Regulatory newsletter on medicines in Eastern Europe and Central Asia

Cratia provides you with a rundown of the most critical developments in medicinal products registration, safety and quality management that became effective at the end of 2021 and the first quarter of 2022 in 11 countries of Eastern Europe and Middle Asia: Azerbaijan, Armenia, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Mongolia, Tajikistan, Turkmenistan, Ukraine, Uzbekistan and the Eurasian Economic Union (EAEU).

The most important in a nutshell:

Azerbaijan:
Since October 2021, it has become possible in Azerbaijan to submit reports on adverse reactions through the online portal on the official website of the regulatory authority.

Armenia:
In February 2022, the Scientific Center of Expertise updated the pricelist for assessment services.

Since the end of March 2022, changes to the rules for registration and examination of medicines have come into force, including the addition of accelerated and simplified registration procedures, reduction of the assessment time for some procedures, and additional possibilities for electronic submissions.

Georgia:
In March 2022, the procedure and rules for submission of the GMP certificate were approved.

Kazakhstan:
The introduction of mandatory digital labeling of medicines continues. At the end of April, a list of medicinal products subject to mandatory digital labeling from July 1, 2022 was approved. It is assumed that until July 1, 2023, all medicines must be labeled with a digital identification.

At the end of December 2021, amendments and clarifications were introduced to the rules for the assessment of medicines, including the procedure of submission of Applications, dossiers and materials, the procedure for appealing against decisions, actions, or inaction of the competent authority.

Kyrgyzstan:
Since the end of March 2022, changes to the rules for registration and examination of medicines have come into force, including the addition of accelerated and simplified registration procedures, reduction of the assessment time for some procedures, and additional possibilities for electronic submissions.

In early February, the competent authority notified about different addresses for PSUR and CIOMS submission.

Moldova:
At the end of April 2022, the competent authority of Moldova announced the possibility of resuming registration after its termination, and also updated the requirements for the submission of samples.

In March 2022, the competent authority launched an electronic system for making an appointment to submit documents and apply for consultations.

In mid-November 2021, changes were made to the authorization procedure for medicines, including the introduction of 3 new accelerated procedures (conditional authorization, accelerated registration and joint authorization); after re-registration under the general procedure, an indefinite registration certificate is issued; the period for the possible import of medicines after the expiration of the registration certificate date has been extended.

Ukraine:
On February 24, 2022, martial law was introduced in connection with the attack of the Russian Federation.

At the end of February, the Ministry of Health approved the 9-days emergency state registration procedure. Emergency registration does not require GMP confirmation; the medicinal product can be supplied in packaging intended for other countries. Registration is issued for a period of 1 year and allows only hospital sales (not for sale through pharmacies).

At the end of February, the public procurement procedure was simplified, the report is published 20 days after the termination or cancellation of martial law.

Since the beginning of March 2022, for the period of martial law, the requirements regarding the expiration date of imported medicines have been canceled and transportation by public transport is allowed.

In mid-April, a number of changes were made to the system of registration, quality control and circulation of medicines, including: the procedure for emergency state registration of medicines under obligations was approved; the validity of registration certificates expiring during martial law is automatically extended; MAHs are allowed to postpone submission of variations that do not affect quality, efficacy and safety; import of registered medicines in foreign packaging is allowed, accompanied by instructions in Ukrainian and a letter of guarantee that the medicinal product is identical to the registered one; the import of unregistered medicines for the provision of the Armed Forces and healthcare institutions without the right to sell is allowed; a conclusion on the quality of an imported medicinal product is issued without laboratory quality control and without a decision on the compliance of manufacturer with GMP requirements.

Uzbekistan:
At the beginning of April 2022, a gradual introduction of mandatory digital labeling of medicines and medical devices was approved. The next stage of introduction: medicinal products with secondary (outer) packaging (except for orphan drugs) are subject to mandatory labeling from September 1, 2022.

EAEU:
Since the end of March 2022, changes to the rules for registration and examination of medicines have come into force, including the addition of accelerated and simplified registration procedures, reduction of the assessment time for some procedures, and additional possibilities for electronic submissions.

Below you can find more information on these and other changes.

Azerbaijan:

The Center for Analytical Expertise (CAE) launched an online system to submit reports on adverse reactions to medicines. The system is connected to the WHO International Adverse Reactions Monitoring Center, and all received reports will be transferred to the WHO Global Adverse Reactions Database.

Armenia:

The competent authority of Armenia, the Scientific Center for Expertise of Medicines and Medical Technologies named Academician E. Gabrielyan, on February 14, 2022 approved a new price list for its services.

Armenia, as an EAEU member state, implemented the EEC Council Decision N 36 dated March 17, 2022 which amends the rules for the registration and assessment of medicines, including:

a new simplified registration procedure for exceptional cases,
a new conditional registration procedure,
accelerated assessment for the orphan, pediatric products, and highly social importance medicines,
remote submission of the Application for registration, renewal and bringing the dossier into compliance with EAEU requirements and other changes.

More detailed information can be found below in the EAEU section.

Armenia is a member state of the Eurasian Economic Union (EAEU). From July 1, 2021, submitting documents for a new registration is possible only under the Rules of the EAEU. Registration certificates obtained under the national registration procedure must be brought into compliance with the EAEU rules by December 31, 2025.

Georgia:

Mandatory submission of the GMP certificate during new registrations and renewals is approved by Decree No. 114 dated March 4, 2022. Submission of the GMP certificate becomes mandatory:

for registration of a medicinal product under the national procedure and under the recognition route – from March 4, 2022,
for re-registration under the national procedure and for the manufacturing site transfer procedure – from June 1, 2022.

For registered products, the GMP certificate must be submitted by March 1, 2023.

Kazakhstan:

We remind that Kazakhstan has introduced inspections of the pharmacovigilance systems under the requirements of good pharmacovigilance practice (GVP). Inspection is performed by experts of the Department of Pharmacovigilance and Monitoring of Safety, Efficacy and Quality of Medical Devices. The inspection is regulated by the Order of the Minister of Health of the Republic of Kazakhstan dated May 3, 2022 No. KR DSM-41.

Order of the Ministry of Health of the Republic of Kazakhstan No. KR DSM-131 dated December 20, 2021 amended the rules for registration of medicines approved by Order No. KR DSM-10 dated January 27, 2021 “On approval of the rules for the examination of medicines and medical devices, including:

the procedure for submission of the Application, registration dossier and materials has been supplemented;
the procedure for a negative decision in case of the untimely or incomplete response of the Applicant to the comments of the competent authority has been clarified;
the appeal procedure against decisions, actions or inaction of the competent authority has been added.

Order of the Minister of Health of the Republic of Kazakhstan No. RK DSM-142 dated December 31, 2021 amended the list of orphan diseases and medicines for their treatment, and inclusion in the Kazakhstan national formulary.

Order of the Minister of Health of the Republic of Kazakhstan No. KR DSM-12 dated February 4, 2022 amended the rules of pharmaceutical inspections regarding the timing of inspections for national manufacturers licensed to manufacture of medicines.

Kazakhstan, as an EAEU member state, implemented the EEC Council Decision N 36 dated March 17, 2022 which amends the rules for the registration and assessment of medicines, including:

a new simplified registration procedure for exceptional cases,
a new conditional registration procedure,
accelerated assessment for the orphan, pediatric products, and highly social importance medicines,
remote submission of the Application for registration, renewal and bringing the dossier into compliance with EAEU requirements and other changes.

More detailed information can be found below in the EAEU section.

From March 30, 2022 submission of Applications and registration dossiers has moved to a new system – the Expertise portal. Applicants can track the stages of the assessment process through its e-office on the portal.

Decree of the Government of the Republic of Kazakhstan No. 242 dated April 25, 2022 approved a list of 93 medicines subject to mandatory digital labeling from July 1, 2022. Digital labeling is applied with a two-dimensional matrix barcode (Data Matrix) on the secondary, and in case of absence – on the primary packaging.

It is assumed that mandatory digital marking will be introduced gradually until July 1, 2023. Medicinal products manufactured in packages without digital labeling before the mandatory implementation date will be allowed for import and sale until the expiry date.

Kazakhstan is a member state of the Eurasian Economic Union (EAEU). From July 1, 2021, submitting documents for a new registration is possible only under the Rules of the EAEU. Registration certificates obtained under the national registration procedure must be brought into compliance with the EAEU rules by December 31, 2025.

Kyrgyzstan:

Order of the Ministry of Health of the Kyrgyz Republic No. 48 dated January 19, 2022 approved the list of medicines and medical devices for the diagnosis and treatment of coronavirus infection (COVID-19).

The Resolution of the Cabinet of Ministers of the Kyrgyz Republic No. 28 dated January 28, 2022 approved the Rules for Conducting Pharmaceutical Inspections, implementing to the national legislation the Rules of Good Pharmaceutical Practices of the EAEU (Decision of the EEC Council No. 77 dated November 3, 2016).

The Department of Medicines and Medical Devices, by letter on February 4, 2022, notified Applicants on the separate addresses for submission of PSUR and CIOMS.

Kyrgyzstan, as an EAEU member state, implemented the EEC Council Decision N 36 dated March 17, 2022 which amends the rules for the registration and assessment of medicines, including:

a new simplified registration procedure for exceptional cases,
a new conditional registration procedure,
accelerated assessment for the orphan, pediatric products, and highly social importance medicines,
remote submission of the Application for registration, renewal and bringing the dossier into compliance with EAEU requirements and other changes.

More detailed information can be found below in the EAEU section.

Kyrgyzstan is a member state of the Eurasian Economic Union (EAEU). From July 1, 2021, submitting documents for a new registration is possible only under the Rules of the EAEU. Registration certificates obtained under the national registration procedure must be brought into compliance with the EAEU rules by December 31, 2025.

Moldova:

Order of the Ministry of Health of the Republic of Moldova No. 1041 dated November 15, 2021, implemented changes to the procedure for authorization of medicines and approving post-registration variations, including:

the new procedure of conditional emergency authorization. The duration of the procedure is not more than 10 working days. The registration certificate is issued for 1 year.
the new fast-track registration procedure has been introduced for medicines approved by the EMA or national regulatory authorities of the USA, Canada, Switzerland, UK, Japan and Australia. The duration of the procedure is not more than 10 working days. The registration certificate is issued for 5 years.
the new joint authorization procedure has been introduced for medicines prequalified by WHO. The duration of the procedure is not more than 45 working days. The registration certificate is issued for 5 years.
after the renewal (re-registration) under the general procedure, the registration certificate is issued without expiry. Deadlines for submission of PSUR have been introduced for the products registered without expiry.
the period for import of medicines after the expiry of the registration certificate has been extended (in case of submission of the renewal Application) from 6 to 12 months.

On March 16, 2022, the Agency for Medicines and Medical Devices (AMDM) of the Republic of Moldova launched an electronic system for making an appointment to submit documents and apply for a consultation.

On April 26, 2022, AMDM announced the possibility of resuming the drug registration procedure after its termination and updated the requirements for providing samples during the registration process.

Ukraine:

On Thursday, Feb 24 at 5 o’clock in the morning, Russia attacked Ukraine. The Law of Ukraine No. 2102-IX imposed martial law from February 24, 2022.

According to the United Nations, as of May 10, the number of confirmed civilian casualties was 7,061; The UN clarifies that the actual number of victims is much higher since each case is confirmed. According to the Ministry of Health, as of May 14, Russian troops damaged 616 hospitals, of which 101 were completely destroyed.

Order of the Ministry of Health of Ukraine No. 384 dated February 26, 2022 approved the procedure for emergency state registration of medicines, medical immunobiological preparations and blood products for use by healthcare professionals, in particular in healthcare institutions, without the right to retail. Registration is carried out based on the registration in the country of the manufacturer / MAH, with a minimum set of documents and translations of the labeling text and instructions for use into Ukrainian, submitted electronically. The assessment period is 9 working days; state fees are absent. Registration is issued for 1 year.

On February 27, 2022, the State Service of Ukraine for Medicines and Drug Control informed on the transition to an electronic format for submission of Applications and obtaining opinions on the quality of medicines.

Decree of the Cabinet of Ministers of Ukraine No. 169 dated February 28, 2022 simplified the procedure for public procurement: the Customer independently determines the lists and volumes of procurement, and procurement is carried out without applying the requirements of the Law of Ukraine “On Public Procurement”. The procurement report is published 20 days after martial law is ended.

Order of the Ministry of Health of Ukraine No. 406 dated March 3, 2022, canceled for the period of martial law the requirements regarding the shelf-life period for imported medicines and allowed transportation by public transport, including those that transport passengers, and in postal or baggage items, provided compliance with their storage conditions specified by the manufacturer.

Decree of the Cabinet of Ministers of Ukraine No. 471 dated April 15, 2022 introduced many changes to the system of registration, quality control and circulation of medicines, including:

the procedure for emergency state registration of medicines under obligations was approved. The procedure is carried out based on registration in the reference country (the list of countries is not limited, except for the aggressor country), the registration dossier of the reference country, translations of the instructions for use, SmPC and labeling. Simultaneous registration of the package artworks from several markets is allowed. The assessment period is 9 working days; state fees are absent. The registration certificate is issued for a period of one year and/or for the period of martial law and/or for six months from the date of its termination. Registration under the emergency procedure gives the right to wholesale, sale to healthcare institutions, military administrations, units of the Armed Forces, volunteer, humanitarian and charitable organizations, without the right for retail sales.
the deadline for submission of the renewal Application is extended for the period of martial law and within 6 months after its termination.
the validity of registration certificates expiring during martial law and within 6 months from the date of termination is extended for a period of 1 year through the update of the information in the State Register of Medicines of Ukraine;
submission of variations can be postponed for the period of the martial law and 6 months after in case if the MAH submits a letter explaining that the changes have no negative impact on the quality, safety and efficiency of the medicinal product with a guarantee letter for later submission;
medicines purchased by specialized organizations under an agreement with the Ministry of Health are exempted from the import quality control procedure;
it is allowed to import registered medicines in foreign packaging (from the market of another country), accompanied by approved instructions for use and a letter of guarantee that the medicine is identical to the registered one;
the import of unregistered medicines for medical use is allowed exclusively for the provision of the Armed Forces and healthcare institutions (except for pharmacies), without the right to sell;
it is allowed to perform import quality control without the Decision on GMP compliance issued by the competent authority of Ukraine and without the laboratory quality control until the end of the martial law or further notice of the competent authority. In this case, the authorized person of the importer is responsible for the quality control of the imported batch.

Uzbekistan:

Decree of the Cabinet of Ministers No. 149 of April 2, 2022 “On the introduction of a system of mandatory digital labeling of medicines and medical devices” approved the gradual introduction of mandatory digital labeling of medicines and medical devices:

medicines with secondary (outer) packaging (except orphan drugs) are subject to mandatory labeling from September 1, 2022;
medicines in primary (inner) packaging, in the absence of secondary (outer) packaging (except for orphan drugs), are subject to mandatory labeling from November 1, 2022;
medicines and medical devices for orphan diseases (according to the list approved by the Ministry of Health) are subject to mandatory labeling from March 1, 2023;
medicines registered under the recognition route are subject to mandatory labeling from March 1, 2023;
medical devices, according to the list determined by the Ministry of Health, will begin to be labeled from February 1, 2025.

The following transitional provisions are established:

medicines and medical devices manufactured without digital labeling before the mandatory implementation date are allowed for sale within 3 years;
foreign manufacturers can certify and import medicines and medical devices manufactured without digital labeling within 180 days from the mandatory implementation date;
foreign manufacturers must either open their representative office in Uzbekistan or conclude an agreement with a local company on the implementation of digital labeling (with the obligatory indication of such a company in the instructions for the medicinal product or medical devices) within 12 months from the date of mandatory labeling for the relevant group. The functions of the representative/local company should also include ensuring the payment of fines in case of violation of the mandatory labeling rules.

Digital labeling is applied with a two-dimensional matrix barcode (Data Matrix) according to ISO/IEC 16022:2008 (IDT ISO/IEC 16022:2006) and includes:

product code GTIN, which consists of 14 digits;
individual serial number of a product item, consisting of 13 characters;
optional additional information, such as expiration date;
verification key consisting of 4 characters;
verification code consisting of 44 characters.

Eurasian Economic Union:

The recommendation of the EEC Board No. 23 of September 13, 2021 approved the guidelines for determining the possibility of using the medicinal product in pediatric practice or concerning a separate group of the pediatric population to indicate the relevant information in the summary of the product’s characteristics and in the instructions for medical use.

On December 21, 2021, the EAEU Board approved guidelines for the pharmaceutical development of medicines for children. The guidelines describe general approaches to pharmaceutical drug development for use in pediatric practice, as well as approaches to the development of various dosage forms used to treat children.

EEC Council Decision No. 36 dated March 17, 2022 implemented changes to the rules for the registration and assessment of medicines, including:

A new simplified registration procedure for exceptional cases when the Applicant cannot provide comprehensive data on the efficacy and safety of the medicinal product due to objective reasons.
A new conditional registration procedure for the treatment, prevention or diagnosis of serious (severe) disabling or life-threatening diseases, before the submission of comprehensive clinical data, provided that the benefit of earlier drug availability outweighs the risk. Registration is valid for 1 year and requires registration confirmation (re-registration) with a reassessment of the benefit-risk ratio annually.
Accelerated assessment within a period of not more than 100 working days for orphan drugs, highly socially important medicinal products and medicines intended for use by minors.
The possibility of importing unregistered medicines for a specific patient or providing medical care to a limited group of patients with rare and (or) especially severe pathologies (similar to the Named Patient Program).
The registration period under the mutual recognition procedure in the reference country has been reduced from 210 calendar days to 140 business days, in the recognition state from 90 calendar days to 60 business days. The registration period under the decentralized procedure has been reduced from 210 calendar days to 140 business days.
Possibilities for digital signature, electronic submission, and dossier management in regulatory procedures are significantly expanded and supplemented.
Possibility to replace the in-registration laboratory quality control with the documentation assessment for the batch release (Lot Release).
Amendments and clarifications have been made to the procedure for bringing the registration dossier of a medicinal product in line with the requirements of the EAEU.

Cratia is a professional regulatory consultant for medicines in 11 countries of Eastern Europe and Central Asia: Azerbaijan, Armenia, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Mongolia, Tajikistan, Turkmenistan, Ukraine, Uzbekistan and the Eurasian Economic Union (EAEU).

If you have any questions, we will be happy to answer them by email at info@cratia.com, by phone at +38(044)364-33-55, or at a meeting in our office.

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