Company: APM
Filing Date: 2025-04-30
Form Type: 20-F
Source: 0001213900-25-037669
Chunk: 145

Company: Aptorum Group Ltd
Filing Date: 2025-04-30
Form: 20-F
Item: Item 4
Chunk 145
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 the competent authority decides,
on justified grounds relating to pharmacovigilance, to proceed with one additional five-year renewal period. Any authorization that is
not followed by the placement of the drug on the EU market (in the case of the centralized procedure) or on the market of the authorizing
Member State within three years after authorization ceases to be valid.

Regulatory Requirements after Marketing
Authorization

Following approval, the holder
of the marketing authorization is required to comply with a range of requirements applicable to the manufacturing, marketing, promotion
and sale of the medicinal product. These include compliance with the EU’s stringent pharmacovigilance or safety reporting rules,
pursuant to which post-authorization studies and additional monitoring obligations can be imposed. In addition, the manufacturing of authorized
products, for which a separate manufacturer’s license is mandatory, must also be conducted in strict compliance with the EMA’s
cGMP requirements and comparable requirements of other regulatory bodies in the EU, which mandate the methods, facilities and controls
used in manufacturing, processing and packing of drugs to assure their safety and identity. Finally, the marketing and promotion of authorized
products, including industry-sponsored continuing medical education and advertising directed toward the prescribers of drugs and/or the
general public, are strictly regulated in the EU under Directive 2001/83EC, as amended.

Orphan Drug Designation and Exclusivity

Regulation (EC) No. 141/2000
and Regulation (EC) No. 847/2000 provide that a product can be designated as an orphan drug by the European Commission if its sponsor
can establish: that the product is intended for the diagnosis, prevention or treatment of (1) a life-threatening or chronically debilitating
condition affecting not more than five in ten thousand persons in the EU when the application is made, or (2) a life-threatening, seriously
debilitating or serious and chronic condition in the EU and that without incentives it is unlikely that the marketing of the drug in the
EU would generate sufficient return to justify the necessary investment. For either of these conditions, the applicant must demonstrate
that there exists no satisfactory method of diagnosis, prevention, or treatment of the condition in question that has been authorized
in the EU or, if such method exists, the drug has to be of significant benefit compared to products available for the condition.

An orphan drug designation
provides a number of benefits, including fee reductions, regulatory assistance and the possibility to apply for a centralized EU marketing