Pharmacovigilance

Order of the Ministry of Health of Ukraine No.898 of 27.12.2006 “Procedure for Performance of Pharmacovigilance” describes the pharmacovigilance system in Ukraine. The PV system is based on international standards and practices, including EU Directive No. 2001/83 and EU Council Regulation No. 2309/93.

The competent state authority is the State Expert Center of the Ministry of Health of Ukraine (SEC). The SEC organizes and coordinates the PV activities, including interaction with Marketing Authorization Holders for medicines approved in Ukraine.

The MAH must establish and maintain the pharmacovigilance system in Ukraine. For this, the MAH should designate the QPPV (Qualified Person for Pharmacovigilance) and, if MAH is located outside Ukraine, the LQPPV (Local Qualified Person for Pharmacovigilance). 

QPPV and LQPPV must comply with the educational and experience requirements. Application for new registration and renewal must be amended with contact information of the QPPV and LQPPV, CV of the LQPPV. Change of the QPPV or LQPPV requires submission of the Application for variations, assessment and approval. 

Under the establishment and maintenance of the PV system in Ukraine, we consider: 

• Designation of the LQPPV in Ukraine and its deputy; 
• Submission of the information on PV system (QPPV and LQPPV data, location and brief description of the PV system) to the competent authority;
• Internal training for the LQPPV and its deputy;
• Establishing and maintaining the system for monitoring, assessment and submission of data adverse events and lack of efficacy, including:
  • 24/7 receipt of information by phone;
  • training of the personnel;
  • signing pf the Safety Data Exchange Agreements (SDEA) with market operators (importers, distributors, marketing organizations, etc.);
  • weekly local monitoring of specialized literature and websites of competent authorities.
• Receiving and evaluating reports on adverse reactions occurring abroad, submission to the competent authority (if necessary);
• Providing prompt and comprehensive information about all adverse reactions and/or all cases involving lack of efficacy of the medicinal product on request of the competent authority;
• Establishing and maintaining the risk management system;
• Approving the PSUR/PBRER submission schedule;
• Establishing and maintaining pharmacovigilance databases;
• Maintaining the register of all pharmacovigilance system events in Ukraine;
• Maintaining the pharmacovigilance quality system, performing internal audits.

The establishment and maintenance of the PV system can be fully or partially outsourced to a third party. 

Since 2006 our company supports the pharmaceutical business in regulatory affairs, pharmacovigilance, and quality. We are a leading regulatory consultant in Ukraine and 11 countries of the CIS region.  We have deep expertise in various types of Applications and procedures. Our team includes more than 120 best experts that are fluent in English and have extensive experience. More than 200 manufacturers trust us for our professional, ethical and supportive approach. We offer: PV outsourcing  in Ukraine and 11 countries of the CIS region; development of documentation and implementation of the PV system; writing of the pharmacovigilance system documents (PSUR, PBRER, RMP, etc.); implementation of computerized databases and pharmacovigilance systems; an independent audit of pharmacovigilance systems, personnel training.

Submission of information on adverse events

Reportable adverse events and timelines for submissions: 

• serious adverse reactions in Ukraine (provided that there is a medical confirmation and a causal link between the adverse reaction and the use of the medicinal product) – within 15 calendar days;
• non-serious adverse reactions in Ukraine (provided that there is a medical confirmation and a causal link between the adverse reaction and the use of the medicinal product) – within 90 calendar days;
• serious unexpected adverse reactions in the territory of other countries, causing the death of the patient or a threat to the patient’s life, as well as about all suspected cases of infection transmission through the medicinal product (provided that there is a medical confirmation and a causal link between the adverse reaction and the use of the medicinal product) – within 15 calendar days;
• violations occurring in the process of manufacture of vaccines or tuberculin – within 48 hours;
• lack of efficacy of the medicinal product in Ukraine – within 15 calendar days, which take place during:
  • treatment of life-threatening or emergency conditions, except for the cases when the lack of efficacy is caused by the progression of the disease and not by the use of the medicinal product,
  • use of vaccines,
  • use of contraception.

Other adverse reaction development cases at the territory of the other country and other cases involving lack of efficacy of the medicinal product are submitted in the scheduled PSUR. 

Format of submission: report form / CIOMS / E2B.

The report on adverse reaction and/or lack of efficacy of the medicinal product may be submitted by the MAH to the State Expert Center via the Automated Pharmacovigilance Information System (APIS) in the form of:

• Completed adverse reaction message form;
• CIOMS forms – PDF format;
• CIOMS forms – Е2В format;

PSUR/PBRER submission

PSUR (Periodic Safety Update Report) is a document containing an evaluation of the benefit-risk ratio of the medicinal product during its entire life cycle, submitted by the marketing authorization holder to the regulatory authorities within certain terms during the post-registration period.

As of now, PSUR is submitted for all medicinal products, except for the following cases:

• medicinal products with a well-established use,
• generic medicinal products,
• traditional medicinal products of plant origin,
• homeopathic medicinal products,

except for the cases when PSUR submission:

• is indicated in the marketing authorization as a condition for its approval; 
• is determined in the PSUR submission term list approved by the Ministry of Health of Ukraine;
• is required by the Ministry of Health or the State Expert Center in connection with safety problems or the lack of PSUR for the active ingredient after the issuance of the marketing authorization (if the reference medicinal product is no more registered in Ukraine).

PSUR submission frequency:
1. After first registration in Ukraine (as the first country in the world), or from the moment of registration of the medicinal product in any country of the world (international birth date of the medicinal product):

• once per 6 months – within the first 2 years after the receipt of the marketing authorization,
• once a year – within the following 2 years,
• later – once per three years, beginning from the date of registration of the medicinal product.

If PSUR submission terms correspond to the terms indicated in their submission frequency, PSUR shall be submitted in accordance with the terms indicated in their submission frequency.

2. Or per the frequency indicated in the marketing authorization,

3. Or per the terms indicated in the PSUR submission frequency,

4. For medicinal products registered after the effective date of Order No. 898, PSUR is submitted by the terms indicated in the PSUR submission frequency or by the Applicant’s choice (but not less than indicated in the established frequency),

5. At the request of the State Expert Center.

PSUR generation terms:

• Within 70 calendar days after the date of closure of the database for generation of PSUR with a reporting period covering 12 months inclusive,
• Within 90 calendar days after the date of closure of the database for generation of PSUR with a reporting period covering more than 12 months,
• Within 90 calendar days after the date of receipt of the request for provision of PSUR.

PSUR submission language:

PSUR is submitted in Ukrainian and in English. In case if the PSUR is submitted in English, the following chapters are to be translated into Ukrainian:

• III “Actions taken in the reporting interval for safety reasons”,
• IV “Changes to reference safety information”,
• XVIII “Integrated benefit-risk analysis for authorized indications” and
• XIX “Conclusions and actions” or other chapters containing such information.

Chapters XVI “Signal and risk evaluation” and XVII “Benefit evaluation” of PSUR are submitted in Ukrainian at the Center’s request (if necessary).

PSUR submission format:

PSUR is submitted to the SEC in hard copy. Annexes to PSUR may be submitted in electronic form. During the period of the COVID-19 pandemic, PSUR may only be submitted in electronic form.

Risk management

A risk management plan (RMP) is a document containing a detailed description of the medicinal product risk management system and reflecting the pharmacovigilance activities aimed at:

• Risk identification,
• Risk characterization,
• Risk prevention or mitigation and
• Assessment of the effectiveness of such measures.

The MAH creates and submits RMP:

1. for all new Applications for registration of medicinal products, including generic medicinal products (except for traditional or homeopathic medicinal products);
2. in case of variations requiring a new registration (new dosage form, new mode of administration, new production process for a biotechnological medicinal product, pediatric indications and other significant changes to indications);
3. in case of occurrence/detection of new data influencing the benefit-risk ratio of the medicinal product, current specification, pharmacovigilance plan, risk mitigation measures or effectiveness thereof, or within 60 days after achieving important results to pharmacovigilance or risk mitigation;
4. in case of re-registration, if RMP is needed per the results of the benefit-risk ratio assessment;
5. at the request of the State Expert Center within 60 days after submission of the request.

RMP is not submitted for the medicinal products re-registered in the European Union before June 2012, except for the cases when RMP is needed per the results of the benefit-risk ratio assessment.

RMP requirements: 

RMP is submitted in the format of a separate document, following the structure provided in Annex 14 to the procedure of performance of pharmacovigilance (Order No. 898) or another structure containing similar modules, parts and chapters. EU requirements to the RMP structure are included in the following documents:

• 25.07.2013 Guidance on the format of the risk management plan (RMP) in the EU – in integrated format;
• 30 March 2017 EMA/PRAC/613102/2015 Rev.2 accompanying GVP Module V Rev.2 Human Medicines Evaluation Guidance on the format of the risk management plan (RMP) in the EU – in integrated format;
• 31 Осtober 2018 EMA/164014/2018 Rev.2.0.1 accompanying GVP Module V Rev.2.0.1 Human Medicines Evaluation.

RMP language and submission format:

During RMP development, consideration must be given to the completion requirements (depending on the type of application for registration of the medicinal product). Each RMP presented should have a unique version number and date of creation thereof.

RMP is submitted in Ukrainian and in English. In case if the RMP is submitted in English, the following parts are to be translated into Ukrainian:

• V “Risk minimization measures”,
• VI “Summary of the risk management plan”.

Module VIII “Summary of the safety concerns”, part III “Pharmacovigilance plan”, part IV “Plans for post-authorization efficacy studies” are submitted in Ukrainian at the request of the State Expert Center.

RMP is submitted in hard copy. Annexes to it may be submitted in electronic form.

Our services 

Since 2006 we support the pharmaceutical business in regulatory affairs, pharmacovigilance, and quality. We are a leading regulatory consultant in Ukraine and 11 countries of the CIS region. Our extensive team has the necessary knowledge, experience, and skills and is proficient in English.

We have provided regulatory services for more than 200 manufacturers of medicines, many of which recommend us as a regulatory partner. 

We offer: 

• establishment and maintenance of the pharmacovigilance system, outsourcing of functions of the local contact person and their deputy in Ukraine and 11 countries of the CIS region;
• development and implementation of the pharmacovigilance quality system (PVMF, Quality Manual, SOP and instructions, logs, etc.);
• personnel training;
• development (writing) of RMP, PSUR / PBRER;
• implementation of pharmacovigilance databases;
• an independent audit of pharmacovigilance systems;

We offer: 

• consultation, development of registration strategy;
• establishment of new registration, renewals, and variations;
• confirmation of manufacturing conditions with GMP requirements through recognition or inspection.
• translation of the scientific, medical, technical, and legal documentation;
• back-office operations: preparation of the registration dossier or any of its parts without submission;
• development and pre-printing verification of labeling artworks and instructions for use;
• medical writing of parts of the registration dossier;
• development of documentation and import licensing;
• writing of documentation for inclusion of the medicinal product in the National List (HTA).