Post-approval variations to dossiers for vaccines: analysis of regulatory and methodological approaches used in the Russian Federation and abroad

The management of post-approval changes to registration dossiers for medicinal products is one of the most important factors for ensuring sustainable quality, safety and efficacy of medicines. Competent authorities that use the module format of the registration dossier, i.e. the regulatory authorities of the European Union, USA and other members of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), and the Eurasian Economic Union (EEU), issue guidelines on changes to registration dossiers for pharmaceuticals and biologicals (immunological products). Vaccines (finished dosage forms) and vaccine antigens (active ingredients) are a specific group of immunobiological products which have great prophylactic importance for healthcare, and which are associated with challenging development and specific methods of manufacturing and quality control. The procedure of introducing post-approval variations to dossiers for immunobiological medicinal products is poorly reflected in the current Russian and EEU regulations. The World Health Organization (WHO) established a procedure described in the «Guidelines on procedures and data requirements for changes to approved vaccines». The purpose of the present study was to compare current Russian and international legislation in terms of regulatory requirements for post-approval сhanges to dossiers for immunobiological products. The Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation is drafting Guideline on introducing post-approval changes into dossiers for immunobiological medicines. The draft includes a detailed review of various categories of changes based on their importance, and a list of conditions and required documents for specific groups of medicines. This article summarises scientific and methodological approaches to evaluation of changes introduced in registration dossiers for vaccines in order to further improve the regulatory framework of the Russian Federation and the EEU.

1. Olefir YuV, Merkulov VA, Soloviev EA, Ustyugova EA, Sayapina LV, Bondarev VP. Russian and foreign legislation on regulation of post-approval variations in the dossier for the medicinal products. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya = The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2015;(4):11–5. (In Russ.)

2. Medunitsyn NV, Mironov AN, Movsesyants AA. Theory and practice of vaccinology: a monograph. Moscow: Remedium; 2015 (In Russ.)

3. Plotkin S, Robinson JM, Cunningham GI, Iqbal R, Larsen S. The complexity and cost of vaccine manufacturing – An overview. Vaccine. 2017;35(33):4064‒71. https://doi.org/10.1016/j.vaccine.2017.06.003

4. Van de Burgwal LHM, Ribeiro CDS, Van der Waal MB, Claassen E. Towards improved process efficiency in vaccine innovation: The Vaccine Innovation Cycle as a validated, conceptual stage-gate model. Vaccine. 2018;36(49):7496‒508. https://doi.org/10.1016/j.vaccine.2018.10.061

5. Dellepiane N, Pagliusi S, Registration Experts Working Group. Challenges for the registration of vaccines in emerging countries: Differences in dossier requirements, application and evaluation processes. Vaccine. 2018;36(24):3389‒96. https://doi.org/10.1016/j.vaccine.2018.03.049

6. Vidor E, Soubeyrand B. Manufacturing DTaP-based combination vaccines: industrial challenges around essential public health tools. Expert Rev Vaccines. 2016;15(12):1575‒82. https://doi.org/10.1080/14760584.2016.1205492