Module 3 - Strategic case studies in practice

and duration) • Allows consistent and

harmonized implementation and follow-up for all medicinal products

• Ensures consistency as

toxicological risks are always assessed for all active substances/ medicinal products (i.e. the same limit for products containing the

same active substance, depending only on the maximum daily dose).

• ICH M7 methodology has already been developed with risk through polypharmacy integrated, resulting in very conservative safety margins • Allows to take all elements (technical feasibility, toxicological risk calculations etc.) for a specific operator (e.g. MAH/API manufacturer) into consideration for determining realistically achievable nitrosamine reductions. • Provides the lowest case specific limit reasonably achievable for every single finished product

• Subjective assessment, as effort to reduce nitrosamines as ‘reasonably practicable’ cannot be measured in an objective, comparable way. • Based on the criterion of ‘reasonably practicable’ which is understood as the cost involved in reducing the risk further would be grossly disproportionate to the benefit gained. This is not adapted for the purpose of defining a limit in medicinal products which should be preferably based on toxicological data rather than a ratio between industrial and public health factors. • Would lead to setting of different limits between manufacturers that would lead to different risks that cannot be justified based on toxicological data. • Elements for a specific operator (in terms of effort needed to

ALARP

EMA/369136/2020

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