The applicant should create, provide and guarantee pharmacovigilance system functioning in Ukraine. This is a necessary requirement of medicinaproduct(MP) presence at Ukrainian market. The pharmacovigilance system should consist of elements, which enable to monitor medicinaproduct safety and define any changes in risk/advantage correlation (p. 8.1., order 898). It should permanently contromanufacturing quality, safety and realize the reevaluation of the risk/advantage correlation regularly, taking into account new information.
The pharmacovigilance system (PV system) should be used for gathering information about medicinaproducts(MP) usage risks for the patient's’ health or population. The information, in particular, goes for adverse reactions, which are being in progress in human body, due to the medicinaproduct administration under and beyond the terms of trade license, and also due to adverse reactions, which are developing during the process of professionaactivities.
1. The owner of the trade license should manage the pharmacovigilance system to complete his pharmacovigilance tasks.
2. The owner of the trade license should evaluate information by the aid of system on the ground of science, take into account minimization and risk prevention variants and take relevant measures, if necessary.
The owner of the trade license should regularly perform an audit of his pharmacovigilance system. He has to give a note concerning main audit results on pharmacovigilance system master-file and according to the results he should guarantee the relevant plan preparation and accomplishment. As far as corrective actions wilbe fully accomplished, the note can be deleted.
3. In the terms of pharmacovigilance system the owner of the trade license should:
a. have a qualified pharmacovigilance specialist in his hand permanently;
b. support and present the pharmacovigilance system master file on demand;
c. use the risk-managing system according to every MP;
d. controthe minimization risks measures results, which are stated in the risks-managing plan or stated as a condition or demand in the trade license.
e. update/implement changes in the risks-managing system and keep an eye on data about the pharmacovigilance to define if there are new or changed risks or if changes in the ratio benefit-risk of medicinaproducts exist.
The qualified specialist should be accountable for the pharmacovigilance system creation and support.
The trade license owner’s elements of the pharmacovigilance system:
1. The authorized person in the staff presence, who’s responsible for PV(pharmacovigilance)
2. Pharmacovigilance organization structured chart presence, it’s updating and support
3. Alproceduraprocesses documentation
4. Relevant databases creation and providing it’s functioning
5. Capturing (if required) different people and organizations to pharmacovigilance accomplishment by way of coming to contract arrangements
6. Providing staff training to accomplish actions, connected with pharmacovigilance
7. Creation of a controsystem (PV)
8. Documentation management (PV), including keeping and archivation
9. Creation of a risk-management system (PV)
The plan of medicinaproducts risks management (PMPRM), allowed to medicausage, is a necessary component of risks-management system of PV, which in it’s turn is a component of the PV system. PMPRM is developed as an independent document, which enables to track potentiaand verified risks permanently, connected with medicinaproduct (MP), and develop correct-preventive measures to minimize risks appearance, guarantee the whole information relevance, which is provided by the company concerning MP, update and inform rapidly regulatory authorities of countries addressed of new information known.
The procedure for PMPRM submission is stated in the Ministry of Health order of 26.08.2005 №426 (with changes). PMPRM should be submitted in a separate document format in accordance with the structure, foreseen by the legislation.
The aim of PMPRM development - most possible advantage of the benefit upon the risk achievement under the medication usage for every separately-taken patient of the target group, because of identification and analysis of potentiaand verified risks under the usage of MP.
The task of PMPRM - data gathering and managing risks during the MP life-cycle - is reached on the basis of:
- the MP safety profile specification and characterization;
- exact definition of supervision aims, methods and stages of the safety of the MP;
- post-approvaobligations, which were the requirements for license distribution for further MP circulation;
- description of how measures effectivity on risks minimization would be valued;
- the view of measures effectivity on risks minimization;
- publication of a short survey (summary) of data about the drug for common usage. If required PMPRM is an argument for implementing changes in MP usage tactic.
The necessity PMPRM or it’s updated version can appear at any moment during the MP life-cycle either in pre- or on post-approvaperiod.
PMPRM is provided for alnew request forms:
- a new pharmaceuticafrom;
- a new entry way;
- a new processing process for biotechnologicaMP;
- other important indications changes for use;
- upon the request of the regulatory agency, if there is a risk, which can influence benefit/risk correlation;
- under reregistration, if the MP already has PMPRM;
- provided that targeted population essentially differs from that, for curing which MP was allowed earlier. It includes it, but doesn’t restrict;
- new indications (another disease) in a new age group (e.g. pediatricaindications), decreasing indications from severe disease degree;
PMPRM or it’s updated version is given according to demands of Ministry of Health order of 26.08.2005 №426 (with changes) in further cases:
- under the registration of any MP, except traditionavegetationaand homeopathic MPs, MPs, which are registered on simplified procedure;
- under the changes , which need a new registration, in particular, a new pharmaceuticaform, a new mode of administration, a new biotechnologicaMP production process, pediatricaindications and other essentiachanges in indications;
- in the context of appearing new data, which influence the correlation benefit/risk of MPs, current specification, plan of PV, measures on minimizing risks or their effectiveness during 60 days after achieving important results on PV or minimization of risks;
- on Center’s request in 60 days after applying the request.
Planning of PMPRM construction takes place accordant with new MP registration plan of Ukraine.
PMPRM consists of 7 main chapters:
- Chapter I Generainformation
- Chapter II Safety specification
- Chapter III Pharmacovigilance plan
- Chapter IV Post-approvaresearches effectiveness plan
- Chapter V Minimization risks measures (including the value of measures effectiveness on managing risks)
- Chapter VI Risks-managing plan survey
- Chapter VII Appendix
Pharmacovigilance system implementation:
- Pharmacovigilance system master file (PSMF) development, reformatting from existing detailed pharmacovigilance system description (DDPS).
- Standard operationaprocedure development in accordance with existing instructions;
- Pharmacovigilance database implementation and validation (in case it’s absent in the company);
- Audit plan and inspection plan development;
- Pharmacovigilance trainings plan development;
- Keeping track of literature, information about MP safety and effectiveness search;
- Risks-management plan development (RMPs)
- Periodically-updated reports on MP safety development (PBRERs/PSURs) and ACOs;
- Reports on developed MP safety preparation (DSURs);
- Setup and further signals management;
- Activity on the work with MP safety specification (CCSI);
- MP specification development (CCDS);
- Quality of the PV system management;
- Holding of seminars on PV;
- Support - development of products and plans related to providing safety reporting;
- Tracking PV system in accordance with the current legislation demands.
- organization of the process of gathering, processing, analysis, coding, entering the information to the database on PV (case processing);
- organization of online, urgent notifications on unwanted consequences (are due to urgent reporting);
- screening of literature (regular monitoring);
- PSURs preparation;
- MP safety signals management;
- authorized person service, who is responsible for PV.