On 3 November 2016, the Council of the Eurasian Economic Commission (the EEC) approved a set of 21 documents in furtherance of the Agreement on Common Principles and Rules for the Treatment of Medicines within EAEU dated 23 December 2014 (the Agreement).
The Agreement, which formally entered into force on 12 February 2016, provides for the establishment of a common market of medicines within the EAEU as well as the free flow of medicines. The process of establishing a common market of medicines continued with the adoption of the unified rules of the EAEU, regulating various aspects of the common pharmaceutical market, including GxP, registration and examination rules, and requirements for labelling and for instructions for medical use.
All documents (save for a few exceptions) will enter into force 10 calendar days from the entry into force of the Protocol of Accession of the Republic of Armenia to the Agreement (i.e., upon the date of receipt by the depositary of the last written notification on the performance of domestic procedures required for such entry into force). The exact timing of completion of the domestic procedures is unknown, but it was reported that 3 out of 5 countries comprising the EAEU have already completed such domestic procedures.
Some documents (like the Rules on Registration and Examination of Medicines for Medical Use (EEC Council Decision No. 78)) provide for a transition period for their implementation. All documents can be found at the official website of the EEC. Below we briefly describe the most important of these adopted documents.
1. Good Manufacturing Practice (GMP) (EEC Council Decision No. 77)
GMP sets out, inter alia, the requirements for: (i) development and maintenance of the pharmaceutical quality system (PQS) (i.e., a documented quality manual that includes, inter alia, information on corrective and preventive actions and quality risk management); (ii) hiring personnel, including an obligation on the manufacturer to appoint a director of manufacturing and a director of quality control, as well as the sufficient number (but at least one) of qualified persons mainly for confirmation of the products’ conformity to authorize the product release and issuance of the products’ release authorization if the functions of the qualified person are not performed by the director of manufacturing and/or the director of quality control; (iii) selecting premises and equipment; (iv) documentation, including an obligation on manufacturers to adopt regulatory documents (e.g., technological instructions, SOPs) and recording documents (e.g., certificate of analysis, reports); and (v) APIs used in the process of manufacturing.
2. Procedure for Attestation of Qualified Persons of Manufacturers of Medicines (EEC Council Decision No. 73)
The Procedure sets out the requirements for qualified persons (e.g., they must have at least three years’ work experience in the sphere of medicinal preparations manufacturing, quality control or quality assurance, as well as a higher education degree in certain related spheres). The Procedure also stipulates that the attested qualified person shall attend a set of specific courses (modules), for example, on physiology and pharmacology1.
3. Decision on Recognition of Results of Inspection of Manufacturing of Medicines (EEC Council Decision No. 93)2
The document provides that until December 31, 2020, authorized bodies of EAEU member states, while performing state registration of medicines (re-registration, confirmation of registration, making amendments to registration dossiers) under the national laws of the member state, shall mutually recognize the documents issued by the authorized bodies of other EAEU member states confirming compliance of the manufacture of medicinal preparations to GMP of the EAEU or the member states of the EAEU.
Clinical Trials, Registration and Further Circulation
4. Good Clinical Practice (GCP) (EEC Council Decision No. 79)
GCP provides, inter alia, the following: (i) the general principles for conducting clinical trials (e.g., all clinical trials shall be conducted in strict compliance with the applicable protocols and all such protocols shall be approved by the Expert Council of Organization); (ii) regulation of the Expert Council of Organization; (iii) requirements, rights and obligations and other rules related to the investigators and sponsors of clinical trials; and (iv) the requirements for clinical study protocols, investigators’ brochures and the main documents of clinical studies.
5. Rules on Conduct of Research on Bioequivalence of Medicinal Preparations (EEC Council Decision No. 85)
The Rules establish the main requirements for conducting and designing research programs, analyzing generics bioequivalence studies, requesting biowaivers (i.e., the procedure for estimating the bioequivalence of generics without carrying out in vivo investigations), as well as the requirements for recording results of studies, etc.
6. Rules on Conduct of Biological Medicines Studies (EEC Council Decision No. 89)
The Rules stipulate the requirements for conducting biological medicines studies, including, inter alia: (i) requirements for the quality of cell substrates and cell banks used during the manufacturing of biological medicines; (ii) estimating the virus safety of biotechnological and biological medicinal preparations derived from human or animal cell lines; (iii) the appropriate methods for ensuring inactivation and elimination of viruses; and (iv) rules related to biosimilars.
7. Rules on Registration and Examination of Medicines for Medical Use (EEC Council Decision No. 78)
The Rules contain, among others: (i) general principles on the registration of medicinal preparations; (ii) general principles on the examination of medicinal preparations; (iii) rules on the registration and examination of medicinal preparations registered by the procedure of mutual recognition (i.e., consecutive procedure – after the medicinal preparation was registered in the reference state, such registration may be recognized in other states chosen by the applicant) and by the decentralized procedure of registration (i.e., simultaneous procedure – in order to register the medicinal preparation, the applicant chooses the reference state and the states of recognition; the registration in all such states is performed simultaneously); (iv) rules on the confirmation of registration; (v) rules on the suspension and recall (cancellation) of registration certificates; (vi) the procedure for making amendments to registration dossiers; and (vii) the obligations of registration certificate holders.
Until 31 December 2020, an applicant may choose whether to register medicinal preparations in accordance with the general EAEU rules or the national rules of a particular EAEU member state. Medicinal preparations which were registered under the national rules of the EAEU member state must be brought in conformity with the EAEU requirements before 31 December 2025. Registration dossiers of medicinal preparations issued in accordance with the national rules of the EAEU member states are valid until their expiration term, but in any case until 31 December 2025. 8. Requirements for Labelling of Medicines for Medical Use and Veterinary Medicines (EEC Council Decision No. 76)
The Requirements establish the general requirements for labelling (including the requirements for the primary, intermediate and secondary packages of medicinal (veterinary) preparations and packages of APIs), requirements to the text of labelling (including language requirements) and methods of application of the labelling.
9. Requirements for Instructions for Medical Use of Medicinal Preparations and General Description of Medicinal Preparations for Medical Use (EEC Council Decision No. 88)
This document was designed to unify the format of the general description of medicinal preparations, as provided in instructions for use. The document sets out the binding patterns of the general description of medicinal preparations which include, inter alia, the following: name of the medicinal preparation, qualitative and quantitative composition, dosage form, clinical data, pharmacology characteristics, pharmaceutical characteristics, information on the holder of the registration certificate and the number of the registration certificate.
10. Good Distribution Practice (GDP) (EEC Council Decision No. 80)
GDP is applicable at the stage of wholesale of medicinal preparations. GDP stipulates, inter alia, requirements for: (i) ensuring the appropriate level of quality (including the obligation to have a documented quality assurance system); (ii) hiring personnel, including an obligation on the distributor to appoint a qualified authorized person; (iii) selecting premises and equipment; and (iv) the distribution process (including the evaluation of suppliers and customers standards, storage and transportation requirements, rules on dealing with claims, etc.).
11. Decision on Separate Issues regarding Circulation of Medicinal Preparations (EEC Council Decision No. 92)
The Decision stipulates that the member states of the EAEU can perform an interchangeability procedure under the national laws of the EAEU member state. The decision on the interchangeability is valid on the territory of the relevant EAEU member state. The decision of the member state on the issuance of a registration certificate valid on the territory of the EAEU is adopted regardless of the results of the interchangeability procedure. The interchangeability procedure does not influence further circulation of the medicinal preparation on the territory of the EAEU.
Good Pharmacovigilance Practice (GPP) (EEC Council Decision No. 87)
GPP establishes rules related to the quality assurance system, pharmacovigilance system master file, risk management system, handling of information on adverse reactions, etc. The most important obligations are imposed on the holder of the registration certificate and include, inter alia, the following: (i) appointment of an authorized person for pharmacovigilance having a relevant qualification (QPPV); (ii) development and introduction of a pharmacovigilance system in the form of master files; (iii) preparation of Periodic Safety Update Reports; (iv) preparation of a Post-Authorization Safety Study; (v) public announcements on product safety; and (vi) adoption of measures in connection with additional monitoring and risk minimization measures.