Renewal of Marketing Authorisation
The renewal of marketing authorisation is initiated by a written application submitted to the Agency for Medicinal Products and Medical Devices (HALMED) in original, in Croatian.
The written application for renewal of marketing authorisation is to be submitted separately for every pharmaceutical form and strength.
The application may be submitted no later than nine months before expiration of the marketing authorisation.
The application for renewal of marketing authorisation contains:
- Name of the medicinal product,
- Active substance,
- Pharmaceutical form and strength,
- Pharmacotherapy group, according to the ATC classification,
- Authorisation number,
- MRP/DCP procedure number, if applicable,
- Applicant's data (name and seat),
- Data about the documentation form (eCTD, NeeS, paper form),
- Date and signature of the applicant's responsible person
- List of documentation to be submitted alongside the application.
Alongside the renewal application, the applicant submits the following:
- Application form for renewal, completed in Croatian or English - it should be submitted separately for every pharmaceutical form and strength of the medicinal product, in original, signed by applicant's responsible person (the application form for renewal of marketing authorisation is available in the Forms section or under the following link: Application forms for granting/renewal/variation of the marketing authorisation for medicinal products in the Republic of Croatia),
- In addition to the application form, the applicant is required to submit all data and documents indicated in the application form, as applicable,
- Written authorisation/s of applicant's responsible person authorising the person for submission, application form signing and communication on behalf and for the account of the applicant during the renewal procedure, in original or certified copy,*
- Written authorisation of applicant's responsible person, if the marketing authorisation holder is not also the applicant, authorising the applicant to submit an application for renewal of marketing authorisation on his behalf, in original or certified copy,*
- Written authorisation of applicant's responsible person authorising the person for submission, signing of the application form and communication on behalf and for the account of the applicant after renewal, in original or certified copy,*
- Written statement of the marketing authorisation holder not having the seat in the republic of Croatia about the appointment of a local representative with the seat in the Republic of Croatia and his contacts
- Agreement between the manufacturer(s) responsible for batch release and marketing authorisation holder or applicant, if the manufacturer and the marketing authorisation holder or applicant are not the same person,
- Proof that the marketing authorisation holder has a qualified person for pharmacovigilance residing in the Republic of Croatia and approved by the Agency (Agency's certified copy),
- Proof of renewal fee payment,
- Proof of paid administrative fee.
*authorisation must be issued also by the responsible person of the legal entity, where the authorised person is employed.
Applications for Module 2 preparation for renewal:
- Module 2.3. Addendum to the quality expert report that should contain:
- Statement of the expert confirming that he/she has followed the newest scientific and technical advancements in the period from the granting of marketing authorisation and that necessary measures are implemented in order to ensure the product manufacturing and that the quality of the product is controlled according to the generally adopted scientific methods,
- Statement that all variations related to the quality of medicine notified and approved and that the medicinal product complies to the current European quality guidelines,
- Statement about the approved specifications for active substance and finished product (date and procedure/authorisation number),
- Qualitative and quantitative composition of active substance/s and excipients (date and procedure/authorisation number).
- Module 2.4. Addendum to the non-clinical expert report that should contain:
- Data for re-assessment of the benefit/risk ratio based on non-clinical data gathered after authorisation, or the last renewal, or based on the new available data. If no new non-clinical data is obtained, this should be indicated in the Addendum to the Clinical Expert report and it is not necessary to attach the Addendum to the Non-Clinical report for renewal.
- Module 2.5. Addendum to the clinical expert report that must refer to the current benefit/risk ratio based on the data from the Periodic safety Update report and data about safety and efficacy gathered after marketing authorisation, or last renewal, or based on the available data and must contain the following data:
- Inspection data of the pharmacovigilance system (date, competent authority that carried out the inspection, inspection site, type mof the inspection, information whether the inspection was carried out for a particular product, list of subject products) and the analysis of the inspection results impact on the benefit/risk ratio,
- Data of the marketing authorisation status worldwide: list of countries where the medicinal product is authorised and placed on the market,
- Data about safety measures undertaken after marketing authorisation, or from the last renewal date until the 90th day before the date of the renewal submission,
- Description of important measures associated with the safe use of the medicinal product having a potential impact on the benefit/risk ratio of the authorised medicine, i.e. temporary suspension, withdrawal, temporary revocation or an earlier termination of clinical trial due to safety reasons etc.,
- Significant changes in the Summary of of Product Characteristics (warnings, contraindications, restrictions in use) after granting of marketing authorisation, or last renewal including the 90th date before the date of submission for renewal or variation in reference safety data having yet to be accepted in the authorised Summary of Product characteristics. Important differences between the safety reference data, the proposal of the Summary of Product Characteristics should be indicated,
- Data on the estimated exposure to the medicinal product including data on the cumulative exposure of subjects in clinical trials, as well as patients after granting marketing authorisation. If the marketing authorisation holder discovers that certain use of the medicinal product requires introduction of new safety data, a short description of the indicated product use, i.e. off-label use,
- Data from tabular summaries that should contain a tabular overview of adverse events from clinical trials, as well as adverse reactions after grantning marketing authorisation, or last renewal concluding with the 90th day before the renewal submission date,
- Summaries of Product Characteristics about the safety and efficacy of the medicinal product from clinical and non-intervention investigations containing a description of all important results of safety investigation having an impact on the clinical or non-intervention trials. Summaries of Product Characteristics indicate whether predicted key objectives from the safety and efficacy after granting marketing authorisation, investigations from the risk management plan and investigations as an obligation and authorisation condition have been met.,
- Scientific data from the literature: review of important scientific articles published after the first authorisation or last renewal concluding with the 90th day before the renewal submission, that may have a possible impact on the benefit/risk ratio,
- Data about the benefit/risk ratio containing a summary overview of the data important for use, assessment and risk characterisation, as well as the efficiency of risk minimisation measures from the first authorisation or from the last renewal concluding with the 90th day before the renewal submission date,
- Data about the estimated benefit of use containing a summary overview of the efficacy (including data about an insufficient efficacy) from the first authorisation or from the last renewal concluding with the 90th day before the renewal submission date,
- Data about the estimation of the benefit/risk ratio for authorised indication,
- Last available data on the safe use, efficacy and efficiency of the medicinal product that are available during the report preparation.
The clinical expert should confirm:
- that all new available clinical data (or non-clinical data, if the non-clinical expert report has not been submitted) that change or lead to a new estimation of the benefit/risk ratio,
- that the authorisation for the medicinal product with regard to safe use may be renewed to an unlimited period or provide data on the proposed or undertaken measures associated with the safe use of the medicinal product,
- that all additional data important for the benefit/risk evaluation are submitted to competent authorities,
- that the medicinal product information is in compliance with the current scientific achievements, conclusions and recommendations published on the EMA web pages.
At Agency's request, the applicant for renewal is required to attach medicinal product samples and the assigned reference standards required for quality control.
Alongside the application for renewal, the marketing authorisation holder may notify changes in the Summary of Product Characteristics, Package Leaflet and Labelling of the medicinal product, namely the following variations:
- for harmonising the name for the pharmaceutical form and components according to the nomenclature in the Croatian Pharmacopoeia,
- for harmonising the form of the summary of product characteristics, package leaflet and labelling with the current templates not affecting the content thereof,
- that result from non-clinical and/or clinical documentation and impact the benefit/risk ratio of the medicinal product.
For any other change in the documentation the marketing authorisation holder is required to submit a separate application for variation approval.
Alongside the renewal of nationally authorised marketing authorisation, the marketing authorisation holder may submit an application(s) for renewal of the same medicinal product but other pharmaceutical form, strength or type and pack size(s), in order to harmonise all available data and product information.
The renewal procedure is set out in the following legislation: