1.7. EAEU Pharmaceutical Market: Conditional Approval, Renewal, Variation & Bringing into Compliance

Similar to the European Union rules, the marketing authorization in the Eurasian Economic Union might be issued subject to one or more conditions. These provisions are described in the Part VIII of the Rules and are very similar to those described in Articles 21a, 22, 22a, and 22b of Directive 2001/83/EC. The authority of the reference Member State should notify the applicant of its decision to impose one or more post-authorization measures. The applicant may dispute those proposals of the reference Member State, but it is the right of the reference Member State to lift or uphold the proposed measures. If the marketing authorization is issued subject to one or more additional conditions or obligations, the risk/benefit balance needs to be reassessed on an annual basis until the reference Member State, taking into account the views of the Member States concerned as appropriate, decides to lift such conditions or obligations and issues a marketing authorization of standard validity. Where during the annual reassessment of benefit/risk balance, the reference Member State establishes that the applicant has failed to comply with the imposed conditions or that the risk/benefit balance is unfavorable, then it may either suspend or revoke the marketing authorization. Having discussed the initial authorization procedures, let’s go over the procedures intended to maintain the marketing authorization, i.e., variation and renewal procedures. It is the responsibility of the applicant to trigger the renewal of the marketing authorization. The procedure should be triggered no earlier than 180 days before the marketing authorization ends to be valid but not later than such a date. During the renewal procedure, the medicinal product may be marketed within the Union. The detailed renewal procedure has not been established so far since the single market should operate at least for 4.5 years before the first renewal application is submitted. The Member States plan to establish the procedure by that time. At the same time, the general provisions of the renewal procedure are set in the Rules. The procedural aspects are quite similar to those of the decentralized procedure, except for the shorter time periods. The assessment of the application is conducted simultaneously in all participating Member States, but the reference Member State leads the procedure.
Although the time limits for the procedure are shorter, the applicant enjoys the same response periods as in the initial authorization procedures.
By the end of day 90, the reference Member State should have drawn up a draft final assessment report and sent it to the Member States concerned.
On the following slides, one can see that the general logic of the renewal procedure is based on the decentralized procedure, yet with shorter time frames. By the end of the procedure, the new certificate of marketing authorization is issued which has unlimited validity. However, based on pharmacovigilance considerations the marketing authorization might be issued for another 5 years requiring another renewal procedure. Should any disagreements arise between the Member States, those are to be resolved using the appropriate dispute resolution procedure.
There are several possible outcomes of the renewal procedure. The marketing authorization may be issued with unlimited validity or valid for another 5 years. In case of conditional marketing authorization, the validity may be limited to another one-year period. If the applicant fails to comply with legal requirements or the competent authorities decide that the benefit/risk balance is not favorable anymore, the renewal may be refused.
Where in the course of the renewal of a marketing authorization the competent authority of the reference Member State finds that the obligations imposed in accordance with the Rules are not complied with due to a valid excuse and the variation to the marketing authorization for a marketing authorization application dossier is needed, the reference Member State may send a request to vary the marketing authorization application dossier. A marketing authorization holder should trigger the variation to the MA via the competent authority of the same reference Member State which has granted the marketing authorization. Variations to the marketing authorization should not have an unfavorable impact on the Benefit/Risk balance. Variations to the marketing authorization should be introduced in accordance with the classification of variations as laid down in Appendix 19 to the Rules using the procedure as laid down in Appendices 19 and 20 to the Rules. Where a need for a variation emerges within the last 90 days of validity of the marketing authorization, the variation may be processed within the renewal procedure. Where a reference Member State furnishes the applicant with a notice to submit additional data or information, the maximum response period is set to 90 days. The variation procedure is very similar to that of the European Union. Appendices 19 and 20 are based on the EU Variation Regulation # 1234/2008 and Variation Guidelines published by the European Commission. The manufacturing or importation of the medicinal product is allowed using the previously authorized packaging and medication guide within 180 days beginning with the day the marketing authorization is renewed or varied. The distribution of a medicinal product is allowed in the amended and not amended packaging and medication guide up until the product is expired where such a distribution does not violate the requirements of the Rules of Good Pharmacovigilance Practice.
Let’s proceed to the final part of the introduction to the single pharmaceutical market of the Eurasian Economic Union and discuss the bringing into compliance procedure as well as several transitional provisions. A marketing authorization application dossier for medicinal products authorized in the Member States before the Agreement on Common Principles and Rules Governing Medicinal Products came into effect or authorized via national procedures before 31st of December 2020 needs to be brought into compliance with the requirements of the Union at the latest on 31st of December 2025.
Bringing the MAA dossier into compliance with the requirements of the Union shall entail submission of a marketing authorization application dossier using the Common Technical Document format. The dossier for bringing into compliance shall contain the same material data as those contained in the dossier approved nationally. Previous non-clinical and clinical studies need not to be reformatted in accordance with the Union requirement concerning the respective study reports whereas all quality information and data shall be in accordance with the Union requirements. Moreover, although non-clinical and clinical reports need not be reformatted, where the nationally authorized dossier lacks non-clinical or clinical information, or this information has material deficiencies, then competent authorities may require provision of what is lacking or amendment of deficiencies. When bringing into compliance the dossier, the marketing authorization holder may not introduce variations negatively impacting the safety, efficacy, quality or the Benefit/Risk balance of the medicinal product under approved conditions of use. Variations and bringing into compliance may be processed concurrently. Where a medicinal product had been authorized in more than one Member State before the Agreement came into effect or via national procedures before 31st of December 2020, the applicant should choose one of them as a reference Member State and submit an application, documents and particulars of the marketing authorization application dossier to the competent authority of that reference Member State. Bringing into compliance should be completed within a maximum of 100 days beginning with the day of submission of an appropriate application. The competent authority of the reference Member State should verify the completeness and accuracy of the format of the documents submitted in the marketing authorization application dossier within 14 days before the assessment of the marketing authorization application dossier is started. In case any irregularities are found, the competent authority may send the applicant a request to amend such irregularities. The applicant should respond within 90 days. Standard rules of termination of the procedure apply. The assessment procedure coincides with those used within authorization, renewal, and variation procedures except for established time limits. The procedure might have several outcomes. If the reference Member State rejects the application, then the national marketing authorizations stop being valid by 2026. However, marketing authorization holders may reapply for bringing into compliance. Where only one or several Member States concerned disagree with the positive decision of the reference Member State and the latter proceeds with issuing a Union marketing authorization, then the national marketing authorizations stop being valid in such Member States concerned by 2026. In case of a favorable decision, the certificate of an MA will be of unlimited validity if the medicinal product has been previously authorized in at least 3 Member States of the Union during at least 5 years; otherwise, the certificate is valid for 5 years.
The validity of the certificate issued by the Member States concerned is equal to that issued by the reference Member State. This concludes our introduction to the Eurasian Economic Union Single Pharmaceutical Market which came into operation on 6th of May 2017. We hope that the provided information will help you to understand the basics of the EAEU Single Market rules better. The rules are quite robust but need to be improved to achieve the level which will be equivalent to that effective in developed countries. The main benchmark is the European Union rules. Currently, great efforts are being made to complement the rules with other documents and procedures. We will also appreciate any feedback, especially if you are interested in further discussion of the EAEU principles. For instance, you can reach me on Facebook or LinkedIn or by other appropriate means. Thanks for listening! Please leave a comment, like, and subscribe. More to come!

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