Kazakhstan

Kazakhstan is one of the largest Central Asian countries with a population of about 18 million people. The county is a member of the Eurasian Economic Union (EAEU). Membership of Kazakhstan in the EAEU significantly influences the regulatory policy of the state.

Kazakhstan is characterized by the most transparent market for foreign manufacturers of pharmaceutical products from the point of view of legislation. Medicinal products of foreign companies occupy a dominant position in the rapidly growing pharmaceutical market of the country.

The Ministry of Health and Social Development of the Republic of Kazakhstan provides marketing authorization (state registration) of finished medicinal products and active pharmaceutical ingredients, medical devices and medical equipment based on expert examination carried out by the National Center for Expert Evaluation of Medicinal Products, Medical Devices and Medical Equipment.

Importation and sales of medicinal products and medical devices are allowed only after obtaining marketing authorization.

Medicinal products
According to the Code of the Republic of Kazakhstan “On the Public Health and the Health Care System”, importation and sales of medicinal products in Kazakhstan are allowed only after state registration (or renewal).

Starting from January 1, 2024, new marketing authorization procedures for medicinal products in the EAEU member states are only possible under the Union’s regulations. By December 31, 2025, medicinal products previously authorized through national procedures must be brought into compliance with the Union’s unified rules.

Kazakhstan is a country with high standards of regulation of marketed medicinal products. Inconsistencies between approved and actual packaging artworks, instructions for medical use (package leaflets), and certificates of analysis may cause the withdrawal of the medicinal product and temporary or permanent prohibition of sales.

Marketing authorization holders may be both residents and non-residents of the Republic of Kazakhstan. The marketing authorization holder is not obliged to establish a representative office or a legal entity in the territory of Kazakhstan. At the same time Applicant (a person performing the submission of documentation and negotiations with competent authorities) must be a resident.

According to local regulations, it is required to indicate the name and address of the entity accepting claims (proposals) to the quality of medicinal products and responsible for post-marketing pharmacovigilance activities for the products in their instruction for medical use (package leaflet).

Registration dossier must be submitted in EAEU e-CTD format. However, for submission of the dossier specific national documents should be developed, namely:

• Application form for registration of a medicinal product.
• A normative document that includes the composition of the finished product, specification for release and shelf life, quality control methods, information on storage conditions, information about manufacturers etc.
• Instruction for medical use.
• Artworks of primary and secondary packaging.

Part of the documents should be translated into Russian or Kazakh language. Package labeling and instructions for medical use are submitted and approved in Russian and Kazakh languages.

During registration, the National Center has the right to request the Applicant to provide additional documents related to the quality, safety, and efficacy of the medicinal product. The Applicant has 90 days to respond to the National Center queries or to justify the timelines necessary to provide replies. In the event the Applicant does not provide the requested data or provides them incomplete the registration materials are withdrawn from examination and payments are not returned.

Registration Certificate (Marketing Authorization) consists of several documents:

• Registration Certificate itself.
• Approved text of instructions for medical use.
• Approved color artworks of primary and secondary packaging.
• Agreed normative document (that includes composition of the product, specification for release and shelf-life, quality control methods, etc.).

Renewal
Application form for renewal should be submitted before the expiry date of the Registration certificate but not later than 6 months after the Registration Certificate expiration.

During renewal examination, the National Center may assign laboratory control of registration samples in case changes in specifications and/or methods of quality control of the finished product take place. The National Center may assign an inspection of the manufacturing site during the renewal procedure as well.

The set duration of the expert examination is not more than 120 calendar days excluding timelines for Applicant to reply to deficiency letters and observations obtained during the expert examination; for organization of inspection of manufacturing facilities and quality assurance system; conducting preclinical and clinical studies, pharmacovigilance system, reconciliation of final documents.

Based on the results of renewal Registration Certificate is issued for a period of validity of five years (or unlimited).

Variations
Application for variations should be submitted within two months from the date of their approval by the authorized body of the country of manufacturing site (if the relevant variations pass the approval procedure).

Variations to the registration dossier of medicinal products are classified as follows:

• Type I variations (divided into variations of type IA and type IB) to registration dossier of medicinal products that do not require new registration:
  • Minor changes related to the correction of registration dossier content during the validity period of the Registration Certificate of medicinal product.
  • Urgent temporary restrictions related to the safety of medicinal products implemented by Applicant in the event of identification of a risk to human health during administration of registered medicinal product; and which should be urgently reported to state authority for making a decision on their implementation. In case of the state authority’s positive decision Applicant should provide the relevant package of documents for variation procedure not later than fifteen working days from the date of implementation of safety restrictions.
• Type II variations require new state registration of medicinal products which are accompanied by significant changes in the characteristics of medicinal products.

Notifications about changes to the registration dossier are not provided according to the legislation of Kazakhstan. All types of variations should be officially approved by the competent authority.

Duration of expert examination of variation procedures is:

• For type IA variations the duration is not more than 30 calendar days excluding timelines for the reconciliation of final documents.
• For type IB and II variations (without laboratory control) the duration is not more than 60 calendar days excluding timelines for Applicant to reply to deficiency letters and observations obtained during the expert examination; for organization of inspection of manufacturing facilities and quality assurance system; conducting preclinical and clinical studies, pharmacovigilance system, reconciliation of final documents.
• For type IB and II variations (accompanied by laboratory control) the duration is not more than 90 calendar days excluding timelines for Applicant to reply to deficiency letters and observations obtained during the expert examination; for organization of inspection of manufacturing facilities and quality assurance system; conducting preclinical and clinical studies, pharmacovigilance system, reconciliation of final documents.

During the variation procedure, the National Center may assign laboratory control of samples in case changes to specifications and/or methods of quality control of the finished product have occurred. The National Center may assign inspection of the manufacturing site (for example, in case of transfer of manufacturing process to another manufacturing site) during variation procedure as well.

Pharmacovigilance
The fundamentals of the pharmacovigilance system in the Republic of Kazakhstan are established by Article 85 of the Code of the Republic of Kazakhstan “On the Public Health and the Health Care System”.

Marketing Authorization Holders as well as health care and pharmaceutical professionals are obliged to submit information on identified adverse reactions, in the order determined by the Ministry of Health of the Republic of Kazakhstan.

Marketing Authorization Holders of medicinal products are obliged to implement, assure, and guarantee the organization and functioning of the pharmacovigilance system in accordance with requirements of Regulations on Pharmacovigilance of medicinal products and monitoring of adverse reactions of medicinal products, medical devices, and medical equipment approved by order of the Minister of Health and Social Development of the Republic of Kazakhstan.

The competent state authority on the pharmacovigilance system in Kazakhstan is the “National Center for Expert Evaluation of Medicinal Products, Medical Devices, and Medical Equipment” of the Ministry of Health and Social Development of the Republic of Kazakhstan.

To ensure the functioning of the pharmacovigilance system Authorized person for pharmacovigilance should be appointed in the territory of Kazakhstan by marketing authorization holder. The pharmacovigilance system of the marketing authorization holder is subject to control by the competent authority.

Manufacturing authorization holders should submit the following information to the competent authority:

• About the location of the master file of the pharmacovigilance system.
• About the specialist responsible for pharmacovigilance activities in the territory of Kazakhstan.
• About any prohibitions or restrictions in use implemented in other countries related to medicinal products registered in Kazakhstan.
• About all cases of adverse reactions identified in the territory of the Republic of Kazakhstan.
• About cases of serious unexpected adverse reactions identified in other countries.

Medical devices
Medical devices and medical equipment of foreign production may be imported and sold in the territory of the Republic of Kazakhstan after state registration. At present Applications for state registration may be submitted both under the “national” Kazakh and under the “unified” procedure of the EAEU.

Registration under the national procedure is performed based on the national legislation: Order of the Minister of Health of the Republic of Kazakhstan No. 735 dated 18 November 2009, Order of the Minister of Health of the Republic of Kazakhstan No. 736 dated 18 November 2009, etc.

Registration Certificate is issued for a period of 5 years and it is valid only for Kazakhstan.

A non-resident manufacturing site should appoint its authorized representative in the territory of Kazakhstan. The authorized representative should be a resident legal entity and it should take responsibility for the quality and safety of the medical device as well as be a facility for storage of documentation and act as a point of contact with the manufacturing site.
It is necessary to appoint a local specialist for pharmacovigilance activities related to adverse reaction (events) reporting.

Registration dossier may be submitted in English with translation of certain sections into Russian. The required languages of package labeling and instructions for use (user manual) text are Russian and Kazakh.

Prior to submission of the Application form for registration, medical devices should pass the expert examination for their safety, efficiency, and quality in the state expert organization. Examination of medical devices and medical equipment during state registration/renewal consists of the following stages:

• Initial expert examination.
• Analytical expert examination (for medical devices).
• Specialized expert examination.
• Issuing conclusions on the safety, efficacy, and quality of medical devices or medical equipment.

Expert activities are carried out by the National Center for Expert Evaluation of Medicinal Products, Medical Devices, and Medical Equipment.

Renewal of medical devices and medical equipment is performed in the event of Registration Certificate expiration.

Application form for renewal should be submitted before the expiry date of the Registration Certificate. After completion of the renewal procedure for medical devices and medical equipment produced in accordance with ISO 13485 requirements, a Registration Certificate is issued for an unlimited period.

During the validity of the Registration Certificate variations procedure can be provided if necessary. The list of variations to the registration dossier of medical devices that do not require new registration is following:

• Change the name of the manufacturing site.
• Change the name of the medical device or medical equipment.
• Changes in accessories, and/or components, and/or consumables.
• Removal/addition of indications for use, intended use, contraindications, and side effects.
• Change of manufacturer(s) of medical device.
• Increase/decrease of shelf-life of medical devices.
• Change in storage conditions of medical devices.
• Change in quality control procedure for finished medical devices.
• Change of packaging of medical devices.
• Change of imprints, primer, or other marking used for labeling.

The introduction of other changes to medical devices or equipment leads to new registration procedures.

   
Cratia supports in state registration of medicinal products, the establishment and maintenance of a pharmacovigilance system, and the registration of medical devices in Kazakhstan.