If you are interested in marketing your medicinal product in the fast-growing pharmaceutical market of the Eurasian Economic Union (EAEU) and if you want to how to apply for market authorization in the EAEU, this blog post is for you. The first part of this article describes why the EAEU is an exciting market for drug registration and outlines the two different pathways for drug registration in the Eurasian Economic Union (EAEU). Additionally, it shares insight into aligning the dossiers of previously registered drugs with the new requirements.
The Eurasian Economic Union
The EAEU consists of Russia, Kazakhstan, Belarus, Armenia, and Kyrgyzstan and has a combined population of more than 185 million people. The GDP is estimated at around $5 trillion, with a fast-growing pharmaceutical market. For Russia, the expected turnover for 2021 is around $39 billion, which is up from $28 billion in 2017.
The EAEU was formed in 2014 and is headed by the Eurasian Economic Commission (EEC). In recent years, the EAEU has taken steps to unify the pharmaceutical market. This includes the creation of common drug registration procedures, and in the future might include a single pharmaceutical regulator similar to the European Medicines Agency (EMA). The EEC has introduced the ‘Agreement on common principles and rules of circulation of medicines within the Eurasian Economic Union’ at the end of 2014, and the ‘Rules of registration and expertise of medicinal products for human use’ (EEC Decision No. 78) on November 3rd, 2016. The decision describes two pathways of registering drugs in the EAEU, which have become the official procedures at the start of 2021. Drugs registered before December 31st, 2020, need to comply with the EAEU requirements by the end of 2025.
Pathways For Drug Registration In The Eurasian Economic Union (EAEU)
As in other pharmaceutical markets, in the EAEU, a Market Authorization Holder (MAH) performs the drug registration and can be a person or company without residing in an EAEU member state.
In the EAEU, you can request market authorization in two ways:
1. The mutual recognition procedure for drug registration in the Eurasian Economic Union (EAEU)
Here you file a Market Authorization Application (MAA) in a member state of choice, and aftermarket approval, you apply for recognition of the approval decision in the other states.
2. The decentralized procedure for drug registration in the Eurasian Economic Union (EAEU)
Here you file an MAA in all (or several) EAEU states simultaneously and choose one member state as a reference to deal with the majority of administrative procedures.
Common Technical Document Format In The Eurasian Economic Union (EAEU)
For the MAA, an electronic Common Technical Document (eCTD) format is used that resembles the ICH CTD format.
The EAEU CTD consists of five modules:
- Administrative information
- Summary of the Common Technical Document
- Reports of pre-clinical studies
- Clinical trial reports
Special requirements may apply for specific medicinal product types, such as generic drugs, vaccines, or Advances Therapy Medicinal Products (ATMPs). Some modules and sections of the CTD are allowed to be submitted in English. Modules 1 and 2 must be submitted in the local language, except for the GMP site inspection reports, the pharmacovigilance system master file (PSMF), and the risk management plan (RMP). For the PSMF and the RMP, local language summaries are required. Modules 4 and 5 can be submitted in English entirely and large parts of Module 3, with a list of sections of Module 3.2 that need to be submitted in the local language.
Appendices 4 and 5 of EEC Decision No. 78 lists all requirements of the eCTD.
Mutual Recognition Procedure For Drug Registration In The Eurasian Economic Union (EAEU)
The MAH first selects a reference state in the mutual recognition procedure and submits the registration dossier and necessary documents to the competent authority (CA) there. The CA makes a preliminary assessment of the documents within approximately two weeks and decides whether to proceed with a complete examination. Subsequent evaluations include reviewing the safety, efficacy, and quality of the medicinal product and the trial data. Additionally, the authorities can conduct an (unscheduled) inspection of manufacturing sites and test drug samples for quality. This process takes approximately six months. Finally, the CA prepares an expert report and decides on drug registration (or rejection of the MAA) within a further approximate two weeks. The overall process has a maximum duration of 210 calendar days, with an extension possible if a CA requests additional information.
Aftermarket authorization in the reference state, the MAH provides access to the eCTD and the expert report in the EAEU unified register for the other member states. Module 1, the Normative Document (ND), the Summary of Product Characteristics (SmPC), labeling, and instructions of use have to be submitted in local languages of the individual member states. CAs from the other member states are then allowed to request further information for 50 days after gaining access to the documentation. If potential requests are answered adequately, the individual member states grant market authorization. If a member state declines to recognize the market approval of another member state, the disagreement is settled by the Expert Committee on Medicines of the EEC. The recognition process has a maximum duration of 90 calendar days, making the maximum duration of the whole mutual recognition procedure 300 calendar days.
Aftermarket approval, a registration certificate is issued with a validity of five years. This certificate has a uniform model for each EAEU member state. When re-registration is applied, the certificate validity is usually without an expiration date.
Decentralized Procedure For Drug Registration In The Eurasian Economic Union (EAEU)
The decentralized procedure is very similar to the mutual recognition procedure, but the approval process by each member state takes place in parallel. The MAH still selects a reference country that will handle the most significant part of the approval process. Module 1, the ND, SmPC, labels, and other relevant documentation have to be submitted in local languages to each CA of the respective member states. The decentralized procedure has a maximum duration of 210 calendar days and is thus faster than the mutual recognition pathway.
Procedure For Previously Approved Drugs In The EAEU
Medicinal products that have received market authorization before December 31st, 2020, are required to comply with the new EAEU standards by December 31st, 2025. MAHs largely follow the mutual recognition procedure: they select a reference state to submit the eCTD and other documents to, harmonized with the new regulations. It is important to note that this harmonization process should not include new information on safety, efficacy, or technical details of the medicinal product; i.e., any variations should first be submitted and processed for the old eCTD. The reference state performs the evaluation and potential inspections and then provides an expert opinion. The other states follow the recognition procedure based on this opinion and the eCTD.
The procedure for bringing a medicinal product in compliance with the new requirements is accelerated and has a maximum duration of 100 calendar days. If the drug was already registered in at least three member states for five years or more, a registration certificate without an expiration date would be issued. In other cases, the authorities grant the standard validity period of five years.
Dossier Maintenance And Re-registration
Aftermarket approval, it is vital to maintain the registration dossier and submit variations to the appropriate CAs. The registration certificate, which among other information, contains the SmPC and labeling, also has to be updated in case variations are submitted. Furthermore, a maximum of 210 days before the expiry of a registration certificate, a re-registration request can be submitted, after which a certificate without an expiration date can be obtained.
Considerations When Registering A Drug In The Eurasian Economic Union (EAEU)
The EAEU pharmaceutical market is an appealing and growing market for medicinal products. Since the start of 2021, the procedure for drug registration in the member states has been unified, and approval for an MAA now has a maximum duration between 210 and 300 days for all EAEU member states. For previously registered drugs, documentation has to be harmonized with the new regulation by December 31st, 2025, for which an accelerated approval procedure with a maximum duration of 100 days exists.
Suppose you are considering bringing your medicinal product to the EAEU market. In that case, you should consult with experts who have extensive knowledge of EAEU regulation and local language knowledge (usually Russian). Knowing the differences in working methods of the national CAs can help you select the best country as a reference for the drug registration process, thereby accelerating and simplifying the approval process.
August 2021 Ola Jeppsson has taken on a leading role as Business Development Director. In addition to his new role, he was appointed as a Chief Executive Officer at Biomapas Nordic AB starting August 2021.Having a management and business development background in the...
Choosing the right set of countries, sites and investigators for a clinical trial are critical success factors in any clinical development program. They can guarantee speedy patient recruitment and timely delivery of study results. It also ensures that you conduct...
Medicine is constantly evolving to invent effective ways to treat diseases. This progress is a never-ending process: the life science industry develops new molecules and treatments and continually improves existing ones. Experimentation and testing have long been a...
Medicine is constantly evolving to invent effective ways to treat diseases. This progress is a never-ending process: life science industry develops new molecules and treatments and improves existing ones continually. Experimentation and testing have long been a part of medicine, and it is up until now as clinical trials have an essential part in the development of new treatments. These reasons allow us to assume that the relevance of clinical trials will not diminish in the future.
Despite the fact that Ukraine is the largest country in Eastern Europe with a large population of treatment-naïve patients, well organized public health care sector and significant number of medical sites accredited for clinical trial conduction, country has utilized only 15% of its current potential for hosting clinical trials. During 2017, the European Medicine Agency (EMA) gave positive recommendations on 94 new drug applications and 49 of them were tested in clinical trials in Ukraine. During the same year, the US FDA approved 151 new drugs, and 28 of them were also studied in Ukraine.
Russia is a very perspective country for international clinical trial conduction. The first international clinical trial was set up in Russia about 20 years ago only, and from than country kept a great potential for market development. In 2018 health authorities (HAs) approved 653 clinical trials (CT) in Russian Federation, less in overall numbers compared to the same indicator from 2016 – 898 approved CTs. However, this decrease was observed across all types of clinical trials except for international multicentre clinical trials (IMCT).
The number of clinical trials worldwide is increasing more than 10% each year due to the new diseases, further research for better health products and development of new drugs. Though, for a successful clinical trial, there is a major challenge – patient recruitment, which is essential and the most challenging factor due to the increasing number of new clinical trials. In order to achieve the required patient recruitment, sponsors are looking for different solutions.
In the past five years, an average of 175 clinical trials are being initiated in the Baltic states each year. An average of 64,8% of the population in the Baltic states are in the age from 15 to 65 years old, the main target audience for clinical trials. Furthermore, a large pool of treatment-naïve subjects is available compared to other EU countries or the US. Patients with special therapeutic diseases are transferred to the main central hospitals.
On 29th March 2017 UK submitted the notification of its intention to withdraw from the EU. This means that UK will become a ‘third country’ from 30th March’19. Even though leaving the EU with a deal remains the Government’s top priority, UK drug agency is publishing a series of guidance documents for industry and other stakeholders covering the proposed arrangements for the regulation of medicines, medical devices and clinical trials, if UK leaves EU with no deal.
World Tuberculosis Day is commemorated every year on 24th March to raise awareness of tuberculosis, which is still causing death of nearly 1.5 million people each year, mostly in developing countries. It marks the day in 1882, when Dr. Robert Koch announced that he had discovered the cause of tuberculosis, the TB bacillus. In comparison to other infectious diseases caused by a single infectious agent, tuberculosis is the second biggest killer worldwide.