure to follow the EMA guidance

https://www.ema.europa.eu/en/human-regulatory/post-authorisation/referral procedures/nitrosamine-impurities#guidance-for-marketing-authorisation-holders section

There is a very low risk that nitrosamine impurities at the levels found in medicines could cause cancer in humans.

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