Preparing the Path for Biologics Registrations in the EAEU

Authorities at the European Economic Commission Council (EEC) have been making progress towards harmonising the registration and assessment of medicines for use in the Eurasian Economic Union (EAEU). Legislation that brings Armenia, Belarus, Kazakhstan, Kyrgyzstan, and Russia under single national laws and legal codes are in force, superseding country-specific legislation. While the regulations mean new requirements for life sciences companies, they also create new opportunities for a single registration with access to all EAEU markets through a mutual recognition procedure.

The authorities began implementing requirements for biologics in January 2016, with the guidance in several areas, including pre-authorisation studies – non-clinical and clinical – registration procedures, and post-marketing activities.

ProductLife Group’s team of Russia-based experts have analysed the latest developments and requirements for non-clinical and clinical studies and the life cycle management of biologics for the initial registration and harmonisation with the EAEU requirement.

Companies seeking approval for biologics in the EAEU must follow requirements aligned with ICH and European Medicines Agency (EMA) guidelines designed to ensure the quality of products and to safeguard patients. The extent and depth of studies that must be undertaken in EAEU markets depends on the type of product. Generally, all ICH non-clinical studies and clinical trials for innovative products must include at least one clinical site in a member state. However, the requirements are made on a case-by-case basis.

Studies required for biosimilars depend on whether the product is highly similar to the reference product. Where the biosimilar is classified as similar rather than highly similar, full non-clinical studies as well as some efficacy, safety and immunogenicity studies should be carried out within the EAEU legislation.

Authorities have also stipulated that study reports need to be carried out and submitted in eCTD format, in general, similar to the ICH and EMA requirements. Modules 4 and 5 (non-clinical and clinical study reports) will be accepted in English; however, Modules 2 and 3 (document summaries and quality reports) should be submitted in Russian in all member states. Russian is also accepted for Module 1, but the local language is required for labelling and additional documentation when required.

Authorities continue to work towards processes for registering biosimilars, although these are expected to align with EU legislation.

The guidance for product registration procedures continues to be updated as the markets gear up for EAEU rules. Since the beginning of 2021, medicines can be registered in the Russian Federation in accordance with the EAEU rules, while other EAEU markets will start the transition to mandatory application of the rules from July 2021. The transition period ends on 31 December 2025, after which registration certificates issued according to national procedures will cease to be valid.

At the point of registration, authorities may require applicants to undergo inspections for good laboratory practice (GLP), good clinical practice (GCP), and good manufacturing practice (GMP). Bulk drug substance and  finished drug product manufacturers could face GMP inspections.

These inspections need to be taken seriously by companies, as evidence so far has shown that 3 deficiency letters with a new registration process can result in immediate rejection of the registration. Applicants will need to ensure that samples and materials are imported for in-country quality control testing. Samples of biologic materials, final drug product, unique equipment, or high-science test methods, need to be provided for all manufacturing supply chains planned for EAEU markets.

Government laboratories need to be able to reproduce the final drug product quality test methods. As such, applicants must ensure their test methods comply with EAEU pharmacopeia or where the methodologies are non-compendial, that they are clearly documented to assist evaluators with their testing.

ProductLife Group’s Russia-based regulatory teams can support all these processes, for example, to prepare the local normative documentation ensuring minimal comments from EAEU authorities, advising on the number of samples for each potency of a final drug product to be registered, supporting documentation, and managing quality assurance of the laboratory processes. Normative documentation used to test the product with in-country testing should be documented in the Module 1 of the CTD.

Exceptions are made for orphan drug products, which are expected to be excluded from in-country quality control testing. Instead, companies simply need to include documentation about the QC expertise involved. It is expected conditional approval with post-marketing commitments will be used for biologics for emergency medicines, or that address unmet needs; however regulations on conditional approval have yet to be finalised.

ProductLife Group’s Russia-based regulatory teams can advise and work on the EAEU labelling materials including summaries of product characteristics (SmPC), the patient leaflet and artwork, including the required serialisation information.

Even after a product is approved, in-country QC testing will continue to be required for each batch of imported products. And any CMC variations will require in-country QC testing with samples and methods used to be provided to local government laboratories. Safety or administrative variations should simply be submitted in the relevant CTD documents within the timeframe established by the regulators.

A local EAEU qualified person or local contact will need to be assigned for each country to ensure oversight of approved products, as well as one qualified person for pharmacovigilance (QPPV) for the EAEU.