Information Center

Please follow the link: Contacts

State Enterprise "STATE EXPERT CENTER

OF THE MINISTRY OF HEALTH OF UKRAINE" (hereinafter referred to as the Center) – a specialized expert institution authorized by the Ministry of Health of Ukraine in the field of preclinical study, clinical trials and state registration of medicinal products (including medical immunobiological preparations) within the limits defined by the Laws of Ukraine "On Medicinal Products" and "On Protection of the Population from Infectious Diseases", which is also the leading organization in the field of pharmacovigilance, standardization of medical care and medical, including pharmaceutical, services, including the development of relevant medical technological documents and draft regulatory acts, which is based on state ownership and belongs to the sphere of management of the Ministry of Health of Ukraine.

More information: History

The production, circulation in Ukraine, control, and importation into the territory of Ukraine of food and dietary supplements, cosmetic products and medical devices, as well as matters of their state registration, are outside the competence of the Center, which is a specialized expert institution authorized by the Ministry of Health of Ukraine in the field of preclinical study, clinical trials and state registration of medicinal products within the limits defined by the Law of Ukraine "On Medicinal Products".

Full name:

In Ukrainian: State Enterprise "State Expert Center

of the Ministry of Health of Ukraine"

In Russian: Государственное предприятие «Государственный

зкспертный центр Министерства здравоохранения Украины»

In English: The State Expert Center of the Ministry of Health of

Ukraine

Abbreviated name:

In Ukrainian: State Expert Center of the MoH
In Russian: Государственный зкспертный центр МЗ
In English: The State Expert Center

According to the Charter and information from the Unified State Register of Legal Entities, Individual Entrepreneurs and Public Associations, the location of the State Enterprise "State Expert Center of the Ministry of Health of Ukraine" (hereinafter – the Center) as of 26.06.2018 is: 03057, Ukraine, Kyiv, Antona Tsedika Street, building 14.

Consultation services, acceptance of materials submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, and acceptance of documents by the Center for Administrative Services of the MoH "Single Window" will be carried out at the address: Kyiv, Smolenska Street, building 10.

Click here

The English version you may find here: http://www.dec.gov.ua/index.php/en/

To make a request information you may contact

Tel. (044) 2021700

Fax (044) 2021700

Provision of public information by the State Enterprise "State Expert Center of the MoH of Ukraine" is carried out in accordance with the provisions of the Law "On Access to Public Information", in response to an information request.

Contacts for filing an information request

orally: telephone (044) 202-17-09;

in writing:

03057 Kyiv, Smolenska Street, 10, State Enterprise "State Expert Center of the MoH of Ukraine".

More information: Forms for submitting an information request in writing: Access to public information

Fax: (044) 202-17-09

E-mail: Chigirick@dec.gov.ua

The cost of the expert evaluation of a medicinal product, as well as of an additional expert evaluation, is not included in the registration fee.

The provisions on the amounts of the fee for state registration (re-registration) of medicinal products were approved by resolution of the Cabinet of Ministers of Ukraine of 26 May 2005 No. 376 (as amended).

Regulatory references: http://zakon2.rada.gov.ua/laws/show/376-2005-%D0%BF

The cost of services for conducting the expert evaluation of materials on medicinal products was approved by an order of the State Expert Center of the MoH and published on the official website of the Center at the link: https://dec.gov.ua/materials/vitrati-na-re-stracziyu/

There is currently no planned event.
Follow the news

There is currently no planned event.
Follow the news

For researchers and representatives of clinical trial sponsors, training seminars "Good Clinical Practice (GCP). Regulatory and legal framework for clinical trials in Ukraine" are held monthly at the State Expert Center of the MoH.
Participation in the seminar is possible only after prior payment by invoice. An invoice for payment can be obtained from the accounting department of the State Expert Center after submitting a completed participant application indicating information about the payer.

Please send the application in electronic form to: GCP@dec.gov.ua

Contact persons:
Olena Yurchenko or Iryna Shura
Tel: +38 (044) 202-17-02
Andrii Samborskyi
Tel: +38 (044) 202-17-00 (5502)

In the case of re-registration of a MIBP that has been reclassified into the category of a medicinal product, the expert evaluation of registration materials is carried out in the same manner as for a medicinal product submitted for registration, in accordance with the provisions of Chapter IV of the Procedure, and a recommendation for registration of the medicinal product is provided.

You need to submit an application for state registration of a medicinal product to the Single Window administrative services center of the MoH. The application form for state registration is established by MoH order No. 707 of 30.10.2015.

After the Center receives a letter of referral from the MoH, the applicant submits to the Center, for expert evaluation, the registration form of the medicinal product submitted for state registration (Appendix 1) to the Procedure. For this group of medicinal products, the registration dossier is submitted in the available format (either in the four-part format or in the CTD format).

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

In accordance with the Procedure for conducting expert evaluation of registration materials, approved by MoH order No. 460 dated 23.07.2015, if the applicant submits a medicinal product for registration to the regulatory authority(ies) of another country for the first time in the world, then the application for registration of this medicinal product in Ukraine and the registration materials may be submitted no earlier than the final expert report on the assessment of the registration dossier for the medicinal product is published on the official website of the regulatory authority. However, the decision on registration of this medicinal product in Ukraine will be made by the MoH after the approval of the relevant decision by the regulatory authority(ies) of the country (countries) in which this medicinal product was submitted for registration.

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

In accordance with the Procedure for conducting expert evaluation of registration materials, approved by MoH order No. 460 dated 23.07.2015, a copy of the document confirming the registration of the medicinal product in accordance with the legislation of the applicant's and/or manufacturer's country shall be provided, and in the absence of such a document – a justification shall be provided indicating the reasons for its absence (not provided by applicants/manufacturers who are residents and use production facilities located outside Ukraine under a contract).

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

According to the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate (Order of the Ministry of Health of Ukraine No. 426 dated 26.08.2005 (as amended by Order of the Ministry of Health of Ukraine No. 3 dated 04.01.2013) the following documents must be returned:

• The original draft of the instruction for medical use and the summary of product characteristics (if available) and additionally three copies with a "live" stamp of the Department for Expert Evaluation of Instructions and Nomenclature;
• The original draft of the quality control methods and additionally one copy with the visa of the applicant's representative on each page.

In accordance with the Procedure for conducting the expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as the expert evaluation of materials on amendments to registration materials during the validity period of the registration certificate (Order of the Ministry of Health of Ukraine 26.08.2005 No. 426 (as amended by Order of the Ministry of Health of Ukraine of 23.07.2015 No. 460) the following documents must be returned:

• The original of the draft package leaflet and summary of product characteristics (if available) and additionally three copies with a "live" stamp of the Department for Expert Evaluation of Instructions and Nomenclature,
• The original of the draft text of the labelling of the primary, secondary (if available) packaging and additionally three copies with "live" stamps of the Department for Expert Evaluation of Instructions and Nomenclature;

The original of the draft quality control methods.

According to the requirements of Order of the Ministry of Health of Ukraine dated 26.08.2005 No. 426 as amended (hereinafter – the Order), for state registration of APIs, documents are submitted according to the list specified in Annex 12 to the Order, taking into account the requirements regarding APIs set out in Annex 6 to the Order. As regards the procedure for making changes to registration materials, registration dossier materials are submitted according to the requirements set out in Annex 17 to the Order.

At the same time, we draw your attention to the need for the applicant to take into account the requirements of guideline EMA/CHMP/BWP/429241/2013 "Guideline on the use of starting materials and intermediates collected from different sources in the manufacturing of non-recombinant biological medicinal products" when preparing registration dossier materials for the above-mentioned APIs.

The applicant submits materials according to the list specified in Annex 12 to the Procedure for conducting expert evaluation of registration materials, approved by Order of the MoH dated 23.07.2015 No. 460. The applicant is guided by the requirements of current legislation, taking into account international standards and recommendations, for example the EMA guideline "Guideline on Active Substance Master File Procedure".

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

Information on the risk management system is provided as part of the registration dossier materials in accordance with Annexes 1 and 5 to the Procedure for the expert evaluation of registration materials for medicinal products, approved by MoH order No. 460 of 23.07.2015.

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

Please note that during the registration/re-registration procedure, a specialised expert evaluation is carried out of the primary materials submitted as part of the registration dossier for a medicinal product, in accordance with the requirements of Annexes 5 and 15 to the Procedure for the expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as the expert evaluation of materials on amendments to registration materials during the validity period of the registration certificate, approved by MoH order of 23 July 2015 No. 460 (hereinafter referred to as MoH order No. 460).

During the specialized expert evaluation of the registration dossier materials for the purpose of obtaining complete data on the efficacy, safety and quality of a medicinal product, each of the Center's expert commissions may twice request from the applicant the necessary materials supplementing the data on the efficacy, safety and quality of the medicinal product, with reference to the numbers of sections, subsections, clauses, subclauses and paragraphs of the Procedure; new requests for materials already reviewed by the expert shall not be allowed, except in cases where the additional materials have been provided incompletely.

If, within 90 working days after the Center's request for additional materials, the applicant does not send these materials or does not justify another deadline for providing the materials, or provides them incompletely, except for a certified copy of the document confirming that the manufacturing conditions of the medicinal product comply with the requirements for the manufacture of medicinal products in Ukraine (good manufacturing practice), the registration materials shall be withdrawn from review, of which the Center shall notify the applicant in writing within three working days.

If the applicant/representative of the applicant has submitted (or has not submitted) a letter(s) on the provision of an Addendum to the clinical data review and/or Risk management plan as part of the registration dossier materials, in view of the above, these documents should not be submitted as revised/additional materials.

If an Addendum to the clinical data review and/or Risk management plan is received as part of revised/additional materials, such documents will not be considered and, accordingly, their specialized expert evaluation will not be carried out.

In terms of fulfilling the obligations, the applicant must submit these documents after completion of the medicinal product re-registration procedure by declaring changes in the manner prescribed by law.»

We inform you that, in accordance with the requirements of Order of the Ministry of Health of Ukraine No. 426 of 26.08.2005 as amended, in particular the requirements set out in Chapter IV, clause 5: Recommended methods of quality control (hereinafter – MQC) shall be drawn up as a separate document on the basis of the specification/methods of control of the medicinal product, which are developed and substantiated by the results of studies conducted by the applicant (manufacturer). The information provided in the MQC shall fully correspond to the information contained in the relevant sections of the registration dossier submitted by the applicant (manufacturer).

According to the requirements of Order of the Ministry of Health of Ukraine No. 426 of 26.08.2005, as amended, Annex 6, clause 3.2, sub-clause 6: "If the API and/or auxiliary substance(s) and the starting material are described in the European Pharmacopoeia, the applicant may provide a certificate of suitability issued by the European Directorate for the Quality of Medicines. In the relevant section of this module, it is considered that certificates of suitability to monographs of the European Pharmacopoeia replace the substantive data in the relevant sections specified in this module. The manufacturer of the substance must confirm in writing to the applicant that the manufacturing process has not changed since the certificate of suitability was issued by the European Directorate for the Quality of Medicines. Thus, providing a reference to the EDQM database is considered insufficient.

When registering a medicinal product, the applicant must specify the grounds for choosing the type of medicinal product to which the set of available registration documents must correspond.

The types of medicinal products and the requirements for the materials of the registration dossier are specified in Section III of the Procedure for the expert evaluation of materials on medicinal products (as amended by Order of the Ministry of Health No. 460).

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

When compiling a registration dossier for a medicinal product manufactured according to an approved formula, the applicant shall be guided by the provisions set out in Annex 8 to the Procedure approved by MoH order No. 426 of August 26, 2005, as amended by MoH Order No. 460 of 23.07.2015.

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

The requirements for the registration form of an API submitted for state registration are contained in Annex 4 to MoH Order No. 426 of 26.08.2005, as amended by MoH order No. 460 of 23.07.2015, and the list of documents is defined by Annex 12 of the same Order; the form of the application for state registration of an API is defined by MoH order No. 707 of 30.10.2015.

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

To undergo the state registration procedure for a medicinal product, it is necessary to:

1. Compile a registration dossier for the medicinal product in accordance with the provisions set out in Annex 6 to the Procedure for conducting expert evaluation of registration materials, approved by MoH order No. 426 of August 26, 2005, as amended by MoH order No. 460 of 23.07.2015.

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

2. Submit an application for state registration of a medicinal product to the Ministry of Health's administrative services center "Single Window". The application form for state registration of an API is defined by MoH order No. 707 dated 30.10.2015.

3. Submit registration materials to the State Expert Center of the MoH for expert evaluation of these materials in accordance with the requirements governed by Article 9 of the Law of Ukraine "On Medicinal Products" in the procedure approved by Cabinet of Ministers of Ukraine resolution No. 376 dated 26.05.2005.

According to the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate (Order of the Ministry of Health of Ukraine No. 426 dated 26.08.2005 (as amended by Order of the Ministry of Health of Ukraine No. 3 dated 04.01.2013) the following documents must be returned:

• The original draft of the instruction for medical use and the summary of product characteristics (if available) and additionally three copies with a "live" stamp of the Department for Expert Evaluation of Instructions and Nomenclature;
• The original draft of the quality control methods and additionally one copy with the visa of the applicant's representative on each page.

According to the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate (Order of the Ministry of Health of Ukraine No. 426 dated 26.08.2005 (as amended by Order of the Ministry of Health of Ukraine No. 460 dated 23.07.2015) the following documents must be returned:

• The original of the draft package leaflet and summary of product characteristics (if available) and additionally three copies with a "live" stamp of the Department for Expert Evaluation of Instructions and Nomenclature,
• Original draft text of the labeling* of the primary, secondary (if any) packaging and additionally three copies with a "live" stamp of the Department of Expert Evaluation of Instructions and Nomenclature

* Upon re-registration, labeling in the form inbulkis not approved.

After the Ministry of Health of Ukraine's referral letter, together with a copy of the application for re-registration of an API, is received by the Center, the Applicant submits to the Center the API registration form in accordance with Annex 4 to the Procedure for Expert Evaluation of Registration Materials, approved by MoH order No. 460 of 23.07.2015, together with a list of all approved changes in the form of a comparison table, including the submission date, approval date, brief description of changes, the MAAs approved in Ukraine, and a certificate of analysis of one batch, in accordance with the requirements of the above-mentioned Procedure. expert evaluation.

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

Please note that during the registration/re-registration procedure, a specialised expert evaluation is carried out of the primary materials submitted as part of the registration dossier for a medicinal product, in accordance with the requirements of Annexes 5 and 15 to the Procedure for the expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as the expert evaluation of materials on amendments to registration materials during the validity period of the registration certificate, approved by MoH order of 23 July 2015 No. 460 (hereinafter referred to as MoH order No. 460).

During the specialized expert evaluation of the registration dossier materials for the purpose of obtaining complete data on the efficacy, safety and quality of a medicinal product, each of the Center's expert commissions may twice request from the applicant the necessary materials supplementing the data on the efficacy, safety and quality of the medicinal product, with reference to the numbers of sections, subsections, clauses, subclauses and paragraphs of the Procedure; new requests for materials already reviewed by the expert shall not be allowed, except in cases where the additional materials have been provided incompletely.

If, within 90 working days after the Center's request for additional materials, the applicant does not send these materials or does not justify another deadline for providing the materials, or provides them incompletely, except for a certified copy of the document confirming that the manufacturing conditions of the medicinal product comply with the requirements for the manufacture of medicinal products in Ukraine (good manufacturing practice), the registration materials shall be withdrawn from review, of which the Center shall notify the applicant in writing within three working days.

If the applicant/representative of the applicant has submitted (or has not submitted) a letter(s) on the provision of an Addendum to the clinical data review and/or Risk management plan as part of the registration dossier materials, in view of the above, these documents should not be submitted as revised/additional materials.

If an Addendum to the clinical data review and/or Risk management plan is received as part of revised/additional materials, such documents will not be considered and, accordingly, their specialized expert evaluation will not be carried out.

In terms of fulfilling the obligations, the applicant must submit these documents after completion of the medicinal product re-registration procedure by declaring changes in the manner prescribed by law.»

An application for re-registration of a medicinal product shall be submitted to the MoH no earlier than one year, but no later than 90 calendar days before the expiry of the registration certificate. If the application is submitted after the specified period, re-registration shall be carried out under the procedure provided for state registration of a medicinal product in accordance with clause 10 of the Resolution of the Cabinet of Ministers of 18 March 2015 No. 125 "On Amendments to the Procedure for State Registration (Re-registration) of Medicinal Products".

It should be noted separately that the date of receipt of the application from the Ministry of Health of Ukraine by the Center is considered to be the date of the referral letter from the Ministry of Health of Ukraine.

Regulatory references: http://zakon3.rada.gov.ua/laws/show/125-2015-%D0%BF

Regarding the submission of an RMP upon re-registration of medicinal products (hereinafter – medicinal products) in Ukraine, if no RMP was compiled at the time of registration of the medicinal product and the benefit/risk ratio of the medicinal product has not changed, as reflected in the Addendum to the Clinical Data Review (hereinafter – CDR) and in the regularly updated safety report (hereinafter – RUSR) of the medicinal product.

In accordance with subparagraph 13 of paragraph 1 of Annex 15 to the Procedure, the documents to be submitted for re-registration of a medicinal product shall include an RMP (if applied*). The RMP is mandatory for submission after 2 years from the date of entry into force of the Procedure. Until the specified period, the RMP is submitted if available. The RMP is not submitted for medicinal products originating from EU countries and re-registered in the territory of the EU before June 2012, except in cases where an RMP is required based on the results of the conducted benefit/risk assessment.

During re-registration of a medicinal product, the RMP is provided as part of the re-registration materials together with the PSUR or RMP update, if during the preparation of one of the documents there is a need to generate/make changes to the RMP (due to new safety concerns or the receipt of new data). In this case, the RMP must reflect the conclusions of the RMP update (for example, if a new signal is assessed in the RMP update as an important identified or important potential risk, this risk must be included as a safety concern in the RMP (its updated version) submitted together with the RMP update).

For medicinal products that do not have an RMP, the applicant must maintain a safety specification file for the medicinal product:

− important identified risks,

− important potential risks, and

− missing information in order to support and prepare the RMP update/PSUR.

We draw the applicant's attention to the fact that, in accordance with subparagraph 8.2 of paragraph 1 of module 1 of appendix 6 to the Procedure, the RMP or its updated version must also be provided in the following cases:

− in the case of changes requiring a new registration, in particular a new pharmaceutical form, a new route of administration, a new manufacturing process for a biotechnological medicinal product, paediatric indications and other significant changes in the indications;

− upon the emergence of new data affecting the benefit/risk balance of medicinal products, the current specification, the pharmacovigilance plan, risk minimisation measures or their effectiveness, or within 60 days after important results regarding pharmacovigilance or risk minimisation are obtained;

− at the request of the Center within 60 days after the request is provided.

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

For the state re-registration procedure of a finished medicinal product, three copies of the registration dossier are submitted to the Center for expert evaluation of the safety of the medicinal product; expert evaluation of the instructions and nomenclature; expert evaluation of the efficacy of the medicinal product. By agreement with the Center, certain parts of the registration dossier may be submitted in electronic form.

For traditional medicinal products, homeopathic medicinal products that comply with the requirements of Annex 7 to the Procedure for Conducting Expert Evaluation of Registration Materials, approved by MoH order No. 460 of 23.07.2015, and medicinal products belonging to the group "Medical Gases" – two copies of the registration dossier for expert evaluation of the safety of the medicinal product; expert evaluation of the instructions and nomenclature.

For medicinal products manufactured in accordance with approved formulations, one copy of the registration dossier is provided for the expert evaluation of the instructions and nomenclature.

In accordance with the Procedure for conducting the expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as the expert evaluation of materials on amendments to registration materials during the validity of the registration certificate (Order of the Ministry of Health of Ukraine 26.08.2005 No. 426 (as amended by the order of the Ministry of Health of Ukraine of 04.01.2013 No. 3) the following documents must be returned:

• Original draft of amendments to the instructions for medical use of the medicinal product and/or amendments to the summary of product characteristics (if available);
• Updated instructions for medical use and/or summary of product characteristics (if available)* with a letter of guarantee;
• Original draft of amendments to the MQC (if necessary)

*The original of the updated instructions for medical use is provided (each page numbered, stamped or initialled by the applicant's representative) + three copies of this original.

In accordance with the Procedure for conducting the expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as the expert evaluation of materials on amendments to registration materials during the validity of the registration certificate (Order of the Ministry of Health of Ukraine 26.08.2005 No. 426 (as amended by the order of the Ministry of Health of Ukraine of 23.07.2015 No. 460) the following documents must be returned:

• Original draft of amendments to the instructions for medical use of the medicinal product and/or amendments to the summary of product characteristics;
• Original draft of amendments to the MQC;
• Original of the draft amendments to the text of the labelling of the primary, secondary (if any) packaging of the finished medicinal product (if necessary) and additionally three copies with the "live" stamp of the Department of Expert Evaluation of Instructions and Nomenclature;
• Updated instructions for medical use and/or summary of product characteristics (if available)* with a letter of guarantee;
• Updated MA** with the text of the labelling of the primary, secondary (if any) packaging of the finished medicinal product (if necessary) with a letter of guarantee

*The original of the updated instructions for medical use is provided (each page numbered, stamped or initialled by the applicant's representative) + three copies of this original.

** The original of the MA is provided (each page numbered, stamped or endorsed by the applicant's representative) + three copies of this original with the Labelling to the MA attached

This change is classified as a type II B.I. x) other changes.

Regulatory references: in accordance with Annex 26 to the Procedure approved by order of the Ministry of Health of Ukraine No. 426 of August 26, 2005 (as amended by order of the Ministry of Health of Ukraine No. 460 of July 23, 2015). http://zakon5.rada.gov.ua/laws/show/z1210-15

In the case of making changes of type IA or IB, or type II to the registration dossier of one medicinal product, the registration form must concern only one change of type IA or IB, or type II. In the case of simultaneous making of several changes of type IA or IB, or type II, a separate registration form is submitted for each change, which must contain references to the other registration forms for making changes.

Regulatory references: in accordance with Chapter VI of the Procedure approved by order of the Ministry of Health of Ukraine No. 426 of August 26, 2005 (as amended by order of the Ministry of Health of Ukraine No. 460 of July 23, 2015). http://zakon5.rada.gov.ua/laws/show/z1210-15

This change is classified as a type IA change A.5. Change of the name and/or address of the site of activity of the manufacturer/importer of the finished medicinal product, including batch release sites or the site of quality control) an activity for which the manufacturer/importer is responsible, including batch release.

This change is classified as a type IA change B.I.8. Introduction of or changes to the summary of the pharmacovigilance system a) maintenance of the summary of the pharmacovigilance system, change of the qualified person responsible for pharmacovigilance; the applicant's contact person for pharmacovigilance for the conduct of pharmacovigilance in Ukraine, if different from the qualified person responsible for pharmacovigilance (including contact details) and/or changes in the location of the pharmacovigilance system master file.

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

When the applicant (holder of the registration certificate) changes, the new applicant (successor) must submit to the Center the documents listed in Annex 28 to the Procedure for the expert evaluation of registration materials, approved by MoH order No. 460 of 23.07.2015.

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

This change is qualified as a type IAinp B.II.g.1 e) variation – introduction of changes to the dossier following the update of the general monograph on the finished pharmaceutical form in the State Pharmacopoeia of Ukraine/European Pharmacopoeia*.

Regulatory references: in accordance with Annex 26 to the Procedure approved by order of the Ministry of Health of Ukraine No. 426 of August 26, 2005 (as amended by order of the Ministry of Health of Ukraine No. 460 of July 23, 2015). http://zakon5.rada.gov.ua/laws/show/z1210-15

In accordance with Annexes 17 and 26 to the Procedure for the expert evaluation of materials on medicinal products submitted for state registration (re-registration), as well as the expert evaluation of materials on the introduction of changes to registration materials during the validity of the registration certificate, approved by order of the Ministry of Health of Ukraine No. 426 of 26.08.2005 (as amended by order of the Ministry of Health of Ukraine No. 460 of 23.07.2015) (hereinafter referred to as the Procedure), a change of the address of the place of business of the manufacturer of the API and/or the finished medicinal product, resulting from the implementation of the Law of Ukraine of 09.04.2015 "On the Condemnation of the Communist and National Socialist (Nazi) Totalitarian Regimes in Ukraine and the Prohibition of the Propaganda of Their Symbols", requires the introduction of changes to the materials of the registration dossier in accordance with the Procedure.

"For type IB changes, the applicant must notify, in accordance with the legislation, of the introduction of such changes before their implementation" in accordance with paragraph 10 of Chapter VI of the Procedure for Conducting Expert Evaluation of Registration Materials, approved by MoH order No. 460 of 23.07.2015.

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

In accordance with paragraph 10 of Section VI "Procedure for conducting expert evaluation of materials on amendments to the materials of the registration dossier for a medicinal product" of the Procedure for conducting expert evaluation of materials on medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity period of the registration certificate, approved by order of the Ministry of Health of Ukraine of 26.08.2005 No. 426 as amended, if the applicant makes type IA amendments to the materials of the registration dossier, the applicant may, at its discretion, notify in accordance with the legislation of the introduction of such amendments no later than 12 months after the applicant implements these amendments. This does not apply to type IAin amendments (type IA amendments with immediate notification). For these amendments, the applicant must notify in accordance with the legislation of the introduction of such amendments immediately after their implementation, indicating the date.

In accordance with Annex 17 to the Procedure for expert evaluation of materials on medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order of the Ministry of Health of Ukraine dated 26.08.2005 No. 426 as amended, in the procedure for introducing amendments under item A.5. Change of the name and/or address of the place of activity of the manufacturer/importer of the finished medicinal product, including batch release sites or the place of quality control, the following documents shall be submitted:

1. A copy of the updated manufacturing licence (if, in accordance with the legislation of the manufacturer's country, the manufacturing licence exists only in electronic form (for example, in the USA), a printout with a reference to the relevant official website, certified by the signature/seal (if any) of the applicant, shall be submitted) or another permit document for the manufacture of the declared dosage form in the manufacturer's country, in which the new name and/or new address is indicated.

2. Amendments to the relevant sections of the registration dossier, including updated: summary of product characteristics, instructions for medical use and text of labelling on the packaging (if necessary).

That is, a document issued by the State Service of Ukraine on Medicines and Drugs Control confirming compliance of production conditions with the requirements of good manufacturing practice is not required.

Medicinal products that are registered, re-registered:

In accordance with the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate (Order of the Ministry of Health of Ukraine 26.08.2005 No. 426 (as amended by the order of the Ministry of Health of Ukraine dated 04.01.2013 No. 3)

Annex 1

A title page to the amendments to the "Labelling to the registration certificate" is envisaged

Medicinal products that are registered, re-registered:

in accordance with the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate (Order of the Ministry of Health of Ukraine 26.08.2005 No. 426 (as amended by the order of the Ministry of Health of Ukraine dated 23.07.2015 No. 460)

Annex 2

Currently, it is not possible to submit a registration procedure for the correction of a technical error in eCTD format. In view of the above and taking into account the recommendations of EU countries, the correction of spelling and/or grammatical errors, including in transliteration, errors related to incorrect translation, and discrepancies within a single document is possible by submitting minor changes of type IA. The classification of these changes depends on the nature of the inaccuracies and the document in which the changes are made.

Yes, if the changes are made to one document of the registration dossier, these technical errors are indicated in the registration form, and they are purely technical in nature (for example, incorrect translation, grammatical errors).

The English translation of the Procedure for Conducting Expert Evaluation of Registration Materials for Medicinal Products, approved by MoH order of 23.07.2015 No. 460, has been published on the official website of the Center at the link https://dec.gov.ua/?ZG93bmxvYWQ=L21hdGVyaWFscy9vcmRlc0yNi0wOC0yMDA1LTQyNi00NjAv

The MoH order of 26.08.2015 No. 426, as amended by the MoH order of 23.07.2015 (new approved version), has been published at the link http://zakon5.rada.gov.ua/laws/show/z1210-15

In accordance with the requirements of Guideline ST-N MoHU 42-7.1:2016 "Medicinal products. Bioequivalence studies" or CPMP/EWP/QWP/1401/98 Rev.1 Guideline on the Investigation on Bioequivalence, p. 4.3.2., the applicant is obliged to provide a statement confirming the absence of changes in the composition of the investigational medicinal product, in the manufacturing process, etc., that could affect the bioavailability of the claimed medicinal product.

Section 2.7.1. must be compiled in accordance with the requirements of Appendix IV of Guideline ST-N MoHU 42-7.1:2016 "Medicinal products. Bioequivalence studies", Appendix IV of the Guideline on the Investigation on Bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1). Please note that the information must be presented for each study.

In vivo bioequivalence studies for additional dosage strengths of modified-release medicinal products shall be conducted in accordance with the requirements of EMA/CHMP/EWP/280/96 "Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms (EMA/CPMP/EWP/280/96 Corr1)".

The investigational medicinal product should generally be taken from a batch whose size is at least 1/10 of the largest production batch (if several production batch sizes exist) or 100 000 units, whichever is greater, unless otherwise justified by the applicant.

If the production batch size is less than 100000 units, a full production batch must be used for the bioequivalence study.

In a bioequivalence study, for the main pharmacokinetic parameters, the 90% confidence interval for the ratio of the investigational and reference medicinal products must be within the acceptance range of 80,00% to 125,00%.

For highly variable medicinal products (intra-subject variability of the parameter is more than 30%), an extended acceptance range for C_max may be considered. In this case, the bioequivalence study must be conducted with a replicate design, where it must be demonstrated that the intra-subject variability for C_max of the reference medicinal product is > 30%.The applicant must justify that the calculated intra-subject variability is reliably estimated and is not the result of outliers.The requirementfor extending the interval must be pre-specified in the protocol with appropriate justification.

The possibility of extending the acceptance criteria based on high intra-subject variability does not apply to AUC; for AUC the acceptance range must remain 80.00-125.00% regardless of variability.

In accordance with the requirements of EMEA/CHMP/EWP/192217/2009 Rev. 1 Corr. 2** "Guideline on bioanalytical method validation", incurred samples reanalysis is mandatory. These requirements entered into force on 1 February 2012.

Not allowed. The similarity factor assessment is based on the results of the release of the active substance from 12 test samples and 12 reference medicinal product samples.

When selecting the reference product, the following conditions must first be followed:

1. First of all, the reference medicinal product should be a medicinal product that is an original medicinal product with proven efficacy, safety and quality.

2. In the absence of an original medicinal product in the world and/or a proven impossibility of identifying it, the following selection procedure should be followed:

2.1. first of all, a medicinal product recommended by the WHO as a reference medicinal product and information on which is posted on the official WHO website is considered;

2.2. in the absence of a WHO recommendation, a medicinal product that was registered as an innovative one on the basis of evidence of efficacy, safety and quality at the national level in countries whose regulatory authorities apply high quality standards is used as the reference medicinal product;

2.3. In the absence of the original medicinal product and/or proven impossibility of identifying it, and in case of non-compliance with paragraphs 1 and 2, a medicinal product for which the following criteria are met is used as the reference medicinal product:

a) widely documented clinical trials published in scientific journals;

b) a long and problem-free period of post-registration control.

The BSC-based biowaiver procedure is applied to medicinal products in solid dosage forms for systemic action with immediate release for oral use that have the same pharmaceutical form. At the same time, the BSC-based biowaiver procedure is not applied to sublingual, buccal medicinal products and medicinal products with modified release. For medicinal products that disperse in the oral cavity, the BSC-based biowaiver approach may be applied only when absorption in the oral cavity can be excluded.

The biowaiver procedure based on the BCS applies to immediate-release medicinal products if it has been demonstrated that the active substance exhibits high solubility and complete absorption (BCS Class I) and the medicinal product is very rapidly dissolving (> 85 % of the active substance within 15 minutes) or rapidly dissolving (85 % within 30 minutes), or the active substance exhibits high solubility and limited absorption (BCS Class III), and the medicinal product is also very rapidly dissolving (> 85 % within 15 minutes).

If multiple strengths of a medicinal product are submitted for state registration, and the biowaiver procedure based on the BCS is used to demonstrate bioequivalence, then a separate report with the relevant conclusion and a complete set of documents on the conducted studies and the results obtained must be provided for each strength.

In the case of active substances of BCS Class I, it is recommended to use a similar amount of the same excipients in the composition of the investigational medicinal product as in the reference medicinal product.

If the biowaiver procedure is applied to Class III active substances according to the BCS, the excipients must be qualitatively the same and quantitatively very similar in order to exclude different effects on membrane transporters.

The report on the bioavailability and/or bioequivalence study shall be prepared in accordance with the requirements of the guideline ICH Topic E 3 CPMP/ICH/137/95 "Structure and Content of Clinical Study Reports" and the Procedure for Conducting Clinical Trials of Medicinal Products and Expert Evaluation of Clinical Trial Materials, approved by order of the Ministry of Health of Ukraine No. 690 dated 23.09.2009, as amended by Orders of the Ministry of Health No. 523 dated 12.07.2012, No. 304 dated 06.05.2014, No. 966 dated 18.12.2014, and shall comply with the requirements of the guidelines EMA CPMP/QWP/EWP/1401/98 Rev. 1 "Guideline on the investigation of bioequivalence", EMEA/CHMP/EWP/192217/2009 Rev. 1 Corr. 2** "Guideline on bioanalytical method validation".

The sample is available on the official website of the Center in the section "Recommendations on formatting the text of packaging labelling of finished medicinal products when forming a registration dossier" at the link https://dec.gov.ua/?ZG93bmxvYWQ=L21hdGVyaWFscy9ha3R1YWxuYS1pbmZvcm1hY3ppeWEtbm9ybWF0aXZuby1wcmF2b3ZpaC1ha3Rpdi8=

During the specialized expert evaluation of the registration dossier materials, the Center may send the medicinal product submitted for registration to the authorized laboratory(ies) (AL) in accordance with the scope of accreditation for laboratory testing. Laboratory testing is carried out in accordance with the provisions of Annex 13 to the Procedure for the Expert Evaluation of Materials on Medicinal Products (as amended by MoH order No. 460) to guarantee that the control methods proposed by the applicant and set out in the registration dossier materials are reproducible.After receiving a letter containing recommendations on the need to conduct testing in an AL, the applicant submits to the Center a letter of request regarding referral to an AL, specifying which one, taking into account the availability in the AL where it wishes to conduct the testing of the appropriate equipment, reagents and reference standards, to guarantee that the control methods are reproducible. The time required for laboratory testing is not included in the timelines for expert work.

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

This is possible provided that the composition of the dosages is proportionally similar and the manufacture of the medicinal product is carried out on the same equipment under the conditions stipulated by the licence for the manufacture of this medicinal product (in accordance with the provisions of Annex 13 to the Procedure for Conducting Expert Evaluation of Materials on Medicinal Products (as amended by MoH Order No. 460).

Regulatory references: http://zakon5.rada.gov.ua/laws/show/z1210-15

Information on the possibility of conducting laboratory control for certain parameters can be found on the home page of the official website of the State Enterprise "State Expert Center" in the section "Laboratory for Quality Control of Medical Immunobiological Preparations" by viewing the Scope of accreditation of the Laboratory. For a more precise answer regarding the possibility of conducting control for individual parameters, the regulatory documentation according to which the control is to be performed must be submitted to the Laboratory for review.

Laboratory analysis is carried out within 30 working days from the date of receipt of the medicinal product samples and standards, or within the period provided for by the relevant quality control methods for MIBPs/medicinal products.

The number of samples of the medicinal product that must be submitted to the Laboratory for laboratory quality control of the medicinal product, as well as the list and quantity of standard samples and reagents required for laboratory control, if they are not available in the Laboratory, are specified in the request letter which the Applicant receives from the Records Management Department of the State Expert Center of the MoH.

Information on the cost of laboratory control for the parameters included in the scope of accreditation of the Laboratory is available on the official website of the State Expert Center of the MoH in the section "REGULATORY AND LEGAL ACTS" (Contract forms, cost of services).

If laboratory testing cannot be carried out after the analysis of information has been performed, the Laboratory notifies the Applicant in writing. If a request is sent to the Laboratory again, the analysis process is repeated, taking into account the new or changed requirements of the Customer.

Procedure for state quality control of medicinal products/medical immunobiological preparations at the Laboratory.

State quality control of medicinal products/medical immunobiological preparations is carried out by the Laboratory on the basis of a referral from the State Service of Ukraine on Medicines and Drugs Control pursuant to the order of the Ministry of Health of Ukraine of 01.10.2014 No. 698 "On Approval of the Procedure for Exercising Control over the Compliance of Immunobiological Preparations Used in Medical Practice with the Requirements of State and International Standards" and Resolution of the Cabinet of Ministers of Ukraine No. 902 of 14.09.2005 "On Approval of the Procedure for Exercising State Quality Control of Medicinal Products Imported into Ukraine".

Laboratory quality control during state control is carried out within 14 days from the date of receipt of samples and other materials, or within the period provided for by the relevant methods of quality control of medicinal products/medical immunobiological preparations.

Laboratory testing of medicinal products/medical immunobiological preparations and reproducibility of control methods during the registration procedure are carried out in accordance with the specification and control methods provided in the regulatory documentation. Laboratory testing is carried out within 45 working days from the date of receipt of samples and other materials, or within the period provided for by the relevant quality control methods for medicinal products/medical immunobiological preparations.

The applicant submits to the Laboratory the original referral F12 from the Scientific Secretary of the Center, 3 copies of the draft regulatory documentation, with the applicant's stamp and signature on the last page, and a quality certificate for the product with the manufacturer's stamp and signature. One copy of the regulatory documentation is returned to the applicant after completion of laboratory testing with stamps as confirmation of the reproducibility of the methods that were controlled.

The number of samples of the product that must be submitted to the Laboratory for laboratory quality control of the medicinal product, as well as the list and quantity of reference standards and reagents required for laboratory control, if they are not available at the Laboratory, are specified in the request letter which the Applicant receives from the Center's records management department.

Information on the possibility of performing laboratory control for certain parameters can be found on the home page of the Center's official website in the section "Laboratory for Quality Control of Medical Immunobiological Preparations" by reviewing the Laboratory's Scope of Accreditation. For a more precise answer regarding the possibility of performing control for individual parameters, the regulatory documentation according to which the control must be performed should be submitted to the Laboratory for review.

Laboratory quality control of medicinal products is performed after concluding a service agreement with the Applicant, paying for the specification, and providing the required number of samples of the medicinal product and reference standards. A sample standard service agreement is posted on the Center's official website.

Quality control/laboratory testing begins after the applicant provides the required number of medicinal product samples, reference standards/reagents, delivered in compliance with the "cold chain" conditions and after full payment of the cost of the work.

The Laboratory for Quality Control of Medical Immunobiological Preparations works with the following types of referrals:

– Registration procedures (under referrals from the Center, Ф12);

– State control (under referrals from the State Service of Ukraine on Medicines and Drugs Control, Ministry of Health of Ukraine);

– By letter from the manufacturer/applicant.

Medicinal products released into circulation during the period in which the medicinal product was authorized for use in Ukraine may be used in Ukraine until the expiry of their shelf life determined by the manufacturer and indicated on the packaging.

Regulatory references: Article 9 of the Law of Ukraine "On Medicinal Products" http://zakon5.rada.gov.ua/laws/show/123/96-%D0%B2%D1%80

Although the deadline for fulfilling the obligations has expired, the applicant must fulfil them. Depending on when this document is provided, it must cover the period:

– from the data lock point of the last periodically updated safety report that was provided as part of the documents during the re-registration of the medicinal product up to 90 days before submission of the application for amendments under clause B.I.11, in accordance with Annex 17 to the Procedure for expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order of the Ministry of Health of Ukraine No. 426 of 26 August 2005, registered with the Ministry of Justice of Ukraine under No. 1210/27655 of 07 October 2015 (as amended by order of the Ministry of Health of Ukraine No. 460 of 23 July 2015)) (hereinafter – the Procedure);

– from the date of registration/penultimate re-registration to 90 days before submission of the application for amendments under paragraph B.I.11, in accordance with Annex 17 to the Procedure.

The authorized person responsible for pharmacovigilance and/or the contact person responsible for pharmacovigilance in Ukraine must have a higher medical or pharmaceutical education (pharmacist, clinical pharmacist). If only a higher pharmaceutical education is held, the QPPV/contact person for pharmacovigilance in Ukraine must be able to consult a person with a higher medical education (if necessary).

Regulatory references: subparagraph 1 of paragraph 2 of chapter 1 of section V of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

If the document describing the applicant's pharmacovigilance system is a pharmacovigilance system master file, an application for changes of type B.1.8, IАнп is submitted. If the document describing the pharmacovigilance system is a detailed description of the pharmacovigilance system, an application for changes of type B.1.9 (a-d), IАнп is submitted.

Regulatory references: Annex 17 to the Procedure for expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order of the Ministry of Health of Ukraine of 26 August 2005 No. 426 (as amended by order of the Ministry of Health of Ukraine of 23 July 2015 No. 460).

An adverse reaction is considered unexpected if its nature or severity is not consistent with the available information about the medicinal product, vaccine, tuberculin specified in the instructions for medical use/summary of product characteristics of the medicinal product, vaccine, tuberculin.

Regulatory references: Section I of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine No. 898 dated 27 December 2006, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine No. 996 dated 26 September 2016).

An adverse reaction is considered expected if the nature or severity of its manifestations is consistent with the available information about the medicinal product, vaccine, or tuberculin specified in the instructions for medical use/summary of product characteristics of the medicinal product, vaccine, or tuberculin.

Regulatory references: Section I of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine No. 898 dated 27 December 2006, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine No. 996 dated 26 September 2016).

The requirements for dossier materials depending on the procedure are clearly set out in the Procedure for conducting the expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as the expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order of the Ministry of Health of Ukraine No. 426 of 26 August 2005, (as amended by order of the Ministry of Health of Ukraine No. 460 of 23 July 2015) (hereinafter referred to as the Procedure). In accordance with subparagraphs 1.8.1 of Annex 6 to the Procedure, the applicant must provide a brief description of the pharmacovigilance system, including evidence that it has at its disposal a qualified person responsible for pharmacovigilance (QPPV) and/or a contact person responsible for pharmacovigilance (hereinafter referred to as the CPRP).

When providing the contact details of the QPPV and/or CPRP, it is necessary to state the surname, given name, patronymic, postal address of the place where pharmacovigilance activities are carried out, telephone (landline, mobile — available around the clock), fax, and e-mail. The QPPV/CPRP in Ukraine must have a higher medical or pharmaceutical education (pharmacist, clinical pharmacist). If only a higher pharmaceutical education is held, the QPPV/CPRP in Ukraine must be able to consult a person with a higher medical education (if necessary).

Information on the qualifications and work experience of the QPPV/Deputy QPPV must also be provided. According to clause 1.4 of Annex 15 to the Procedure, this information may be presented in the form of a biographical note, documentary confirmation of qualifications (a copy of the education diploma), or job description.

In addition, the location where the applicant's main pharmacovigilance activities are carried out must be indicated, namely: the full actual postal address, telephone number, and e-mail address must be specified (it often coincides with the location of the applicant's head office, but may differ from it).

When providing information on the pharmacovigilance system master file, the postal and/or e-mail address where it is kept and its number, if available, must be indicated.

The documents submitted must include a letter of guarantee from the applicant confirming that it has the necessary resources to perform the tasks and obligations relating to pharmacovigilance in Ukraine, in accordance with the legislation, indicating the location where the pharmacovigilance system master file is kept and its number, if available.

An example of what a brief description of the applicant's pharmacovigilance system should look like can be found at the link: http://www.apteka.ua/article/392009.

Regulatory references: subparagraph1.8.1 of Annex 6, clause 1.4 of Annex 15 to the Procedure for expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order of the Ministry of Health of Ukraine of 26 August 2005 No. 426 (as amended by order of the Ministry of Health of Ukraine of 23 July 2015 No. 460).

Subparagraph 1 of clause 2 of Chapter 1 of Section V of the Procedure for pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

The summary data on the safety of the medical use of the medicinal product in Ukraine for the period of validity of the latest registration certificate shall reflect: the number of adverse reactions, sales volume (completed at the request of the Center), and the medicinal product exposure indicator (the exposure indicator is specified in accordance with the indicator specified in section "Calculation of exposure and regimens of use" of the Addendum to the clinical data review in accordance with subparagraph 2.3 of paragraph 2 of Annex 15 to the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order of the Ministry of Health of Ukraine dated 26 August 2005 No. 426, registered with the Ministry of Justice of Ukraine on 07 October 2015 under No. 1210/27655 (as amended by order of the Ministry of Health of Ukraine dated 23 July 2015 No. 460), or in section V "Assessment of exposure and regimens of use" of the latest generated periodically updated safety report of the medicinal product in accordance with the requirements of Annex 12 to the Procedure for pharmacovigilance, approved by order of the Ministry of Health of Ukraine dated 26 September 2016 No. 996).

Regulatory references: Annex 13 to the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine No. 898 of December 27, 2006, registered with the Ministry of Justice of Ukraine on December 19, 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine No. 996 of September 26, 2016).

Statistics on patient-years (or person-years) are often used in clinical trials and statistical risk assessments.

As an example, if 15 patients participated in a study on the assessment of heart attacks over 20 years, then such a study included 300 patient-years (15 x 20). This number can be divided by the number of patients in whom a certain condition or event was observed. For example, six cases of heart attack are equivalent to one heart attack per every 50 patient-years of the study (300/6 = 50).

a) a request for information on cases of adverse reactions and/or lack of efficacy of a medicinal product shall be submitted by the applicant addressed to the Director of the State Expert Center of the MoH in free form.

b) the letter must state:

– information about the medicinal product – the trade name of the medicinal product, dosage form, strength (dose of the preparation);

– information about the applicant of the medicinal product, the manufacturer, the number of the registration certificate;

– the period for which information on adverse reactions (ARs) of the medicinal product must be obtained;

– the grounds for providing the information, for example, for conducting a safety data analysis, for preparing a periodically updated safety report, etc.

You can find the updated safety information specified in the package leaflet for the original (reference) product, approved by the relevant Order of the Ministry of Health of Ukraine, on:

– the website of the State Register of Medicinal Products of Ukraine http://www.drlz.kiev.ua /;

– the website of the State Expert Center of the MoH http://www.dec.gov.ua / under the heading "State Register of Medicinal Products of Ukraine"

Changes to the summary of the pharmacovigilance system relate to changes subject to immediate notification in accordance with clause B.1.8 of Annex 26 to the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by MoH order No. 426 dated 26.08.2005 (as amended by MoH order No. 460 dated 23.07.2015) (hereinafter referred to as the Procedure).

In accordance with clause 10 of Chapter VI of the Procedure, for the introduction of such changes the applicant must notify immediately after their implementation, indicating the date. This is due to existing cases of late submission by the applicant of such changes. Accordingly, at the stage of expert evaluation of the registration dossier materials during the re-registration procedure or the introduction of other changes, a need is identified to introduce changes to the pharmacovigilance system, which the applicant is recommended to make. The specialized expert evaluation of the declared changes is carried out simultaneously with the expert evaluation of the materials for re-registration of the medicinal product.

There are cases when such changes cannot be made due to the expiry of the registration certificate. Given that changes to the pharmacovigilance system do not affect the benefit/risk balance, in accordance with paragraph 9 of Chapter IV of the Procedure, the medicinal product may be recommended for re-registration for 5 years

Regulatory references: https://zakon.rada.gov.ua/laws/show/z1210-15

A clinical expert statement is a document provided as part of the documents for the re-registration procedure together with an addendum to the clinical data review. This document must contain confirmation that:

– there are no new clinical data that could change or lead to a new assessment of the risk/benefit balance;

– the medicinal product, after the expiry of the 5-year period following registration, may be re-registered for an unlimited period, or all recommended or initiated measures must be specified and justified;

– the competent authority has been informed of all important additional data relevant to the assessment of the benefit/risk balance of the medicinal product;

– the information on the medicinal product provided in the draft updated package leaflet for medical use, for approval in Ukraine, is current and consistent with contemporary scientific knowledge about the medicinal product.

More information: order of the Ministry of Health of Ukraine dated 26 August 2005 No. 426 (as amended by the order of the Ministry of Health of Ukraine dated 23 July 2015 No. 460) http://zakon2.rada.gov.ua/laws/show/z1210-15

The causal relationship between the clinical manifestations of any adverse reaction/adverse event following immunization/tuberculin diagnostics and the use of a medicinal product, vaccine, tuberculin is defined as: "a degree determined by an acceptable method (the World Health Organization qualitative methodology, the Naranjo scale, the binary method, etc.) according to certain criteria and indicating the interconnection/relationship of the observed adverse reaction/adverse event following immunization/tuberculin diagnostics with the use of a medicinal product, vaccine, tuberculin".

Regulatory references: Section I of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine No. 898 dated 27 December 2006, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine No. 996 dated 26 September 2016).

Adverse reaction – any unintended and harmful reaction to a medicinal product; any unintended and harmful reaction to a vaccine, tuberculin, if it is caused or accelerated by the active component (one of the other components) or is associated with irregularities arising in the manufacturing process of the vaccine, tuberculin, including the administration device provided by the manufacturer;

Regulatory references: paragraph 2 of Chapter I of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

After completing the report and sending it to the State Expert Center of the MoH, you can print the report as a form, save it in pdf format on your computer, and also print the "Report on sending the notification to the SEC". If problems arise, you can contact us by e-mail: aisf@dec.gov.ua.

The applicant must provide information on cases of adverse reactions to a medicinal product, vaccine, tuberculin, and/or lack of efficacy of a medicinal product, and/or an adverse event following immunization/tuberculin diagnostics to the Pharmacovigilance Department of the Center, in accordance with the requirements of Chapter 2 of the Section of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

The applicant may provide information on the specified cases to the Center's e-mail in the appropriate format (for example, pdf) at cioms@dec.gov.ua (for medicinal products) and sayenko@dec.gov.ua (for medical immunobiological preparations), or using https://aisf.dec.gov.ua/Account/LogOn, which eliminates the need to submit paper report forms.

Information about cases of adverse reactions to a medicinal product, vaccine, tuberculin, and/or lack of efficacy of a medicinal product, and/or an adverse event following immunization/tuberculin diagnosis must be analyzed by the applicant, entered into the database and taken into account when analyzing safety data.

If an Addendum to the clinical data review is provided as part of the re-registration materials, information about an independent clinical expert must also be provided.

Regulatory references: Annex 15 to the Procedure for expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order of the Ministry of Health of Ukraine dated 26 August 2005 No. 426 (as amended by order of the Ministry of Health of Ukraine dated 23 July 2015 No. 460).

A copy of the notification card is submitted to the responsible person for pharmacovigilance of the healthcare institution. This is required for drawing up a report under form No. 69 in accordance with paragraphs 2 and 3 of paragraph 4 of Section IV of the Procedure for Pharmacovigilance (as amended by MoH order No. 996 of September 26, 2016).

Regulatory references: paragraph 9 of Section IV of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine No. 898 of December 27, 2006, registered with the Ministry of Justice of Ukraine on December 19, 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine No. 996 of September 26, 2016).

When registering any medicinal product in Ukraine, except for traditional herbal and homeopathic medicinal products registered under a simplified procedure, as well as medicinal products belonging to the group "Medical gases", the applicant must provide a Risk Management Plan or its updated version, which must be submitted as a separate document (separate volumes in paper or electronic form) in accordance with the structure provided for by legislation, regardless of whether the medicinal product was registered in the EU and underwent re-registration in the EU before 2012 or not.

During re-registration in Ukraine, the RMP is not submitted for a medicinal product originating from EU countries and re-registered in the territory of the EU before June 2012, and if no new important risks are identified in accordance with the submitted addendum to the clinical data review. An exception is cases where the RMP is required based on the results of the conducted benefit/risk assessment.

More information: order of the Ministry of Health of Ukraine dated 26 August 2005 No. 426 (as amended by the order of the Ministry of Health of Ukraine dated 23 July 2015 No. 460) http://zakon2.rada.gov.ua/laws/show/z1210-15

At the following link: https://aisf.dec.gov.ua/ you can access the website supporting the process of monitoring adverse reactions or lack of efficacy of medicinal products in Ukraine in the Automated Information System for Pharmacovigilance (AISF) and complete the electronic form "Report on adverse reactions (AR) and/or lack of efficacy (LE) of a medicinal product (MP), vaccine, tuberculin and an adverse event following immunization (AEFI)". To complete the reporting card, AISF user authorization is not required.

Yes, it is necessary, in accordance with the requirements of the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by MoH order No. 426 dated 26.08.2005 (as amended by MoH order No. 460 dated 23.07.2015), by declaring the relevant changes taking into account the data that became the basis for generating/updating the RMP.

No, in accordance with the requirements of Annex 13 to the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996), in column 2 of the table of summary data on the safety of medical use of a medicinal product in Ukraine for the period of validity of the latest registration certificate, data should be provided on the number of adverse reactions (serious/non-serious) (the ratio of serious/non-serious adverse reactions reported to the applicant (or its representative) in the territory of Ukraine is indicated, except for information received from the State Enterprise "State Expert Center of the Ministry of Health").

Regulatory references: Annex 13 to the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine No. 898 of December 27, 2006, registered with the Ministry of Justice of Ukraine on December 19, 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine No. 996 of September 26, 2016).

If the applicant is located in Ukraine, the QPPV must be on the applicant's staff. If the applicant is not located in Ukraine, a single LPPV in Ukraine, subordinate to the applicant's QPPV, must be designated in the territory of Ukraine. The LPPV must have an appropriate document confirming its appointment and authority. Data on the QPPV and the LPPV in Ukraine must be contained in the applicant's PSMF.

Regulatory references: paragraph 9 of Section II, subparagraph 1 of paragraph 2 of Chapter 1 of Section V of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

During the registration of any medicinal product, except traditional herbal and homeopathic medicinal products registered under the simplified procedure, and medicinal products belonging to the group "Medical gases", the Risk Management Plan must be submitted in the format of a separate document (separate volumes on paper or electronic media) in accordance with the structure provided for by legislation.

Regulatory references: Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order 26 August 2005 No. 426 (as amended by the order of the Ministry of Health of Ukraine of 23 July 2015 No. 460), registered with the Ministry of Justice of Ukraine on 07 October 2015 under No. 1210/27655.

Information on identified cases of lack of efficacy of a medicinal product, if they were recorded in the territory of another country and became known to the applicant, must be provided by the applicant as part of the next periodically updated safety report of the medicinal product authorized for medical use.

Regulatory references: subparagraphs 7 of paragraph 1 of chapter 2 of section V of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by the order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

The Addendum to the Clinical Data Review is submitted for all medicinal products, except traditional medicinal products, homeopathic medicinal products that comply with the requirements of Annex 7 to the Procedure (order of the Ministry of Health of Ukraine No. 460), and medicinal products belonging to the group "Medical gases", as part of the registration dossier materials submitted for the re-registration procedure.

Regulatory references: paragraph 2.3 of Annex 15 to the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order of the Ministry of Health of Ukraine of 26 August 2005 No. 426 as amended.

As part of the documents for the re-registration procedure, the Addendum to the Clinical Data Review must be submitted. Submission of this document is mandatory, since the transitional period provided for by the Procedure for conducting expert evaluation of registration materials for medicinal products (order of the Ministry of Health No. 460) has expired.

More information: order of the Ministry of Health of Ukraine dated 26 August 2005 No. 426 (as amended by the order of the Ministry of Health of Ukraine dated 23 July 2015 No. 460) http://zakon2.rada.gov.ua/laws/show/z1210-15

Yes, the risk management plan may be submitted in English. If the risk management plan is submitted in English, Parts V "Risk Minimisation Measures" and VI "Summary of the Risk Management Plan" shall be submitted in Ukrainian translation. Module CVIII "Summary of Safety Concerns", Part III "Pharmacovigilance Plan", Part IV "Plans for Post-authorisation Efficacy Studies" shall be submitted in Ukrainian translation at the request of the Center. The description of the applicant's pharmacovigilance system used by the applicant in respect of one

Regulatory references: paragraph 6 of chapter 4 of section V of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

The requirements for the procedure for submitting the Clinical Expert Statement have not changed: the Clinical Expert Statement is submitted together with the Addendum to the Clinical Data Review in accordance with paragraph 2.3 of Annex 15 to the Procedure for Conducting Expert Evaluation of Registration Materials for Medicinal Products Submitted for State Registration (Re-registration), as well as Expert Evaluation of Materials on Amendments to Registration Materials During the Validity of the Registration Certificate, approved by MoH order of 26.08.2005 No. 426 (as amended by MoH of Ukraine order of 23.07.2015 No. 460) (hereinafter referred to as the Procedure),

The Clinical Expert Statement may be requested separately in the event of:

– its absence from the Addendum to the Clinical Data Review;

– detection of errors in it or non-compliance of its content with the requirements provided for by the Procedure.

Regulatory references: https://zakon.rada.gov.ua/laws/show/z1210-15

Yes, unless otherwise specified as a condition for issuing the registration certificate. Where appropriate, a risk management plan (RMP) may be drawn up for medicinal products, vaccines containing the same APIs, belonging to the same applicant and which may fall under (be the subject of) a single RMP. If the RMP concerns more than one medicinal product, vaccine, tuberculin, the RMP summary is drawn up for each medicinal product, vaccine, tuberculin.

Regulatory references: paragraph 5, paragraph 8 of chapter 4 of section V of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

The Addendum to the Clinical Data Review is submitted for all medicinal products, except traditional medicinal products, homeopathic medicinal products that comply with the requirements of Annex 7 to the Procedure (order No. 460), and medicinal products belonging to the group "Medical gases" as part of the registration dossier materials submitted for the re-registration procedure.

Regulatory references: paragraph 2.3 of Annex 15 to the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order 26 August 2005 No. 426 (as amended by the order of the Ministry of Health of Ukraine of 23 July 2015 No. 460), registered with the Ministry of Justice of Ukraine on 07 October 2015 under No. 1210/27655.

The description of the applicant's pharmacovigilance system, which is used by the applicant in relation to one or more medicinal products, vaccines, tuberculin, is provided in the pharmacovigilance system master file (PSMF). This document is compiled in accordance with the structure given in Annex 11 to the Procedure for pharmacovigilance (as amended by the MoH order of 26 September 2016 No. 996), and contains information on:

1 the applicant's qualified person responsible for pharmacovigilance and/or the contact person responsible for pharmacovigilance;

2) the organizational structure of the applicant, including a pharmacovigilance system that ensures the collection, identification, evaluation and submission of reliable information on adverse reactions, lack of efficacy, SUI, as well as any other data necessary for assessing the risk and benefit of the use of a medicinal product, vaccine, tuberculin;

3) natural and/or legal persons engaged by the applicant to carry out pharmacovigilance;

4) sources of information on the safety of the use of medicinal products, vaccines, tuberculin;

5) a list and brief functional description of the databases used by the applicant in carrying out pharmacovigilance;

6) pharmacovigilance processes, including a list of standard operating procedures used in carrying out pharmacovigilance, a description of pharmacovigilance documentation, including documentation kept in the archive, and other types of documentation relating to the carrying out of pharmacovigilance;

7) the effectiveness of the pharmacovigilance system;

8) a quality system in pharmacovigilance, including a description of the applicant's personnel training system, indicating information about training, taking into account the functional duties of the applicant's personnel, and providing a concise description of the applicant's obligations to ensure the quality of the pharmacovigilance system audit, including an audit of the pharmacovigilance system and an audit of the natural and/or legal persons engaged by the applicant to carry out pharmacovigilance.

Regulatory references: subparagraph 1 of paragraph 2 of chapter 1 of section V of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

Information on the safety and efficacy of medicinal products, vaccines, tuberculin may be provided to the Center by:

1) healthcare professionals;

2) legal entities and natural persons engaged in economic activity in medical practice;

3) healthcare institutions;

4) applicants;

5) patients and/or their legal representatives, using the notification card form for the provision by a patient and/or their legal representative of information on an adverse reaction to a medicinal product, vaccine, tuberculin, and/or lack of efficacy of a medicinal product, and/or an adverse event following immunization/tuberculin diagnostics, as set out in Annex 2 to this Procedure;

6) the State Service of Ukraine on Medicines and Drugs Control and its territorial bodies;

7) representatives of the Center for pharmacovigilance matters in administrative-territorial units

a) payment is made when the Center provides detailed information on cases of adverse reactions and/or lack of efficacy of a medicinal product in the form of information notices, in cases where the applicant states in a letter of request to the Center that the information is needed for conducting safety data analysis, for preparing a periodically updated safety report, etc.;

b) the information provided by the Center on the number of cases of adverse reactions and/or lack of effectiveness of a medicinal product without providing detailed information on cases of adverse reactions and/or lack of effectiveness of a medicinal product and information notices does not require payment.

"...Information on an adverse reaction to a medicinal product, vaccine, tuberculin, and/or lack of effectiveness of a medicinal product, and/or an adverse event following immunization/tuberculin diagnosis shall be entered by the physician into the primary accounting medical documentation...".

Regulatory references: paragraph 10 of Chapter IV of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

A risk management plan or its updated version must be submitted as a separate document (separate volumes in paper or electronic form) in accordance with the structure provided for by legislation, in the following cases:

– upon registration of any medicinal product, except traditional herbal and homeopathic medicinal products registered under a simplified procedure, as well as medicinal products belonging to the group "Medical gases";

– upon re-registration of any medicinal product, except traditional herbal and homeopathic medicinal products that comply with the requirements of Annex 7 to the Procedure, and medicinal products belonging to the group "Medical gases". An RMP is not submitted for medicinal products originating from EU countries and re-registered in the EU territory before June 2012, except in cases where an RMP is required based on the results of the benefit/risk assessment:

– in case of changes requiring a new registration, in particular a new pharmaceutical form, a new route of administration, a new manufacturing process for a biotechnological medicinal product, paediatric indications and other significant changes in indications;

– when new data emerge that affect the benefit/risk balance of medicinal products, the current specification, the pharmacovigilance plan, risk minimisation measures or their effectiveness, or within 60 days after important results regarding pharmacovigilance or risk minimisation are obtained;

– at the request of the Center within 60 days after the request is provided.

Regulatory references: paragraph 4 of Section IV, paragraph 1.8.2 of Annex 6, paragraph 1.13 of Annex 15 to the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order of the Ministry of Health of Ukraine of 26 August 2005 No. 426 (as amended by order of the Ministry of Health of Ukraine of 23 July 2015 No. 460), registered with the Ministry of Justice of Ukraine on 07 October 2015 under No. 1210/27655.

The person responsible for pharmacovigilance at a healthcare institution shall compile and provide to the person responsible at the structural healthcare unit consolidated data on cases of adverse reactions following the use of vaccines and tuberculin, monthly by the 05 day of the month following the reporting month, in the form set out in Appendix 3 to the Procedure. If this deadline falls on a weekend or public holiday, the consolidated data on cases of adverse reactions following the use of vaccines and tuberculin shall be provided on the first working day thereafter. The consolidated data shall be submitted in paper and electronic form together with a covering letter signed by the head of the healthcare institution to the postal and electronic addresses of the relevant structural healthcare unit.

The person responsible at the structural healthcare unit shall compile quarterly a report on the consolidated data on cases of adverse reactions following the use of vaccines and tuberculin (hereinafter – the consolidated data). The consolidated data shall be provided to the Center in electronic and paper form together with a covering letter signed by the head of the relevant structural healthcare unit, in the form set out in Appendix 3 to the Procedure, to the postal and electronic addresses specified in the requirements for compiling

of the consolidated data, within the period until the 10 day of the month following the reporting month. If this period falls on a weekend or holiday, the consolidated data shall be submitted on the first working day after it.

Regulatory references: subparagraph 7, paragraph 4 and subparagraph 6, paragraph 1 of Section IV. of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

The reporting card shall be submitted to the Center within the following timeframes:

• in the case of a non-serious adverse reaction – within 90 days;
• in the case of a serious adverse reaction to a medicinal product – within 15 days;
• in the case of lack of efficacy of a medicinal product – within 48 hours;
• in the event of an adverse reaction to a medicinal product, vaccine, tuberculin, and/or lack of effectiveness of a medicinal product, and/or an AEFI/tuberculin diagnosis, which resulted in the death of a patient – within 48 hours.

If the specified time limits fall on a weekend or public holiday, the information shall be provided on the first working day thereafter.

Healthcare professionals shall also promptly submit to the rapid response group for adverse events following immunization (AEFI) of the relevant structural healthcare units notification cards on AEFI following the administration of a vaccine or tuberculin within no later than 48 hours after the registration of the AEFI. If this time limit falls on a weekend or public holiday, the information shall be provided on the first working day thereafter.

Regulatory references: paragraph 9 of Section IV of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine No. 898 of December 27, 2006, registered with the Ministry of Justice of Ukraine on December 19, 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine No. 996 of September 26, 2016).

The responsible person of the structural unit for healthcare issues compiles a general report based on the data from the epidemiological investigation cards. The general report in electronic form, together with a cover letter, is submitted to the Center at the email address specified in the requirements for its completion, annually by 30 January of the year following the reporting year. If this deadline falls on a weekend or holiday, the information is provided on the first working day after it.

Regulatory references: paragraph 16, Section IV of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine dated 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine dated 26 September 2016 No. 996).

If it is necessary to make safety-related changes to the instructions for medical use of a medicinal product, the applicant shall notify the Center thereof in any manner and submit an application for changes no later than 60 calendar days from the date of receiving information on the need to make such changes.

Regulatory references: paragraph 12 of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

In paper form, the healthcare professional must send the notification card to the address of the State Enterprise "State Expert Center of the Ministry of Health of Ukraine": State Enterprise "State Expert Center of the Ministry of Health of Ukraine", Pharmacovigilance Department, Anton Tsedyk St., 14, Kyiv, 03057; telephone for questions on completing the notification card: +38 (044) 202 1700 (extension 4310),

The electronic form of the notification card can be completed interactively:

– on the website "State Register of Medicinal Products of Ukraine" http://www.drlz.kiev.ua /, where in the upper right corner there is a section "Notification of an adverse reaction to a medicinal product" in interactive format;

– on the website of the State Expert Center of the MoH http://www.dec.gov.ua / in the "Pharmacovigilance" section (subsection "Notification card on ARs to medicinal products").

– at the link https://aisf.dec.gov.ua/Account/LogOn

Telephone for questions on completing the notification card when using the analytical information system of pharmacovigilance (https://aisf.dec.gov.ua): +38 (044) 202 1700 (extension 4320).

Healthcare professionals must also promptly submit to the Center and to the rapid response group of the relevant structural units for healthcare (hereinafter – the regional rapid response group) a notification card on adverse events following immunization (AEFI) after the use of a vaccine or tuberculin within a period no later than 48 hours after the registration of the AEFI. If this period falls on a weekend or holiday, the information is provided on the first working day thereafter. The notification card is submitted to the Center and to the regional rapid response group in paper and/or electronic form.

A copy of the notification card is provided to the person responsible for pharmacovigilance of the healthcare institution for compiling form No. 69.

Regulatory references: paragraph 11, 12. Section IV. of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

The requirements of Annex 8 to the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order 26 August 2005 No. 426 (as amended by the order of the Ministry of Health of Ukraine of 23 July 2015 No. 460), registered with the Ministry of Justice of Ukraine on 07 October 2015 under No. 1210/27655, do not provide for the submission of a risk management plan for medicinal products manufactured according to formulations.

Regulatory references: Annex 8 to the Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order 26 August 2005 No. 426 (as amended by the order of the Ministry of Health of Ukraine of 23 July 2015 No. 460), registered with the Ministry of Justice of Ukraine on 07 October 2015 under No. 1210/27655.

An application for amendments after the same amendment has been made by the reference product is submitted in accordance with Annex 17 to the Procedure (MoH order No. 460), under type B.I.2 - type of amendment IB: Amendments to the summary of product characteristics, package leaflet of generic medicinal products after the same amendment has been made by the reference product,

a) the amendment does not require the submission of any new additional data

Documentation that must accompany such an amendment:

1. Request of the national competent authority and/or MoH decision (if necessary).

2. Updated summary of product characteristics, package leaflet.

Regulatory references: Procedure for conducting expert evaluation of registration materials for medicinal products submitted for state registration (re-registration), as well as expert evaluation of materials on amendments to registration materials during the validity of the registration certificate, approved by order of the Ministry of Health of Ukraine dated 26 August 2005 No. 426 (as amended by order of the Ministry of Health of Ukraine dated 23 July 2015 No. 460) http://zakon2.rada.gov.ua/laws/show/z1210-15.

Note: * – follow the frequency of submission taking into account the INN of the medicinal product//generation at the central level until such deadlines for submitting the PSUR coincide with the List – thereafter the PSUR is submitted in accordance with the List

Medicinal product – medicinal product

RC – registration certificate

INN – international nonproprietary name

API – active pharmaceutical ingredient

PSUR – periodically updated safety report

List – List of deadlines for submitting periodically updated safety reports for medicinal products by the international non-proprietary name of the API or a combination of APIs, in accordance with Annex 10 to the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

Regulatory references: Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

Information specific to the pharmacological group to which the medicinal product for which the RMP is being developed belongs may be reflected in sections CVII.1 – CVII.5.2 of Part II of the RMP.

If properties characteristic of the pharmacological group of the medicinal product were not detected during the preclinical, clinical pre-registration and post-registration study of the medicinal product, they may be reflected in section CVII.5.2 of part II of the SmPC.

The reporting form on any adverse reactions of medicinal products, vaccines, tuberculin, lack of efficacy of a medicinal product and on adverse events following immunization, as well as the requirements for completing it, can be found:

– on the website "State Register of Medicinal Products of Ukraine" http://www.drlz.kiev.ua /, where in the upper right corner there is a section "Notification of an adverse reaction to a medicinal product" in interactive format;

– on the website of the State Expert Center of the MoH http://www.dec.gov.ua / in the "Pharmacovigilance" section (subsection "Notification card on ARs to medicinal products").

– in the State Formulary of Medicinal Products (in Appendix 7);

In addition, the reporting form can be completed on the website https://aisf.dec.gov.ua/Account/LogOn in the sections "Report from a healthcare professional"; "Report from the applicant"; "Report from a patient".

The State Expert Center of the MoH provides information to the State Service of Ukraine on Medicines and Drugs Control about:

– unforeseen adverse reactions, adverse reactions that resulted in the death of a patient, group adverse reactions and/or lack of efficacy of medicinal products (except vaccines, tuberculin) where there is a causal relationship between them and the use of the medicinal product (except vaccines, tuberculin);

– group adverse reactions and/or serious adverse reactions associated with violations arising in the manufacturing process of a vaccine, tuberculin, including the administration device provided by the manufacturer of the vaccine, tuberculin, where there is a causal relationship between them and the use of the vaccine, tuberculin.

Regulatory references: subparagraph 1 of paragraph 2 of Chapter III of the Procedure for Pharmacovigilance, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 19 December 2016 under No. 1649/29779 (as amended by order of the Ministry of Health of Ukraine of 26 September 2016 No. 996).

a) a response to an applicant's request that does not require the provision of detailed information on cases of adverse reactions and/or lack of efficacy of a medicinal product in the form of information notices shall be provided no later than the 30st calendar day from the date of receipt of the request;

b) a response to an applicant's request that requires the provision of detailed information on cases of adverse reactions and/or lack of efficacy of a medicinal product in the form of information notices shall be provided no later than the 10st working day from the date of receipt of information on payment from the accounting department.

Yes, this change is consistent and may be declared in a "package".

Preclinical studies of medicinal products in Ukraine are conducted in accordance with the "Procedure for Conducting Preclinical Study of Medicinal Products and Expert Evaluation of Preclinical Study Materials of Medicinal Products" approved by order of the Ministry of Health of Ukraine No. 944 dated 14.12.2009, (clause 1 ch. 1 section IV, taking into account the belonging of the investigated medicinal product to the relevant pharmacological group and its origin), as well as in accordance with the guideline "Preclinical Safety Studies as a Basis for Human Clinical Trials and Registration of Medicinal Products (ICHM3 (R2))", approved by order of the Ministry of Health of Ukraine No. 661 dated 19 September 2014.

One should contact the Ministry of Health of Ukraine

On the official website of the Ministry of Health of Ukraine

Official website of the MoH

For researchers and representatives of clinical trial sponsors, training seminars "Good Clinical Practice (GCP). Regulatory and legal framework for clinical trials in Ukraine" are held monthly at the State Expert Center.
Contact persons:

• Serhii Rasputniak

tel.: +38 (044) 498-43-27, tel./fax: 498-43-29, e-mail: rasputnyak@dec.gov.ua

• Olena Yurchenko

tel.: +38 (044) 498-43-69, tel./fax: 498-43-29, e-mail: yurchenko@dec.gov.ua
More information: https://dec.gov.ua/?ZG93bmxvYWQ=L21hdGVyaWFscy9uYXZjaGFsbmktc2VtaW5hcmktemFwbGFub3ZhbmktZGVjei8=

the criteria for selecting medicinal products for the State Formulary are:

1. Availability of state registration of the medicinal product (as of 01 September of the current year) and at least two years of experience of its use in Ukraine. If there are no therapeutically equivalent medicinal products, experience of use of the medicinal product in Ukraine is not required.
2. Availability of high indicators of quality, efficacy, safety and cost-effective use of medicinal products, confirmed by:

2.1. Availability of a document confirming that the manufacturing conditions comply with the requirements of good manufacturing practice (for domestic manufacturers – a valid license for the manufacture of medicinal products).

2.2. Evidence-based medicine data, including the results of pharmacoeconomic studies.

2.3. The practice of medical use, including the results of the assessment of the safety of medical use of the medicinal product, as defined by the Procedure for Pharmacovigilance of Medicinal Products Authorized for Medical Use, approved by order of the Ministry of Health of Ukraine of 27 December 2006 No. 898, registered with the Ministry of Justice of Ukraine on 29 January 2007 under No. 73/13340.

In accordance with: clause 6. of the Methodology for Creating Medicinal Product Formularies, approved by order of the MoH of Ukraine of 22.07.2009 No. 529 (as amended).

1. A cover letter addressed to the Director of the Center requesting the expert evaluation.
2. Application regarding the possibility of including a medicinal product in the State Formulary of Medicinal Products:

• Arguments regarding the possibility of including a medicinal product in the State Formulary (in accordance with the Methodology for Creating Medicinal Product Formularies, approved by order of the Ministry of Health of Ukraine No. 529 dated 22 July 2009, registered with the Ministry of Justice under No. 1003/17019 dated 29 October 2009):

• Availability of medicinal products in tertiary information sources (international guidelines, prototype medicinal product formularies, medical technological documents approved by orders of the Ministry of Health of Ukraine, the National List of Essential Medicines of Ukraine);
• Availability of medicinal products in secondary (meta-analyses and systematic reviews) and primary (randomized controlled trials, cohort studies, case-control studies, diagnostic studies, economic studies) information sources (if available)

In the absence of any information regarding the Arguments regarding the possibility of including a medicinal product in the State Formulary, the Application is not accepted for review.

The package of documents is submitted in the general procedure to the Records Management Division of the Center in 2 copies (provided the medicinal product is included in one section).

In accordance with the order of the Ministry of Health of Ukraine of 22.07.2009 No. 529 "On the establishment of the formulary system for the provision of medicinal products to healthcare institutions" (as amended), all decisions on the inclusion, non-inclusion or exclusion of a medicinal product in the State Formulary are taken at meetings of the Central Formulary Committee of the Ministry of Health of Ukraine. The Central Formulary Committee of the Ministry of Health of Ukraine (hereinafter – the Central Formulary Committee) is a permanent working body under the Ministry of Health of Ukraine, established for the purpose of developing and continuously updating the State Formulary and introducing the formulary system, which organises its activities on the basis of the State Enterprise "State Expert Center of the Ministry of Health of Ukraine".

Yes, they can, if a medicinal product has already been included in the State Formulary but over time has ceased to meet the requirements of any of the significant criteria:

• the state registration has expired;
• there have been changes in the instructions for medical use of the medicinal product which have indications that do not correspond to the section in the structure of the Formulary where this medicinal product was previously included;
• new data from clinical trials and observations have emerged regarding the absence of quality, efficacy or safety parameters (reports of serious adverse reactions) of a medicinal product, and the results of pharmacoeconomic studies regarding the absence of high indicators of cost-effective use of the medicinal product.

Such a medicinal product is subject to exclusion. Because, in accordance with the Methodology approved by order of the Ministry of Health of Ukraine dated 22.07.2009 No. 529 "On the Creation of a Formulary System for the Provision of Medicinal Products to Healthcare Institutions" (as amended), the State Formulary of Medicinal Products is a list of medicinal products registered in Ukraine that includes medicines with proven efficacy, acceptable safety and cost-effective use.

It is necessary to immediately notify the Register Administrator in any form about the loss of the login and password and to obtain other means of identification.

If a level I or level II user has not consented to providing their mobile phone number to the Registry Administrator, they must obtain identification means personally from the Administrator.

The Administrator of the Registry of patients requiring insulin therapy provides (organizes) technical support for the Registry software, processing and analysis, as well as storage and protection of the data contained in the Registry (order of the Ministry of Health of Ukraine dated 23.12.2015 No. 890 "On approval of the Regulation on the registry of patients requiring insulin therapy", as amended).

In accordance with the order of the Ministry of Health of Ukraine dated 23.12.2015 No. 890, level I users are designated by orders of healthcare institutions from among their staff employees, level II users are designated by orders of the Ministry of Health of Ukraine, structural units for healthcare of the regional, Kyiv and Sevastopol city state administrations, and territorial information and analytical centers for medical statistics from among their staff employees. Information about the user (order, full name, name of the institution, user's position, phone number and email) is sent to the Administrator's email address to obtain identification means (login and password).

Information on the identification of level III users within the relevant administrative-territorial unit is collected and summarised by the structural subdivisions for health care of the regional, Kyiv and Sevastopol city state administrations. Information about a level III user (full name of the user, its EDRPOU code, location, contact telephone number and e-mail address) is sent to the Administrator's e-mail address to obtain identification means (login and password).

It is necessary to call the number (044) 247-04-43 and receive advisory assistance.

Yes, within 3 working days it is necessary to notify the Register Administrator in writing about the changes in order to cancel the identification means. When appointing new level I and II users, or when signing an agreement with another level III user, provide all the necessary information provided for by paragraphs 4, 5 of section II of the order of the Ministry of Health of Ukraine dated 23.12.2015 No. 890, within 3 working days to the Register Administrator.

In accordance with the order of the Ministry of Health of Ukraine dated 23.12.2015 No. 890, a level I user is a physician specializing in "Therapy", "Endocrinology", "Pediatric Endocrinology", "General Practice – Family Medicine", who holds the relevant physician position in a healthcare institution of state or municipal ownership (hereinafter – HCI), authorized to enter information about patients requiring insulin therapy into the Register. A level II user is a person who is a staff member of the Ministry of Health of Ukraine, a structural unit for healthcare of the regional or Kyiv city state administration, or a territorial information and analytical center for medical statistics, authorized to review and analyze depersonalized data. A level III user is a pharmacy that holds a license to conduct economic activity in retail trade of medicinal products.

Medical technological documents – a generalized name for clinical guidelines, standards of medical care, unified clinical protocols of medical care, new clinical protocols of medical care

The topic of medical technological documents is a medical problem relevant to the healthcare system and healthcare facilities (a disease or other pathological condition, adherence to a healthy lifestyle), rather than a medical specialty. Topics may correspond to current international classifications and other patient characteristics (for example, ICD-10, ICPC-2, patient age categories, etc.)

Modern medical technological documents include medicinal products with proven efficacy that are present in clinical guidelines, as sources of best clinical practice, registered in Ukraine and available in the State Register of Medicinal Products, approved by resolution of the Cabinet of Ministers of Ukraine of 31 March 2004 No. 411 (as amended).

In the Register of Medical Technological Documents, methodological materials on standardization of medical care, news, etc. are also available

In order to ensure transparency of its activities when providing recommendations for state registration of medicinal products, the Center has introduced the publication of information reports on the results of the expert evaluation of registration materials for medicinal products submitted for state registration (Public Reports).

This Public Report is intended for the general public – consumers, healthcare professionals, public organizations, manufacturers and representatives of manufacturers of medicinal products, etc. – and has been prepared for the purpose of providing information about a registered medicinal product.

The Public Report contains information, with the exception of confidential information, on the content of the data provided to confirm the safety, efficacy and quality of medicinal products, and the conclusions of the experts regarding the assessment of these data. The annexes to the Public Report contain publicly available information about the medicinal product – the instruction for medical use, data on the type of packaging, labelling, shelf life, manufacturer, etc., as well as, if available, a summary of product characteristics.

Applications for state registration/re-registration received by the Center

For applicants/authorized representatives of applicants for expert evaluation of medicinal products, it is necessary to submit a Letter of request addressed to the Director of the Center and a Authorization regarding consent to access the Service Center of the SEC.

For applicants/authorized representatives of clinical trials of medicinal products, it is necessary to submit a Letter of application addressed to the Director of the Center and a Authorization regarding consent to access the Service Center of the SEC, issued by the sponsor to represent interests at the Center (if necessary). Please note that to obtain access to the "Visualization" system, the applicant's name must be identical in the agreement between the applicant and the Center on conducting expert evaluation, and in the Letter of application to the Center.

Samples of these documents are available on the official website of the Center under the heading "For applicants -> Visualization".

Proposals and suggestions regarding the operation of the updated "Visualization 2.0" system should be sent to the email address eias@dec.gov.ua

If you have any questions, please contact by phone (044) 202-17-07

With the aim of establishing information communications, in 2012 the Center introduced the "Visualization" system on its official website, which in the first stages of development gave any website user the opportunity to familiarize themselves with the general scheme of the application process and highlighted statistical data at each stage of expert evaluation.

As part of the ongoing improvement of the information and technical content of the official website, following the modernization of the above-mentioned system, the Center now offers applicants/representatives of applicants and users with the appropriate authority to use the new version of the information system "Visualization 2.0".

The "Visualization 2.0" system is presented on the Center's official website for users as a schematic visualization of the status and number of applications being processed by the Center's structural units, in a certain status in accordance with the procedure – authorized users (applicants/representatives of applicants) receive information displayed in the form of lists and tables on the status and number of applications, indicating the stage of their processing and the expert responsible for receiving and reviewing the application.

The visualization provides applicants or their representatives with the ability to track on-line the progress of the applications/registration forms they have submitted for registration, re-registration, amendments to registration materials for medicinal products/medical immunobiological preparations, and the conduct of clinical trials of a medicinal product/applications for a substantial amendment and materials thereto.

You need to make sure that the power of attorney specified by you in the letter of request for access to the Visualization has not expired. If the validity period has expired, a letter of request with the details of the valid power of attorney should be submitted to the Service Center of the Center; if the validity period of the power of attorney has not yet expired, please contact the email address eias@dec.gov.ua or by phone (044) 202-17-07.

Lists of medicinal products recommended for registration, re-registration and amendments to registration materials