According to the Code of the Republic of Kazakhstan “On the public health and the healthcare system”, import and sale of medicinal products in Kazakhstan are only allowed after state registration (re-registration). Finished medicinal products are subject to registration.

Registration of medicinal products may be performed under the “national” procedure until 31 December 2020, or under the “centralized” procedure; and only under the “centralized” procedure of the EAEU after 31 December 2020.

Expert evaluation during registration of finished medicinal products is performed by 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 (website: http://www.ndda.kz/).

Kazakhstan is a country with high standards of regulation of marketed medicinal products. Inconsistencies between approved and actual packaging layouts, instructions for use, quality certificates may cause rejection of the medicinal product and temporary or permanent prohibition on sales.

The owner of the registration (MAH – Marketing Authorization Holder) may be either a resident or non-resident of the Republic of Kazakhstan. For MAH it is not required to open a representative office or to create a legal entity in the territory of Kazakhstan. At the same time, the Applicant of registration (the person performing submission of the documentation and negotiations with the competent authorities) must be a resident.

It is also necessary to indicate the name and address of the organization, to which claims (proposals) on the quality of the medicinal product in the territory of the Republic of Kazakhstan should be addressed to, and is responsible for post-marketing safety surveillance for the medicinal product, and must be indicated in the instructions for the use of the medicinal product.

The procedure for national registration is described below. You can get information about registration under the EAEU’s unified rules by clicking on the link.

The national procedure for state registration

The procedure for registration is carried out in accordance with the Order of the Ministry of Health of the Republic of Kazakhstan No. 736 “On approval of the Rules for the examination of medicinal products, medical devices and medical equipment” dated October 18, 2009.

The registration dossier is accepted in the CTD format. However, for submitting the registration dossier, specific national documents should be developed:

• Application form for registration of the medicinal product.
• ND (Normative document): regulatory document that includes the composition of the finished product, specification for release and shelf life, quality control methods, information on storage conditions, information on the manufacturers, etc.
• Instructions for medical use (package insert); 
• Graphical layouts (artworks) of the primary and secondary packaging.

The dossier is submitted in electronic form, part of the documentation must be submitted with translation into Russian and/or Kazakh. 

The administrative documentation is submitted according to the requirements for international legalization of documents. 

The registration procedure may be presented as the following stages:

• The conclusion of the contract for the expert evaluation.
• Obtaining and settling the invoice for the expert evaluation.
• Obtaining permission to import samples of the medicinal product and the required standards.
• Submission of the documentation and samples to the National Center for expert evaluation.
• Expert evaluation:
  • initial expert evaluation,
  • specialized expert evaluation,
  • laboratory tests. 
• Inspection of the manufacturing site, if necessary. 
• Reconciliation of final documents.
• Obtaining the conclusion on safety, efficacy and quality of the medicinal product.
• Applying for registration of the medicinal product to the Ministry of Health.
• Payment of the registration fee.
• Issuing the Order, obtaining the Registration Certificate.

During the registration, laboratory quality control of samples, for the purposes of which it is necessary to import samples and standards in the required quantities, is carried out.

The period of the expert assessment of the dossier for state registration is 7 months (no more than 210 calendar days, excluding the term given to the MAH to answer on the deficiencies identified during the expert evaluation, to organize the evaluation of manufacturing conditions and quality assurance system (inspection of the site), to conduct the preclinical, clinical trials, establish the pharmacovigilance system, to reconcile the final documents.

During registration, the National Center for expert evaluation has the right to request (deficiency letter) the necessary additional documents regarding the quality, safety and efficacy of the medicinal product from the MAH. The MAH has 60-90 days to respond to these observations or to justify the period for the response. If the MAH does not provide the requested data or provides it incomplete, the registration materials are withdrawn from assessment, and paid state fees are not returned.

Inspection of the manufacturing site

Inspection of the manufacturing site is necessary if the manufacturing site responsible for release, which was not previously registered in the territory of Kazakhstan, is submitted for registration. The procedure for inspection was approved by Order of the Ministry of Health and Social Development of the Republic of Kazakhstan No. 742 “On approval of Rules for inspection in the sphere of circulation of medicinal products, medical devices and medical equipment” dated November 19, 2009.

The procedure determines the following reasons for the inspection:

• obtaining a certificate (conclusion) or extending its validity, as well as in accordance with Good pharmacovigilance practices (GVP);
• for the purposes of licensing of pharmaceutical activities, registration, expert evaluation of medicinal products or conducting investigations related to the safety, quality and effectiveness of medicinal products, medical devices, in accordance with the pharmaceutical inspection program;
• based on the results of a previous pharmaceutical inspection in order to confirm the elimination of identified nonconformities;
• for confirmation by entities that have received a certificate confirming that the facility meets the requirements of Good pharmaceutical practice in the sphere of circulation of medicinal products at least once every two years in accordance with the inspection schedule approved by the Head of the state body or territorial division.

Inspection is carried out to confirm the compliance of manufacture with the national GMP requirements for sites performing the batch release. Inspection is carried out by a group of state experts. The applicant of registration pays for the cost of the inspection activities, as well as transport and accommodation expenses.

Supervision for maintenance of GMP requirements is carried out with intervals of two years.

Language and labeling

The package labeling and instructions for medical use are submitted and approved in Russian and Kazakh.

The requirements for the instructions for medical use and the patient leaflet were approved by Order of the Ministry of Health of the Republic of Kazakhstan No. 414 “The Rules of creation and execution of instructions for medical use and the general characteristics of medicinal products and medical devices” dated May 29, 2015.

The requirements were revised and amended in April 2019, additional information was added and each paragraph of the Procedure for creation of instructions for medical use (patient information leaflet) was detailed. The Procedure also contains instructions on how to execute instructions for medical use.

The requirements for the labeling of medicinal products and medical devices were approved by Order of the Ministry of Health of the Republic of Kazakhstan No. 227 “On approval of Rules for labeling of medicinal products and medical devices”. Samples of graphic design are approved after the registration procedure and are posted on the site.

Registration Certificate

The Registration Certificate consists of several documents:

• The registration certificate itself; 
• Approved text of the instructions for medical use (package insert); 
• Approved color layouts (artwork, mock-ups) of the primary and secondary packaging; 
• Analytic normative document that includes the composition of the product, specification for release and expiration date, quality control methods, etc.

The validity period of the Registration Certificate is 5 years. Generally, for products registered in countries with strict regulatory policies, the indefinite Registration Certificate is issued after the re-registration procedure. The medicinal product that has been placed on the market during the period of the registration certificate validity is allowed to be marketed until the expiration date.

Variations 

The MAH is obliged to approve any changes/variations prior to the entry of medicinal products into circulation. The Application for variations should be submitted within two months from the date of approval by the authorized body of the manufacturing country (if this amendment requires the approval procedure).

Amendments to the registration dossier of medicinal products are classified:

• Type IA changes, which do not require new registration (minor changes, that have negligible or no effect on quality, safety and effectiveness of the medicinal product, and are regarding to amendments to the content of the registration dossier materials submitted during the validity period of the Registration Certificate of the medicinal product).
• Type IB changes, that do not require new registration (minor changes, that are not changes of type IA and type II).
• Type II changes – any changes to the registration dossier materials that do not require a new registration of the medicinal product and which may have a significant impact on its quality, safety and effectiveness.
• Urgent changes related to the safety of the medicinal product.

Notification changes are not defined in the legislation of Kazakhstan. All types of changes must be officially approved by the competent authority.

The duration of the expert evaluation procedure for variations is:

• For type IA variations the duration is no more than 30 calendar days, excluding the term of reconciliation of final documents.
• For type IB and II variations (without laboratory tests) the duration is no more than 60 calendar days, excluding the term provided to the Applicant for elimination of the observations identified during the expert evaluation, for development of the assessment of the manufacturing conditions and quality assurance system, preclinical, clinical studies, pharmacovigilance system, reconciliation of final documents.
• For type IB and II variations (with laboratory tests) the duration is no more than 90 calendar days, excluding the term given to the Applicant to eliminate the observations identified during the expert evaluation, to organize the evaluation of manufacturing conditions and quality assurance system, to conduct the preclinical, clinical trials, pharmacovigilance system, to reconcile the final documents.

Laboratory testing of samples may be requested during the variation procedure if changes in the specifications and/or methods of quality control of the finished product have occurred. Inspection of the manufacturing site (for example, in the case of moving the manufacturing lines to another manufacturing site) may be also assigned during the variations procedure.

Renewal of registration 

The application for renewal must be submitted before the expiration of certificate validity. The re-registration procedure is similar to the registration procedure in Kazakhstan.

Laboratory testing of samples may be assigned during re-registration if changes in the specifications and/or methods of quality control of the finished product have occurred. Inspection of the manufacturing site may be also assigned during renewal.

The period of expert examination is not more than 120 calendar days, excluding the term given to the Applicant to answer on the deficiencies, to organize the evaluation of manufacturing conditions and quality assurance system.

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

Cratia provides professional services of state registration (renewals, variations) of medicinal products in Kazakhstan. We have an excellent knowledge of national legislation, necessary experience and resources. 

To start cooperation or get advice, please contact us by phone: +38 068 064-78-31, +38 044 223-61-67, by e-mail: info@cratia.ua, or visit our office.