Pharmacovigilance

Scientific Advice - Pharmacovigilance System Description

Scientific advice on the procedure for drafting the pharmacovigilance system description that is part of the dossier for granting marketing authorisation

Under Art 14 of the Medicinal Products Act (Official Gazette, No. 71/07, 45/09 and 124/11) stipulating the documentation that should be attached to the application for granting marketing authorisation and under Art. 120 based on which the Agency provides the scientific advice in the field of its competencies and under Art 145, based on which the Agency for Medicinal Products and Medical Devices is oblige to comply with the provisions of the Medicinal Products Act within three months after coming into effect of the Act, the Agency provides the scientific advice about the format, content and procedure for documentation submission for granting marketing authorisation under Art. 14, paragraphs k) and p) of the Act.

Proof that the applicant have at his disposal a qualified person responsible for pharmacovigilance and that complies with the requirements regarding the provision of information about all suspected adverse reactions discovered either in Croatia or in other countries

It is recommended that the proof that the applicant has at his disposal a qualified person responsible for pharmacovigilance and that complies with the requirements regarding the provision of information about all suspected adverse reactions discovered either in Croatia or in other countries be submitted in a written form signed by the marketing authorisation holder’s responsible person and marketing authorisation holder’s qualified person for pharmacovigilance. (Annex 1: example of the Statement).

The statement should be accompanied by the CV of the qualified person for pharmacovigilance.

It is recommended that the statement and the CV of the qualified person for pharmacovigilance be documented in the Part I, which means in the Modul I, after the IA Administrative information part.

Pharmacovigilance System Description

It is recommended to document the Pharmacovigilance System Description in the end of the Part I, which means in the 1.8.1. part of the Module I in the marketing authorisation dossier.

The Pharmacovigilance System description should be submitted with every application for granting the marketing authorisation.

Taking account that with the coming into effect of the Medicinal Products Act (Official Gazette, No. 71/07, 45/09 and 124/11), the Pharmacovigilance system description became part of the marketing authorisation dossier, the marketing authorisation holder is obliged to submit an application for variation to the marketing authorisation for every change within the Pharmacovigilance System Description.

It is recommended that the marketing authorisation holder for finished medicinal products manufactured outside the Republic of Croatia provides the Pharmacovigilance System Description prepared by the manufacturer (central office) as well as the Pharmacovigilance System description of the applicant for granting marketing authorisation in the Republic of Croatia (local system).

Preparation of the Pharmacovigilance System Description in Croatia

It is recommended that the Pharmacovigilance System Description include the information from the global and local system that may be part of the Pharmacovigilance Description System prepared by the manufacturer 8central office) and/or Pharmacovigilance Description System of the applicant for granting marketing authorisatioj in Croatia.

Parts of the Pharmacovigilance Description System marked with an asterisk are recommended to be described by the marketing authorisation holder in Croatia.

1. Marketing authorisation holder's responsible person qualified for pharmacovigilance in the Republic of Croatia*:

  • Summary of the activities of the qualified person for pharmacovigilance
  • Description of the support system in the case of QP's absence
  • Annex 1 should be attached hereto comprising of:
    • QP's CV (if preferred a reference should be made to the attached CV in the Part I, or Module I, following the IA Administrative information part)
    • CV of the QP's deputy if such exists
    • QP's contact details and support system (address, phone, mobile, e-mail etc.)

2. Pharmacovigilance System Organisation:

  • Name and seat of the central (global) pharmacovigilance office
  • site of access of all pharmacovigilance data (ICSRs, PSURs and global pharmacovigilance data)
  • schematic diagram of organisational units of the pharmacovigilance system with a brief description of activities performed by each unit, including associated organisations*
  • schematic flow chart of analysing and reporting of ICSRs, PSURs and other pharmacovigilance data (the link between the reporter-central office-marketing authorisation holder-Agency should be indicated)*

3. Documented procedures:

- indicate for which of the following topics exist written procedures:

  • activities of the Qualified person responsible for pharmacovigilance in the Republic of Croatia and support in the case of QP's absence*
  • collection, analysing, quality control, coding, classification, medical evaluation and reporting of individual cases of adverse reactions (separately for local, separately for reports from other countries)*
  • request of further information for reported adverse reactions*
  • detection of adverse reaction report duplicates*
  • procedure of urgent adverse reaction reporting*
  • preparation, analysing, quality control , evaluation and submission of PSURs*
  • continuous monitoring of medicines safety profiles (signal detection, risk/benefit ratio assessment, informing regulatory authorities and healthcare professionals on changes in medicines safety profiles...)
  • association between the safe use of medicine and quality defect*
  • responses to regulatory authorities requests*
  • procedure in the case of extraordinary safety measures and variations to the marketing authorisation based on the medicine's safety profile*
  • accomplishment of regulatory authority's request*
  • use of databases and other data reporting systems*
  • internal audit of the pharmacovigilance system
  • staff training*
  • archiving*

4. Databases

  • The list of principal databases, their location and brief description (commercial or in-house developed database), validation method

5. Contractual relations

  • indicate principal contractual relations related to pharmacovigilance
  • system description should contain: roles of licensed partners, co-marketing responsible person for PhV, urgent adverse reaction reports, adverse reaction database managing, benefit/risk assessment, drafting of PSURs. (could be placed in product specific addendum)

Taking account that details on licensed partners may differ for every finished medicinal product, it is recommended that details on licensed partners be documented as an annex to the Pharmacovigilance Description System for every individual application. (see also Annex 2 - licensed partners).*

6. Staff training

Staff training system should be described and indicated where records on training, CVs and job descriptions are being kept. Pharmacovigilance training is mandatory not only for the staff involved directly in pharmacovigilance, but for the staff involved in sales/promotion of marketing authorisation holder's products also.

7. Documentation

Description of original documents location (adverse reaction reports from the Agency, healthcare professionals, minutes from the meetings etc.) including archiving.

8. Quality assurance system

Briefly describe the quality assurance system that monitors the Pharmacovigilance System including contractual organisations.

9. Accompanying documentation

The Pharmacovigilance System Description should demonstrate that such system exists and that it is adequately documented. It is not necessary to attach all the accompanying documentation (SOPs, instructions etc.), but it should exist, be accessible and provided at Agency's request.

In addition to the Pharmacovigilance Description System, for certain medicinal products a so-called Product-specific addendum should be attached, hence certain procedures may relate to a particular medicinal product.

It is recommended that the Pharmacovigilance system description be prepared in Croatian or English. It is also recommended to prepare the Pharmacovigilance Plan Description in the Republic of Croatia based on the global pharmacovigilance plan (in certain paragraphs of the local plan a reference could be made to the global one - it is not necessary to copy parts contained in the global plan).

Risk management plan

It is recommended that the Risk Management Plan be attached to the marketing authorisation dossier in the following cases:

  • for medicinal products containing new active substance (not previously authorised in the Republic of Croatia)
  • for biosimilar medicines
  • for essentially similar medicines (generics) if risk minimisation measures have been required for the reference product in the case of major changes
  • in the dossier where a new application for granting marketing authorisation should be submitted (Art. 45 of the Ordinance on procedures and methods for granting marketing authorisation for medicinal product, Official Gazette, No. 113/08 and 155/09) such as i.e. extensions with new pharmaceutical forms, new routes of administration, new doses

In the case when the requirement for preparation and submission of the Risk Management Plan is not regulated, an opinion from the Agency should be requested.

It is recommended to place the Risk Management Plan in the 3end of the Part I, or in the part 1.8.1 of the Module 1 in the marketing authorisation dossier.

Top