For import and sale of medicines on the territory of Ukraine it is required to obtain the state registration and fulfil specific requirements regarding quality and safety. 

Since 2005, the legislation of Ukraine in relation to the registration and circulation of medicinal products started harmonisation with EU. The general requirements for documentation and expert assessment procedures are similar to the European ones, but there are many national features that significantly affect all regulatory processes.

The definition of “medicinal product” includes:

• finished medicinal and immunobiological products; 
• in-bulk products; 
• Active Pharmaceutical Ingredients (APIs).

As of the end of 2019, there are three different registration procedures for medicinal products:

• Order No. 426, which describes the general requirements for the registration of medicinal products, including simplified (accelerated) registration of medicinal products for the treatment of socially dangerous diseases; 
• Order No. 1245, which establishes a simplified registration procedure (so-called “recognition”) for medicinal products registered by the competent authorities of the United States of America, Switzerland, Japan, Australia, Canada, and medicinal products registered under a centralized procedure by the competent authority of the European Union; 
• Order No. 721, which establishes the procedure for the registration of medicinal products that are subject to purchase by specialized international organizations (so-called “authentication”). 

The Applicant (Marketing Authorization Holder – MAH) can choose the procedure. However, registration under Orders No. 1245 and No. 721 implies certain conditions, and is applicable only to certain groups of medicinal products.

The MAH for registration can be both a resident and a non-resident of Ukraine (for example, the manufacturer itself). According to the legislation, MAH is responsible for the quality, safety and efficacy of the medicinal product in Ukraine.

The non-resident MAH is not required to create a representative office or to have another person in Ukraine, however, it is required to:

• establish and maintain a pharmacovigilance system in Ukraine, designate a local contact person responsible for pharmacovigilance in Ukraine (LCP);
• designate a person in Ukraine who will be responsible for the quality of the medicinal product.

MAH’s obligations for regulatory affairs, safety and quality management can be outsourced to Cratia. 

Registration dossier

The CTD format has been introduced in Ukraine since 2005, and for more than 10 years it has been the only applicable format, with the exception of registration procedures under Orders No. 1245 and No. 721. The CTD format requirements are based on ICH (The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) standards, but the registration dossier is still submitted in paper form.

The documentation for the standard procedure for a new registration under Order No. 426 includes the following parts:

• National Application form;
• Registration form (legal and administrative documentation amending the Application);
• Registration dossier in CTD format consisting of 5 Modules (Modules 2-5 comply with ICH CTD requirements);
• Translation of specific parts of the registration dossier into Ukrainian or Russian;
• Specific national documents:
  • expert reports on non-clinical and clinical data, prepared according to national forms and recommendations;
  • MQC (MKK or AND) – methods for quality control of a medicinal product, which include the composition of the product, specification for release and shelf-life, a detailed description of the methods, information about the manufacturers, description of the packaging system, shelf life and storage conditions;
  • instructions for use – information on the use of a medicinal product, which is most often supplied in the form of a leaflet;
  • text for the package labeling – a description of the information printed on the primary and secondary packaging of the medicinal product.

The following documents are submitted in the Ukrainian language:

• Application form; 
• all documents from Registration form; 
• Module 1 (translation); 
• parts of Module 2, in required; 
• parts of Module 3.2.P; 
• translation of some other parts of the dossier;
• specific national documents (reports, MQC, instructions for use, packaging labeling).

There are strict requirements for registration dossiers: the number of pages in a file, cross-numbering and table of contents, sidebars etc.

Administrative documentation is submitted in a properly legalised form. The registration dossier must be submitted in paper form, in some cases parts of the dossier are allowed to be submitted in electronic form.

New registration

Depending on the type of medicinal product, indications for use, market authorisation status and other characteristics, various types of Applications and different expert evaluation periods are used. It should be noted that Ukraine follows the harmonization procedure with the EU, but still has its own independent legislation and expert evaluation procedure.

Medicines are classified under the following types:

• full Application (stand-alone dossier);
• generic, hybrid medicinal product or biosimilar;
• well-established use (WEU);
• fixed combination;
• informed consent;
• traditional medicinal product;
• in-bulk.

For each type of a medicinal product, the legislation stipulates certain requirements for the content of the registration dossier, the timing of the expert evaluation and other issues.

Registration procedure begins with the submission of the Application form to the single-window system of the Ministry of Health, and ends with the signing of the Order of the Ministry of Health and receiving of the hard original Marketing Authorization Certificate.

Both MAH and competent authority must follow strict timelines as soon as the Application form is submitted. If the MAH does not perform a specific action, or submits the necessary documents not in the full amount, or the documentation is filled incorrectly, then the registration procedure may be canceled, and all paid state fees will not be returned.

During the registration, it is necessary to make several payments to the accounts of state bodies, including:

1. payment of the state fee for a medicinal product registration to the account of the State Treasury of Ukraine;
2. payment of the cost of expert works to the account of the State Expert Center;
3. (if necessary) payment of the cost of laboratory quality control of a medicinal product samples to the account of an authorized laboratory.

Terms of expert evaluation of the registration dossier for a medicinal product depending on the type of Applications and chosen registration route:

• 210 business (working) days: a medicinal product submitted for registration on a full Application (stand-alone dossier); medical immunobiological products and biosimilars;
• 90 business days: for other types of medicinal products (generics, well-established and other types);
• 45 working days: for orphan products and medicinal products for the treatment of socially dangerous diseases (HIV, viral hepatitis, tuberculosis, cancer etc.);
• 10 business days (assessment under Order 1245): for medicinal products registered by the competent authorities of the United States of America, Switzerland, Japan, Australia, Canada and medicinal products registered by the competent authority of the European Union according to a centralized procedure;
• 5 business days (assessment under Order No. 721): for medicinal products subject to purchase by specialized international organizations.

The indicated timelines are duration of expert evaluation of materials, and do not include:

• period of the initial assessment of the Application form and registration form;
• period for payment of state fees and receiving payment confirmation;
• period for answers on the deficiencies;
• time needed for import of samples and standards, laboratory analysis (if required);
• finalizing actions after expert evaluation (verification/proofreading of draft of registration certificate and its annexes);
• signing the Order of Ministry of Health on the registration of a medicinal product.

The realistic timelines of the registration procedure includes the expert evaluation period, plus several months for the mentioned actions.

Language and labeling

The only official language in Ukraine is Ukrainian. Suggested text for labeling and instructions for use (leaflet, package insert) of the medicinal product are submitted for expert evaluation in Ukrainian language.

The labeling information and instructions for use are assessed during the state registration and approved as the annexes to the registration certificate. During the expert evaluation the text may be amended repeatedly at the discretion of state experts. Other languages ​​(for example, Russian, English) may also be presented on the packaging and in the instructions provided the complete identity of the text to the Ukrainian text.

After receiving a Marketing Authorization, but before importing the medicinal product, the Applicant should develop graphic packaging mock-ups and submit them for registration to the Unified Automated Information System (UAIS) of the State Service of Ukraine on Medicines and Drugs Control.

Layouts submitted for registration should include:

• approved text;
• graphical representation of the precise placement of text and other packaging elements;
• size and shape of layouts;
• graphical representation and/or description of security elements;
• designation of printing inks that will be used in the production;
• inscriptions in Braille and their placement (if applicable);
• barcode;
• positioning of technical elements;
• other additional information (if necessary).

The packaging of a medicinal product is checked at the stage of import of the batch (obtaining an opinion on the quality of the imported batch), and the slightest discrepancy can lead to deficiency letter, suspension of the quality conclusion issuance and corrective actions.

Exceptions are medicinal products purchased by specialized international organizations, which are allowed to be supplied in packaging labeled in the original language.

Marketing Authorization

Marketing Authorization after the initial registration is issued for a period of 5 years. After renewal, an unlimited Marketing Authorization is issued (unless the Ministry of Health decides to conduct additional renewal after 5 years for justified reasons related to pharmacovigilance).

Marketing Authorization consists of:

• the Marketing Authorization itself issued on a special hologram form;
• appendix to the Marketing Authorization: methods of quality control of a medicinal product;
• appendix to the Marketing Authorization: instructions for human use of a medicinal product;
• appendix to the Marketing Authorization: labeling of packaging materials.

All amendments (of any type) are also an integral part of the Marketing Authorization.

Maintenance of Marketing Authorization and changes

In Ukraine there are no monthly or annual payments related to maintaining registration. However, the Applicant must maintain a pharmacovigilance system and a quality management system in Ukraine.

Therefore, the Applicant must provide:

• continuous presence of a person responsible for pharmacovigilance;
• continuous presence of a person responsible for quality, safety and efficacy.

Fulfillment of the Applicant’s obligations with regard to maintaining quality and safety may be outsourced to Cratia Ltd.

All changes to the Marketing Authorization are made by submitting the Application and a package of documents, payment of the cost of expert evaluation, approval by the Order of the Ministry of Health of Ukraine.

The Applicant must submit an Application for Variations related to safety to the instructions for human use of a medicinal product within the 60 calendar days from the date of receipt of information on amendment necessity.

The types of variations are similar to those in the EU:

• correction of a technical error: correction of inconformity made during the registration, renewal or amendment procedure;
• change of the Applicant (Holder) of the Marketing Authorization;
• type IA: minor variations that do not have a significant impact on quality, safety and efficacy;
• type ІА-IN: type IA variations with immediate notification;
• type IB: minor variations, which are neither a type IA variation nor a type II variation;
• type II: changes that affect quality, safety and efficacy;
• changes that lead to a new registration.

The concept of “notification” in Ukraine differs from European practice: in fact, “notification” changes do not imply any errors or questions of the competent authorities, since a comment means refusal to conduct an expert evaluation.

Marketing Authorization Renewal

It is possible to submit an Application for renewal of  marketing authorization not later than 180 calendar days before its expiry (the recommended period for application is 12 months).

Renewal process starts from the moment the Application is submitted to the Ministry of Health of Ukraine, and ends by approving the renewal of the authorization by the Order of the Ministry of Health of Ukraine and the issuance of a new Marketing Authorization. In this case, the Marketing Authorization number remains the same.

 A significantly smaller package of documents is required for renewal procedure compared to an initial registration. During renewal process, the main emphasis is made on the managing medicinal product safety, i.e., on the pharmacovigilance system documentation and instructions for human use of the medicinal product.

Before filing the Renewal Application, it is necessary to submit separate Applications for all changes. Such submitted Applications (variations and renewal) undergo expert evaluation concurrently and independently.

Once renewed, the Marketing Authorisation shall be valid for an unlimited period, unless the Ministry of Health decides to conduct additional renewal procedure after 5 years on justified reasons relating to pharmacovigilance.

Cratia provides professional services on establishment and maintenance of state registration of medicines in Ukraine. 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.