If the revisions come into force, the Commission will change some of the key definitions detailed in the regulation. The definition of “similar active substance” is among those set to be changed. As it stands, the regulation defines such a substance as being identical to or having “the same principal molecular structural features” as another substance with the same mechanism of action. This text fit the developmental candidates of 2000. That is no longer the case.
Researchers cannot fully identify the principal molecular structural features of advanced therapy medicinal products. This makes it impossible to tell if two substances are similar using the current definition. To address this shortcoming, the Commission wants to expand the definition to allow similarity to be assessed “on the basis of the biological and functional characteristics” if the principal molecular structural features are unknown. This change is aimed squarely at advanced therapy medicinal products, such as cell-based and gene therapies. The Commission also wants to add text that unpacks how the change will apply to these two therapeutic modalities.
In the case of cell-based therapies, substances are not similar if there are differences in the starting materials, final product or manufacturing technology that affect its biological characteristics or “activity relevant for the intended therapeutic effect of the product.” Products can have different starting materials and still be similar, meaning it is possible to have similar autologous cell therapies.
The Commission has applied similar thinking to gene therapies. Differences in the therapeutic sequence, viral vector, transfer system or regulatory sequences can render two gene therapies not similar, provided these differences affect the biological characteristics and therapeutic effect of the product. Otherwise, the Commission will see the gene therapies as similar, regardless of underlying differences.
These definitions are important, as they dictate whether drugs can come to market in the 10-year window of therapeutic indication exclusivity enjoyed by orphan products in the European Union. Applicants facing such situations need to submit a similarity report to help the Committee for Medicinal Products for Human Use assess whether a potentially similar drug can come to market.
The Commission used the update process to make other changes to the content and format of the regulation, some of which were motivated by the experience it has gained since passing the original text. Changes made by the Commission include the removal of the definition of “active substance.”
The draft text is open for comment until 27 November.
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