The Pharma Legal Handbook: Croatia

Key legal info on litigation in Croatia. Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for GB 119.

 

1.Who has the burden of proof in litigation for drug side effects?

The burden of proof is on the plaintiff, there is no automatism. The parties are obliged to state all the facts on which their claims are based in the lawsuit and the response to the lawsuit, and at the latest at the preparatory hearing, to propose the evidence necessary to establish the stated facts and to state the facts and evidence of the opposing party. During the main hearing, the parties may present new facts and propose new evidence only if they could not present them without their fault, ie propose them before the conclusion of the preliminary proceedings.

The court must take into account the factual allegations and evidentiary motions of the parties that are legally relevant, but the court must not take into account facts and evidence to which neither party has relied on, no matter how relevant they might otherwise be in the dispute.

2. Can a party to the proceedings influence the selection of an expert witness? Can there be different expert witness findings?

The party proposing the presentation of evidence by an expert witness may propose the person of an expert witness. The court will allow the opposing party to comment on the proposed expert witness. The court will appoint a proposed expert if the opposing party does not object to the proposed expert, if the opposing party objects to the proposed expert witness, the expert witness shall be appointed by the court.

Exceptionally, the court may appoint another expert if it deems that the complexity of the expertise so requires, or if it deems it necessary to prevent the parties from disposing of requests which they cannot dispose of. In that case, the civil court may authorize the presiding judge or the requested judge to appoint experts if they are entrusted with the presentation of evidence by an expert witness.

The court manages the expertise, marks the expert subject for review, asks him questions and, if necessary, seeks explanations regarding the given finding and opinion. The expert witness may be given clarifications and may be allowed to review the file. At the expert’s request, new evidence may be presented in order to determine the circumstances that are important for the formation of the expert’s opinion.

The court will determine whether the expert witness will present his / her findings and opinion only orally at the hearing or will also submit them in writing before the hearing. The court shall set a deadline for the written submission of findings and opinions, which may not exceed 60 days. The expert must always explain his opinion.

If more than one expert is appointed, they may submit a joint finding and opinion when they agree on the finding and opinion. If they do not agree with the finding and opinion, each expert shall present his / her finding and opinion separately. If the expert’s information on their finding differs significantly, or if the finding of one or more experts is unclear, incomplete, or in conflict with itself or with the circumstances, and these deficiencies cannot be remedied by re-examining the expert, the expert examination shall be renewed by other experts.

If there are contradictions or shortcomings in the opinion of one or more experts, or there is reasonable doubt in the correctness of the given opinion, and these shortcomings or doubts cannot be eliminated by re-hearing the expert, the opinion of other experts will be sought.

3. Can an expert witness be an organization or must he or she be a person? Must a person be locally registered and have a practice in the country of litigation?

Expert examination, as a rule, is performed by one expert; and when the court finds that the expertise is complex, it may appoint two or more experts. Experts are appointed primarily from the ranks of permanent court experts for a certain type of expertise that is registered in Croatia.

The expertise can also be entrusted to a professional institution in Croatia (hospital, chemical laboratory, faculty, etc.). If there are special institutions for certain types of expertise such expertise, and especially more complex ones, will be entrusted, first of all, to these institutions.

 

4. Who has the right to choose the place of the court?

In the place of the plaintiff and in the place of the defendant if it is a claim for damages.

 

5. Are there different categories of damages to be compensated?

In Croatian obligation law, there are three basic forms of reparation: in-kind restitution, damages, and satisfaction.

In-kind restitution is the restoration of a condition that existed before the damage occurred.

Compensation is a form of reparation that consists of a monetary equivalent.

Satisfaction, as a form of repairing the damage that is recognized to the injured party as a certain subjective satisfaction (etc. moral satisfaction, monetary satisfaction).

Croatian law doesn’t recognize punitive damages.

 

6. Is there a pecuniary damages principle in litigation?

In Croatian litigation, there is a pecuniary and non-pecuniary damages principle.

 

7. Are there legal or practical limits on the amounts of compensation to be paid?

At the second session of the Civil Division of the Supreme Court of the Republic of Croatia held on 5 March 2020 and 15 June 2020, the orientation criteria and amounts for determining the amount of fair monetary compensation for non-pecuniary damage were changed.

These orientation criteria should enable the uniform application of the Law on Obligations.

They do not represent a mathematical formula that is used automatically to calculate fair monetary compensation. In the application of this regulation, one should always keep in mind all the circumstances of the case, where the duration and severity of physical and mental pain and fear have only the significance of particularly important, but not the only circumstances that the court must keep in mind when determining the amount of fair compensation.

The amendment to the Guidance Criteria applies to all civil proceedings for compensation of non-pecuniary damage in all stages of the trial (in the future), ie from the day of acceptance at the session of the Civil Department of the Supreme Court (June 15, 2020).

For example, in case of death a maximum compensation of 330.000,00 kuna, maximum compensation for physical and mental health: mental pain due to a decrease in life activity 67.500,00 kuna, the right to mental health 50.000,00 kuna, suffered fear 45.000,00 kuna.

 

8. How common are settlements?

Litigation settlements are an extremely rare way to end a dispute in Croatia. However, the trend of increasing settlements is noticeable. Many Attorneys are also authorized mediators.

 

9. Are there specialized judges or courts dealing with damages?

There are no specialized courts or judges that deal with damages, Civil divisions of municipal and county courts in addition to the civil division of the Supreme Court of the Republic of Croatia deal with damages.

 

10. How many stages of the trial are there?

There is three-stage litigation in Croatia. Commencement of litigation in the Municipal Court and the County Court as an appellate court, and the possibility to appeal on points of law and constitutional claim before the Supreme court respectively.

 

11. What are the costs of a regular dispute? Who bears the costs of litigation?

Initiating a lawsuit and litigation involves a number of costs that are difficult to fully comprehend before concluding. The total costs are largely related to the length of the litigation and the value of the dispute, which is determined based on the amount indicated in the lawsuit. Therefore, in practice, it is not uncommon for costs to reach enormous proportions after years of litigation.

Litigation costs are expenses incurred in the course or in preparation of the proceedings. In practice, the most common costs of civil proceedings are attorney’s fees, court fees, costs of court experts, costs of witnesses, court interpreters, and advances for the presentation of evidence.

The rule is that in the preparation and during the trial, each party pays the costs caused by its actions. Evidence includes all the facts that are important for making a decision, and each party is obliged to present the facts and propose evidence on which to base its claim or to refute the allegations and evidence of the opponent. When a party proposes the taking of evidence, he is obliged to deposit in advance by court order the amount necessary to cover the costs that will be incurred in connection with the taking of evidence.

The court fee is determined by the Law on Court Fees and the Tariff of Court Fees, which is an integral part of the said law. The court fees are determined based on the value of the subject matter of the dispute at the time the lawsuit is filed. For a claim of 100.000 EUR fee per hearing or a written statement is 1.000 EUR. In other words, the higher the claim – the higher the court fee, there is no upper limit on fees. According to experience, the costs are usually around 50.000,00 -100.000,00 kuna.

As in the case of court fees, attorneys’ fees in civil proceedings are determined based on the indicated value of the case or the type of dispute. The lower and upper limits are defined by the Tariff on Remuneration and Reimbursement of Attorneys’ Fees, which is determined by the Croatian Bar Association.

The basic rule is that the party who loses the lawsuit in its entirety is obliged to reimburse the opposing party for the costs. However, if a party succeeds in part in the proceedings, the court may order that each party bear its own costs or that one party reimburse the other for a proportionate part of the costs. In that case, the court first determines the costs of each party and then offsets the stated amounts and awards the difference to the party who is entitled to compensation of a larger amount. Reimbursement of costs is decided by the court at the request of the party. In doing so, the party is obliged to state the individual costs for which it seeks compensation and attach evidence (invoices, contracts, etc.) on the occurrence of the said cost and its settlement. When deciding what costs will be reimbursed to the party, the court determines the costs necessary to conduct the litigation and only recognizes them.

The plaintiff who withdraws the lawsuit is obliged to reimburse the opposing party for litigation costs. But if the suit is withdrawn immediately after the defendant has complied with the plaintiff’s request, the costs of the proceedings shall be reimbursed to the plaintiff by the defendant

You are entitled to an exemption from paying the costs of the proceedings if, according to your general financial situation, you cannot cover those costs without prejudice to the necessary maintenance of yourself and your family.

 

12. What is a statute of limitations for a lawsuit?

The three-year limitation period applies to claims for damages counting from when the injured party learned of the damage (when the damage occurred or when medical treatment was completed) and the person who caused the damage. 

Also from this Legal Handbook

Preclinical and Clinical Trial Requirements in Croatia – an overview. Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for GB 119.

 

1. Are clinical trials required to be conducted locally as a condition (stated or implicit) for marketing approval?

Clinical trials are not required to be conducted locally as a condition for marketing approval.

 

2. How are clinical trials funded?

Clinical trials are usually funded by a sponsor. A sponsor of a clinical/non-interventional clinical trial is a private individual or business entity who takes responsibility for the initiation of a clinical/non-interventional clinical trial, the management of a clinical/non-interventional clinical trial and/or the financing of a clinical/non interventional clinical trial.

A contract between the applicant and the legal entity in which the clinical trial is planned to be carried out has to establish:

• total cost of clinical trial,
• costs incurred by the applicant, including costs of medical and other services of a legal entity conducting clinical trials,
• the amount of compensation to legal persons, examinees and respondents,
• obligations of the applicant to bear the costs of all diagnostic procedures and examinations provided for in the test plan.

 

3. What are the requirements for preclinical and clinical trial protocols? Who must approve the protocols?

Clinical trials of medicinal products, including non-profit clinical trials, in Croatia may not commence without a favourable opinion of the Central Ethics Committee and the authorization of the Ministry of Health.

Protocol is a document that describes the objective(s), design, methodology, statistical considerations, and organisation of a trial. The protocol usually also gives the background and rationale for the trial, but these could be provided in other protocol referenced documents.

The contents of a trial protocol generally includes the following topics:

• general information;
• background information;
• trial objectives and purpose;
• trial design;
• selection and withdrawal of subjects;
• treatment of subjects;
• assessment of efficacy;
• assessment of safety;
• statistics;
• direct access to source data / documents;
• quality control and quality assurance;
• data handling and record keeping;
• financing and insurance;
• publication policy, and
• supplements.

 

4. What are the requirements for consent by participants in clinical trials?

Informed consent has to be written, signed by the subject, and dated, to take part in a clinical trial, taken freely further to duly received and appropriately documented information of its nature and significance, and implications and risks.

Where the person is not capable of giving consent, i.e. where a trial subject is unconscious, or suffering from severe mental impairment, or has no capacity to exercise her/his rights or where the person is under age, the consent is signed by his or her legal representative or guardian, after he had been made aware of the risks and the objectives of the trial. If the person concerned is illiterate or is unable to write, oral consent in the presence of at least one witness who is not a member of the investigating team may be given. Trial subjects may at any time withdraw their informed consent for the participation in the clinical trial. Prisoners or persons who might be coerced into giving consent to participate in a clinical trial, cannot be trial subjects by definition.

In obtaining and documenting informed consent, the investigator should comply with the applicable regulatory requirement(s) and should adhere to Good Clinical Practice and to the ethical principles that have their origin in the Helsinki Declaration. Prior to the beginning of the trial, the investigator should have the Committee’s written approval/favourable opinion of the written informed consent form and any other written information to be provided to subjects.

The written informed consent form and any other written information to be provided to subjects should be revised whenever important new information becomes available that may be relevant to the subject’s consent. Any revised written informed consent form, and written information should receive the Committee’s approval/favourable opinion in advance of use. The subject or the subject’s legally acceptable representative has to be informed in a timely manner if new information becomes available that may be relevant to the subject’s willingness to continue participation in the trial. The communication of this information has to be documented.

Neither the investigator, nor the trial staff, should coerce or unduly influence a subject to participate or to continue to participate in a trial.

None of the oral and written information concerning the trial, including the written informed consent form, should contain any language that causes the subject or the subject’s legally acceptable representative to waive or to appear to waive any legal rights, or that releases or appears to release the investigator, the institution, the sponsor, or their agents from liability for negligence.

The investigator, or a person designated by the investigator, should fully inform the subject or, if the subject is unable to provide informed consent, the subject’s legally acceptable representative, of all pertinent aspects of the trial including the written information and the approval/ favourable opinion by the Committee.

The language used in the oral and written information about the trial, including the written informed consent form, should be as non-technical as practical and should be understandable to the subject or the subject’s legally acceptable representative and the impartial witness, where applicable.

Before informed consent may be obtained, the investigator, or a person designated by the investigator, should provide the subject or the subject’s legally acceptable representative sample time and opportunity to inquire about details of the trial and to decide whether or not to participate in the trial. All questions about the trial should be answered to the satisfaction of the subject or the subject’s legally acceptable representative.

Prior to a subject’s participation in the trial, the written informed consent form should be signed and personally dated by the subject or by the subject’s legally acceptable representative, and by the person who conducted the informed consent discussion with the subject/legally acceptable representative.

If a subject is unable to read or if a legally acceptable representative is unable to read, an impartial witness should be present during the entire informed consent discussion. After the written informed consent form and any other written information to be provided to subjects, is read and explained to the subject or the subject’s legally acceptable representative, and after the subject or the subject’s legally acceptable representative has orally consented to the subject’s participation in the trial and, if capable of doing so, has signed and personally dated the informed consent form, the witness should sign and personally date the consent form. By signing the consent form, the witness attests that the information in the consent form and any other written information was accurately explained to, and apparently understood by, the subject or the subject’s legally acceptable representative, and that informed consent was freely given by the subject or the subject’s legally acceptable representative.

Both the informed consent discussion and the written informed consent form and any other written information to be provided to subjects should include explanations of the following:

1. That the trial involves research;
2. The purpose of the trial;
3. The trial treatment(s) and the probability for random assignment to each treatment;
4. The trial procedures to be followed, including all invasive procedures;
5. The subject’s responsibilities;
6. Those aspects of the trial that are experimental;
7. The reasonably foreseeable risks or inconveniences to the subject and, when applicable, to an embryo, fetus, or nursing infant;
8. The reasonably expected benefits. When there is no intended clinical benefit to the subject, the subject should be made aware of this;
9. The alternative procedure(s) or course(s) of treatment that may be available to the subject, and their important potential benefits and risks;
10. The compensation and/or treatment available to the subject in the event of trial-related injury;
11. The anticipated prorated payment, if any, to the subject for participating in the trial;
12. The anticipated expenses, if any, to the subject for participating in the trial;
13. That the subject’s participation in the trial is voluntary and that the subject may refuse to participate or withdraw from the trial, at any time, without penalty or loss of benefits to which the subject is otherwise entitled;
14. That the monitor(s), the auditor(s), the Committee, and the regulatory authority(ies) will be granted direct access to the subject’s original medical records for verification of clinical trial procedures and/or data, without violating the confidentiality of the subject, to the extent permitted by the applicable laws and regulations and that, by signing a written informed consent form, the subject or the subject’s legally acceptable representative is authorizing such access;
15. That records identifying the subject will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. If the results of the trial are published, the subject’s identity will remain confidential;
16. That the subject or the subject’s legally acceptable representative will be informed in a timely manner if information becomes available that may be relevant to the subject’s willingness to continue participation in the trial;
17. The person(s) to contact for further information regarding the trial and the rights of trial subjects, and whom to contact in the event of trial-related injury;
18. The foreseeable circumstances and/or reasons under which the subject’s participation in the trial may be terminated;
19. The expected duration of the subject’s participation in the trial,
20. The approximate number of subjects involved in the trial.

Prior to participation in the trial, the subject or the subject’s legally acceptable representative should receive a copy of the signed and dated written informed consent form and any other written information provided to the subjects. During a subject’s participation in the trial, the subject or the subject’s legally acceptable representative should receive a copy of the signed and dated consent form updates and a copy of any amendments to the written information provided to subjects.

When a clinical trial (therapeutic or non-therapeutic) includes subjects who can only be enrolled in the trial with the consent of the subject’s legally acceptable representative (e.g., minors, or patients with severe dementia), the subject should be informed about the trial to the extent compatible with the subject’s understanding and, if capable, the subject should sign and personally date the written informed consent.

Non-therapeutic trial (i.e. a trial in which there is no anticipated direct clinical benefit to the subject), should be conducted in subjects who personally give consent and who sign and date the written informed consent form.

Exception, non-therapeutic trials may be conducted in subjects with consent of a legally acceptable representative provided the following conditions are fulfilled:

1. The objectives of the trial cannot be met by means of a trial in subjects who can give informed consent personally;
2. The foreseeable risks to the subjects are low;
3. The negative impact on the subject’s wellbeing is minimised and low;
4. The trial is not prohibited by law, and
5. The approval/favourable opinion of the Committee is expressly sought on the inclusion of such subjects, and the written approval/favourable opinion covers this aspect. Such trials, unless an exception is justified, should be conducted in patients having a disease or condition for which the investigational product is intended Subjects in these trials should be particularly closely monitored and should be withdrawn if they appear to be unduly distressed.

In emergency situations, when prior consent of the subject is not possible, the consent of the subject’s legally acceptable representative, if present, should be requested. When prior consent of the subject is not possible, and the subject’s legally acceptable representative is not available, enrolment of the subject should require measures described in the protocol and/or elsewhere, with the documented approval/favourable opinion by the Committee, to protect the rights, safety and wellbeing of the subject and to ensure compliance with applicable regulatory requirements. The subject or the subject’s legally acceptable representative should be informed about the trial as soon as possible and consent to continue and other consent as appropriate should be requested.

 

5. May participants in clinical trials be compensated?

The clinical trial sponsor has to pay compensations to the trial subjects and to the business entity with whom the sponsor has signed the clinical trial agreement.

The total costs of the clinical trial and expenses of the applicant include compensations to investigators and subjects and are determined by a contract.

 

6. How are participants in clinical trials protected and indemnified against any harm that arises as a result of participation in the trial?

Before the beginning of a clinical trial, clinical trial sponsors or their authorized representatives established in the European Union have to be insured against liability for injury, death, or treating of trial subjects, related to the clinical trial.

Sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator/the institution against claims arising from the trial, except for claims that arise from malpractice and/or negligence.

The sponsor’s policies and procedures should address the costs of treatment of trial subjects in the event of trial-related injuries in accordance with the applicable regulatory requirement(s).

When trial subjects receive compensation, the method and manner of compensation should comply with applicable regulatory requirement(s).

 

Also from this Legal Handbook

Orphan drugs & rare diseases in Croatia – a legal guide. Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for GB 119.

 

1. What is the definition of Rare Diseases in your country?

Simply put, an orphan drug is indicated for the treatment of a very rare disease. Such diseases are often caused by genetic defects and therefore children and newborns are affected to a great extent. Rare diseases are defined as life threatening diseases or diseases that may lead to chronic weaknesses, affecting maximally five out of 10,000 people in the EU. In other words, between 27 and 36 million people in the EU are affected by a rare disease.

 

2. Does the designation of ‘Orphan Drug’ exist in your country? (Does it correspond with the definition of Rare Diseases?)

Since Croatia is an EU member, all EU regulations are directly applicable, thus Regulation (EC) 141/2000 (so called “Orphan” Regulation) and Regulation (EC) 847/2000 are binding in their entirety and directly applicable in all Member States. A product can gain orphan drug status if it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than five in 10,000 people in the EU. A medicinal product shall be designated as an orphan medicinal product if its sponsor can establish: that it is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition in the Community and that without incentives it is unlikely that the marketing of the medicinal product in the Community would generate sufficient return to justify the necessary investment. Also the product shall be designated as an orphan drug if there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorised in the Community or, if such method exists, that the medicinal product will be of significant benefit to those affected by that condition.

 

3. What is the regulatory framework for the authorization of an Orphan Drug? (Is this regulatory framework based on Rare Disease status or can it alternatively be based on Orphan Drug foreign status?)

The Regulation (EC) 141/2000 also establishes the Committee for Orphan Medicinal Products (COMP) within the European Medicines Agency (EMA), which is responsible for examining applications for orphan medicinal product designations. Regulation (EC) No 726/2004 provides the legal framework for the centralised authorisation and supervision of medicines for human and veterinary use. It determines that all marketing authorisations for orphan medicines in the EU should follow the centralised authorisation procedure and that the Committee for Medicinal Products for Human Use (CHMP) can issue guidance regarding compassionate-use programmes. After finalising the designation procedure, the sponsor needs to apply for an authorisation to place the product on the market.

 

4. Does your country have provisions for relaxed clinical trial/scientific evidence requirements in respect of Orphan Drugs as compared to other drugs?

The overall procedure for designation as an orphan drug (for the entry into the Community register for orphan medicinal products), in theory takes approximately six to eight months until the designation is granted. The whole process starts with an application for designation by the sponsor. All documents and information necessary for applying are more or less broadly formulated. The exact time of filing the application is not fixed; the only thing to keep in mind is that one has to apply for an orphan drug designation before making the marketing authorisation application.

The addressee of that application is the EMA. The EMA verifies the validity of the application and prepares a summary report to the Committee for Orphan Medicinal Products (COMP) which is set up within the agency. The COMP has to submit an expert’s opinion within 90 days of receiving the valid application. If everything goes according to plan, and there are no discrepancies within the COMP, the EMA forwards this opinion to the European Commission, which in turn has to render a decision within 30 days – as long as COMP’s opinion and the Commission’s decision correspond.

 

5. Is there an expedited pathway for Orphan Drugs?

In the EU, conditional marketing authorization was instituted in 2006 and the requirements are as follows: (1) It must fulfill an unmet medical need; (2) it must be applicable to life-threatening, serious, or emergency diseases, or orphan products; (3) The company must be able to provide clinical data comprehensively; and (4) There must be a positive benefit/risk balance. Conditional marketing authorization is active for one year only and annual renewal of the approval will continue until the EMA converts the conditional approval to standard authorization. In addition, conditional approval is applicable to applications of initial marketing authorization only, and efficacy supplement applications are beyond the scope of the conditional approval.

 

6. Are foreign marketing authorizations recognized in your jurisdiction for Orphan Drugs? If yes, marketing authorizations from which countries are recognized?

The European Medicines Agency (EMA) is responsible for the scientific evaluation of marketing authorisation applications for all orphan medicines in the European Economic Area (EEA), as they fall under the mandatory scope of the centralised procedure. The marketing authorisation is valid in the whole European Union. The sponsor does not need to apply for an authorisation in all – still – 28 Member States separately. It will have to be seen if and how that will change for the UK, with Brexit on the horizon. However, the granting of a marketing authorization (the list of marketed orphan drugs in Europe) does not mean that the drug is available in all EU Member States. The marketing authorization holder must decide in advance on his commercialization within each country and only then the remedy goes through the necessary national procedures to meet the conditions for the refund and often its price.

 

7. Can Orphan Drugs be reimbursed? If so, is there a specific reimbursement procedure for Orphan drugs?

The objective is to assess shares of reimbursed orphan drugs and agreement in reimbursement decision-making in different European Union member states as well as to define odds for reimbursement influenced by the presence of conditional approval or exceptional circumstances granted by the European Medicines Agency (EMA) or by type of disease. Access to reimbursed orphan drugs varies significantly across EU countries. The highest, substantial agreement in reimbursement decisions was observed between Italy and Spain and the lowest between Germany and England. Conditional approval and approval under exceptional circumstances were significant negative predictors of reimbursement in some countries and they were significantly associated with the type of the disease (oncology or metabolic).

 

8. How are the prices of Orphan Drugs regulated?

Pricing and accessibility of orphan drugs varies among countries in the EU. Although orphan designation and marketing authorisation is at a European level, pricing and reimbursement are on a national level, often driven by health technology assessment (HTA) outcomes and with variable impact from external reference pricing. In these HTAs, evidence requirements, pricing and reimbursement decision frameworks, and budget ceilings vary. Also, national responsibilities for price listing and the process in which prices are granted vary widely. As a consequence, prices and levels of access may vary.

 

9. In case of reference price based on a basket of countries, what countries are included?

The basis for determining the comparative price of a wholesale drug is the wholesale price of the same medicine (medicine of the same generic name and of the same pharmaceutical form) in Italy, Slovenia and the Czech Republic, and if there is no information on the prices of medicines for one or more countries, then the prices of medicines in Spain and France are used for comparison.

 

10. Have there been any significant legal/judicial developments in relation to Orphan Drugs in your country?

There is no national legislation that applies only to Orphan Drugs and that unites all legal provisions about Orphan Drugs, because the aforementioned EU regulations are directly applicable and are a part of domestic law.

Medicines for the treatment of symptoms of rare diseases very often belong to the groups of innovative and especially expensive drugs, that is, a separate group of “orphan” medicines. Croatia adopted new Ordinance on the criteria for placing medicinal products on the list of medicinal products of the Croatian Health Insurance Fund (CHIF). The adopted Ordinance did not clearly define the arrival of orphan medicines on the CHIF list, and by restricting the availability of the arrival of innovative medicines and extending the indications of medicines in the CHIF list, it limits the availability of treatment. However, Orphan drugs problem is in the vision of the Croatian Government. National Program for Rare Diseases 2015-2020 was adopted at the session of the Government, held on March 5, 2015. The program encompasses nine strategic areas of activity: education and information for professionals, people with illness and wider population, prevention and early detection of rare diseases, integrated health and social protection and promotion of rare diseases.

 

11. Are there proposals for reform or significant change to the regulation of Orphan Drugs? If yes, when are they likely to come into force?

The Regulation (EC) 141/2000 (Orphan Drug Regulation) which has – nowadays, rather surprisingly – only undergone one amendment in 2009. Considering the regulation has been in force for 20 years already without any major changes, it seems that the European legislator has succeeded in passing a profound and mature law that is worth taking a closer look at. At this moment there are no proposals for reform or significant change to the Regulation. However, on the national scale, it is still not foreseen by the National program for Rare Diseases 2015-2020 to pass the law related to Orphan Drugs. The highlights of the National program that are pointed out as the main problems in Croatian system of Orphan drugs that need to be solved are: improving the knowledge and availability of rare disease information, support for the development of rare diseases registers and their permanent financing, supporting the work and development of network of reference centres and relevant scientific organizations for rare diseases, improving availability and quality of health care (diagnosis, treatment and prevention) for people with rare diseases, ensuring availability of medications for rare diseases, improving the realization of social rights of rare diseases, empowering Associations of Rare Diseases, encouraging scientific research in the field of rare diseases, international networking and cooperation in the field of rare diseases.

 

Also from this Legal Handbook

An insight into upcoming regulatory reforms affecting Croatia pharma. Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for GB 119.

 

1. Are there proposals for reform or significant change to the healthcare system?

Bill of Ordinance on benchmarks for the classification of medicinal products on basic and additional list of medicinal products of the Croatian Health Insurance Fund and on benchmarks on pricing of medicinal products is drafted.

 

2. When are they likely to come into force?

Above-mentioned Ordinance comes into force in July 2019.

 

Also from this Legal Handbook

Key legal info on biosimilars & biologics in Croatia. Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for GB 119.

 

1. Are biosimilar medicines considered the same as generic medicines in your country?

Biosimilar medicines are not the same as generic drugs (a drug that contains the same molecule as an existing non-biological medicine, such as aspirin). Namely, biological medicine, unlike non-biological medicines, cannot reproduce correctly (see the above-mentioned explanation). Biosimilar medicines have nothing to do with complementary or natural medicines or herbal medicines.

The generic medicinal product shall mean a medicinal product which has the same qualitative and quantitative composition in active substances and the same pharmaceutical form as the reference medicinal product, and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies.

A biosimilar medicinal product is a medicinal product with a proven similarity in terms of quality, biological activity, safety and efficacy as the approved original biological medicinal product. Due to complex active substance structure and manufacturing procedure of biological medicinal products it is unlikely to produce a biological medicine with a completely identical active substance structure as the original biological medicine. Therefore, the standard approach in development and approval of generic chemical medicines, based on bioequivalence with original medicine, may not be applied to biosimilar medicinal products, but rather their similarity with original medicines should be proved through further studies during the product development and marketing authorisation procedure.

 

2. Are all biologic medicines, including biosimilar medicines patentable in your country?

Once EMA has thoroughly assessed their quality, efficiency and safety, the European Commission can approve biosynthetic medicines for marketing throughout the EU. Their availability then depends on the decision to place medicines on the market that the company brings together with the institution responsible for medicines and health care services in each EU country. In Republic of Croatia the institution responsible for medicines and health care services is called The Agency for Medicinal Products and Medical Devices (HALMED). It was established on October 1^st, 2003. as a legal successor to the Croatian Institute of Medicines Control and the Croatian Institute of Immunobiological Preparations Control, albeit with a considerably broader scope of work. The Agency was established by the Republic of Croatia. Legal compliance of the Agency is supervised by the Ministry of Health. The Agency provides services pertaining to medicinal products, medical devices and homeopathic medicinal products in accordance with the primary and secondary legislation of the Republic of Croatia.

 

3. Is there a specific regulatory framework for the marketing authorization of biosimilar medicines in your country? If yes, what is the regulatory framework for the authorization of biosimilar medicines?

All biosimilar medicinal products currently approved in the Republic of Croatia have been authorised via centralised procedure for granting marketing authorisation, which means that the European Medicines Agency (EMA) scientifically reviewed the products and the European Commission has granted marketing authorisations. The quality, efficacy and safety assessment at the EMA is carried out at the highest scientific and technical level involving experts from all the EU Member States. The scientific opinion is adopted at the Committee for Medicinal Products for Human Use (CHMP) and the Pharmacovigilance and Risk Assessment Committee (PRAC). Within the scope of its work, the CHMP is additionally advised from working groups of experts with narrow specialisation in biological medicinal products (Biologics Working Party, BWP) and biosimilar medicinal products (Biosimilar Medicines Working Party, BMWP).

 

4. What kind of data package is needed to obtain approval for a biosimilar drug? Is this any different to the requirements for the original Biologics drug?

In order to obtain marketing authorisation, the manufacturer is required to perform comprehensive testing as evidence that the biosimilar medicinal product is very similar to the original biological medicinal product in terms of quality, safety and efficacy.

 

5. What are the requirements for the choice of the reference comparator product?

In cases where the reference medicinal product referred to in Article 29 paragraph 4 of the Promulgating the Medicinal Products Act is not authorised for marketing in the Republic of Croatia, the applicant for marketing authorisation of a generic product shall indicate the EU Member State in which the reference medicinal product is or has been authorised, as well as the date of the initial authorisation. In cases where the reference medicinal product is or has been authorised for marketing in the Republic of Croatia, on request of the competent authority of the EU Member State, the Agency shall within a month submit a certificate showing that the reference medicinal product either is or has been authorised for marketing in the Republic of Croatia, accompanied by the data on the general composition of the reference medicinal product and also, if required, by any other information from the medicinal product dossier.

In cases where the medicinal product does not fall within the definition of a generic medicinal product as provided in Article 29 paragraphs 5, 6, 7 and 8 of this Act or where the bioequivalence cannot be demonstrated through bioavailability studies or in case of variations in the active substance(s), therapeutic indications, strength, pharmaceutical form or route of administration, the marketing authorisation applicant referred to in Article 26 paragraph 1 of this Act shall be required to attach to the application the results of the appropriate pre-clinical tests and clinical trials in accordance with Article 26 paragraph 3 (k) of this Act.

 

6. Can the comparator product be sourced from another regulatory jurisdiction? If yes, what are the data needed to support this approach?

Without prejudice to the regulations relating to the protection of industrial and intellectual property, the applicant referred to in Article 26 paragraph 1 of this Act shall not be required to provide the results of pre-clinical tests and of clinical trials, referred to in Article 26 paragraph 3 item (k) of this Act, if he can demonstrate that the medicinal product is a generic which is or has been authorised for not less than eight years in an EU Member State based on the centralised marketing authorisation procedure.

 

7. How are the prices of biosimilar medicines regulated? Is this any different to the requirements for the original Biologics drug?

The price of the first biosimilar medicines proposed for listing should not exceed 80% of the cost of the drug with the same active ingredient (the same unprotected name) that is already on the list of medicines of the Institute.

The price for each next generic medicine proposed for placing on the list of drugs and for the biosimilar medicines biosynthesis drug proposed for inclusion on the list of medicines, should not exceed 95% of the cost of the same unprotected name as defined in this article.

 

8. What is the reimbursement policy for biosimilar medicine? Is this any different to the requirements for the original Biologics drug?

The share of expenditures on reimbursement of biosimilars in the total pharmaceutical budget differed between the EU countries, with lowest observed value for Croatia. In Croatia only Budget Impact Analysis (BIA) is required for biosimilars, and in certain cases, the Croatian HALMED Agency performs Health technology assessment or (HTA) evaluation.

 

9. Does biosimilar competition impact the reimbursement policy of the originator reference products?

Usually, the price difference between the biosimilar and originator medicine was set at a lower percentage rate than that between the generic and originator (e.g., 30%—generics, 15%—biosimilars in Croatia. European countries tend to in general apply similar pricing policies for generic and biosimilar medicines.

 

10. What is the legal framework for biosimilar medicines prescribing (clinical decision maker) and dispensing (pharmacy level, hospital or retail)? Is this any different to the requirements for the original Biologics drug?

Substitution and interchangeability are generally allowed, although they are at the discretion of the physician after a clinical assessment. Decision-making process for purchasing and procurement always involve a committee involving medical or scientific advice. There are not any quotas on biological drugs.

 

11. Is the system considering physician-led switching and/or pharmacy-level substitution (without involvement of the clinical decision maker)?

Substitution refers to the practice of dispensing one medicine instead of another equivalent and interchangeable medicine at the pharmacy level without consulting the prescriber, in Croatia it is not possible, and there are no propositions about switching to pharmacy level substitution.

 

12. What are the post – authorisation requirements (including pharmacovigilance, risk management plans, post-approval studies) for biosimilar medicines? Is this any different to the requirements for the original Biologics drug?

After obtaining a marketing authorisation for a medicinal product, the marketing authorisation holder shall be required to:

1. take account of scientific and technical progress and introduce any variations that may be required to enable the medicinal product to be manufactured and checked by means of generally accepted scientific methods,
2. forthwith provide the Agency with any new information which might entail amendments to the data, documents and files of the medicinal product provided in the frames of the marketing authorisation procedure or the arbitration proceedings in the European Union and/or the ordinance referred to in Article 26 paragraph 7 of this Act,
3. forthwith inform the Agency of any restriction or prohibition imposed by the competent authorities of other states in which the medicinal product is marketed and of any other new information which might influence the benefits and risks of the medicinal product concerned. The marketing authorisation holder shall supply the Agency with both positive and negative results of clinical and other studies in all indications and populations of subjects, whether or not included in the marketing authorisation, as well as data on the use of the medicinal product where such use is not covered by the marketing authorisation,
4. ensure that the product information is kept up to date with the current scientific knowledge, including the conclusions of public reports relating to assessment of the medicinal product dossier and recommendations of the EMA made public by means of the European medicines web-portal.

In the case referred to in paragraph 1 of this Article the Agency may require that the marketing authorisation holder initiates the procedure for variation(s) approval or to amend, ex officio, the authorisation for placing the medicinal product on the market.

In order to enable continuous assessment of the risk-benefit balance, the Agency may at any time ask the marketing authorisation holder to forward data demonstrating that the risk benefit balance of the medicinal product remains favourable.

The Agency may at any time ask the marketing authorisation holder to submit a copy of the pharmacovigilance system master file. The marketing authorisation holder shall submit the copy at the latest seven days after receipt of the request.

 

13. Are there specific policies and requirements in terms of biosimilar medicines labelling in the event of second medical use patents? Is this any different to the requirements for the original Biologics drug?

Labels on medicinal products contain information for pharmacists, physicians and patients. This information is presented in the Summary of Product Characteristics (SmPC), the Patient Leaflet (PL) and the immediate label on the outer product packaging, referred to as ‘labelling’. Once authorized, the European Medicines Agency (EMA) applies a ‘same-label’ (generic) approach to biosimilar product labels. This means that the information on the labelling of the biosimilar should be a copy of the approved labelling of the reference product, with the exception of the pharmaceutical particulars. Section 5.1 of the SmPC, a document not usually available to patients, will include a statement declaring that the product is a biosimilar, but this is the only part of the labelling where this information can be found. Neither PLs nor the immediate labels contain this information.

 

14. Have there been any significant legal/judicial developments in relation to biosimilars in your country? (Including but not limited to IP, procurement, competition, misleading information campaign, access to reference comparator product)

There have not been any significant developments in relations to biosimilars but are expected.

 

15. Are there proposals for reform or significant change to the legal, regulatory, procurement of biosimilars? If yes, when are they likely to come into force?

No, there are no proposals for comprehensive reform that would redact the legislation of biosimilars.

 

Also from this Legal Handbook

All about traditional medicines and OTC products in Croatia. Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for GB 119.

 

1. What are the regulatory requirements for traditional, herbal, complementary, or alternative medicines and devices?

Regulatory requirements for traditional herbal or homeopathic medicinal products are regulated by the provisions of Medicinal Products Act and traditional herbal medicinal products are also regulated by Ordinance on the Marketing, Labelling and Advertising of Traditional Herbal Medicinal Products (only for advertising).

The provisions of Medicinal Products Act relating to the placement of a medicinal product on the market, production, classification, advertising, distribution, importation, quality control, pharmacovigilance, suspension of marketing and withdrawal from the market and supervision appropriately applies also to the traditional herbal medicinal products, except if not otherwise provided for by this Act or an ensuing regulation.

The registration of a traditional herbal medicinal product is refused if the data and documents accompanying the motion differ from those required and if one of the following reasons is established:

• the quantitative and/or qualitative composition is not as declared, or
• the indications do not comply with the conditions laid down by Medicinal Products Act, or
• the traditional herbal medicinal product could be harmful under usual conditions of use, or
• the data on traditional use are insufficient, especially if pharmacological effects or efficacy are not plausible on the basis of long-standing use and experience, or
• pharmaceutical quality is not satisfactorily demonstrated.

Agency informs the European Commission, and any other competent authority that may so require, about the decision to refuse the registration of a traditional herbal medicinal product as well as about the reasons behind such decision.

Placing on the market homeopathic medicinal products is subject to the possession of a marketing authorisation granted by the Agency or a decision on enrolment in the register issued by the Agency pursuant to the provisions of this Act and the ensuing regulations.

The provisions of this Act relating to homeopathic medicinal products applies to anthroposophic medicinal products prepared by a homeopathic method, described in the current version of pharmacopoeias being in effect in EU Member States.

A simplified procedure for obtaining marketing authorisation for homeopathic medicinal products, or a register enrolment procedure for homeopathic medicinal products, is conducted for homeopathic medicinal products placed on the market without therapeutic indications.

The enrolment in the register of homeopathic medicinal products is conducted for homeopathic medicinal products complying with the following requirements:

• that they are intended for oral or topical administration;
• that there is no reference to their therapeutic indications or data referring to the indication in the package leaflet or on the product label of the homeopathic medicinal product, and
• that they are sufficiently diluted to guarantee safe use of the medicinal product; in particular, homeopathic medicinal products do not contain more than one part per 10.000 mother tincture, or more than 1/100th of the smallest therapeutic dose of the active substance which would be required for the medicinal product referred in Medicinal Product Act to be dispensed on medical prescription.

In the register enrolment procedure for a homeopathic medicinal product the Agency specify dispensing classification of the homeopathic medicinal product.

The provisions of Medicinal Products Act concerning the product label and the package leaflet appropriately apply to homeopathic medicinal products.

Homeopathic nature of the medicinal product is clearly and legibly indicated on the outer and immediate packaging of the homeopathic medicinal product.

The provisions of Medicinal Products Act concerning advertising of medicinal products also appropriately apply to homeopathic medicinal products.

The provisions of Medicinal Products Act concerning marketing, manufacture, distribution, import, quality control, suspension of marketing and withdrawal from the market and supervision of medicinal products also appropriately apply to homeopathic medicinal products, if not otherwise laid down by this Act.

The provisions of Medicinal Products Act concerning pharmacovigilance also appropriately apply to homeopathic medicinal products with marketing authorisation.

 

2. Can these traditional, herbal, complementary, or alternative products be advertised directly to the public?

Traditional herbal and homeopathic medicinal products are not subject to medical prescription so they may be advertised to the public.

 

3. What health, advertising, and marketing claims may be made for traditional, herbal, complementary, or alternative products?

Advertising of traditional herbal and homeopathic medicinal product falls under the same regulation as advertising other medicinal products. Advertising of all medicinal products must meet the general requirements provided by Medicinal Products Act.

When advertising traditional herbal medicinal product the following message has to be contained within the advertisement or notice: “Traditional herbal medicinal product for use for the listed indications based on the experience of long-term use”.

The advertising of a product cannot contain any claim on its medicinal properties unless the product is authorised as a medicinal product or registered as a traditional herbal medicinal product.

The provisions of Ordinance on the Manner of Advertising Medicinal Products regulating manner of advertising medicinal products in general apply appropriately to homeopathic medicinal products.

All claims listed in the advertisements for the medicinal product have to be aligned with the claims from the most recent approved package leaflet and summary of product characteristics of the medicinal product in Croatia.

Advertising on the medicinal product ensures the transfer of true and scientifically proven information on the medicinal product, with the abidance of ethical criteria, for the purpose of the proper and rational treatment of patients, without misleading healthcare professionals to recommend, prescribe or dispense medicinal products and medicinal product users in cases when advertising is permitted towards the population.

When advertising homeopathic medicinal products only the following data may be used:

• the scientific name of a homeopathic source or sources and the indication of dilution using pharmacopoeial symbols; where the homeopathic medicinal product contains two or more homeopathic sources, in addition to the scientific names of the sources, an invented name of the medicinal product may appear on the label;
• the name and address of the holder of the decision of enrolment in the register of a homeopathic medicinal product and, in necessary, the manufacturer’s name and address;
• the pharmaceutical;
• the indication » homeopathic medicinal product without proven therapeutic indications;
• the method of administration and, if necessary, the route of administration;
• the content of the packaging expressed in weight, volume or units of dos-age of the homeopathic medicinal product;
• special storage precautions, if applicable;
• expiry date of the homeopathic medicinal product (month and year), a warning instructing patients to consult a physician if symptoms fail to disappear during use of the homeopathic medicinal product;
• a special warning, if necessary;
• dispensing of the homeopathic medicinal product;
• batch number, and
• number of the decision on the enrolment in the register of the homeopathic medicinal product.

 

4. What are the regulatory requirements for over-the-counter (non-prescription) medications?

Over the counter medications are regulated by Medicinal Products Act and its regulations. Requirements for development, manufacture, authorization and pricing are in general the same for all medicinal products.

Medicinal products are subject to medical prescription where they:

• are likely to present a danger either directly or indirectly, even when used correctly, if utilized without medical supervision;
• are frequently and to a very wide extent used incorrectly, and as a result are likely to present a direct or indirect danger to human health;
• contain substances or preparations thereof, the activity and/or adverse reactions of which require further investigation, or
• are normally prescribed by a doctor to be administered parenterally.

Medicinal products not covered by these criteria may be dispensed without medical prescription.

 

5. Are there any limitations on locations or channels through which OTC products may be sold?

Medicinal products not subject to medical prescription are dispensed in pharmacies and also in specialized retail sale outlets for medicinal products in line with the marketing authorisation granted by the Agency.

Private individual and business entitiy engaged in pharmacist activity in Croatia may over the Internet offer for distance selling, in line with a special regulaton, medicinal products which are not subject to medical prescription.

 

6. What health, advertising, and marketing claims may be made for OTC products?

In the advertising of a medicinal product that is dispensed without a prescription, the following message has to be contained within the advertisement or in the notification: “Prior to use, carefully read the instructions for use, and consult your doctor or pharmacist about the possible risks and adverse reactions”.

The warning has be prominent (e.g. in a noticeable colour or in a frame) and takes up at least one-tenth of the size of the advertisement, and has to be written in a font size that can be read without difficulty.

For television advertisements, the warning has to be shown independently (in its own shot) and has to be read in a clearly understandable voice.

For television and radio advertisements, advertisements serving as a reminder are implemented in such a way that in the promotional block, the entire advertisement of the medicinal product is played in its entirety, and following this in the same promotional form, the advertisement may follow as a reminder.

In internet advertising, the warning has to be an integral part of the main page of the advertisement, and not a link.

The advertisement of the medicinal product may not be misleading, and it has to be clearly visible that it is an advertisement. In printed articles and articles published on the internet which advertise the medicinal product, it is necessary to state: “Sponsored advertisement of a medicinal product” in a visible part of the article, with a font size equal to or larger than the font size in the remainder of the article.

The advertisement on the medicinal product for which advertising is permitted towards the population, contains at least the following information:

1. name of the medicinal product, if the medicinal product contains only one active substance and the international name of the active substance;
2. necessary notification for proper use, and
3. informing patients to carefully read the package leaflet or the instructions on the external packaging or container of the medicinal product.

Advertising on a medicinal product that serves as a reminder and consists exclusively of the name of the medicinal product or joint name of multiple medicinal products, is exempted from the motion of the above-mentioned requirements from, and the requirement Ordinance on the Manner of Advertising Medicinal Products.

The following is not permitted in advertising a medicinal product towards the population:

1. claims that the medicinal product has no adverse reactions, is not toxic or has no risk of addiction, or diminishing the significance and frequency of adverse reactions;
2. giving the impression that the medicinal product guarantees success in the treatment of disease;
3. suggesting that a specific medicinal product is undoubtedly better than other medicinal products;
4. claims that the medicinal product may be taken when there are no signs of disease, i.e. that it improves health;
5. claims that not taking the medicinal product may negatively impact health, except in the case refulated by Ordinance on the manner of advertising medicinal products;
6. suggesting that the medicinal product is safe and efficient due to its natural origin;
7. claim that the medicinal product represents a dietary, cosmetic or other mass use product;
8. suggesting that by taking the medicinal product a person may avoid a physician’s exam, advise or surgical procedure, and giving diagnoses or offering advise on treatment via post or e-mail;
9. suggesting that a prescribed medicinal product be replaced by another;
10. advertisement directed exclusively or primarily towards children, show-ing children taking the medicinal product on their own, or that the medicinal product is within their reach without the presence of an adult;
11. including the recommendation of healthcare professionals or scientists, or including in the advertisement persons whose popularity could stimulate the use of the medicinal product;
12. listing the notice of the inclusion of the medicinal product on the list of medicinal products prescribed in Croatia at the expense of the mandatory  healthcare insurance fund in the system of primary, secondary and tertiary  healthcare, except in the cases from Article 7, paragraph 3 of this Ordinance;
13. use of the medical history or simulation of diagnostic procedures that could lead to incorrect self-treatment or self-diagnosis;
14. use of illustrative displays of changes to the human body caused by dis-ease, injury or effect of a medicinal product on the human body or parts of the body in an inappropriate, disturbing or misleading manner, or
15. referring to evidence of cures in an inappropriate, disturbing or misleading manner.

 

7. Can OTC products be marketed or advertised directly to the public?

Yes. Advertising towards the population is permitted exclusively for medicinal products that are dispensed without a prescription (over-the-counter), pursuant to the marketing authorisation for the medicinal product.

 

8. What is the mechanism by which a prescription-only product can be converted to an OTC product?

Mechanism by which a prescription-only product can be converted to an OTC product is regulated by Ordinance on Granting Marketing Authorisations for Medicinal Products and Medicinal Products Act.

The conditions, documentation and manner of approving changes to the manner of dispensing medicinal products is conducted pursuant to the valid guidelines of the European Commission, recommendations of the European Directorate for the Quality of Medicines (hereinafter: EDQM) and the provisions of this Ordinance on Granting Marketing Authorisations for Medicinal Products (Official Gazette No. 83/13).

Alongside the documentation on the medicinal product for which the authorization holder wants to change the manner of dispensing, the authorisation holder is obliged to submit:

• the proposal of the Summary of product characteristics, package leaflets and labelling of the medicinal product, including a mock-up of the external and internal packaging of the medicinal product;
• risk management plan that defines the possible risks stemming from the changes to the manner of dispensing the medicinal product, and the proposal for managing those risks, if necessary, and
• results of testing the comprehensibility and simplicity of the package leaflet.

The authorisation holder is obliged to submit the request for approval of the changes of the manner of dispensing the product.

Alongside the request for a change of the place of dispensing the medicinal product, the authorisation holder is obliged to submit the following documentation:

• expert report on the clinical documentation that should contain a critical review of the safety of the medicinal product, with regard to the dispensing of the medicinal product outside of pharmacies;
• data on the expert for the clinical documentation;
• proposal of the Summary of product characteristics, package leaflets, labelling of the medicinal product and mock-up of the external and internal packaging of the medicinal product;
• risk management plan that defines the possible risks stemming from changes to the place of dispensing the medicinal product, and proposals for managing those risks, if necessary, and
• results of testing the comprehensibility and simplicity of the package leaflets, if applicable.

The Agency website provides the conditions for approval of the place and/or manner of dispensing the medicinal product, taking into account the safety profile of the active substance, motion route of the medicinal product, pharmaceutical, size of packaging, maximum individual daily dose, indications or other conditions of use of the medicinal product.

For medicinal products meeting the prescribed conditions, the authorization holder is obliged to confirm that all the prescribed conditions have been met in full.

On its website, the Agency publishes the list of medicinal products having marketing authorisation in Croatia, with regard to the manner and place of dispensation.

By way of derogation, the Agency may, pursuant to new findings about the medicinal product, re-examine its prior decision on classification of the medicinal product, if it deems that it is necessary, for the purpose of protecting the health of the population, to alter the manner and/or place of dispensation of the medicinal product, and has to inform the marketing authorisation holder thereof. The marketing authorisation holder, pursuant to the Agency notification, is obliged within a deadline of 30 days from the date of delivery of the notification, to initiate the appropriate procedure for the authorisation of amendments to the manner and place of dispensation of the medicinal product, in accordance with the Medicinal Products Act and the ordinances adopted pursuant to the Act.

 

9. What are the requirements for the importation of either traditional medicines or OTC products?

Only medicinal products in respect of which a marketing authorization has been granted and medicinal products in respect of which an authorisation for parallel imports or parallel distribution has been granted may be distributed in Croatia.

Provisions of Medicinal Products Act relating import appropriately applies to the traditional herbal medicinal products as well as to OTC medicinal products.

Import of medicinal products is conducted by importers of medicinal products complying with the requirements of Good Manufacturing Practice in the extent that applies to them. For conducting the above-mentioned activity, a manufacturing authorization is required.

Importers importing medicinal products from third countries, and who do not have at their disposal premises and equipment for quality control of every batch of imported medicinal products, may for that purpose conclude a contract with a business entity or private individual possessing a manufacturing authorisation that covers quality control of medicinal products.

Batches of medicinal products on which quality control was conducted in an another Member State of the European Union or, are not be subject to additional quality control, but can also be released in Croatia on the basis of a certificate of quality control of a medicinal product in a Member State of the European Union signed by a responsible person for release of a medicinal product batch.

When a medicinal product is imported from a state which has concluded an agreement on mutual recognition in the field of medicinal products with the European Union, a medicinal product is placed on the market in Croatia on the basis of a certificate of quality control from the exporting country.

Business entity and private individual seated in Croatia conducting the activities of manufacture, import and supply of active substances are enroled in the register of manufacturers, importers, or wholesalers of active substances.

The certificate of the compliance with the Good Manufacturing Practice is issued by the Agency inspection, within 90 days from conducting supervision of the Good Manufacturing Practice at the request of the manufacturer or the importer.

The Minister of Health lays down in an ordinance the method of the issuing the certificate of compliance with the Good Manufacturing Practice.

Agency’s approval for entry or import is not required for:

• medicinal products authorised for wholesale distribution by the Agency or the European Commission;
• medicinal products authorised for parallel importation or parallel  distribution;
• active substances and excipients, and
• intermediate products or medicinal products, where some production processes are carried out in Croatia.

The above-mentioned exemptions do not apply to the approval for entry or importation of:

• medicinal products made of human blood or plasma;
• immunological medicinal products, and
• radiopharmaceuticals.

The Minister issues an ordinance establishing detailed conditions for granting the approval for entry or importation of medicinal products in these cases

 

Also from this Legal Handbook

Want to know more about localization in Croatia? Read on! Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for GBP 119.

 

1. Are there any rules or regulations requiring and/or encouraging localization in your country? What is the legal framework defining these localization rules and policies?

There are not any specific rules or regulations regarding localization in Croatia. There are only general rules about support that apply to all investors such as tax aid for small, medium and large enterprises, support for the eligible costs of job creation linked to the investment project, support for eligible training costs associated with the investment project, and support for R&D activities.

For investments in the amount of EUR 150,000.00, to EUR 1,000,000.00, the income tax rate is reduced by 50% of the prescribed income tax rate for the period up to 10 years from the beginning of the investment, provided that at least five new jobs are opened related to the investment.

For investments in the amount of EUR 1,000,000.00, to EUR 3,000,000.00, to the aid beneficiary, the corporate income tax rate shall be reduced by 75% of the prescribed corporate income tax rate for up to 10 years from the beginning of the year. investments, subject to the completion of at least 10 new investment-related jobs.

For investments in the amount of more than EUR 3,000,000.00, to the aid beneficiary, the profit tax rate shall be reduced by 100% of the prescribed income tax rate for a period of up to 10 years from the start of the investment, subject to opening at least 15 investment-related new jobs.

 

2. Have there been any recent significant changes involving localization rules? If yes, when did they take place and what did they involve?

New legislation, Investment Promotion Act (Official Gazette No. 63/2022,) had been adopted quite recent, but models of support have stayed the same.

 

3. Is the process of obtaining a marketing authorization impacted by localization policies in your country? If yes, how so (what are the incentives received or the requirements)?

The process of obtaining a marketing authorization is not impacted by localization.

 

4. Is the pricing process for pharmaceutical products impacted by localization policies in your country? If yes, how so (what are the incentives received or the requirements)?

The pricing process for pharmaceutical products is not impacted by localization.

 

5. Is the reimbursement of pharmaceutical products impacted by localization policies in your country? If yes, how so (what are the incentives received or the requirements)?

The reimbursement of pharmaceutical products is not impacted by localization.

 

6. Is the access to public or public tenders of pharmaceutical products impacted by localization policies in your country? If yes, how so (what are the incentives received or the requirements)?

Access to public or public tenders of pharmaceutical products is not impacted by localization.

 

7. Are import tariffs, importation and/or exportation permits, trade and/or taxation of pharmaceutical products impacted by localization policies in your country ? If yes, how so?

Localization has no effect.

 

8. Are there any other incentives or advantages offered by the current local localization rules in your country? If yes, what are they?

There aren’t any other incentives.

 

9. Are there discussions about the possibility of implementing localization policies in your country? If yes, what are the proposed reforms and when should they come into place?

No, only those set out in point 1.

 

Also from this Legal Handbook

All legal aspects surrounding cannabinoid drugs, medical cannabis and opioids in Croatia. Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for GB 119.

 

Cannabinoid Drugs

 

1. Are Cannabinoid Drugs authorized in your country?

Cannabinoid Drugs are authorized only in the form of Medicinal Cannabis.

 

2. What are the regulatory authorities with jurisdiction over Cannabinoid Drugs?

Office for Suppression of Drug Abuse has jurisdiction over Cannabinoid Drugs.

Agency for Medicinal products and Medical devices of Croatia is the regulatory authority with jurisdiction over medicinal products containing tetrahydrocanabinol (hereinafter: THC).

 

3. Is there a specific regulatory framework for the authorization, pricing, and reimbursement of Cannabinoid Drugs?

The authorization, pricing, and reimbursement of Medicinal Cannabis is regulated by Ordinance on Benchmarks for the Classification of Medicinal Products and on the Prescription and Dispensing of Prescription Medicinal Products (Official Gazette Nos. 86/2013, 90/2013, 102/2014, 107/2015, 72/2016) and also all other regulations that concern authorization, pricing, and reimbursement of medicines in Croatia. This Ordinance has been issued by the Minister of Health.

 

4. Which are the cannabinoid drugs that have received market approval to date?

Cannabinoid drugs have received market approval only in the form of medicinal products containing THC.

 

5. Who can prescribe Cannabinoid Drugs?

Medicinal products containing THC dronabinol or nabilon are prescribed by the selected medical doctor in the activity of general/family medicine, health care of preschool children and health care of women at the recommendation of a medical doctor of the specialisations neurology, internal medicine in oncology, oncology and radiology, infectology and paediatrics with a subspecialisation in neuropaediatrics on a non-repeatable prescription.

 

6. Is there a list of doctors authorized to prescribe Cannabinoid Drugs?

There is no list of doctors authorized to prescribe Medicinal Cannabis.

 

7. What approvals or notifications are required to prescribe Cannabinoid Drugs?

Regulations only specify the selected medical doctor that can prescribe medicinal products containing THC and illnesses for which the medicinal product containing THC can be prescribed.

 

8. Which organizations are authorized to sell/distribute Cannabinoid Drugs available?

Medicinal Cannabis can only be given in pharmacies with presentation of the prescriptions. The medicinal products containing THC are not on the list of approved Croatian Health Insurance Fund medicinal products, which means that patients pay the medicines full price.

 

9. Is there a list of retailers/distributors authorized to sell Cannabinoid Drugs?

Medicinal product containing THC are only available in pharmacies with the presentation of a doctor’s prescription.

 

10. Are there proposals for reform or significant change to the regulation of Cannabinoid Drugs?

Three years ago, a Bill of Amendments of the Drug Prevention Act was passed which formally allows the cultivation of hemp for medicinal purposes, but the list of drugs has not been revised, nor has an ordinance been adopted that regulates it and without which it is not possible to obtain approval. These steps need to take place in the following period, the reason for this postponement is lack of inter-sectoral cooperation and actual local investors. 

 

11. When are they likely to come into force?

Bill of Amendments of the Drug Prevention Act was passed. The moment when other accompanying decisions will be brought is unknown and depends on political will of the government, but is not considered a priority at the moment.

 

 

Medicinal Cannabis

 

12. Is Medicinal Cannabis authorized in the country?

Medicinal Cannabis is authorized in Croatia.

 

13. What are the regulatory authorities with jurisdiction over Medicinal Cannabis?

The Agency for Medicinal products and Medical devices of Croatia has regulatory authority over medicinal products containing THC.

 

14. What is the regulatory framework for the authorization, pricing, and reimbursement of Medicinal Cannabis?

The authorization, pricing, and reimbursement of Medicinal Cannabis is regulated by Ordinance on Benchmarks for the Classification of Medicinal Products and on the Prescription and Dispensing of Prescription Medicinal Products (Official Gazette Nos. 86/2013, 90/2013, 102/2014, 107/2015, 72/2016) and also all other regulations that concern authorization, pricing, and reimbursement of medicinal products in Croatia. This Ordinance has been issued by the Minister of Health.

 

15. How is the production and import of Medicinal Cannabis regulated and by which agencies/authorities?

The import of Medicinal Cannabis is regulated by Drug Abuse Prevention Act (Official Gazette Nos. 107/2001, 87/2002, 163/2003, 141/2004, 40/2007, 149/2009, 84/2011, 80/2013, 39/19). Provisions of this Act regulate the obligation of the Minister of Health to issue a license for import, export, transport and transit of drugs, drug-containing drugs and parts of plants from which the drug is manufactured at the request of a legal entities that carry out wholesale of medicinal products, if the conditions laid down by Drug Abuse Prevention Act, other regulations and international treaties the Republic of Croatia is party to.

The Agency for Medicinal products and Medical devices of Croatia gives authorization for wholesale of medicinal products according to the provisions of Ordinance on Good Practice in the Distribution of Medicinal Products, on Issuing Authorisations for Wholesale Distribution of Medicinal Products, Registration for Brokering of Medicinal Products and on Issuing Certificates on Good Practice in Wholesale Distribution of Medicinal Products (Official Gazette No. 83/13). This Ordinance has been issued by the Minister of Health.

Production of Indian-based drug remedies is in fact not possible in Croatia for now.

 

16. What approval or notifications are necessary to produce or import Medicinal Cannabis?

A license for import issued by the Minister of Health to legal entities that carry out wholesale of medicinal products. Authorization for wholesale of medicinal products given by the Agency for Medicines and Medical Products is required to carry out wholesale of medicinal products.

Production of Medicinal Cannabis in the Republic of Croatia is in fact currently not possible.

 

17. What is the regulatory framework for the marketing and distribution of Medicinal Cannabis?

The import of herbal preparations from Indian hemp to the Republic of Croatia is regulated by Ordinance on Benchmarks for the Classification of Medicinal Products and on the Prescription and Dispensing of Prescription Medicinal Products and Ordinance on Amendments to the Ordinance on Benchmarks for the Classification of Medicinal Products and on the Prescription and Dispensing of Prescription Medicinal Products. These ordinances have been issued by the Minister of Heath.

 

18. How can patients obtain Medicinal Cannabis?

Medicinal products containing THC, dronabinol and nabilon may be prescribed to alleviate the symptoms of multiple sclerosis, carcinoma, epilepsy and AIDS.

Medical doctors are obliged to stipulate the following on a prescription for a magistral preparation:

• the quantity of THC per individual dose,
• the type of herbal drug and herbal preparation from which the magistral preparation is made,
• number of individual doses,
• medicinal form,
• dosage and instructions for use.

Medicinal products containing THC may be prescribed on a prescription in the quantity necessary for treatment for up to 30 days. The total quantity of prescribed THC for 30 days of treatment may not exceed 7.5 g.

 

19. Who can prescribe Medicinal Cannabis?

Medicinal products containing THC, dronabinol or nabilon are prescribed by the selected medical doctor in the activity of general/family medicine, health care of preschool children and health care of women at the recommendation of a medical doctor of the specialisations neurology, internal medicine in oncology, oncology and radiology, infectology and paediatrics with a subspecialisation in neuropaediatrics on a non-repeatable prescription.

 

20. Is there a list of doctors authorized to prescribe Medicinal Cannabis?

There is no list of doctors authorized to prescribe Medicinal Cannabis.

 

21. What approvals or notifications are required to prescribe Medicinal Cannabis?

Regulations only specify the selected medical doctor that can prescribe medicinal products containing THC and illnesses for which the medicinal product containing THC can be prescribed.

 

22. Where is Medicinal Cannabis available?

Medicinal products can only be given in pharmacies with presentation of the prescriptions. The medicinal products that containing THC are not on the list of approved Croatian Health Insurance Fund medicinal products, which means that patients pay the medicines full price.

 

23. Is there a list of retailers authorized to sell Medicinal Cannabis?

The medicinal product that containing THC is provided for only in pharmacies with presentation of doctor’s prescription.

 

24. Are there proposals for reform or significant change to the regulation of Medicinal Cannabis?

Three years ago, a Bill of Amendments of the Drug Prevention Act was passed which formally allows the cultivation of hemp for medicinal purposes, but the list of drugs has not been revised, nor has an ordinance been adopted that regulates it and without which it is not possible to obtain approval. These steps need to take place in the following period, the reason for this postponement is lack of inter-sectoral cooperation and actual local investors. 

 

 

Opioid Drugs

 

25. Are Opioid Drugs authorized in your country?

Opioid Drugs are not authorized in Croatia.

 

26. What are the regulatory authorities with jurisdiction over Opioid Drugs?

The Office for Suppression of Drug Abuse has jurisdiction over Opioid Drugs.

 

27. Is there a specific regulatory framework for the authorization, pricing, and reimbursement of Opioid Drugs?

Opioid Drugs are not authorized in Croatia.

 

28. Which are the Opioid drugs that have received market approval to date?

No Opioid drugs have received market approval to date.

 

29. Who can prescribe Opioid Drugs?

No one can prescribe Opioid Drugs.

 

30. Is there a list of doctors authorized to prescribe Opioid Drugs?

There is no list of doctors authorized to prescribe Opioid Drugs.

 

31. What approvals or notifications are required to prescribe Opioid Drugs?

Prescription of Opioid Drugs is not possible.

 

32. Which organizations are authorized to sell/distribute Opioid Drugs available?

No organizations are authorized to sell/distribute Opioid Drugs.

 

33. Is there a list of retailers/distributors authorized to sell Opioid Drugs?

There is no list of retailers/distributors authorized to sell Opioid Drugs.

 

34. Are there proposals for reform or significant change to the regulation of Opioid Drugs?

There are no proposed reforms or changes considering Opioid Drugs.

 

35. When are they likely to come into force?

N/A.

 

Also from this Legal Handbook

Patents and trademarks in Croatia – a comprehensive legal overview. Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for GB 119.

 

1. What are the basic requirements to obtain patent and trademark protection?

In the territory of Croatia the State Intellectual Property Office (hereinafter: the Office) carries out patent and trademark granting procedure in compliance with the Patent Act (Official Gazette No. 111/2021), Trademarks Act (Official Gazzete No. NN 14/19) and other regulations.

A) PATENTS

The procedure for granting patents having effect in the territory of Croatia may also be carried out through the European Patent Office, by filing a corresponding motion directly to the European Patent Office, then the European Patent Office carries out the decision on granting patent, and the Office acknowledges the patent by entering it in the Patent Register of Croatia, after which he is equal as if the patent was obtained through national means.

The patent granting procedure consists of several phases in which particular elements of a patent motion are examined. The procedure is instituted by filing the motion, and after its formal examination the motion is published in the Office official gazette. A published patent motion becomes available to the public, whereby it forms part of the state of the art, and any interested person is entitled to inspect the text of the motion. After the publication of the motion the procedure is continued only under condition that the applicant files one of the requests for examination of the requirements for the patent grant. If, within the prescribed time limit, one of the specified requirements has not been filed and the corresponding fee and procedural charges have not been paid, the patent motion will be considered to be withdrawn, and the Office will suspend the patent granting procedure.

After one of the specified requests for examination has been filed, the Office carries out a corresponding additional procedure comprising the examination as to the substance of the patent motion. The procedure may result in the grant of a patent for a proposed invention, provided that the prescribed requirements are complied with, or in the refusal of a request for the grant of a patent, if such requirements are not complied with. It is important to point out that before the final decision on the refusal of a request for the grant of a patent, the applicant is given the opportunity to possibly amend the claims or to file additional arguments and to change the outcome of the procedure in his favour.

The protection for a patent granted on the basis of the results of substantive examination lasts for 20 years as from the filing date of a patent motion and for a consensual patent lasts for 10 years. For the maintenance of a patent the prescribed annual maintenance charges have to be paid. Failing this, the protection has to be terminated even before the expiration of the mentioned terms, namely, immediately after the expiration of the time limits prescribed for the annual payment of charges.

A patent is the exclusive right protecting a patent owner in respect of the economic exploitation of an invention.

Foreign business entity or private individual not having a principal place of business, a domicile or a habitual residence in the territory of Croatia enjoys the protection provided by Patent Act, if that results from international treaties binding Croatia, or from the motion of the principle of reciprocity.

Any sign capable of being represented graphically, particularly words, including personal names, designs, letters, numerals, the shape of goods or of their packaging, three-dimensional forms, colors, as well as the combinations of all the above indicated signs, may be protected as a trademark, provided that such signs are capable of distinguishing the goods or services of one undertaking from goods or services of another undertaking.

A patent is granted for any invention, in any field of technology, which is new, which involves an inventive step, and which is eligible for industrial motion and meets the requirements set out by the Patent Act.

 

B) TRADEMARKS

Any sign applying for the trademark protection has to be applied for by a separate motion, the constituent element of which is a list of the goods and/or services to which the sign relates, being drawn up in accordance with the Nice Classification. A list of the goods and/or services included in the motion may not be subsequently extended. Therefore, the list has to be drawn up very carefully, since it determines the scope of protection of the trademark concerned.

If the list of products and services consists of the title of the Nicene Classification category, the scope of protection covers only the products / services that derive from the literal and unambiguous meaning of the term in the title.

When submitting a trademark motion, for the purpose of delivering an orderly alphabetical product / service delivery within a particular class, it is recommended to use the terms of the Croatian version of the TMclass database, the harmonized EU Product and Service Classification Database (EUIPO) on the web site of the State Intellectual Property Office or on the EUIPO website.

A trademark motion has to be filed on prescribed form and has to be supported by the evidence on payment of the prescribed administrative fee and examination charges. The protection requirements and the whole procedure concerning the motion is prescribed by the Trademarks Act and its regulations.

Before filing a motion, a good thing would be to carry out a similarity search of earlier trademarks, as to avoid unnecessary problems.

The registration of a trademark registration in Croatia can also be filed via the internet using the e-Application service, which, besides the effective motion process, also reduces its costs.

Any sign capable of being represented graphically, particularly words, including personal names, designs, letters, numerals, the shape of goods or of their packaging, three-dimensional forms, colors, as well as the combinations of all the above indicated signs, may be protected as a trademark, provided that such signs are capable of distinguishing the goods or services of one undertaking from goods or services of another undertaking.

Any business entity or private individual may be a holder of a registered trademark or an applicant for the registration of a trademark. Foreign business entity and private individual not having a principle place of business or a domicile or a habitual residence, respectively, in Croatia , under Trademark Act, enjoy the same rights as are enjoyed by the persons having a domicile or a real and effective industrial or commercial principle place of business in Croatia, if it results from the international treaties binding Croatia or from the motion of the principle of reciprocity.

The invention has to be patentable under the conditions set out by the Trademark Act. In Croatia a trademark is acquired by registration.

 

 

2. What agencies or bodies regulate patents and trademarks?

State Intellectual Property Office regulates patents and trademarks.

 

3. What products, substances, and processes can be protected by patents or trademarks and what types cannot be protected?

A) PATENTS

A patent is granted for any invention, in any field of technology, which is new, which involves an inventive step, and which is eligible for industrial motion. Requirements for granting a patent and exclusion from patentability are regulated by the provisions of Patent Act.

According to the conditions set out in Patent Act, a patent is also granted for an invention which concerns:

1. a product consisting of or containing biological material;
2. a process by means of which the biological material is produced, processed or used, and
3. a biological material isolated from its natural environment or produced by means of a technical process, even if it previously occurred in nature.

The referred biological material is any material containing genetic information and capable of reproducing itself or being reproduced in a biological system.

An invention which concerns plants or animals is considered patentable if the technical feasibility of the invention is not confined to a particular plant or animal variety and if the process for carrying out the invention is not essentially biological.

Process for the production of plants and animals referred to is essentially biological if it entirely consists of natural processes such as crossing or selection.

The following in particular is not considered to be the inventions within the meaning of the Patent Act:

1. discoveries, scientific theories and mathematical methods;
2. aesthetic creations;
3. rules, instructions or methods for performing mental activities, playing games or doing business;
4. presentation of information, and
5. computer programs.

These objects or activities are excluded from patentability only to the extent that the patent or patent motion refers to such objects or activities as such.

From from patent protection are excluded:

1. inventions which concern animal breeds, plant varieties and essentially biological processes for the production of plants or animals, with the exception of inventions which concern non-biological and microbiological processes and products resulting from such processes, as provided for in Patent Act; a microbiological process implies, under the Patent Act, any process involving or performed upon or resulting in microbiological material;
2. the human body, at the various stages of its formation and development, and the simple discovery of one of its elements, including the sequence or partial sequence of a gene. An invention relating to an element isolated from the human body or otherwise produced by means of a technical process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if the structure of that element is identical to that of a natural element. The industrial motion of a sequence or a partial sequence of a gene is disclosed in the patent motion as originally filed, and
3. inventions which concern diagnostic or surgical methods or methods of treatment practiced directly on the human or animal body, with the exception of the products, in particular substances or compositions used in such methods.

Inventions are considered unpatentable where their commercial exploitation would be contrary to public order or morality, but not only because such exploitation is prohibited by law or other regulation.

The following, in particular, is considered as above-mentioned unpatentable inventions:

1. processes for cloning human beings;
2. processes for modifying the germ line genetic identity of human beings;
3. uses of human embryos for industrial or commercial purposes, and
4. processes for modifying the genetic identity of animals which are likely to cause them suffering without any substantial medical benefit to man or animal, and also animals resulting from such processes.

 

B) TRADEMARKS

Any sign capable of being represented graphically, particularly words, including personal names, designs, letters, numerals, the shape of goods or of their packaging, three-dimensional forms, colors, as well as the combinations of all the above indicated signs, may be protected as a trademark, provided that such signs are capable of distinguishing the goods or services of one undertaking from goods or services of another undertaking. Absolute and relative grounds for refusal are regulated by provisions of Trademarks Act.

Absolute grounds for refusal are regulated by above-mentioned Act. The following signs cannot be registered:

1. signs, which may not be protected as trademarks in accordance with the requirements set out by Trademark Act;
2. signs, which are devoid any sort of distinctive character in relation to the goods or services for which registration is requested;
3. signs which consist exclusively of signs or indications which may serve, in trade, to designate the kind, quality, quantity, intended purpose, value, geographical origin, or the time of production of the goods or of providing of the service, or to designate other characteristics of the goods or services;
4. signs which consist exclusively of signs or indications which have become customary in the everyday language or in good faith and the established practices of trade;
5. signs which consist exclusively of the shape which results from the nature of the goods as such, or the shape of goods which is necessary to obtain a technical result, or the shape which gives substantial value to the goods;
6. signs, which are contrary to public policy or to accepted principles of morality;
7. signs which are of such a nature as to deceive the public, for instance as to the nature, quality or geographical origin of the goods or services;
8. signs, which have not been authorized by the competent authorities and are to be refused pursuant to Article 6ter of the Paris Convention for the Protection of Industrial Property (hereinafter: “the Paris Convention”.);
9. signs for wines which contain or consist of geographical indications identifying wines and signs for spirits which contain or consist of geographical indications identifying spirits with respect to such wines or spirits not having that geographical origin;
10. signs, which contain the name or abbreviation of the name, national coat of arms, emblem, flag or other official sign of Croatia, or a part thereof, and the imitation thereof, except with the authorization of the competent authority of Croatia, and
11. signs, which contain or consist of indication of origin or geographical indication in the territory of Croatia if the motion for registration of the trademark is filed after the date of filing the motion for the registration of a designation of origin or geographical indication in the extent provided for by the regulations on the basis of which those are registered and which refer to the same type of product and service.

Registration cannot be refused to signs specified in above-mentioned items 2 to 4, if the applicant for the registration of a trademark proves that the sign has, before the date of filing of the motion for the registration and following the use which has been made of it acquired a distinctive character in respect of the goods or services for which registration is requested.

Relative grounds for refusal are also regulated by Trademark Act. Upon an opposition as filed, a sign cannot be registered:

1. if it is identical with an earlier trademark registered for identical goods or services, and
2. if because of its identity with, or similarity to, the earlier trademark and the identity or similarity of the goods or services, there is a likelihood of confusion on the part of the public, which includes the likelihood of its association with the earlier trademark.

For the purposes of this Act, “earlier trademark” means:

1. trademarks registered in Croatia, enjoying priority right regulated in Trademark Act;
2. trademarks registered under international treaties, having effect in Croatia, and enjoying priority right refulated in Trademark Act;
3. motions for the registration of trademarks enjoying priority, provided that the trademarks become registered, and
4. trademarks which, on the date of motion for the registration of a trademark, or, if priority is claimed, on the date of priority right claimed in the motion, are well known in Croatia, in the sense in which the words “well known” are used in Article 6bis of the Paris Convention.

Upon opposition as filed by the holder of an earlier trademark, a sign cannot be registered if it is identical with, or similar to, an earlier trademark and the registration has been requested for goods or services which are not similar to those for which the earlier trademark is registered, where the earlier trademark has a reputation in Croatia and where the use of the later trademark without due cause would take unfair advantage of, or be detrimental to, the distinctive character or the reputation of the earlier trademark.

Also, opposition as filed, a sign cannot be registered if its use would infringe one of the following earlier rights:

1. a right to a personal name;
2. a right of personal portrayal;
3. a copyright, and
4. industrial property rights.

For the purposes of Trademark Act, “earlier right” means rights acquired on the date which is earlier than the date of motion for the registration of a trademark, or, if priority right is claimed, as from the date of priority claimed in the motion.

On the basis of opposition as filed, a sign cannot be registered if its use would infringe the right of the person who, at the time of filing of a motion for the registration of a trademark, had a firm, provided that such firm or the essential part thereof is identical with or similar to the sign in respect of which the motion is filed and provided that identical or similar goods or services are the subject matter of the firm’s activity, unless the applicant had the identical or similar firm at the time of filing the motion for registration of a trademark.

On the basis of opposition as filed, a sign cannot be registered if it is identical with, or similar to, an earlier trademark which was registered for identical or similar goods or services and conferred on them a right which has expired for failure to renew the registration of the trademark within a period of not more than two years as from the expiry of the trademark, unless the holder of the earlier trademark gave his consent for the registration of the later trademark or did not use his trademark.

On the basis of opposition as filed, unless a trade agent or representative justifies his action, the trademark will not be registered on behalf of the trade representative or the representative of the trademark holder without his consent.

 

4. How can patents and trademarks be revoked?

A) PATENTS

In order to maintain the rights from the motion of a patent and a recognized patent, it is obligatory to pay the prescribed annual fee, the amount of which varies depending on the year of validity. Otherwise, the patent ceases to be valid even before the expiration of the estimated duration, immediately after expiry of the prescribed deadlines for the annual payment of costs.

The first two years of patent maintenance are covered by the fee and the costs of filing the motion, so that the first obligation to maintain the rights from the motion is due for the third year of its maintenance.

The patent is the private property of its holder, and therefore the sole responsibility for maintaining a patent is exclusively on the holder, without the prior invitation of the Office.

After the protection expires, any interested person may freely use the invention without the need of obtaining the permission of the previous patent holder.

If the patent owner surrenders a patent, it will be terminated on the day following the day on which a certified written declaration concerning the surrender thereof has been filed to the Office.

The patent holder may waive the patent in whole or in part in a written statement of the waiver, certified by a notary public. The effect of the waiver statement commences on the next day following the date of delivery to the Office.

If a particular right on behalf of third persons has been entered into the register, the patent owner may not surrender a patent without the prior certified written consent of those persons.

Disclaimer of the patent has to be entered in the register and published in the official gazette of the Office.

 

B) TRADEMARKS

The value of the trademark can be terminated in several ways:

1. Undoing the value after the expiry of the protection period

The bearer of the trademark should take care of the expiry of the protection period, and apply for the extension of the value before the expiry of that period. The request for the extension of the value can be submitted even in the additional period of six months with the payment of double fees and reimbursement.

 

2. Recall

The bearer is obliged to use the trademark and to ensure that the trademark does not mislead the public or becomes a common name for the products and / or services for which it is registered in the stores.

An interested party may apply for a trademark revocation to the Office, and in such case the holder has to demonstrate the actual use of the trademark in relation to the products and / or services for which it is registered, or to justify the reasons for the revocation

 

3. Disclaimer

The trademark holder may waive the trademark in full or in relation to certain products and / or services on the basis of a written statement at any point in the duration of the protection.

 

4. Announcing the nullity of the registration decision

A stamp that has not been registered in accordance with legal provisions may be canceled in a special procedure, which is initiated ex officio, at the request of a state attorney or an interested person.

 

The request for revocation of a trademark may be filed with the Office by any private individual or business entity. A trademark may be revoked if, within a continuous period of five years, it has not been put to genuine use in Croatia in relation to the goods or services in respect of which it is registered, and there are no justified reasons for non-use.

A trademark may also be revoked if, after the date on which it was registered,

1. in consequence of acts or inactivity of the holder, it has become a common name in the trade for products or services in respect of which it is registered,
2. in consequence of the use made of it by the holder of the trademark or with his authorization, in respect of the goods or services for which it is registered, it is liable to mislead the public, particularly as to the nature, quality or geographical origin of those goods or services.

 

 

5. Are foreign patents and trademarks recognized and under what circumstances?

Foreign business entities or private individuals not having a principal place of business, a domicile or a habitual residence in the territory of Croatia enjoy the protection provided by Patent Act, if that results from international treaties binding Croatia, or from the motion of the principle of reciprocity.

Foreign business entities and private individuals not having a principle place of business or a domicile or a habitual residence, respectively, in Croatia, under Trademark Act, enjoy the same rights as are enjoyed by the persons having a domicile or a real and effective industrial or commercial principle place of business in Croatia, if it results from the international treaties binding Croatia or from the motion of the principle of reciprocity.

Croatia is a member of all relevant international treaties regulating patent and trademarks protection.

 

6. Are there any non-patent/trademark barriers to competition to protect medicines or devices?

A barrier to competition is time barrier applicable to generic medicinal product. Requirement for the protection is the following: marketing authorisation applicant cannot place on the market the generic medicinal product until 10 years have elapsed from the initial authorisation of the reference product.

 

7. Are there restrictions on the types of medicines or devices that can be granted patent and trademark protection?

A trademark cannot be registered if it fullfils the requirements for absolute or relative grounds for refusal set out by Trademark Act.

An invention is not patentable is it fullfils the requirements for exclusion from patentability set out by Patent Act.

Above mentiones is assessed based on criteria applicable in the European Union.

 

8. Must a patent or trademark license agreement with a foreign licensor be approved or accepted by any government or regulatory body?

A) PATENTS

According to Patent Act the conclusion of the license agreement or the contract on the transfer of a joint patent requires the consent of all the owners thereof.

The license agreement and the agreement on the transfer of a patent is concluded under the conditions and in a manner as prescribed by the Obligatory Relations Act

 

B) TRADEMARKS

The holder of a trademark may transfer his trademark to other persons in respect of some or all of the goods or services for which it is registered. On request of one of the parties, the transfer of rights will be entered in the register, if a certified copy of the transfer contract, or the certified part of the contract, or the original certificate of the transfer signed both by the former and the new holder of the right is submitted to the Office.

 

Also from this Legal Handbook

Key legal info on product liability in Croatia. Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for GB 119.

 

1. What types of liability are recognized in your jurisdiction?

Types of liability recognized in Croatian jurisdiction are civil liability as contractual liability and non- contractual (liability as a result of fault, liability for another person, liability for damage caused by dangerous thing or activity, liability for defective product and other special cases of liability such as liability of events organiser, liability for a refusal to provide emergency aid, liability for a failure to conclude the contract and liability concerning the performance of activities of public interest – the so called out-of-contract liability, tort) and also a criminal liability.

 

2. How do these types of liabilities apply to the manufacturers of medicines and devices?

Liability for defective product (out-of-contract, tort) is regulated by Civil Obligations Act (Official Gazette Nos. 35/2005, 41/2008, 125/2011, 78/2015, 29/2018, 126/21).

Authorization of a medicinal product does not affect the financial and criminal liability of the manufacturer and/or of the marketing authorization holder.

A manufacturer who has placed a product on the market is liable for damage caused by defectiveness of that product, regardless of fault. Above-mentioned refers to material damage caused by death or physical injury and damage caused by destroying or damaging the injured party’s thing, different from the defective product, if the nature of the product is such that it is generally intended for personal use and if the injured party mainly used this thing for that purpose.

The injured party has a right to a compensation for damage caused by destroying or damaging the thing, only for the portion of damage which does not exceed the kuna equivalent of EUR 500. Compensation for a non-material damage caused by defective product may only be requested in accordance with the general rules concerning liability for damage.

Special provisions of Civil Obligations Act concerning the compensation for material damage in the case of death, physical injury or health impairment apply, as appropriately, to the scope of compensation for material damage caused by death or physical injury.

Provisions regulating liability for defective product preclude the motion of rules on liability for damage caused by a dangerous thing or dangerous activity, rules on liability for material defects of performance, and rules on contractual and non-contractual liability for damage.

The injured party has to prove the defect of a product, damage and causality between product defect and damage.

The manufacturer of a medical device has to be insured against harmful effects which might occur by the use of the medical device.

 

3. Does potential liability extend to the manufacturer only or could claims extend to corporate executives, employees, and representatives?

Recourse liability is regulated by Labour Act. A worker who at the workplace or in relation to the work, either intentionally or due to utmost negligence, causes damage to a third party, and compensation for damages has been paid by the employer, has to pay to the employer the amount of compensation paid to the third party.

Potential liability by the general regime of tort law is regulated in a manner that board of directors are not held liable for the omissions done by the company.

 

4. How can a liability claim be brought?

The injured party has to prove the defect of a product, damage and causality between product defect and damage. Time limits for exercising the rights are 10 years from the date when the injured party has become aware or should have become aware of damage, defect and a person who produced the product.

A right to a redress for damage caused by a defective product expires within ten years from the date of its placing on the market, unless within that period, a procedure before court or some other competent authority has been initiated against the manufacturer for the purpose of establishing or settling the claim for a redress for referred damage.

Liability claims can be brought through court proceedings.

 

5. What defenses are available?

Manufacturer is not liable for damage arising from a product if the manufacturer proves that:

• he did not place the product on the market;
• it is evident from the circumstances that neither a defect nor its cause existed at the time the product was placed on the market;
• the product is not produced for sale, lease or any other business purpose, not that it is produced or placed on the market within his operations;
• the defect results from non-compliance with the enforcement measures that were in force at the time the product was placed on the market;
• the development stage of science or technical knowledge, at the time the product was placed on the market, did not allow for detection of defects, and
• damage is caused exclusively by the action of the injured party or a person for whom that party is liable, or by the action of a third party which could not have been foreseen by the manufacture or the consequences of which could not have been avoided or eliminated.

Manufacturer of raw material or a part of the product is also exonerated from liability if he proves that a defect is caused as a result of construction of the main product or the instructions issued by the manufacturer of the main product.

The manufacturer has to be partially exonerated from liability if the injured party, or a person for whom that party is liable, has partially contributed to the occurrence damage.

Where a third party has partially contributed to the occurrence of damage, that party is liable solidarily with the manufacturer.

 

Also from this Legal Handbook

An insight into marketing, manufacturing, packaging & labeling, and advertising in Croatia. Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for GB 119.

 

1. What is the authorization process for the marketing of new drugs, biologics, medical devices, over-the-counter medications, and other medicinal products?

B) MEDICINAL PRODUCTS

Only those medicinal products having a marketing authorisation granted by the Agency for Medicinal Products and Medical Devices (HALMED – abbreviation of the Croatian name of this agency is commonly used) or the European Commission (EC) may be placed on the market in Croatia.

HALMED grants a marketing authorisation for medicinal products authorised via national procedure and authorised via common European procedures: mutual recognition procedure (MRP) and decentralised procedure (DCP), whereas the European Commission grants marketing authorisations for centrally authorised products.

Marketing authorisations may be granted only for those medicinal products having an adequate quality and proved by scientific assessment of the product’s documentation and having a positive benefits/risks ratio for use.

The scientific assessment is based on in advance defined criteria and established standards found in Croatian and European regulations and guidelines on medicines and their newest scientific findings.

There are four marketing authorisation procedures for medicinal products in the European Union regulatory environment: centralised procedure, decentralised procedure, mutual recognition procedure and national procedure.

The following sections describe in detail these procedures and provides instructions for submitting respective motions.

Centralised Procedure (CP)

The documentation for centrally authorised medicinal products is scientifically assessed by the European Medicines Agency (EMA) and the marketing authorisation valid in all EU Member States is granted by the European Commission. Experts from all EU Member States including Croatia participate in quality, safety and efficacy assessment of every medicinal product.

This procedure is mandatory for medicinal products for HIV/AIDS, cancer, diabetes, neurodegenerative disorders, autoimmune disorders and other immunologic dysfunctions and viral diseases; medicinal products manufactured by biotechnology procedures (i.e. genetic engineering), advanced therapy medicinal products (gene therapy, somatic cell therapy or tissue engineering) and orphan medicinal products. Also, the centralised procedure is possible, but not mandatory for all medicinal products with a significant therapeutic, scientific or technical innovation or the granting of their marketing authorisation is in the EU public health interest and for generics of centrally authorised medicinal products.

With the accession date of Croatia to the EU, all decisions for granting marketing authorisations for medicinal products based on the CP in the EU came also into effect in Croatia.

More information on centrally authorised medicinal products and instructions how to access their relevant data are available in the Find medicine Section of the EMA webpages, or in the HALMED Medicines Database accessible under the link Medicinal products/HALMED data base.

Submission of a Motion for Initiating a Procedure

For the centralised procedure, the motion and documentation are submitted to the EMA and more information on the centralised procedure, motion procedure and progress is available on the EMA webpages, or here.

Mutual Recognition Procedure (MRP) and Decentralised Procedure (DCP)

MRP and/or DCP procedures are based on mutual recognition and recognition of the scientific assessment one of the EU member states, with the aim to grant marketing authorisations in all other member states where the same motion has been submitted. Croatia may participate in these procedures as a reference member state (RMS) that is leading the documentation assessment process or concerned member state (CMS) in the procedure. The medicinal product authorised in either of these two procedures may be on Croatian market and on the market of more EU member states, depending on the number of member states participating in the procedure.

The decentralised procedure (DCP) for granting a marketing authorisation means that the marketing authorisation procedure starts at the same time in the reference member state and other EU member states participating in the procedure. It is mandatory for those medicinal products that fall outside of the scope of the centralised procedure, products that have not been previously granted marketing authorisations in the EU and products that will be on the market of more than one EU member state. It is about the procedure that is initiated if the product has not been previously authorised in any member state and the marketing authorisation holder wishes to place it on the market of two or more member-states. In this case, the reference member state asseses the product documentation for the first time with active participation of all member states concerned.

On the other side, the mutual recognition procedure (MRP) for granting a marketing authorisation starts after medicinal product has been authorised in the reference member state. According to marketing authorisation holder’s choice, other EU member states may take part in the procedure. It is obligatory for all medicinal products that fall outside the scope of the CP or DCP and that will be on the market of more than one EU member state. The reference member state, where the product has been authorised via national procedure forward its assessment report to other member states in the procedure. Also, like in the DCP procedure, after the completion of the procedure, all documents are harmonised (Summary of Product Characteristics, Package leaflet and Labelling) and the national marketing authorisation is valid for the member state territory.

Submission Procedure

More information on MRP and DCP procedures are accessible on the webpages of the Co- ordination Group for Mutual recognition and Decentralised Procedure (CMDh), or on official site of the Agency.

In the MRP/DCP procedures section of its webpages, HALMED has made publically available the procedure for initiating a MRP/DCP procedure, including the explication how the procedure is initiated in the case where Croatia acts as a reference member stats (RMS), what information should be included in the motion form for granting a marketing authorisation and specific requirements Croatia in MRP/DCP procedures are described in more details.

National Procedure (NP)

The last, fourth procedure for granting a marketing authorisation in the EU is the national procedure, that is being carried out when the applicant wishes to market the product in only one member-state and the marketing authorisation is granted nationally and valid only on this country’s territory.

Submission of motions for initiating MRP/DCP or national procedures in Croatia:
The procedure for submitting motions for granting a marketing authorisation in Croatia is set out in the Medicinal Products Act and Ordinance for granting marketing authorisations for medicinal products.
Motion for granting a marketing authorisation may be submitted to HALMED by a private individual or business entity with the seat in the European Union (hereinafter: applicant).

Medicinal Product Documentation:

In addition to the motion, the applicant should attach the medicinal product documentation that should be prepared in the Common Technical Document (CTD) form.

The essential parts of the CTD are the following:

Module 1: Administrative data and product information
Module 2: Documentation summaries
Module 3: Quality
Module 4: Reports on non-clinical trials
Module 5: Reports on clinical trials

The documentation content may vary depending on the group that the product is belonging to and the chosen legal base for granting a marketing authorisation.

The medicinal product documentation may be in electronic (eCTD or NeeS) or in paper form.

The medicinal product documentation is submitted in Croatian or English, except for the documentation stipulated by the Ordinance for granting marketing authorisation to be submitted in Croatian and attached as a copy, except for those documentation parts, stipulated by the Ordinance to be submitted in original, or copy certified by a notary.

In the Useful notes for applicant – documentation Section of its webpages, HALMED has made publically available Instructions for applicants with regard to preparation and submission of electronic and/or paper documentation.

The entire electronic documentation may be submitted via CESP or mail/courier on CD or DVD to the following address:

Agency for Medicinal Products and Medical devices (HALMED)
Ksaverska cesta 4
HR10000 Zagreb

The paper documentation may be sent to this address, where the applicant is obliged to submit Modules 1, 2, 3, 4 and 5 in paper form. In addition, Modules 4 and 5 should be also in an electronic form.

In addition to the documentation, the marketing authorisation holder is obliged to submit the following documents:

Documents that should be submitted in the original or in a certified copy:

1. Motion for granting a marketing authorisation is submitted in the original, in Croatian, separately for every pharmaceutical and strength, signed by the applicant’s responsible person. The cover letter form for motion for granting a marketing authorisation is available on the official website of the Agency.
2. Motion is submitted in original, separately for every pharmaceutical and strength, and signed by applicant’s responsible person. It is completed in Croatian or English language. The motion form for granting a marketing authorisation is available in the Forms section or under the following link: Motion forms for granting/renewal/variation of the marketing authorisation for medicinal products in Croatia.
3. Written authorisations:

1. 1. written authorisation by which the applicant’s responsible person authorises a person for submitting motions, signing of the motion form and contact on behalf and for the account of the applicant during the marketing authorisation procedure;
   2. written authorisation of the future marketing authorisation holder’s responsible person, authorising the applicant to submit motions on his behalf, if the future marketing authorisation holder is not at the same time the applicant, and
   3. written authorisation of the applicant’s responsible person by which he authorises a person for submitting motions, signing of the motion form and contact on behalf and for the account of the applicant after granting a marketing authorisation.

If the responsible person for submitting motions, signing of motion forms and contact on behalf and for the account of the applicant during and after the marketing authorisation procedure is not employed by the applicant, written authorisation of the legal entity’s responsible person whose, authorised person is employed by the legal entity (employer’s authorisation for employee to perform tasks on behalf of another legal entity) should be attached.

Documents to be submitted in electronic form:

1. proof of the legal entity’s seat, if the future marketing authorisation holder is a private individual or business entity than the applicant, proof that the seat of the future marketing authorisation holder is in the EU, valid no longer than six months from the submission date;
2. written statement of the marketing authorisation holder not having seat in Croatia about the appointment of a local representative with the seat in Croatia with his contacts;
3. contract between the manufacturer(s) responsible for batch release and future marketing authorisation holder or applicant, if the manufacturer and future marketing authorisation holder or applicant are not the same person;
4. proof that the future marketing authorisation holder has by the Agency authorised qualified person for pharmacovigilance with residence in Croatia, or proof on submitted motion to the Agency for approval of the qualified person for pharmacovigilance with residence in Croatia;
5. proof of the paid marketing authorisation procedure;
6. proof of the paid administrative fee in the amount of HRK 225 (approx. EUR 30) for every pharmaceutical and strength.

 

Marketing Authorisation Process at HALMED:

Documentation Validation

After receiving motions, HALMED begins with motion validation where HALMED’s regulatory experts review administrative data, verify their compliance with current regulations and further assess whether the submitted motion is complete and in the current format according to the proposed legal base and product group.

During the validation process, the following aspects are being reviewed: the completeness of the documentation in general, completeness of attached forms and other documents, whether requested documents are submitted in adequate format, compliance of submitted documentation with the proposed legal base according to national and EU regulations and guidelines, whether all manufacturing sites have an adequate manufacturing license, etc.

For all identified deficiencies, the applicant will be sent a Notice on invalid motion with a deadline for completing the documentation.

After the motion has been assessed as valid, the motion is forwarded to the relevant co-ordination of the Regulatory affairs Department (national or MRP/DCP co-ordination), depending of the type of motion. Regulatory experts in co-ordinations follow and co-ordinate the circulation of casefiles until the issuing of marketing authorisations.

Documentation Assessment

After the motion has been successfully validated, coordinators forward the motion to the assessment procedure. The documentation assessment represents a critical overview on submitted data with regard to current regulations and guidelines in Croatia and European Union and with regard to the newest scientific and technical achievements in research, development, manufacturing, quality control, safety and efficacy testing of medicines.

Quality assessors review the pharmaceutical, chemical and biological documentation on pharmaceutical-chemical development, manufacturing and quality control.

Non-clinical and clinical assessors review the documentation on non-clinical investigations in animals and clinical investigations in humans carried out during the medicinal product development phase in order to prove the safety and efficacy.

The quality assessment and non-clinical and clinical assessment are carried out in the Department for quality, safety and efficacy assessment.

Assessors in the Department for pharmacovigilance and rational pharmacotherapy review the documentation on the safe use, i.e. documentation on reported adverse reactions and risk management plan.

Assessors in the Department for regulatory affairs review results of package leaflet readability testing.

Allocated assessors write a detailed report on the documentation assessment. It is an internal document of the Agency, where information on the content review of every documentation part is documented with a critical overview on the essential data for adopting an opinion. Also, questions that need to be addressed to the applicant are indicated where necessary.

Questions addressed to the applicant are divided in questions related to potential human health risks (major deficiencies) and questions needing further clarification (minor deficiencies).

If the applicant has not provided satisfying answers to questions on the potential risk for public health, this represents an obstacle to granting a marketing authorisation.

During the documentation assessment procedure, it is possible to request samples and documentation for laboratory testing depending on the decision and scope defined by the Head of the Department for assessment in agreement with the Head of the OMCL Division. Testing results from the assessment procedure and eventual comments regarding these results and analytical procedure are part of the medicinal product’s quality assessment.

In addition, every assessment report is reviewed, revised by the HALMED’s most experienced assessors in certain areas, who present the final opinion and co-sign the assessment report. In the case of very complex issues, the casefile is discussed at the internal assessors working groups to ensure consistency of decisions and opinions and to ensure an identical interpretation of regulations and guidelines by all assessors.

If additional specific knowledge is needed for the assessment, the Agency may appoint external experts strictly specialised in certain areas.

The review of proposals for the summary of product characteristics, package leaflet and labelling are an integral part of the documentation assessment. The product information has to comply with the submitted documentation and current guidelines stipulating its format and content.

Committee for Medicinal Products

After completing the assessment, the assessor informs the concerned co-ordination of the Department for regulatory affairs. After the co-ordinator has collected all reports in a single marketing authorisation procedure, the casefile is forwarded to the Committee for medicinal products composed of HALMED staff members and depending on the occasion, from external experts. For the assessment of the full non-clinical and clinical documentation, or all motions encompassing proper non-clinical and clinical trials, or those published in the literature, in addition to HALMED’s assessors, external experts mostly doctors who are specialists in certain therapeutic areas, having specific practical knowledge and experience in the treatment of indications concerned are appointed, thus contributing to the quality of assessment. Final conclusions and questions are defined at meetings of the Committee as well as questions to be forwarded to applicants. Meetings of the Committee are held every week in permanent assembly and depending on the need in extended assembly. The schedule of meetings is available on the official website of the Agency.

Conclusions on Deficiencies

After the meeting and endorsement of minutes, according to the Committee’s conclusions, individual co-ordinations prepare the Conclusion on deficiencies in the documentation and an official letter to the applicant containing questions and comments with regard to the submitted documentation and request for additional documentation, if the submitted data is not sufficient for a positive quality, safety and efficacy assessment of the medicinal product.

Finalisation of Procedures

When the requested additional documentation has been submitted and assessed by reviewers who previously asked questions, the procedure ends up in granting or rejecting a marketing authorisation.

Authorised texts of summary of product characteristics, package leaflet and labelling are issued attached to the marketing authorisation and the concerned medicinal product may be placed on the Croatian market.

In addition to the marketing authorisation, it is possible to propose measures that the applicant is obliged to carry out (Follow-up measure, FUM, or Post-authorisation measures, PAM). Follow-up measures after granting a marketing authorisation should not be a condition for placing the medicinal product on the market nor should the fulfilling of these measures influence the product’s benefit/risk ratio. Only those data not available to the applicant during the marketing authorisation procedure and not crucial for concluding the quality, safety and efficacy assessment may be requested. If after the submission of additional data, the opinion is to reject the granting of a marketing authorisation, the casefile is discussed again at the Committee for Medicinal Products.

Medicines Database

After granting a marketing authorisation, basic information on the authorised medicine, including the approved summary of product characteristics and package leaflet and the public assessment report for medicines whose motions were submitted after Croatia’s accession to the EU (1st July 2013) are being published in the Medicinal Products Database of the HALMED webpages and are publically available. The public assessment report on the medicinal product’s documentation is a summary of complete detailed product reports not containing commercially sensitive details.

Public Assessment Report is a summary of complete detailed asssessment reports which does not contain confidential data.

 

A) MEDICAL DEVICES

Authorization of medical devices is not necessary to market a medical device.

Medical devices may be made available on the market of Croatia only if they do not compromise the safety and health of patients, users and other persons and only if they have been properly manufactured, correctly installed, maintained and used in accordance with their intended purpose.

Medical devices must meet the essential requirements taking into account the intended use of a particular medical device.

Any manufacturer of a medical device who has his registered place of business in Croatia and any authorised representative of the manufacturer of the medical device with its registered place of business in Croatia who place a medical device classified as Class I on the market has to inform the Agency and thereby apply for the registration of the medical device concerned in the register of the medical devices within the time period not exceeding 15 days from the day on which the medical advice was first placed on the market.

 

2. What is the authorization process for the marketing of generic versions of these products?

The authorization process for the marketing of generic version of products is regulated by Medicinal Products Act and Ordinance on Granting Marketing Authorisations for Medicinal Products.

Without prejudice to the regulations relating to the protection of industrial and intellectual property, the applicant for the marketing authorization is not required to provide the results of pharmaceutical and pre-clinical tests and of clinical trials, if he can demonstrate that the medicinal product is a generic which is or has been authorised for not less than eight years in an EU Member State based on the centralised marketing authorisation procedure.

The marketing authorisation applicant cannot place on the market the generic medicinal product until 10 years have elapsed from the initial authorisation of the reference product.

The 10-year period may be extended to a maximum of 11 years if, during the first eight years of the ten-year period the marketing authorisation holder obtains an authorisation for one or more new therapeutic indications which, during the scientific evaluation prior to their authorisation, are held to bring a significant clinical benefit in comparison with existing therapies.

The referred reference medicinal product means the one which is or has been authorised in an EU Member State in accordance with Directive 2001/83/EC or provisions of Regulation (EC) No 726/2004, based on fully documented quality, efficacy and safety of the medicinal product.

Generic medicinal product means a medicinal product which has the same qualitative and quantitative composition in active substances and the same pharmaceutical as the reference medicinal product, and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability studies.

Diifferent salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance are considered to be the same active substance, unless they differ significantly in properties with regard to safety and/or efficacy. In such cases, additional information providing proof of the safety and/or efficacy of various salts, esters or derivatives of an authorised active substance has to be supplied by the applicant.

Various immediate-release oral pharmaceuticals are considered to be one and the same pharmaceutical.

Bioavailability studies need not be submitted by the applicant if he can demonstrate that the generic medicinal product meets the relevant criteria as defined in the guidelines of the European Commission and of the EMA. For the purpose of submitting motions and placing generic medicinal products on the market, the protection periods is calculated as of the date of the initial authorisation within the global authorization.

The protection periods (10 or 11 years) also applies to the reference medicinal products with a view to the submission of motions in accordance Medicinal Products Act.

Alongside the motion for the granting of marketing authorisation for a generic medicinal product, the applicant is obliged to append Modules that contain the data prescribed by the Medicinal Products Act and Ordinance on Granting Marketing Authorisations for Medicinal Products, and data on bioavailability and bioequivalence with the reference medicinal product, in line with the guidelines of the European Union.

The applicant requesting grant of marketing authorisation for a generic medicinal product is obliged to prove that the motion and casefiles are in compliance with the Medicinal Products Act.

The proposed Summary of product characteristics of the medicinal product and package leaflets for Croatia is aligned with the Summary of product characteristics of the medicinal product and package leaflets of the reference medicinal product authorised in Croatia or a European Union Member State, as listed in the motion form for the granting of authorisation.

The appended expert report/summary on preclinical and clinical documentation in Module 2 is particularly directed at:

• an assessment of the foundedness of claims of the equivalence of the medicinal product with the reference medicinal product;
• an assessment of the acceptability of impurities present in the active substance(s) and impurities in the medicinal product (including degradation products arising during storage) for medicinal products under preparation;
• an assessment of the conducted bioequivalence testing or substantiation as to why such testing was not conducted in accordance with the valid guidelines of the European Union for testing bioavailability and bioequivalence;
• a new review of the published literature pertaining to the active substance and the submitted motion (for this purpose, articles from peer-reviewed scientific journals may be accepted), and
• for each claim in the Summary of product characteristics of the medicinal product not ensuing from the properties of the medicinal product and/or its therapeutic groups, a critical overview should be provided and supported by the published literature and/or additional testing.

The different salts, esters, ethers isomers, mixtures of isomers, complexes or derivatives of an active substance are considered to be the same active substance, unless they differ significantly in properties with regard to safety and/or efficacy. In such cases, alongside the motion for the granting of marketing authorisation for a generic medicinal product, additional information providing proof of the safety and/or efficacy of various salts, esters or derivatives of an authorised active substance are supplied by the applicant.

Variations and Renewals

After granting a marketing authorisation, the marketing authorisation holder is obliged to report to HALMED all variations to the previously authorised documentation throughout the medicinal product life cycle. Variations may be administrative variations (i.e. change of the manufacturer’s address), change in the documentation on quality (i.e. change in the manufacturing procedure, quality control methods), change in safety information resulting through new post-authorisation studies (i.e. including of new side effects in the package leaflet) and changes in indications (adding or omitting certain indications). The marketing authorisation holder is required to follow the newest scientific and technological advances in the field of development, testing and regulations of medicines and implement them through variations of the medicinal product that is on the market.

Five years after the first marketing authorisation, the benefit/risk ratio of the authorised medicinal product is once again reviewed in the renewal process. Depending on the result of the review, the marketing authorisation may be renewed for an unlimited period or the marketing authorisation is to be renewed after the following five years.

 

3. What are the typical fees for marketing approval?

A) MEDICINAL PRODUCTS

An administrative fee of HRK 225 (approx. EUR 30.00) has to be paid for each pharmaceutical and strength of the drug.

 

B) MEDICAL DEVICES

Specific authorization for manufacture of medical devices and marketing authorization of a medical device is not required.

 

4. What is the period of authorization and the renewal process?

The Agency grants marketing authorisations for medicinal products for the period of five years.

Not later than nine months before the marketing authorisation ceases to be valid, motion for its renewal may be submitted to the Agency. The Agency may renew the marketing authorisation for a further period of next five years subject to reassessment of the product‘s risk-benefit balance.

In addition to the motion for renewal of the marketing authorisation, the marketing authorisation holder provides the Agency with a consolidated version of the file in respect of quality, safety and efficacy, including the evaluation of data contained in suspected adverse reactions reports and in the periodic safety update reports submitted in accordance with pharmacovigilance provisions of Medicinal products, and information on all variations introduced since the marketing authorisation was granted till the date of motion for its renewal.

Once renewed, the marketing authorisation is valid for an unlimited period, unless the Agency decides, on justified grounds relating to pharmacovigilance, including exposure of an insufficient number of patients to the medicinal product concerned, to proceed with one additional five-year renewal.

The written request of the applicant is submitted separately for each pharmaceutical and strength of the medicinal product.

The marketing authorisation renewal request for a medicinal product contains:

1. name of the medicinal product;
2. active substance;
3. pharmaceutical and strength;
4. pharmacotherapeutic group according to the ATK classification;
5. authorisation number;
6. number of the MRP/DCP procedure, if applicable;
7. data on the applicant (name and seat);
8. data on the form of a casefile (eCTD, NeeS, hardcopy);
9. date and signature of responsible person in the applicant, and
10. list of documentation on the medicinal product enclosed with the motion.
    Alongside the motion for renewal of the marketing authorisation, the authorization holder is obliged to submit the documentation containing the data and documents pursuant to Ordinance on Granting Marketing Authorisations for Medicinal Products.

 

5. What are the requirements, if any, for post-approval pharmacovigilance?

Requirements for post-approval pharmacovigilance are regulated by the Medicinal Products Act and Ordinance on Pharmacovigilance.

Upon request by the Agency, particularly in the context of pharmacovigilance, the marketing authorisation holder submits the data relating to the volume of sales of the medicinal product and data relating to the volume of prescriptions.

The Agency may lay down that medicinal products approved for placement on the market be additionally monitored due to their safety profile. These medicinal products bear a special label.

Any healthcare professional who comes in contact with patients/users of a medicinal product, any manufacturer of a medicinal product and a marketing authorisation holder, holder of an authorisation for parallel import and wholesaler has to notify the Agency in writing about any suspected adverse reactions, in particular about serious and unexpected adverse reactions, while in the case of vaccines they have to also notify the Croatian National Institute of Public Health.

A healthcare professional has to report serious adverse reactions to the Agency within 30 days after their knowledge and later as necessary by filing subsequent reports. Serious adverse reactions with a fatal outcome has to be forthwith reported to the Agency in writing or by phone, subject to the subsequent written notification.

A healthcare professional who participates in a clinical trial as investigator has to forthwith report all serious adverse events to a clinical trial sponsor, except if he is not required to do this by the trial protocol and the investigator‘s brochure.

The marketing authorisation holder operates a pharmacovigilance system for the fulfilment of his pharmacovigilance tasks provided for by the provisions of Medicinal Products Act and the ensuing Ordinance on Pharmacovigilance.

The marketing authorisation holder has to, by means of the pharmacovigilance system, evaluate all information scientifically, consider options for risk minimisation and prevention and take regulatory action as necessary.

The marketing authorisation holder performs a regular audit of the pharmacovigilance system. He places a note concerning the main findings of the audit on the pharmacovigilance system master file (PSMF) and, based on the audit findings, ensure that an appropriate corrective action plan is prepared and implemented. Once the corrective actions have been fully implemented, the authorisation holder may remove the above referred note.

As part of the pharmacovigilance system, the marketing authorisation holder has to:

1. have permanently and continuously at his disposal:
   – an appropriately qualified person responsible for pharmacovigilance in the European Union and
   – an appropriately qualified person responsible for pharmacovigilance in Croatia;
2. maintain and make available on Agency‘s request a pharmacovigilance system master file;
3. operate a risk management system for each authorised medicinal product;
4. monitor the outcome of risk minimisation measures which are contained in the risk management plan or which are laid down as conditions pursuant to Medicinal Products Act, and
5. update the risk management system and monitor pharmacovigilance data to determine whether there are new risks or whether risks have changed or whether there are changes to the benefit-risk balance of medicinal products.

Tasks of the person responsible for pharmacovigilance in the European Union and in Croatia, referred above may be performed by a single person.

The marketing authorisation holder has to:

• keep records of all suspected adverse reactions in Croatia, other Member States of the European Union or third countries reported to him, either spontaneously by patients/users of the medicinal product or a healthcare professional or reported during the post-authorisation study, and
• make available the above-mentioned data at one location in the European Union.

Marketing authorisation holders has to submit electronically to the Eudravigilance database:

• information on all non-serious suspected adverse reactions that occur in Croatia within 90 days following the day on which the marketing authorisation holder concerned gained knowledge of the event;
• information on all serious suspected adverse reactions that occur in Croatia within 15 days following the day on which the marketing authorisation holder concerned gained knowledge of the event;
• information on all non-serious suspected adverse reactions that occur in the Member States of the European union, within 90 days following the day on which the marketing authorization holder concerned gained knowledge of the event;
• any information on all serious suspected adverse reactions that occur in the Member States of the European union within 15 days following the day on which the marketing authorization holder concerned gained knowledge of the event, and
• information on all serious suspected adverse reactions that occur in the third countries following the day on which the marketing authorisation holder concerned gained knowledge of the event.

Marketing authorisation holders have to establish procedures in order to obtain accurate and verifiable data for the scientific evaluation of suspected adverse reaction reports. They also have to collect follow-up information on these reports and submit the updates to the Eudravigilance database.

Marketing authorisation holders have to collaborate with the Agency and the EMA in the detection of duplicates of suspected adverse reaction reports.

Marketing authorisation holders submits electronically all suspected adverse reactions regulated by the Medicinal Products Act to the Agency until the functional system for their submission to the Eudravigilance database has been established.

The Agency submits all suspected adverse reactions reports received to the Eudravigilance database in accordance with above-mentioned timeframes (15 or 90 days).

The authorisation holder has to submit to the Pharmacovigilance Risk Assessment Committee a draft protocol of the study, which is to be conducted pursuant to the obligations stipulated by provisions of Medicinal Products Act. Except in the case when the authorisation holder submits to the Agency a draft protocol of the study, which is to be conducted only in Croatia, subject to the request by the Agency.

In that case 30 days before the submission of the draft, the Agency has to:

1. provide a written notification of approval for the draft protocol, or
2. provide a written notification about the shortfalls when:
   – it considers that the conduct of the study promotes the use of a medicinal product,
   – it considers that the design of the study does not fulfil the study objectives, or
3. provide a letter notifying the marketing authorisation holder that the study is a clinical trial falling under the scope of Directive 2001/20/EC.

The study for which the authorization holder has to submit draft protocol to the Pharmacovigilance Rish Assessment Committe may commence in Croatia subject to a written endorsement by the PRAC and following the submission of the approved draft study protocol to the Agency by the authorisation holder.

The study for which the authorization holder has to submit a draft protocol of the study to the Agency, the study may commence following the written approval by the Agency.

After a study for which the authorization holder submits draft protocol to the Pharmacovigilance Rish Assessment Committee has commenced, the marketing authorisation holder has to submit to the PRAC and obtain their written endorsement for any substantial amendments to the protocol, before their implementation.

The marketing authorisation holder notifies the Agency of any approved substantial amendments to the study protocol prior to their implementation.

Following the commencement of the study for which the authorization holder submits a draft protocol of the study to the Agency, the marketing authorisation holder has to submit to the Agency any substantial amendments to the draft study protocol and obtain their written approval prior to their implementation.

Upon the completion of the study for which the authorization holder submits draft protocol to the Pharmacovigilance Rish Assessment Committee, the marketing authorisation holder has to submit, within 12 months from the end of data collection, a final study report and a summary of the study results to the PRAC, unless a written postponement or a written waiver has been granted by the PRAC.

Upon the completion of the study for which the authorization holder submits a draft protocol of the study to the Agency, the marketing authorisation holder has to submit, within 12 months from the end of data collection, a final study report and a summary of the study results to the Agency, unless a written postponement or a written waiver has been granted by the Agency.

If the results of both studies have any impact on the marketing authorisation, the marketing authorisation holder has to submit a motion to vary the marketing authorisation.

The marketing authorisation holder submits periodic safety update reports to the Agency immediately upon request or in accordance with the following:

• where a medicinal product has not yet been placed on the market, at least every 6 months following authorisation and until the placing on the market, and
• where a medicinal product has been placed on the market, at least every 6 months during the first 2 years following the initial placing on the market, once a year for the following two years and at three-yearly intervals thereafter.

The healthcare professional, the applicant for marketing authorizations, marketing authorization holder, authorization holder for parallel imports, importer, and wholesale report the therapeutic failure of the medicinal product in accordance with the Guideline on good pharmacovigilance practices (GVP) Module VI – Management and reporting of adverse reactions to medicinal products.

The respective pharmacovigilance systems of the Agency and marketing authorization holders have defined algorithms for the assessment of the causal relationship between an adverse event and the medicinal product in the case of an adverse reaction to the medicinal product, in accordance with the Guideline on good pharmacovigilance practices (GVP) Module VI – Management and reporting of adverse reactions to medicinal products.

 

6. Are foreign marketing authorizations recognized?

The Agency grants marketing authorisations for medicinal products through the national procedure, the mutual recognition procedure and the decentralised procedure by means of the decision which marks the completion of the authorisation procedure carried out in accordance with Medicinal Products Act and ensuing regulations. Croatia can be either the reference state or the concerned state in the mutual recognition procedure and decentralised procedure.

European Commission grants marketing authorisations based on the centralized procedure in accordance with the provisions of the Regulation (EC) No 726/2004.

There are four marketing authorisation procedures for medicinal products in the European Union regulatory environment: centralised procedure, decentralised procedure, mutual recognition procedure and national procedure.

Please see chapter 3 question 1 for more information on marketing authorization procedures.

 

7. Are parallel imports of medicines or devices allowed?

Procedure of parallel import is regulated by Ordinance on Granting Authorisation for the Parallel Import of Medicinal Products (Official Gazette Nos. 38/20., 32/21). Written request to the Agency is required for parallel import.

The procedure for granting the authorisation for parallel import is initiated with a written motion submitted to the Agency pursuant to the provisions of the Medicinal Products Act and Ordinance on Granting Authorisation for the Parallel Import of Medicinal Products.

Documents and information required for granting approval for the parallel import of a medicinal product into the Republic of Croatia may be in Croatian or English, except for the documentation for which this Ordinance stipulates that it be submitted in the Croatian language. The applicant submits together with request a completed Form for granting approval for parallel import of medicine. 

The condition for granting approval for the parallel import is to determine whether the Medicinal Product for which approval for parallel import is requested and which has a valid marketing authorization in the country of export is basically similar to a Medicinal Product that has a valid authorization in the Republic of Croatia.

The motion for the issuance of authorisation for parallel import may be submitted by a wholesaler holding a permit for the wholesale of medicinal products issued by the Agency or competent body of another European Union Member State, and which is not in business relations with the marketing authorisation holder for the medicinal product that is the subject of the motion. 

 

8. What are the restrictions on marketing practices such as gifts, sponsorships, consultancy agreements, travel and entertainment, or other incentives for healthcare organizations and individual medical practitioners?

A) MEDICINAL PRODUCTS

While advertising the medicinal product, it is not permitted to stimulate the healthcare professional authorised to recommend, prescribe or dispense medicinal products to prescribe, dispense, procure or recommend medicinal products by providing rewards in money, gifts or enabling any other material gain, or promise of benefit or reward, unless such are small and of symbolic value (to HRK 70, approx. EUR 9.00) and are related to the practice the healthcare professional performs. Healthcare professionals may not request nor accept stimulations for the prescription, dispensing, sale or consumption of medicinal products. Above-mentioned does not apply to existing measures or trade practices that pertain to the determination of the price of the medicinal product, accompanying margin and discounts.

Professional and scientific meetings and lectures organised or financed by manufacturers, marketing authorisation holders and importers, or wholesale distributers of medicinal products, have to be scientifically founded and educational. The content of such meetings primarily has a professional character. All other content of the meetings have to be auxiliary in relation to the main purpose and content of the meeting. Meeting has to be intended exclusively for healthcare professionals. During the organisation of meetings, it is permitted to cover the costs of the registration fee, travel, accommodation and food for healthcare professionals that participate in the meeting, to the level of the actual value of the said costs. It is not permitted to cover the said costs of persons who are not participants of the meeting (e.g. persons accompanying the healthcare professional). In selecting the venue for the meeting, the manufacturers, marketing authorisation holders and importers, or wholesale distributers of medicinal products, are obliged to select an appropriate venue, with services of a primarily business and/or congress content.

The marketing authorisation holder may secure free trial samples of a medicinal product to a healthcare professional authorised to recommend, prescribe or dispense medicinal products, under the condition that it does not differ from the usual packaging, that it is the smallest packaging having marketing authorisation in Croatia and which is available on the market, and that the sample is clearly labelled with the words “free sample – not for sale”. In the storage and dispatch of the free samples, it is necessary to handle them in accordance with the good practice requirements in the wholesale trade of medicinal products. Free samples have to be equipped and include the package leaflet pursuant to the marketing authorisation. The healthcare professional may, upon written request and with the signature of receipt, receive a free sample of a medicinal product only once in the course of a year, and that in the amount of a maximum of two of the smallest original packages, and the marketing authorisation holder is obliged to keep a record thereof. The record states the name and surname of the healthcare professional, the name of the institution or private practice and the date the free sample was given to the healthcare professional, and information on the lot number and expiry period of the sample. Records have to be kept for a minimum of two years from the date the healthcare professional received the sample.

It is not permitted to perform advertising towards healthcare professionals by handing out trial samples of medicinal products containing narcotic drugs and psychotropic substances, pursuant to a special regulation governing the prohibition of drug abuse, nor medicinal products from the list of especially expensive medicines.

In the procedure of advertising the medicinal product towards healthcare professionals, the following is not permitted:

1. convincing the healthcare professional to replace one medicinal product with another from the therapeutic group, without the existence of a clear medical indication to do so;
2. making claims or conclusions on the efficacy of medicinal products in indications that are the subject of clinical trials in the country or abroad;
3. making claims that a medicinal product has no adverse reactions and that it is not toxic or that there is no risk of forming an addiction, if such claims are not corroborated by evidence;
4. indicating the summary of product characteristics of a medicinal product, significant information from the summary of product characteristics of the medicinal product or approved instructions for use, using a font size smaller than 3 mm;
5. use of postcards or other forms of postal consignments whose content may be accessible and legible to other person other than healthcare professionals, and
6. use of the telephone, fax, electronic mail and other electronic systems without the prior consent of the healthcare professional as the preferred form of advertising.

 

B) MEDICAL DEVICES

There are no specific requirements and restrictions on marketing practices of medical devices such as gifts, sponsorships, consultancy agreements, travel and entertainment or other incentives for healthcare organizations and individual medical practitioners.

 

9. How is the manufacturing of medicines and devices regulated and by which agencies?

A) MEDICINAL PRODUCTS

Primary legislation for the manufacturing approval and manufacture is the Medicinal Act and its regulations.

Private individuals or entities who manufacture medicinal product have to comply at least with the following requirements:

• given the scope and complexity of manufacture of a medicinal product or a group of medicinal products, they must have the adequate number of qualified persons in the field of in pharmacy, chemistry, biology, biochemistry, biotechnology, chemical technology, medicine, dental medicine, veterinary medicine or other corresponding professions;
• they must have employed a qualified person for the release of a medicinal product batch who should be permanently available;
• they must have employed key personnel for the manufacture, quality checks and distribution of medicinal products;
• they must have at their disposal suitable premises and equipment requisite for the manufacture, quality control, storage and delivery of medicinal products, and
• they must observe the principles and guidelines of Good Manufacturing Practice

Manufacture of medicinal products is regulated by the Agency.

 

B) MEDICAL DEVICES

Manufacture of medical devices does not require a specific authorization.

Private individual or legal entity with its registered place of business in Croatia who manufactures or makes a medical device, including the medical devices referred to in has to:

• ensure that the medical device that he manufactures has been designed and manufactured in
  accordance with the requirements provided by Medical Devices Act;
• carry out the classification of the medical device according to the associated risk, draw up the relevant technical documentation and conduct or ensure the conduct of an applicable conformity assessment procedure for the medical device concerned;
• draw up the conformity declaration and affix the CE marking to the medical device in
  question;
• keep available the technical documentation and the conformity declaration for at least five years after the medical device has been placed on the market;
• ensure the procedures with the view to pertaining the conformity of the batch or serial;
• properly label and mark the medical device and supplement it with the instructions for use;
• undertake corrective actions where it can be assumed or where there is a reason to believe that the medical device which has been placed on the market does not comply with the provisions of Medical Devices Act,

The manufacturer of a medical device shall be insured against harmful effects which might occur by the use of the medical device.

The Agency makes a decision on the entry of a manufacturer of a medical device into the register of manufacturers.

 

10. Are local manufacturing requirements compatible with Good Manufacturing Practices (GMPs) as defined by the U.S. Food & Drug Administration and/or the European Medicines Agency?

Manufacturing requirements of the European Medicines Agency are fully applicable in Croatia.

 

11. What is the inspection regime for manufacturing facilities?

A) MEDICINAL PRODUCTS

The supervision of the implementation of the provisions of Medicinal Products Act in respect of production and manufacture is carried out by the pharmaceutical inspectorate of the Ministry of Health.

The supervision of the implementation of the provisions of Medicinal Products Act in regard of the production of medicinal products is performed by the Agency.

 

B) MEDICAL DEVICES

Supervision of the implementation of provisions of Medical Devices Act and the bylaws adopted on the basis of this Act has to be carried out by pharmaceutical inspectors of the Ministry of Health.

The Agency can remove the manufacturer from the register of manufacturers of medical devices.

 

12. Are manufacturing facilities open for inspection by foreign inspectors or third-party inspectors as authorized by the FDA/EMA?

The Medicinal products Act and Medical Devices Act regulate only inspection by the pharmaceutical inspectorate of the Ministry and supervision performed by the Agency. Foreign inspector are not empowered to exercise supervision in Croatia.

 

13. What are the requirements for storage, packaging, and handling of medicines and devices and their constituent components?

A) MEDICINAL PRODUCTS

Wholesaler distributors are required to provide suitable premises, installations and equipment so as to ensure the performance of wholesale distribution of medicinal products; such premises should be located, designed, constructed, adapted and maintained in such a way as to enable the undisturbed flow of operation and safe and compliant placement, holding and distribution of medicinal products.

Working and storage areas have to be clean, dry and maintained within acceptable temperature limits stipulated for the storage of medicinal products.

The equipping and size of storage areas have to be suitable for the type of medicinal products and the scope of envisaged distribution.

Where premises are not directly operated by the wholesale distributor, a contract should be in place with authorised wholesale distributors for medicinal products that have their own premises.

Medicinal products have to be stored in segregated areas which are clearly marked and have access restricted to authorised personnel only.

Wholesale distributors have to take security measures to prevent unauthorised access to to all areas. Visitors have to be accompanied by authorised persons.

There has to be adequate separation of the receipt and dispatch area from the storage area, and both medicinal products and investigational medicinal products have to be protected from prevailing weather conditions.

Medicinal products with special storage conditions (e.g. medicinal products containing narcotics and psychotropic substances of the types II and III, radiopharmaceuticals, dangerous substances, medicinal products requiring special safety measures due to the risk from fire and/or explosion, such as medical gases, combustibles and flammables) should be segregated and stored in accordance with prescribed conditions. Storage methods should be defined by written procedures and harmonised with special regulations.

The distribution of radioactive medicinal products may be performed by wholesale distributors that meet the requirements laid down by regulations on protection against ionizing radiation.

Medicinal products pending a decision as to their use or products that have been recalled due to damaged integrity of the packaging, damaged packaging, or those suspected of contamination or being falsified, as well as returned medicinal products have to be segregated either physically or through an equivalent electronic system.

Any recalled medicinal products, medicinal products that may not be used pursuant to a decision (rejected medicinal products), whose shelf-life has expired and falsified medicinal products should be immediately physically segregated and stored in a dedicated area, so as not to be placed on shelves and sold by mistake or released to circulation.

Medicinal products received from third countries, which are not intended for the European Union market, but for the export into third countries, have to be stored in a physically segregated area.

In addition to storage areas, the wholesale distributors have to also provide auxiliary rooms, a toilet with entry area, and a wardrobe that has to be separated from the area in which medicinal products are kept.

Bringing, storing and consumption of food, drink, tobacco products or medicinal products for personal use should be prohibited in the area intended for the storage of medicinal products.

The wholesale distributor is required to provide suitable equipment and prescribe procedures to check the environment (temperature and moisture, light and cleanliness) where medicinal products are stored. A temperature mapping exercise should be carried out on the storage area under representative conditions.

All equipment used for the storage and distribution of medicinal products should be designed, located and maintained to a standard which suits its intended purpose. Planned maintenance should be in place for key equipment vital to the functionality of the operation.

Equipment repair, maintenance and calibration operations should be carried out in such a way that the integrity of the medicinal products is not compromised, and records should be kept thereof.

Premises, equipment and software used for wholesale distribution have to be adequately qualified and/or validated. The subject and scope of qualification and/or validation activities should be determined using a documented risk assessment approach/analysis.

When electronic records are used in the good practice in the wholesale distribution, protection from unauthorised access to the database has to be in place. Data should be secured by physical or electronic means and protected against accidental or unauthorised modifications, and checked for availability, durability and accuracy. Backup data should be stored at regular intervals, so that they are retained at a separate and secure location for a minimum period of five years.

Medicinal products have to be transported in such a way so that:

• their quality and identification is not lost;
• contamination is avoided;
• appropriate measures are taken against damage, spillage, breakage or theft;
• they are protected from adverse effects of heat, cold, exposure to light, moisture, etc.;
• they are protected from microorganisms or pest infestation, and
• temperature conditions are observed, as prescribed by the manufacturer or indicated on the outer packaging and monitored with calibrated equipment during transportation.

Risk assessment of delivery routes should be used.

If a deviation such as temperature excursion has occurred during transportation, this should be reported to the distributor and recipient of the affected medicinal products, and a procedure should be in place for investigating temperature excursions.

The wholesale distributor is responsible to ensure that vehicles and equipment used to distribute, store or handle medicinal products are suitable for their use and appropriately equipped to prevent exposure of the products to conditions that could affect their quality and packaging integrity.

For emergency deliveries outside normal business hours, persons should be designated, and prescribed procedures should be available.

Where transportation is outsourced by the wholesale distributor, the contract should encompass the requirements of Ordinance on Good Practice in the Distribution of Medicinal Products, on Issuing Authorisations for Wholesale Distribution of Medicinal Products, Registration for Brokering of Medicinal Products and on Issuing Certificates on Good Practice in Wholesale Distribution of Medicinal Products and transportation providers should be made aware by the wholesale distributor of the prescribed transport conditions applicable to the transportation of medicinal products.

Measures should be taken to minimise the duration of temporary storage while awaiting the next stage of the transportation route.

Medicinal products should be transported in containers that have no adverse effect on the quality of the products, and that offer adequate protection from external influences, including contamination. Containers should bear labels providing sufficient information on handling and storage requirements and precautions to ensure that the products, the contents of the containers and the source are properly handled at all times.

In relation to deliveries containing medicinal products requiring special conditions such as narcotics or psychotropic substances, the wholesale distributor should maintain a safe and secure supply chain for these products with an additional control system for delivery of these products. There has to be a protocol to address the occurrence of any theft. Medicinal products comprising highly active and radioactive materials have to be transported in safe, secure containers and vehicles intended for such purpose. For temperature-sensitive products, qualified equipment is used to ensure that correct transport conditions are maintained between the manufacturer, wholesale distributor and customer.

 

B) MEDICAL DEVICES

The premises have to be functionally connected to enable the undisturbed flow of operation and safe placement and keeping of medical devices and be equipped in such a way as to enable the establishment, maintenance and monitoring of the keeping conditions stipulated by the manufacturer.

The area for the receipt of medical devices has to be separate from the area for the dispatch and the area for the storage of medical devices.

The premises have to be constructed of solid materials and connected to the municipal infrastructure, with appropriate access for incoming and outgoing deliveries of medical devices that is protected from weather conditions. The walls and ceilings of the premises have to be such that enables cleaning and washing. The floors of wholesale premises have to be smooth and made in a way that enables cleaning, washing and, if necessary, disinfection.

All premises have to be ventilated, clean and dry. If natural air flow is insufficient, it is necessary to install effective artificial ventilation.
The premises and positioning of equipment has to enable the implementation of pest control measures, the appropriate cleaning and washing measures, measures against spillage and breakage, and against the effects of microorganisms and cross-contamination of products.

All wholesale premises have to have natural lighting or the appropriate artificial lighting in accordance with the prescribed conditions of keeping medical devices.

The size and equipping of premises is suitable for the nature of the medical devices and the scope of envisaged distribution.

All consignments are examined upon receipt to determine whether the packaging is damaged and whether it corresponds to the consignment order.

Medical devices requiring keeping under specific conditions are immediately identified and placed in the space that corresponds to the keeping conditions as stipulated by the manufacturer.

Medical devices are kept separate from other products, protected from light, moisture and inadequate temperature, in accordance with the prescribed storage conditions.

The space in which the medical devices are kept requires regular cleaning, and a record are kept with the date and time and manner of cleaning performed.

When specific temperature storage conditions are required for a particular medical device, it is necessary to monitor the temperature and keep records thereof, and storage areas are equipped with devices that indicate changes in temperature outside the stipulated range.

In handling stock, there should be a system to ensure stock rotation depending on the date of receipt or the date of expiry. It is compulsory to conduct regular controls of the functioning of the system.

Medical devices whose shelf-life has expired, that have damaged packaging, or for which there is a suspicion of contamination, are kept separately.

All deliveries of medical devices are accompanied by a document containing at least the following information:

• date;
• name of medical device;
• received or issued quantity and price of medical device;
• lot number or serial number of the medical device, and
• name and address of the supplier or recipient.

Prior to delivery, the wholesale distributor is obliged to verify whether the medical device has been properly labelled and is accompanied by instructions for use, if applicable.

Medical devices are transported in such a way that:

• their identification is not lost;
• adequate precautions are taken against spillage, breakage or theft;
• they are protected from unacceptable heat, cold, light, moisture, microorganisms or pests, or other adverse effects;
• the appropriate storage conditions are met as prescribed by the manufacturer.

The vehicle in which the medical devices are transported has to be clean and adequately equipped so as to enable the maintenance of special storage and keeping conditions.

If the wholesale distributor does not have its own transport vehicles, it is obliged to contract transport services in such a way that the service provider is obliged to abide by the requirements.

In the case of urgency, the wholesale distributor may enable urgent delivery of medical devices.

 

14. What information must be included in medicine and device labeling?

A) MEDICINAL PRODUCTS

The following particulars appear on the outer and immediate packaging of a medicinal product in the Croatian language or, where there is no outer packaging, only on the immediate packaging:

1. the name of the medicinal product followed by its strength and pharmaceutical, and, if appropriate, whether it is intended for infants, children or adults; where the product contains up to three active substances, the international non-proprietary name (INN) is included, or, if one does not exist, another common name;
2. the qualitative and the quantitative composition in active substances, using common names, for each dosage unit of the medicinal product, or depending on the pharmaceutical per volume or weight;
3. the pharmaceutical and content in weight, volume or units of dosage;
4. list of excipients of known action or efficacy and, in the event of medicinal products intended for parenteral or topical use or for ophthalmologic medicinal products, all excipients are indicated;
5. the method of administration and, if necessary, the route of administration; space is provided for the prescribed dose to be indicated;
6. a special warning that the medicinal product is stored out of the reach and sight of children;
7. specific precautions, if necessary;
8. clearly indicated expiry date (month and year);
9. special storage precautions, if applicable;
10. special waste management measures for unused medicinal products or waste materials;
    derived from such medicinal products, if appropriate, along with instructions for the appropriate system for their collection;
11. name and address of the marketing authorisation holder, or, where applicable, name of the authorised representative of the marketing authorisation holder;
12. number of the marketing authorization;
13. batch number;
14. in case of over-the-counter medicinal products, the instructions for use of such medicinal products, including the indications, and
15. dispensing of the medicinal product.

Medicinal products, with the exception of radiopharmaceuticals, have to have a safety indication on the packaging, the types of medicinal products that contain a safety label and the means of labeling the medicinal product with a safety label are regulated by the Delegated Commission Regulation (EU) 2016/161 of 2 October 2015 on a supplement to Directive 2001/83 / EZ of the European Parliament and of the Council by laying down detailed rules for the safety labels on the labeling packs of medicines for human use. Excipients are listed in accordance with a European Commission guideline.

Where the immediate packaging takes the form of a blister or in case of a small packaging, not all above-mentioned data are required.

Where the immediate packaging takes the form of a blister and it is placed in the outer packaging which complies with requirements of Medicinal Products Act, it has to contain at least the following information:

• name of the medicinal product of Medicinal Products Act;
• name of the marketing authorisation holder, or the name of the manufacturer;
• expiry date, and
• batch number.

In the event of a small immediate packaging that cannot contain all data it has to contain at least the following:

• name of the medicinal product and, if necessary, administration route;
• method of administration;
• expiry date;
• batch number, and
• content in weight, volume or units of dosage.

 

B) MEDICAL DEVICES

Each medical device is accompanied by the information needed to use it safely and properly, taking account of the training and knowledge of the potential users, and that identify the manufacturer.

This information comprises the data on the label or in the instructions for use of the medical device.

By way of derogation in duly justified and exceptional cases no such instructions for use are needed for medical devices that are set out by the Medical Devices Act, if they can be used properly and safely without them.

By way of derogation in duly justified and exceptional cases no such instructions for use are needed for in vitro diagnostic medical devices which if they can be used properly and safely without them.

The instructions for use and labelling of the medical device are in Croatian language and appear in a visible and legible and form.

Where the instructions for use and labelling are translated into Croatian language, the translation of the instruction for use and marking of the medical device are equally correspond to the original instructions for use and marking of the medical device.

The instructions for use of medical devices exclusively intended for use by medical institutions must be supplied in a language which is known by the user. The instruction for medical devices referred to in Article 3 paragraph 1 of the Commission Regulation (EU) No 207/2012 of 9 March 2012 on electronic instructions for use of medical devices, may be in electronic form in line with the provisions of the latter.

The CE marking of conformity appears in a visible, legible and indelible form on the device or its sterile pack, where practicable and appropriate, and on the instructions for use.

The CE marking has to be accompanied by the identification number of the notified body responsible for conformity assessment if the body concerned has been involved in the conformity assessment procedure.

 

15. What additional information may be included in labeling and packaging?

Only informations enacted by the Medicinal Products Act and its regulation may be included in labelling. Outer packaging and the package of medicinal product leaflet may contain symbols or pictograms approved by the Agency, to clarify certain information in accordance with the text of the summary of product characteristics that are useful for the user but excluding any elements of promotional nature.

 

16. What items may not be included in labeling and packaging?

A) MEDICINAL PRODUCTS

Informations and items not foreseen by the Medicinal Products Act and its regulations may not be included in labeling and packaging.

Therapeutic indications cannot be stated on the outer and immediate packaging of the product and in the package leaflet, if the product does not have a marketing authorisation as a medicinal product or a homeopathic medicinal product.

 

B) MEDICAL DEVICES

Informations and items not foreseen by the Medical Devices Act and its regulations may not be included in labeling and packaging.

It is prohibited to affix CE marks of conformity to medical devices if the medical device concerned does not meet the criteria laid down by Medical Devices Act.

It is prohibited to affix CE marks within the meaning of Medical Devices Act if the device concerned does not constitute a medical device.

It is prohibited to affix marks or inscriptions which are likely to mislead third parties with regard to the meaning or the graphics of the CE marking.

 

17. What are the restrictions and requirements for the marketing and advertising of medicines and devices?

A) MEDICINAL PRODUCTS

Advertising of medicinal products includes;

• advertising towards the population;
• advertising towards healthcare professionals who are authorised to recommend, prescribe or dispense medicinal products;
• advertising towards healthcare professionals;
• distributing samples;
• organising promotional meetings attended by persons authorised to recommend, prescribe or dispense medicinal products;
• organize professional and scientific congresses intended for healthcare professionals, and in particularly the payment of their travel costs, registration fees and accommodation at such meetings, and
• provision of support activities to professional associations and patient association, if medicinal products are promoted through such activities.

The following is not considered as advertising of medicinal products:

1. labelling of medicinal products, summary of product characteristics and package leaflet;
2. correspondence between healthcare professionals, representatives of the pharmaceutical industry and relevant marketing authorisation holders in promotion, to which materials are appended that do not serve for promotional purposes, and which is in response to a specific question pertaining to a specific medicinal product;
3. informative notices on the facts and professional materials that, for example, pertain to changes in packaging, warnings of adverse reactions or other amended safety information, trade catalogues and price lists, under the condition that they contain no promotional claims on the medicinal product, and
4. all unbiased, objective information about diseases, prevention or the available methods of treatment, including pharmacological measures, in which it is not permitted to single out any specific medicinal product.

Advertising of medicinal products includes any form of information which is designed to promote its prescription, supply, sale or consumption and which is provided in a written, oral, pictorial, audio, electronic, digital or any other form.

Medicinal products subject to medical prescription as well as medicinal products not subject to medical prescription may be advertised in scientific literature, at symposia and conferences and to healthcare professionals.

Medicinal products not subject to medical prescription may be advertised to the public.

The advertising of medicinal products subject to medical prescription to the public is prohibited. The prohibition contained does not apply to public health campaigns for the promotion of vaccination, seroprophylaxis and chemoprophylaxis programmes drawn by the Minister in accordance with the Act on the Protection of the Population against Communicable Diseases.

The advertising of any medicinal product unauthorised in Croatia, except at symposia and conferences and in scientific literature and provided that the procedure for granting of the marketing authorisation has been instituted and that only common name of the medicinal product is used, without any mentioning of the manufacturer, is prohibited. Restrictions do not apply to scientific and expert meetings held in Croatia.

When advertising homeopathic medicinal for which a simplified procedure for obtaining marketing authorization is conducted only the data specified in Medicinal Products Act may be used.

 

B) MEDICAL DEVICES

Advertising of medical devices within the meaning of Medical Devices Act means any activity designed to promote the prescription, sale or consumption of a medical device, in any written or oral form, using picture and sound, in electronic, digital or other form.

It is prohibited to advertise any medical device which does not meet the requirements laid down by Medical Devices Act, with the exception of the medical devices intended to be used in exhibitions, demonstrations, fairs etc. Such devices are provided a visible sign clearly indicating that they cannot be marketed or put into service.

Misleading advertising of medical devices are prohibited.

Medical devices which are intended for use exclusively by healthcare practitioners may be advertised but the advertising in such a case is targeted exclusively to a healthcare professional.

Advertising of medical devices is banned in case of information which:

• gives the impression that a medical device can guarantee recovery from the illness and that the health of the subject can be enhanced exclusively by using the advertised medical device, whereas the objective judgement is furnished by evidence;
• suggests that the health of the subject could be affected by not using the medical device that has been advertised;
• encourage the patients to abandon the generally accepted treatment procedures;
• is directed exclusively or principally at children;
• confuse by the use of scientific terms unknown to the general public for common health conditions;
• refers to a recommendation by scientists, health professionals or persons who are neither of the foregoing but who, because of their celebrity, could encourage the use of the medical device;
• suggests that the safety of the medical device is due to the fact that it is natural;
• could, by a description or detailed representation of a case history, lead to erroneous selfdiagnosis;
• refers, in improper, alarming or misleading terms, to claims of recovery;
• refers, in improper, alarming or misleading terms, pictorial representations of changes in the human body caused by disease, and
• assaults human dignity.

 

18. Where can medicines and devices be sold or delivered? Can medicines and devices be sold or delivered via post?

A) MEDICINAL PRODUCTS

Retail sale of medicinal products is carried out by business entities and private individuals authorised to engage in pharmacist activity in accordance with a special act as well as by specialised retail stores authorised by the Agency to engage in retail sale of medicinal products. Medicinal products subject to medical prescription are dispensed exclusively in pharmacies, while medicinal products not subject to medical prescription can be also dispensed in specialized retail sale outlets for medicinal products in line with the marketing authorisation granted by the Agency. If the medicinal product can be dispensed in specialized retail sale outlets for medicinal products, the Agency may determine restrictions in respect of its strengths and pack sizes.

Private individual and business entity engaged in pharmacist activity in Croatia may over the Internet offer for distance selling, in line with a special regulaton, medicinal products which are not subject to medical prescription.

Medicinal products not subject to medical prescription can be sold and delivered via post.

 

B) MEDICAL DEVICES

The retail sale of medical devices is performed by private individual and business entity who, have received authorisation for performance of pharmacy activities, and specialised shops for the retail sale of medical devices that have received a permit from the Agency for the retail sale of medical devices. Specialised shops may only sell those medical devices that meet all the requirements stipulated by the Medical Devices Act and are suitable for such sale with regard to their intended purpose, and the environment in which the medical devices are envisaged for use.

Business entities and private individuals engaged in pharmacy activity in Croatia, specialized retail stores selling medical devices and wholesale distributors may offer for sale medical devices via Internet (distance selling) in line with their line of business and in compliance with the separate rules.

Medical devices can be sold and delivered via post.

 

19. What are the restrictions and requirements for electronic marketing and advertising via email, by Internet, social media, and other channels?

Requirements and restrictions are the same for all channels of advertising. Advertising must comply with restrictions and requirements deccribed in question 17 of this chapter.

 

20. May medicines and devices be advertised or sold directly to consumers?

A) MEDICINAL PRODUCTS

The advertising of medicinal products products that are subject to medical prescription to the public is prohibited. Medicinal products not subject to medical prescription may be advertised to the public.

Retail sale of medicinal products is carried out by business entities and private individuals authorised to engage in pharmacist activity in accordance with a special act as well as by specialised retail stores authorised by the Agency to engage in retail sale of medicinal products.

 

B) MEDICAL DEVICES

In the retail of medical devices has to be engaged business entity and private individual who, in accordance with a separate law, has been authorised to carry out pharmacy activities and specialised retail stores selling medical devices who have been licenced by the Agency to carry out the activities involving the retail of medical devices.

Advertising of medical devices to public and directly to consumers is allowed.

 

21. How is compliance monitored?

A) MEDICINAL PRODUCTS

The supervision of the implementation of the provisions of Medicinal Products Act in respect of distribution and advertising of medicinal products is carried out by the pharmaceutical inspectorate of the Ministry of Health.

 

B) MEDICAL DEVICES

The pharmaceutical inspections regarding the implementation of the provisions of Medical Devices Act and the bylaws adopted on the basis of this Act is performed by pharmaceutical inspectors of the Ministry of Health.

 

22. What are the potential penalties for noncompliance?

A) MEDICINAL PRODUCTS

According to Medicinal products Act private individual or business entity is liable to a fine of between HRK 100,000.00 (approx. EUR 13,500.00) and HRK 150,000.00 (approx. EUR 20,200.00) for advertising medicinal products contrary to the provisions of Medicinal Products Act Act and the ensuing regulations and for claiming that the product has medicinal properties in the advertisement if the concerned product is not authorised as a medicinal product or registered as a traditional herbal medicinal product. For the same misdemeanours responsible persons of business entity are also be liable to a fine of between HRK 10,000.00 (approx. EUR 1,300.00) and HRK 15,000.00 (approx. EUR 2,000.00).

According to Medicinal Products Act private individual or business entity can also liable to a fine of between HRK 70,000.00 (approx. EUR 9,400.00) and HRK 100,000.00 (approx. EUR 13,500.00) for advertising homeopathic medicinal in a manner that not only the data specified in Medicinal Products Act were used. For these misdemeanours, responsible persons of business is also be liable to a fine of between HRK 7,000.00 (approx. EUR 900.00) and HRK 10,000.00 (approx. EUR 1,300.00).

 

B) MEDICAL DEVICES

According to Medicinal products Act private individual or business entity is liable to a fine of between HRK 100,000.00 (approx. EUR 13,500.00) and HRK 150,000.00 (approx. EUR 20,200.00) for advertising medicinal products contrary to the provisions of Medicinal Products Act Act and the ensuing regulations and for claiming that the product has medicinal properties in the advertisement if the concerned product is not authorised as a medicinal product or registered as a traditional herbal medicinal product. For the same misdemeanours responsible persons of business entity are also be liable to a fine of between HRK 10,000.00 (approx. EUR 1,300.00) and HRK 15,000.00 (approx. EUR 2,000.00).

According to Medicinal Products Act private individual or business entity can also liable to a fine of between HRK 70,000.00 (approx. EUR 9,400.00) and HRK 100,000.00 (approx. EUR 13,500.00) for advertising homeopathic medicinal in a manner that not only the data specified in Medicinal Products Act were used. For these misdemeanours, responsible persons of business is also be liable to a fine of between HRK 7,000.00 (approx. EUR 900.00) and HRK 10,000.00 (approx. EUR 1,300.00).

 

Also from this Legal Handbook

An intro to the legal situation for regulatory, pricing and reimbursement of drugs in Croatia. Prepared in association with Danijel Pribanić, a leading global law firm, this is an extract from The Pharma Legal Handbook: Croatia, available to purchase here for GB 119.

 

1. What are the regulatory authorities with jurisdiction over drugs, biologicals, and medical devices in your country?

The regulatory authorities with jurisdiction over drugs, biologicals, and medical devices in Croatia is the Agency for Medicinal products and Medical devices of Croatia (HALMED or Agency).

The legal aspects of the Agency‘s operations are supervised by the Ministry of Health. The Agency submits annual reports on its work to the Minister of Heath and to the Government of Croatia.

 

2. What is the regulatory framework for the authorization, pricing, and reimbursement of drugs, biologicals, and medical devices?

The primary national legislation for the authorization and pricing of medicinal products and biologicals is the Medicinal Products Act (Official Gazette Nos. 76/13, 90/2014, 100/2018), Medical Devices Act (Official Gazette No. 76/13) and its regulations (bylaws).

Authorization of medical devices is not necessary to market a medical device. Requirements that have to be fulfilled in order for the medical device to be placed on the market and administered are set by Medical Devices Act (Official Gazette No. 76/13).

(The criteria for the pricing of medical devices are regulated by the Minister of Health in Ordinance on determination of prices of orthopedic and other aids. Reimbursement of medicinal products and medical devices is mainly regulated by Health Insurance Act and its regulations.)

 

3. What are the steps to obtain authorization to develop, test, and market a product?

A) MEDICINAL PRODUCT

The Agency or the European Commission grants marketing authorisations for medicinal products in Croatia. For the purpose of placing a medicinal product on the market, its quality, safety and efficacy have to be determined.

The Agency grants marketing authorisations for medicinal products through the national procedure, the mutual recognition procedure and the decentralised procedure by means of the decision which marks the completion of the authorisation procedure carried out in accordance with Medicinal Products Act and ensuing regulations. Croatia can be either the reference state or the concerned state in the mutual recognition procedure and decentralised procedure.

The European Commission grants marketing authorisations based on the centralized procedure in accordance with the provisions of the Regulation (EC) No 726/2004.

Marketing authorisation is also granted for radionuclide generators, radionuclide kits, radiopharmaceuticals, radionuclide precursors and industrially produced radiopharmaceuticals.
When a medicinal product has been granted an initial authorisation for marketing in the European Union, any additional strengths, pharmaceutical, administration routes, types and sizes of packaging, as well as any variations and extensions have to also be granted an authorisation or have to be included in the initial marketing authorisation. All refered authorisations are considered as belonging to the same global marketing authorisation.

Please see chapter about Marketing, Manufacturing, Packaging and Labeling Advertising, question 1 for details on different procedures for obtaining a marketing authorization in Croatia.

Private individuals and business entities seated in Croatia may manufacture intermediate products, medicinal products and/or investigational medicinal products only in accordance with a manufacturing authorization. The manufacturing authorisation is compulsory for:

• a factory where a pharmaceutical and/or a group of medicinal products will be manufactured;
• the entire manufacturing process or certain parts of the manufacturing process, and
• manufacture of medicinal products intended only for exports and/or exit.

Importers of medicinal products from third countries have to obtain a manufacturing authorisation.

For marketing authorization, private individuals or business entities engaged in manufacturing, have to comply with the following requirements:

• given the scope and complexity of manufacture of a medicinal product or a group of medicinal products, an adequate number of qualified persons in the field of pharmacy, chemistry, biology, biochemistry, biotechnology, chemical technology, medicine, dental medicine, veterinary medicine or other corresponding professions are required;
• a qualified person for the release of a medicinal product batch who should be permanently available has to be emoployed;
• key personnel for the manufacture, quality checks and distribution of medicinal products have to be employed;
• suitable premises and equipment requisite for the manufacture, quality control, storage and delivery of medicinal products are required, and
• observation of principles and guidelines of Good Manufacturing Practice is neccessary.

For the purpose of obtaining a manufacturing authorisation, a private individual or a business entity seated in Croatia has to submit a motion to the Agency.

Along with the motion and the evidence about the compliance with the requirements of the Good Manufacturing Practice the applicant has to enclose a file containing the following data and documents:

1. name and head office of the business entity or private individual;
2. evidence of registration within a companies registry;
3. evidence of entry of the activity in the companies registry;
4. evidence of professional competencies and employment contract with a person responsible for the release of a medicinal product batch;
5. evidence of professional competencies and employment contract with the key personnel corresponding to the scope of manufacture;
6. personal data of the person responsible for the release of a medicinal product batch and for the key personnel;
7. data on the premises and equipment for manufacture, quality control and storage of medicinal products;
8. description of the manufacturing process or a part of the manufacturing process of a medicinal product for which the authorisation is applied for, or for other parts of the manufacturing process, such as sterilisation of active substances or excipients;
9. a list of medicinal products and pharmaceutical for which the authorisation is applied for, and
10. master file of the manufacturing site.

In the procedure of granting the manufacturing authorisation, an Agency inspector delivers an opinion on the compliance with the requirements of Good Manufacturing Practice.

The Agency grants or refuses the manufacturing authorisation for a medicinal product within 90 days from the date of receipt of a duly filed motion. If the applicant complies with all the requirements laid down by provisions of Medicinal Products Act and the ensuing ordinances, the Agency grants the manufacturing authorisation for an indefinite period of time.

Clinical trials of medicinal products, including non-profit clinical trials, in Croatia may not commence without a favourable opinion of the Central Ethics Committee and the authorisation of the Ministry of Health. If the Ministry does not authorise or refuses to authorise a clinical trial within the referred period, the authorisation is deemed issued, unless a written approval of the Ministry is required before the commencement of a clinical trial in the case of clinical trials intended for gene therapy or somatic cell therapy or medicinal products containing genetically modified organisms, and xenogenic cell therapy.

Clinical trials involving persons with mental disorders cannot start without obtaining a positive opinion from the Commission for the Protection of Persons with Mental Disorders of the Ministry of Justice.

The applicant, who has been approved by the Ministry for conducting clinical trials on the basis of a positive opinion of the Central Ethics Commission and seeking approval for conducting clinical trials in additional legal entities, is obliged to obtain the consent of the Central Ethics Committee for each of the following business entity to be included in the clinical testing, as well as obtaining approval from the Ministry of Health.

The Central Ethics Committee has a period of up to 30 days from the date of receipt of a valid request prescribed in Ordinance on Clinical Trials on Medicinal Products and on Good Clinical Practice to give its written opinion concerning the acceptability of the proposed clinical trial. The Central Ethics Committee has to deliver the opinion to the applicant and to the Ministry of Health in written form. The applicant, after a positive opinion of the Central Ethics Committee is obtained, has to submit a request to the Ministry for the implementation of a clinical trial in Croatia. The Ministry either authorises or refuses to authorise a clinical trial within 30 days of the day of receipt of a duly submitted request. The deadline may be extended by a further period of 90 days where consultations with experts or committees are necessary. In the case of xenogenic cell therapy, there is no time limit for the issuing of an opinion on the acceptability of implementing the clinical trial.

A duly submitted request within the meaning of the above mentiones Ordinance means the submission of a complete set of documents prescribed by this Ordinance.

The Ministry notifies the applicant within 5 days of the receipt of the request, in writing (by electronic means or telefax), if it establishes that the set of documents submitted is not complete. If no notification is given, the request is deemed to have been duly submitted.

The applicant may supplement the request, and the referred period begins on the day of receipt of a duly submitted request. Within this period, the applicant may amend its request before the issuing of a decision of the Ministry of Health. The period may be extended in the case of a clinical trial intended for gene therapy or somatic cell therapy or medicinal products containing genetically modified organisms, and xenogenic cell therapy.

If the Ministry does not authorise or refuses to authorise a clinical trial within the referred period, the authorisation is deemed issued, unless a written approval of the Ministry of Health is required before the commencement of a clinical trial in the case of clinical trials intended for gene therapy or somatic cell therapy or medicinal products containing genetically modified organisms, and xenogenic cell therapy.

The Ministry shall refuse to authorise a clinical trial for gene therapy if there is risk of changes in the reproductive cell genome of the subject.

The Ministry notifies the applicant about defects in the request and request the documentation to be supplemented. The applicant may make a single amendment to the request.

If the applicant does not submit supplementary documents or a written explanation stating the period of delivery of supplementary documents (by electronic means or telefax) within 5 days of the receipt of the conclusion, the Ministry issues a decision rejecting the request.

The applicant notifies the Ministry of the intention to withdraw a request that was submitted for the authorisation of a clinical/non-profit trial as soon as possible following the issuing of a decision. The notification submitted by electronic means or telefax has to be delivered to the Ministry within the shortest term possible, in writing, with a brief description of the grounds for withdrawing the request.

Where the applicant intends to re-submit a request for authorisation that was withdrawn, the applicant has to state on the request to the Ministry and on the EudraCT Clinical Trial Request Form (hereinafter: EudraCT Form) that the request is being re-submitted in accordance with the Communication from the Commission 2010/C 82/01 — Detailed guidance on the request to the competent authorities for authorisation of a clinical trial on a medicinal product for human use, the notification of substantial amendments and the declaration of the end of the trial (CT-1).

The authorisation to conduct a clinical trial, including a non-profit clinical trial, is issued or denied by the Ministry in a decision against which no appeal is allowed, but an administrative dispute may be initiated.

The Ministry has to deliver the authorisation to conduct a clinical trial to the applicant, the Central Ethics Committee, the Agency, the Croatian Institute for Health Insurance, and the pharmaceutical inspection of the Ministry.

 

B) MEDICAL DEVICES

Specific authorization for manufacture of medical devices is not required.

The manufacturer of a medical device has to, within the period not exceeding 15 days from the start of performing its economic activity, file a motion for entry into the register of medical devices manufacturers kept by the Agency.

Motion for entry into the register of manufacturers of medical devices has to be submitted by:

• the manufacturers of medical devices with their place of establishment in Croatia, and
• the authorised representatives of manufacturers from third countries, who have their seat in
  Croatia.

The decision of the Agency on the entry of a manufacturer of a medical device into the registry of manufacturers of medical devices has to be adopted within the time period of 60 days from the day of the receipt of the complete request.
The authorisation for the clinical investigation of a medical device is issued by the Minister of Health on the basis of the complete documentation and the positive opinion of the Central Ethics Committee.

The authorisation for the clinical investigation of a medical device is given or rejected within a time period of 60 days from the day of the receipt of the complete motion.

Where the minister does not give or reject the authorisation for the conduct of a clinical trial within the time period of 60 days, the authorization is deemed granted.

Medical devices may be made available on the market in other words placed on the market and administered if they meet the essential requirements, if they have been issued a certification of conformity and if they have been affixed the CE marking. The essential requirements for medical devices are regulated by the Minister of Health in an ordinance.

The conformity assessment procedure relating to a medical device is a procedure on the basis of which it is established and assessed whether the medical device or the manufacturing of the medical device meets the requirements laid down by Medical Devices Act and the bylaws adopted pursuant to this Act.
The conformity assessment procedure relating to a medical device establishing its conformity with the essential requirements is conducted in accordance with the classification of the medical product concerned.

Before placing on the market of a medical device the manufacturer draws up a declaration on conformity in respect with the medical device in question and affix the CE marking of conformity.

Business entity or private individual who place on the market of Croatia medical devices classified as Class IIa, IIb and III, in vitro diagnostic medical devices and active implantable medical devices have to notify the Agency thereof within a time period not exceeding 15 days from the day on which these products are placed on the market.

Medical devices may be made available on the market of Croatia only if they do not compromise the safety and health of patients, users and other persons and only if they have been properly manufactured, correctly installed, maintained and used in accordance with their intended purpose.

 

4. What are the approximate fees for each authorization?

A) MEDICINAL PRODUCTS

The expenses incurred in the process of granting, renewing, amending, transferring and repealing of an authorisation are determined by the Agency, with the consent of the Minister, and have to be covered by the applicant.

An administrative fee of HRK 225 (approx. EUR 30) has to be paid for each pharmaceutical and strength of the drug.

 

B) MEDICAL DEVICES

Specific authorization for manufacture of medical devices and marketing authorization is not required.

 

5. For how long are marketing authorizations/registrations valid? How are marketing authorizations/registrations renewed?

The Agency grants marketing authorisations for medicinal products for the period of five years. Not later than nine months before the marketing authorisation ceases to be valid, a motion for its renewal may be submitted to the Agency.

Risk and benefit ratio of the approved drug is once again assessed in the renewal procedure five years after first granting approval. Depending on the outcome of this assessment, the approval may be renewed for an unlimited period or the renewal process has to be carried out again after five years.

Once renewed, the marketing authorisation is valid for an unlimited period, unless the Agency decides, on justified grounds relating to pharmacovigilance, including exposure of an insufficient number of patients to the medicinal product concerned, to proceed with one additional five-year renewal.

 

6. How does the authorization process differ between brand-name products and generic products? Are there differences for local manufacturers versus foreign-owned manufacturers?

Without prejudice to the regulations relating to the protection of industrial and intellectual property, the applicant for the authorization of generic products is not required to provide the results of pre-clinical tests and of clinical trials, if he can demonstrate that the medicinal product is a generic which is or has been authorised for not less than eight years in an EU Member State based on the centralised marketing authorisation procedure.

Please see chapter about Marketing, Manufacturing, Packaging and Labeling Advertising, question 2 for more information on authorization process of generic products.

There are no differences for local manufactures versus foreign-owned manufactures.

 

7. How are combination products (drug + drug, drug + biologic, drug + device, biologic + device, drug + biologic + device) regulated?

Combination products are not particulary regulated.

The provisions of Medical Devices Act apply to any medical device intended for administration of a medicinal product. Where a medical device incorporates a medicinal product as an integral part and where this integral product is intended exclusively for use in the given combination and which is not reusable, the Act on Medicinal Products applies. As far as the safety and performance relate device features of the medical device are concerned, they have to comply with the essential requirements under Medical Devices Act.

Where a medical device make up an integral part an ancillary medicinal substance which may be used separately and acts upon the body with action that is ancillary to that of the device, this medical device has to be assessed under the provisions of Medical Devices Act, whereas the medicinal substance has to be assessed under the Act on Medicinal Products and the relevant bylaws adopted on the basis of the latter.

The provisions of Medical Devices Act apply also to in vitro diagnostic medical devices manufactured from tissues, cells or substances of human origin.

 

8. How is compliance with regulation monitored and evaluated? Is the regulatory regime comparable with the U.S. Food and Drug Administration or the European Medicines Agency expectations and requirements?

A) MEDICINAL PRODUCTS

The supervision of the implementation of the provisions of Medicinal Products Act in respect of medicinal products, investigational medicinal products, active substances and excipients, and especially the supervision of testing, production and manufacture, distribution, brokering, quality control, pharmacovigilance and advertising of medicinal products is carried out by the pharmaceutical inspectorate of the Ministry.

The supervision of the implementation of the provisions of this Act in regard of the production of medicinal products, investigational medicinal products, active substances and excipients, and the supervision of pharmacovigilance is performed by the Agency.

When conducting an inspection, the pharmaceutical inspector and the Agency inspector may:

• inspect business premises, facilities, installations, devices, equipment;
• inspect raw materials, active substances, excipients, intermediate products, medicinal products;
• inspect agreements, records and any other quality system documents or other business documents; if documents are supplied electronically, he may require seeing them and have their printout;
• take copies of documents, subject to making the relevant note in the inspection report;
• take free samples of medicinal products and raw materials for quality control purposes;
• take and use free data from official records and other databases related to persons, if necessary, for inspection;
• remove medicinal products from the market if they do not comply with the provisions of Medicinal Products Act;
• inspect personal documents for the purpose of identification, and
• take photographs or record data on other visual media about persons, premises, facilities, installations, equipment for the purpose of presentation of evidence.

In addition to the above listed rights, the pharmaceutical inspector has the right to exclude from trade medicinal products which do not comply with the provisions of Medicinal Products Act.

The pharmaceutical inspector and the Agency inspector have the right to conduct unannounced inspections.

 

B) MEDICAL DEVICES

Supervision of the implementation of provisions of Medical Devices Act and the bylaws adopted on the basis of this Act is carried out by the Ministry of Health. The pharmaceutical inspections regarding the implementation of the provisions of this Act and the bylaws adopted on the basis of this Act is performed by pharmaceutical inspectors of the Ministry of Health.

In carrying out the inspection the pharmaceutical inspector inspects the business premises, facilities, devices, equipment and documentation.

The regulatory regime of the European Medicines Agency is generally applicable in Croatia.

 

9. What is the potential range of penalties for noncompliance?

The potential range of penalties are regulated by the Medicinal products Act and Medical devices Act and depend on the misdemenaour and the perpetrator.

A) MEDICINAL PRODUCTS

In the performance of the inspection, the pharmaceutical inspector has both the right and duty to:

1. order the performance of activities in accordance with the conditions laid down by this Act and other regulations;
2. order the removal of identified irregularities and deficiencies within a specified time limit;
3. prohibit the performance of activities which are contrary to this Act and other regulations;
4. temporarily prohibit the work to any legal or natural person who does not satisfy the conditions in respect of employees, equipment, instruments and rooms;
5. prohibit the work to any private individual or business entity engaged in testing, production and manufacture distribution, brokering and quality control of medicinal products without the Agency’s authorisation or licence;
6. order the ban on placing of the medicinal product on the market:
   – if the medicinal product is falsified;
   – if the shelf life of the medicinal product has expired;
   – if it has been established that the medicinal product is kept or handled contrary to regulations;
   – in the cases where Medicinal Products Act stipulates product suspension and recall, and
   – prohibit the performance of a clinical trial of a medicinal product or the performance of a clinical trial at any individual investigation site if it is not performed in accordance with the provisions of Medicinal Products Act, the ensuing regulations and good clinical practice.
7. file a motion with the Agency for the suspension or recall of the batches which do not comply with the conditions laid down by Medicinal Products Act and other regulations;
8. declare the product which is found defective as waste and order its handing over to the person authorised in accordance with the rules and regulations governing waste management;
9. prohibit the work and submit a proposal to the Agency for the revocation of the authorisation if noncompliance with the conditions laid down by Medicinal Products Act or any other regulation may jeopardise the life and health of people;
10. prohibit the sale of the product if therapeutic indications are given on its immediate or outer packaging and the product is not authorised as the medicinal product or as the homeopathic medicinal product;
11. prohibit the advertising of the product which is attributed medical indications and which is not a medicinal product within the meaning of Medicinal Products Act;
12. prohibit the distribution of the product if it is established that it contains an active substance or a substance related to the active substance and it is not a medicinal product within the meaning of Medicinal Products Act;
13. temporarily suspend the execution of the decision on the marketing authorisation for a medicinal product due to a violation of the provisions of Medicinal Products Act, and
14. order other measures to be taken as authorised by this Act and other regulations.

In the performance of the inspection, the Agency inspector has both the right and duty to:

1. prohibit the work to any private individual or legal entity engaged in the production without the authorisation or the Agency‘s licence;
2. order the performance of activities in accordance with the conditions laid down by Medicinal Products Act and other regulations;
3. order the removal of identified irregularities and deficiencies within a specified time limit;
4. prohibit performance of activities that are contrary to this Act and other regulations;
5. temporarily prohibit working to any private individual or legal entity who does not satisfy the conditions in respect of employees, equipment, instruments and premises;
6. submit a proposal for revocation of the marketing authorisation if the marketing authorisation holder does not operate a pharmacovigilance system, have a person qualified for pharmacovigilance or fulfil other pharmacovigilance tasks laid down by the provisions of Medicinal Products Act, and
7. order other measures to be taken as authorised by this Act and other regulations.

According to Medicinal products Act private individual or business entity is liable to a fine of between HRK 100,000.00 (approx. EUR 13,500.00) and HRK 150,000.00 (approx. EUR 20,200.00) for the misdemeanours prescribed by this Act. For the same misdemeanours responsible persons of business entity are also be liable to a fine of between HRK 10,000.00 (approx. EUR 1,300.00) and HRK 15,000.00 (approx. EUR 2,000.00).

According to Medicinal Products Act private individual or business entity can also liable to a fine of between HRK 70,000.00 (approx. EUR 9,400.00) and HRK 100,000.00 (approx. EUR 13,500.00) for the misdemeanours regulated by the provisions of this Act. For these misdemeanours, responsible persons of business are also be liable to a fine of between HRK 7,000.00 (approx. EUR 900.00) and HRK 10,000.00 (approx. EUR 1,300.00).

Any business entity or private individual who provides incorrect data during the procedure for issuance of the authorisation for entry or import of a medicinal product which has not obtained the marketing authorisation in Croatia is liable to a fine of between HRK 50,000.00 (approx. EUR 6,700.00) and HRK 70,000.00 (approx. EUR 9,400.00). For above-mentioned misdemeanor the responsible person of the business entity is also liable to a fine of between HRK 5,000.00 (approx. EUR 670.00) and HRK 7,000.00 (approx. EUR 900.00).

A medical doctor or a dental medicine doctor who prescribes a medicinal product in respect of which the marketing authorisation has not been granted in Croatia, contrary to Medicinal Products Act and the ordinance, is be liable to a fine of between HRK 5,000.00 (approx. EUR 670.00) and HRK 7,000.00 (approx. EUR 900.00).

Private individual or business entity is liable to a fine of between HRK 30,000.00 (approx. EUR 4,000.00) and HRK 50,000.00 (approx. EUR 6,700.00) in cases regulated by the Medicinal Products Act. The responsible person of the legal person is also be liable to a fine of between HRK 3,000.00 (approx. EUR 400.00) and HRK 5,000.00 (approx. EUR 670.00) for these misdemeanours.

 

B) MEDICAL DEVICES

In carrying out the inspections the pharmaceutical inspector has the following rights and duties:

• to order particular inspections and investigations relating to the medical device after it has been placed on the market or put into service;
• to order the recall of the medical device from the market or from the service;
• to order proper labelling of the medical device;
• to order the medical device which does not meet the statutory requirements to be properly disposed where this is necessary for the protection of health of humans;
• to order private individual or legal entity the performance of the activity in conformity with the criteria set out by Medical Devices Act and other rules;
• to order rectification of established irregularities and deficiencies with a set time period,
• to order the implementation of other measures in accordance with the powers stipulated under Medical Devices Act and other rules;
• to order suspension or termination of a clinical trial where the latter has not been carried out in conformity with the provisions of this Act and the ordinance adopted pursuant to Medical Devices Act;
• to restrict or suspend placing on the market or putting into service, in other words prohibit the use of a medical device which is not in conformity with the requirements stipulated by the provisions of this Act and other rules adopted pursuant to Medical Devices Act;
• to temporarily prohibit placing on the market, putting into service or advertising of the medical device where there is reasonable doubt regarding the conformity of the medical device with statutory requirements;
• to prohibit placing on the market and putting into service of a medical device where there has been suspected that the medical device or the documentation has been counterfeited;
• to prohibit distance sale for private individual or legal entity of the medical devices via the Internet where it does not meet the requirements stipulated under Medical Devices Act;
• to temporarily prohibit the operation of a private individual or legal entity where they do not meet the requirements stipulated under Medical Devices Act and the rules adopted pursuant to this Act;
• to prohibit the operation of private individual or legal entity where they are engaged in conformity assessment, manufacturing, designing and placing on the market without the authorisation of the Minister of Health, in other words, without having been licenced to do so by the Agency;
• to prohibit advertising of a medical device which is in contravention of the provisions of Medical Devices Act, and
• to prohibit the carrying out of the activities which are in contravention of Medical Devices Act and other rules.

The potential range of penalties is regulated by the Medical Devices Act. A fine in the amount ranging from HRK 70.000.00 (approx. EUR 9,400.00) to HRK 100.000.00 (approx. EUR 13,500.00) is imposed on a business entity and private individual if they commit misdemenours prescribed on the list in the provisions of Medical devices Act. For these minor offences the responsible person in the business entity is also fined the amount ranging from HRK 7.000.00 (approx. EUR 900.00) to 10.000.00 (approx. EUR 1,300.00).

A fine in the amount ranging from HRK 50.000.00 (approx. EUR 6,700.00) to HRK 80.000.00 (approx. EUR 10,700.00) is also imposed on a business entity and private individual if they commit minor offences on the list regulated in provisions of Medical devices Act. For these minor offence the responsible person in the business entity is also fined the amount ranging from HRK 5.000.00 (approx. EUR 600.00) to HRK 8.000.00 (approx. EUR 1,000.00).

 

10. Is there a national healthcare system? If so, how is it administered and funded?

The national healthcare system is run by the Croatian Health Insurance Fund (HZZO – abbreviation commonly used localy is the Fund’s acronym, or the Fund). The Fund is a public institution. Fund’s rights, obligations and responsibilities are established by the Law on Compulsory Health Insurance and the Statute of the Croatian Health Insurance Fund.

Supervision of the legality of the work of the Fund is performed by the Ministry of Health. The Office is managed by a Governing Board of nine members appointed by the Government of Croatia. The Administrative Council makes decisions and general acts of the Fund.

The work of the Fund is managed by the director The Director of the Fund is responsible for the financial operations of the Fund. The Office conducts the tasks through 7 departments headed by Assistant Directors.

The Fund is established through the Directorate and four regional offices (Zagreb, Osijek, Split, Rijeka), has 16 regional branches and 134 municipal locations. Since 2012 the total number of employees in the Fund was 2,422.

Within the mandatory health insurance, there are about 4,300.000 insured persons (99.7% of the Croatia’s population). Within the supplementary health insurance (also being provided by private insurerres along with the HZZO supplementary health insurance scheme), around 2,500.000 persons are insured.

(The health system of Croatia does not function solely according to a single financing model but is a combination of the so-called Bismarck’s model (based on social security, or contributions that citizens stand out from salaries) and the so-called Beveridge model based on budget revenues, all due to a revenue shortage based solely on Beveridge- this model of financing.)

 

11. How does the government (or public) healthcare system function with private sector healthcare?

HZZO covers 80% of healthcare costs within the “basket of services” (commonly used reference for a list of services) covered by compulsory health insurance, which includes the right to primary healthcare, specialist-healthcare, hospital healthcare, the use of drugs listed on the HZZO list, healthcare abroad, dental-prosthetic services, surgeries, and orthopedic and other aids. The remainder of the service cost (20%) is compulsory for the insured person to pay. If the amount that the personal insured person pays exceeds HRK 2,000.00 (approx. EUR 175) per hospital account personal insured person pays only up to that amount.

Insured persons may carry out their right to healthcare in health institutions or with private healthcare professionals with whom the Fund has concluded a contract on the implementation of healthcare in the manner and under conditions determined by Compulsory Insurance Act (Official Gazette Nos. 80/2013, 137/2013, 98/19) and by the general acts of the Fund.

 

12. Are prices of drugs and devices regulated and, if so, how?

A) MEDICINAL PRODUCTS

The Croatian Health Insurance Fund publishes an annual calculation of the cost of medicines on its website.

The procedure for determining the prices of medicinal products is carried out according to the Ordinance on standards and the manner of determining the prices of wholesale medicinal products and the manner of reporting on wholesale prices (Official Gazette Nos. 83/2013, 12/2014, 69/2014, 22/2015, 84/2015).

HZZO is obliged to conduct the procedure of the public procurement for the determination of the prices of medicines that are already on the valid basic and supplementary list of HZZO medicinal products in accordance with the provisions and according to the prescribed procedure established by the said Ordinance if medicines are found in the current lists of HZZO drugs different prices within the reference groups.

HZZO sets out the medicines in the defined groups and subgroups. The level of drug cost for the HZZO is established depending on which drug has 5% of turnover for the last 3 months.

After the publication of the public bid on the HZZO website, there is a possibility of appeal. Approval holders has to submit their responses on the published prices.

After the decisions are made on the complaints filed and based on the submitted responses of the Approval Holder to accept / not accept the reference price for each medicine, HZZO begins the preparation of a full list of pricelist prescription drugs.

The medicines are classified into the basic and supplementary list of medicines and as such, HZZO immediately instructs the HZZO Governing Board to make final decisions on the acceptance of medication prices (then the proposals for the adoption of the Decision on the establishment of the basic list of medicines and the Decision on the establishment of supplementary lists of medicines are prepared).

The basic list of medicines includes medicines which prices are at the reference price level or lower; the supplementary list includes medicines whose price level is higher than the reference price. No drug price needs to be “unalterable” if there is some justification for the deviation from the said Ordinance, because it is permissible for the approval holders to propose, with detailed explanation, a higher cost price for which the consent of the Minister of Health is necessary.

The entire bidding procedure for the basic and supplementary list of medicines usually lasts several months from the first decision to the decision on the final price in the lists, to over a year.

 

B) MEDICAL DEVICES

The criteria for the pricing of medical devices are regulated by the Minister of Health in Ordinance for the determination of prices of orthopedic and other aids.

The prices are determined by legal entities or private individuals with a registered office in Croatia who are licensed for the marketing of medical devices and who are the holders of the entry in the medical device and the medical device manufacturer’s records at the Agency.

Measures for determining prices are as follows:

• the existing price of aids in Croatia;
• comparative prices in other countries, and
• health and economic analysis.

 

13. How are drugs and devices used by patients paid for? What roles do public and private payers play?

The Croatian Health Insurance Fund covers 80% of healthcare costs within the “basket of services” covered by compulsory health insurance, which includes the right to primary healthcare, specialist-healthcare, hospital healthcare, the use of drugs listed on the HZZO list, healthcare abroad, dental-prosthetic services, surgeries, and orthopedic and other aids. The remainder of the service cost (20%) is compulsory for the insured person to pay. If the amount that the personal insured person pays exceeds HRK 2,000.00 (approx. EUR 175) per hospital account personal insured person pays only up to that amount.

Additional health insurance is intended to provide for a higher standard of healthcare than that provided under the mandatory health insurance scheme, and for broader rights than those provided under the mandatory health insurance scheme.

The medicines are divided into two lists: the basic for which the costs for medicines are fully covered by HZZO and the supplementary for which part of the cost is covered by the HZZO, and the remainder of the cost the insured person or supplementary insurance of the insured person.

The Croatian Chamber of Pharmacists regulates pricelists and compulsive margins for medicines and for most over the counter medicines and medical devices.

 

14. Who dispenses drugs and devices to patients and how are those dispensers compensated?

Retail sale of medicinal products or medical devices can be carried out by private individual and business entity authorised to engage in pharmacist activity in accordance with a special act as well as by specialised retail stores authorised by the Agency to engage in retail sale of medicinal products or medical devices. (If the patient is insured by the Croatian Health Insurance Fund and the product is included in the list of products of the Fund, the product is compensated by the Fund in the extent enacted by the applicable legislation.)

Decision on the method of calculating the retail prices of medicinal products and other medicines that are not part of the treatment with HZZO, which sets out how to shape retail prices of medicines, regulates that the lowest number of margins is 10% and the highest is 35%.

Particular medical devices may be sold outside the pharmacy stores and specialised retail stores selling medical devices. The list of the reffered medical devices has to be drawn up by the Agency and made available of the web site of the Agency.

Medicinal products subject to medical prescription can be dispensed exclusively in pharmacies, while medicinal products not subject to medical prescription can also be dispensed in specialized retail sale outlets for medicinal products in line with the marketing authorisation granted by the Agency. If the medicinal product can be dispensed in specialized retail sale outlets for medicinal products, the Agency may determine restrictions in respect of its strengths and pack sizes.

 

15. What are the professional and legal responsibilities of those who dispense drugs and devices? What role do they play in providing patient care, information, and safety?

A specialized shop has to employ a responsible person of the appropriate professional qualifications.

The responsible person in specialized shops for retail of medical devices performs the following tasks:

• procurement, receipt, warehousing and keeping of medical devices;
• sale of medical devices;
• informing, advising and familiarising customers with the proper use of medical devices, and
• keeping records on the quantities and types of medical devices.

The responsible person in specialized shops for retail of medicinal products is a pharmacist holding a master’s degree.

The responsible person is responsible for:

• procurement, takeover, warehousing and storage of medicinal products;
• issuance of medicinal products to the end user;
• notification of users on the manner of use of the medicinal product, precautionary measures
  and possible adverse reactions;
• keeping records on the type and quantity of medicinal products;
• keeping records on the storage of medicinal products that require special storage conditions;
• reporting of adverse reactions of medicinal products, and
• drafting the annual report on consumption of medicinal products.

A pharmacist holding a master’s degree is obliged to apply his knowledge to all patients in accordance with Code of Pharmacy Ethics and Deontology. Pharmacist has to be fully involved with other health professionals in training and providing guidelines for safe and rational use of medicines. The activity of pharmacist is public, their relation toward all patients has to be the same.

A pharmacist holding a master’s degree is obliged to apply its knowledge and art to all patients in accordance with Code of Pharmacy Ethics and Deontology. He has to perform his work conscientiously, with respect for man and his life.

Pharmacists are sometimes obliged, in the interest of the health of the patient, to refuse to issue the medicine. If such medicine is issued on prescription, it is mandatory for the pharmacists to seek for a medical advice. Pharmacists issue over the counter medicine at their own risk.

Pharmacists are obliged to:

• treat all patients with the same sense of responsibility;
• recommend such methods of treatment, medicines and other preparations whose use is ethical and professionally advocated;
• to advise all patients on the most appropriate way within his knowledge and if necessary, timely refer them to the physician’s care;
• to deny the issue of medicines in the event of a legitimate suspicion that the patient will use the medicine in a manner which would harm his or her health, or
• to make unlawful gain.

All that a pharmacist, performing his pharmacy duty, learned about a patient is considered a professional secret.

The Chamber of pharmacists will institute disciplinary proceedings against each pharmacist that violates the provisions of the Code through the Disciplinary Chamber.

 

Also from this Legal Handbook

Lawyer Ira Perić Ostojić highlights recent regulatory updates in Croatia, where the legal status of cultivating and producing cannabis for medical purposes has been liberalised.

 

On 25 April 2019 the Amendments to the Act on Combating Drugs Abuse entered into force in Croatia, which liberalizes the cultivation and production of low THC cannabis for medicinal purposes.

With the new law going into effect, companies which have a manufacturing authorization for drugs or active substances from the Croatian Agency for Medicinal Products and Medical Devices (HALMED) will be able to grow low-THC cannabis for medicinal purposes subject to prior approval obtained from the Croatian Ministry of Health.

The same companies will also be able to produce/process low THC cannabis for medicinal purposes with the prior approval of HALMED.

In the next six months, an Ordinance will be passed that will elaborate in detail the requirements and procedure for granting the necessary licenses.

This legislative change is expected to increase the availability and reduce the costs of medicinal products made from cannabis which until now could only be imported to Croatia from abroad.

Also from this Legal Handbook

Lawyer Ira Perić Ostojić outlines two major new regulatory updates regarding pricing and reimbursement for drugs in Croatia.

 

1. Bylaw regulating the maximum permitted wholesale price of the prescription medicinal products

The bylaw regulates the detailed criteria for determining the maximum permitted wholesale price of prescription medicinal products in Croatia and the calculation of such prices by the Croatian Agency for Medicinal Products and Medical Devices (HALMED).

Generally, the calculation by HALMED is mandatory and is carried out: (i) when the products are being first placed on the Croatian market; and (ii) on an annual basis, once a year, starting on the first working Monday in February.

With the annual calculation, HALMED is obliged to publish on its website the list of new maximum permitted wholesale prices in Croatia within 100 days from the beginning of the annual calculation, whereas the new maximum prices (will) start to apply 60 days from the date of such publication.

The wholesale prices of the products that are above the new maximum prices calculated by HALMED (will) need to be reduced to the new prices determined by HALMED, while the prices that are below the new prices calculated by HALMED (will) remain the same.

The bylaw also provides for the possibility, in specific cases and under specific conditions, to request from HALMED permission to have/set the prices of the products higher than the new maximum permitted wholesale prices.

The beginning of the annual calculation of prices for 2019 based on the new bylaw is set for 15 April 2019.

 

2. Bylaw regulating listing of the products on the Croatian Health Insurance Fund’s (HZZO) reimbursement lists and determination of prices covered by the HZZO

The new bylaw sets out:

a) detailed criteria for listing of the medicinal products on the HZZO reimbursement lists;

b) a comprehensive list of reasons and requirements in connection to the requests for listing the medicinal products, supplementing the reimbursement lists and amending the information contained on the lists as well as documents that need to accompany such requests;

c) HZZO’s decision making process;

d) possibility to enter into financing agreements regarding the listed medicinal products;

e) deletion of medicinal products from the list;

f) measures and methods for determining the price of the listed medicinal products that will be covered by HZZO; and

g) alignment of the prices of the listed medicinal products (i.e. after the annual calculation of the maximum permitted wholesale prices by HALMED, in case of medicinal products intended for hospital use and alignment through reference products’ groups and subgroups).