Russian Government Decree No. 1583, dated October 1, 2020, approved the Rules for the Circulation of Generic Medicines and Biosimilars Prior to the Expiration of the Period Established for Conducting Bioequivalence or Therapeutic Equivalence Studies (hereinafter the "Rules"), which took effect on October 5, 2020.

The Rules govern the circulation procedure prior to the expiration of the period for conducting bioequivalence or therapeutic equivalence studies relative to the reference medicinal product, or for aligning the indications and contraindications for use in the instructions for medical use of such drugs with those of the reference product.

Crucially, the regulatory framework establishes the following quality and safety control measures for medicinal products during this period:

• Selective quality control monitoring;

• Submission of periodic safety update reports to Roszdravnadzor (the Federal Service for Surveillance in Healthcare) by the marketing authorization holder or owner every three months, calculated from the date the requests are issued.

The procedure for establishing interchangeability and introducing amendments to the registration dossier documentation involves the following stages:

1. Within three business days from receiving information from the FSBI "Scientific Center for Expert Evaluation of Medicinal Products" of the Ministry of Health of the Russian Federation regarding the absence of bioequivalence or therapeutic equivalence study results relative to the reference drug in the registration dossier of a generic drug (whose interchangeability has not been established) or a biosimilar (biolike) product, the Ministry of Health of the Russian Federation shall issue a request to the marketing authorization holder or owner of the generic or biosimilar product requiring the submission of a clinical trial results report.

2. The authorization holder shall submit an application for a clinical trial permit within 180 business days in response to this request. Furthermore, the holder must submit the clinical trial results report for the generic or biosimilar product within a period not exceeding three months from its completion.

3. Subsequently, within 10 business days, the Ministry of Health of the Russian Federation shall forward the report to the FSBI "Scientific Center for Expert Evaluation of Medicinal Products" to obtain an expert opinion on the interchangeability of the medicinal products or a determination that the medicinal product is non-interchangeable.

4. Within three business days from the receipt of information concerning discrepancies in indications and contraindications within the instructions for medical use of interchangeable medicinal products, the Ministry of Health of the Russian Federation shall issue a request to the marketing authorization holder or owner of the generic or biosimilar medicinal product (or their authorized legal entity). This request shall mandate aligning the indications and contraindications in the drug's instructions for medical use with those of the reference product within a prescribed timeframe not exceeding six months.

5. Within 30 business days from receipt of the request, the marketing authorization holder or owner shall submit an application to amend the documentation contained in the registration dossier of the registered medicinal product.

6. Within 10 business days from the date the amendments are introduced into the registration dossier documentation, the Ministry of Health of the Russian Federation shall forward the information to the expert institution to obtain an expert opinion regarding the interchangeability of the medicinal products or a determination that the medicinal product is non-interchangeable, taking into account the updated instructions for medical use of the generic or biosimilar medicinal product.