Company: APM
Filing Date: 2025-04-30
Form Type: 20-F
Source: 0001213900-25-037669
Chunk: 142

Company: Aptorum Group Ltd
Filing Date: 2025-04-30
Form: 20-F
Item: Item 4
Chunk 142
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 Canada to initiate review
and inspection of the facility or the facilities at which the drug is manufactured are compliant with GMP requirements. Health Canada
will not approve the product unless compliance with cGMP - a quality system regulating manufacturing - is satisfactory and the
NDS contains data that provide substantial evidence that the drug is safe and effective in the indication studied. In addition, before
approving an NDS, Health Canada will typically inspect one or more clinical sites to assure compliance with GCP.

The testing and approval process
for an NDS requires substantial time, effort and financial resources, and may take several years to complete. Data obtained from preclinical
and clinical testing are not always conclusive and may be susceptible to varying interpretations, which could delay, limit or prevent
regulatory approval. Health Canada may not grant approval of an NDS on a timely basis, or at all. In Canada, NDSs are subject to user
fees and these fees are typically increased annually to reflect inflation.

Even if Health Canada approves
a product candidate, the relevant authority may limit the approved indications for use of the product candidate, require that contraindications,
warnings or precautions be included in the product labeling, including a black box warning, require that post-approval studies, including
Phase 4 clinical trials, be conducted to further assess a drug’s safety after approval, require testing and surveillance programs
to monitor the product after commercialization, or impose other conditions, including distribution restrictions or other risk management
mechanisms.

Health Canada may prevent
or limit further marketing of a product based on the results of post-marketing studies or surveillance programs. After approval, some
types of changes to the approved product, such as adding new indications, manufacturing changes, and additional labeling claims, are subject
to further testing requirements, notification, and regulatory authority review and approval. Further, should new safety information arise,
additional testing, product labeling or regulatory notification may be required.

European Union Regulation

Regulation in the European Union

The process governing approval
of medicinal products in the EU generally follows the same lines as in the United States. It entails satisfactory completion of pharmaceutical
development, non-clinical studies and adequate and well-controlled clinical trials to establish the safety and efficacy of the medicinal
product for each proposed indication. It also requires the submission to relevant competent authorities for clinical trials authorization
and to the European Medicines Authority, or EMA, for a marketing authorization application, or MAA, and granting of a marketing authorization
by