null New policy for the development of monographs on medicinal products containing chemically defined active substance hydrates or solvates

EDQM Strasbourg, France 05/05/2022
New policy for the development of monographs on medicinal products containing chemically defined active substance hydrates or solvates

At its 172nd session in March 2022, the European Pharmacopoeia (Ph. Eur.) Commission approved a new policy for the development of monographs on medicinal products containing chemically defined active substances in hydrate or solvate form.

This policy differentiates between hydrates, which have water as the solvent molecule, and other solvates that involve an organic solvent (hereinafter referred to as “solvates”).

For hydrates, a common individual monograph will be developed for medicinal products containing one or several hydration forms of the active moiety. This approach is based on the EMA’s “Reflection paper on the use of cocrystals of active substances in medicinal products” (EMA/CHMP/CVMP/QWP/284008/2015). The title of the medicinal product monograph will not state the hydration form(s) but its Definition section will include a cross-reference to the relevant individual monograph(s) for the active substance hydrates or the water-free active substance. No test for water or for loss on drying will be included in the Tests section of the medicinal product monograph.

Conversely, for solvates, separate individual monographs will be developed for medicinal products containing different active substance solvates. The title of these monographs will refer to the corresponding active substance solvate and the Definition section will include a cross-reference to the corresponding individual active substance solvate monograph. While no test for the control of the organic solvent will be described in these monographs, the Production section will state “Manufacturers are expected to evaluate whether the presence of the active substance as a solvate is critical to the quality, efficacy and/or safety of the medicinal product and where applicable, to implement a control strategy for the corresponding solvent in the medicinal product, to the satisfaction of the competent authorities”.

There are several advantages to this new policy on active substance solvates in medicinal product monographs:

  • enhanced clarity for users as the scope of the monograph will be indicated in the title (no need to read the Definition to learn about the scope);
  • direct link between the active substance and medicinal product monographs;
  • greater flexibility in case of development and revision of both active substance and medicinal product monographs: a new medicinal product monograph will be developed when a medicinal product containing a new active substance solvate is approved instead of revising the existing monograph to cover the new active substance solvate.

The “Technical Guide for the elaboration of monographs on medicinal products containing chemically defined active substances” has been revised to reflect this new policy and a previously adopted policy (March 2021) for medicinal products containing active substance salts or bases/acids.

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