The regulatory regimei Classification
As briefly outlined above, medicinal products are defined by the Act on Pharmaceuticals, which also provides for an exhaustive list of particular types of medicines, such as human medicines, veterinary medicines or human immunological medicines. Likewise, definition and classification of medical devices is subject to the Act on Medical Devices. The definitions reflect the respective EU directives; however, they have been slightly adjusted and the wording is thus not identical to the EU legislation. For example, the definition of a medicinal product under Czech law is a bit more specific and reads as follows:
A medicinal product shall mean:
a) a substance or combination of substances presented as having therapeutic or preventive properties in the case of human or animal diseases; or
b) a medicinal product shall also mean any substance or combination of substances which may be used or administered to human beings or used or administered to animals with a view to restoring, correcting or modifying the physiological functions by means of a pharmacological, immunological or metabolic effect or with a view to making a medical diagnosis.
In addition, the definition of medicinal products also includes medicines for veterinary use, as the two separate EU directives concerning human and veterinary medicinal products have been implemented by the Czech legislator into a common act. The statutory definitions provide a starting point for differentiating between strictly regulated medicinal products, and products such as dietary supplements or cosmetic products that do not fall within the scope of the Act on Pharmaceuticals. In the borderline issues, if the categorisation of a certain product is not clear, the Institute decides whether the product may qualify as a medicine or a medical device under the respective laws and, where relevant, under which category it falls. For the sake of completeness, dietary supplements are governed by the Act on Food and Tobacco Products and are assessed and approved by the Ministry of Health, not the Institute.ii Non-clinical studies
Under the Act on Pharmaceuticals, operators conducting non-clinical safety studies are obliged to proceed in compliance with the principles of good laboratory practice. The procedures for non-clinical safety studies on medicinal products within laboratory tests, according to the principles of good laboratory practice, are laid down in the Ministerial Decree implementing the EU Directive on the inspection and verification of good laboratory practice. Furthermore, in the case of studies on animal models, the operators conducting non-clinical safety studies must observe the Act on the Protection of Animals against Cruelty.iii Clinical trials
A clinical trial on medicines may only be commenced if (1) the Institute has issued an authorisation to commence the trial (or, in the case of clinical trials that are subject to the notification requirement only, the Institute has not rejected such a trial), and (2) the ethics committee has issued a positive opinion on the study. A mere notification is sufficient if the tested medicinal products are EU-authorised products or, if the products are not authorised in any EU Member State, where the products are not obtained by biotechnological processing or where the products containing substances of human or animal origin are not concerned. In addition, a clinical trial may only be undertaken in relation to trial subjects that have consented in writing to the trial after being informed of its nature, significance, implications and potential risks. The informed consent may be revoked by the trial subject at any time.
The ethics committee, consisting of healthcare professionals and non‐medical members, shall protect the rights, safety and health of trial subjects and provide assurance of that protection by, for example, expressing an opinion on the clinical trial protocol. Furthermore, as a general rule, clinical trials on human medicines involving natural persons as trial subjects have to be governed by the rules of good clinical practice. Further guidelines as well as application forms for clinical trial authorisation and clinical trial notification are available in electronic form on the Institute's website.
Recently, the Act on Pharmaceuticals has been amended to comply with the EU Clinical Trials Regulation. The amendment is not yet effective, however, and therefore the above procedure applies until the amendment legally comes into effect.
As regards the clinical trials on medical devices, the requirements for their commencement are to a certain extent similar to clinical trials on medicines. If the medical device is not CE-marked or if it is used for other than the original purpose within the scope of the clinical trial, the clinical trial requires a prior authorisation by the Institute, and the application should be submitted by the sponsor in electronic form via the Registry of Medical Devices. The ethics committee, which is an advisory body of the healthcare service provider, supervises the clinical trial and provides a written approval therewith. Subject to limited exceptions, a written informed consent by the trial subject must be obtained before the commencement of the clinical trial on medical devices.iv Named-patient and compassionate use procedures
As a general rule, only authorised medicinal products may be prescribed to patients, placed on the market and used in the delivery of healthcare services. However, an exception from this rule may apply in the delivery of healthcare services to individual patients. If the following statutory requirements are met, the attending doctor may prescribe or use a medicinal product that has not been authorised in accordance with the Act on Pharmaceuticals:
- no medicinal product of adequate composition or similar therapeutic properties, for which a marketing authorisation exists, is distributed or marketed in the Czech Republic;
- the medicinal product has been authorised abroad or it qualifies as a product for modern therapies, the manufacturer of which is a manufacturing authorisation holder in relation to the relevant pharmaceutical form;
- use of the medicinal product is sufficiently justified by scientific findings; and
- the medicinal product does not contain any genetically modified organisms.
Under the Act on Pharmaceuticals, only medicinal products authorised by the Institute or medicinal products authorised in accordance with the EU Regulation laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use may be placed on the market in the Czech Republic. In the first case, the application for marketing authorisation shall be lodged with the Institute and the authorisation may only be granted to an applicant that resides or is established in the territory of any of the EU Member States. The Act on Pharmaceuticals sets out a list of documents and information that must accompany the application.
In respect of certain categories of medicinal products, such as human homeopathic products or traditional herbal medicinal products satisfying the statutory requirements, a simplified registration procedure may apply. If a homeopathic product has been authorised through the simplified procedure, that information must be clearly stated on the label as well as in the package leaflet. In the case of traditional herbal products, the labelling must state that use of the product is based exclusively on experience from long-standing use.
During the marketing authorisation procedure, the Institute should first assess the completeness of the application and, where it is found to be complete, the Institute must make a decision within 150 or 210 days of provision of the information about completeness of the application. The exact period depends on the type of medicine to be assessed. The marketing authorisation is valid for five years and may be subsequently renewed, based on a review of the risk-benefit ratio by the Institute. During the five-year term, the marketing authorisation may be changed, suspended or revoked if, for example, the medicinal product is harmful or the risk-benefit ratio of the product is not favourable.
Under the Act on Medical Devices, registration of persons intending to place medical devices on the market is required (in the form of a notification submitted electronically via the Registry of Medical Devices). Registration is completed once the Institute issues a certificate of compliance with the notification requirement and is subsequently valid for a period of five years, which may be repeatedly extended. The Act on Medical Devices also regulates the notification requirement in respect of medical devices that have been placed on the market. This notification is also valid for five years, and repeated extensions are possible.vi Regulatory incentives
Under the Act on Inventions, a supplementary protection certificate may be granted for substances protected in the territory of the Czech Republic by a valid patent, if they are the active substances of the medicinal products registered in accordance with the Act on Pharmaceuticals. An application for a certificate may be filed by the proprietor of the patent protecting the substance under the following requirements:
- the basic patent is valid in the territory of the Czech Republic;
- the product contains the active substance protected by the basic patent and has a valid marketing authorisation;
- the certificate has not yet been granted for the substance; and
- the marketing authorisation is the first authorisation to place the mass-produced medicinal product on the Czech market.
The certificate takes effect for a period equal to the period that elapsed between the filing date of the basic patent application and the date of the first marketing authorisation enabling the medicinal product to be placed on the market in the Czech Republic, reduced by five years. That being said, the certificate may only be effective for a maximum period of five years.
There is no such supplementary protection in respect of medical devices.vii Post-approval controls
The rules concerning staffing of the marketing authorisation holders, their risk management and safety reporting include a requirement to ensure that the sales representatives are qualified adequately to the nature of the medicinal product or, where a risk to the health of treated persons arises, a requirement to adopt all measures available to remedy the situation and limit the adverse effects of the medicinal product concerned. If a defect in the quality of the medicinal product is identified by the marketing authorisation holder or if a defect is found by a third person and notified to the Institute, the marketing authorisation holder must ensure that the patients can have the defective medicinal product exchanged by any pharmacy or, if that is not possible, ensure a complete recall of the product from the market.
The marketing authorisation holder is obliged to operate a pharmacovigilance system to collect information on the risks associated with the medicinal products, subject to the marketing authorisation, which will be subsequently evaluated by the marketing authorisation holder in terms of risk minimisation and prevention. Based on the evaluation, appropriate measures should be adopted to limit potential risks. Furthermore, the marketing authorisation holder must have permanently and continuously at their disposal a qualified person responsible for pharmacovigilance who ensures development and maintenance of the pharmacovigilance system; that person must be domiciled within the territory of the European Union. The Institute may request the marketing authorisation holder to appoint a contact person in the Czech Republic who would deal with pharmacovigilance issues and be subordinate to the qualified person domiciled in another EU Member State.
As regards variations to marketing authorisation, marketing authorisation holders must submit any change in an authorisation to the Institute for approval or, as the case may be, announce or notify the change. Variations to marketing authorisations are regulated by the directly applicable EU Regulation on assessment of variations to marketing authorisations for human and veterinary products. The marketing authorisation holder may also apply for transfer of the marketing authorisation to another natural or legal person. The Institute must decide about the application within 30 days of its delivery and specify, if the application is not rejected, the date on which the transfer is to be conducted.
As briefly discussed above, the Institute may change, suspend or revoke the marketing authorisation if, for example, the medicinal product is harmful or lacks therapeutic efficacy. Other reasons for revocation, suspension or change of the marketing authorisation of the medicinal product include findings that the risk-benefit balance is not favourable or that the qualitative and quantitative composition of the medicinal product is inconsistent with the documentation submitted.
Reporting and evaluation of adverse incidents and safety corrective actions regarding medical devices is carried out through a vigilance system. Generally speaking, an adverse incident is defined under the Act on Medical Devices as any failure or deterioration of characteristics or efficacy of a medical device which resulted or could have resulted in the death or serious deterioration of health of the medical device's user or another individual. Accordingly, a field corrective action is defined as an action determined by the manufacturer with the aim of reducing the risks associated with the adverse incident. The Act on Medical Devices also stipulates a number of obligations for healthcare service providers at whose premises a suspected adverse incident has occurred.
In the event of discrepancies regarding inclusion of the CE mark (e.g., the medical device that has been placed on the market is CE-marked without authorisation), the Institute is entitled to issue a decision for withdrawal of a medical device from the market.viii Manufacturing controls
Manufacturing of medicinal products is subject to an authorisation from the Institute. An application for the authorisation must contain, among other things, specification of the site where the medicinal products are to be manufactured and evidence that the applicant has at their disposal suitable and sufficient premises, technical equipment and control facilities for the required activity. Based on the information provided, the manufacturing authorisation must specify the premises in which the manufacture may be carried out. Furthermore, within the inspection activities, the Institute may conduct ad hoc inspections of the designated premises.
Contrary to legal regulation of medicinal products, the Act on Medical Devices does not contain any specific provisions concerning manufacturing facilities.ix Advertising and promotion
Advertising and promotion of medicines is specifically addressed by the Act on Advertising. As a general rule, only medicines authorised under the Act on Pharmaceuticals may be advertised. The Act on Advertising distinguishes between two categories of advertising of medicines – advertising aimed at the general public and advertising aimed at healthcare professionals. As regards advertising aimed at the general public, it cannot promote, inter alia, prescription-only medicines. Such products may only be the subject of advertising aimed at healthcare professionals. This form of advertising may be carried only through information channels targeting healthcare experts, such as professional magazines, and must include accurate, current and verifiable information, basic information according to the summary of product characteristics, information about the manner of dispensing the product according to the registration, and information about the reimbursement status of the product under the public health insurance system. Furthermore, it is prohibited for advertising aimed at healthcare professionals to offer, promise or provide them with any gifts or other benefits, unless they are of insignificant value and relate to the activities of the professional.
Any advertising of over-the-counter medicines aimed at the general public must clearly state that the product being advertised is a human medicine and include the brand name of the product as stated in the marketing authorisation. In addition, potential customers must be provided with the information necessary for the proper use of the medicine and be given a clear instruction to read the package leaflet. The Act on Advertising also provides for a list of prohibited actions (e.g., the advertising must not suggest that the human medicine is a food or cosmetic product or that consultation with a healthcare professional is not necessary).
As the advertising of medical devices it not subject to any specific rules, the general provisions of the Act on Advertising apply.x Distributors and wholesalers
Medicinal products may be distributed in the territory of the Czech Republic either by (1) persons authorised directly by the Institute to conduct this activity or (2) a holder of a distribution authorisation granted by a competent authority of another EU Member State. In the latter case, the EU-based distributor is, however, obliged to give prior notice to the Institute to show evidence of the distribution authorisation and provide information regarding the scope of distribution and the location of distribution stores.
To obtain the authorisation, the applicant must:
- have suitable and adequate premises, installations and equipment, so as to ensure proper storage and distribution of the medicinal products;
- have ensured the services of persons who are eligible under the Act on Pharmaceuticals to handle the medicinal products, and the services of a qualified person designated as being responsible for compliance with the statutory requirements; and
- show evidence of the prerequisites to fulfil the obligations imposed on distributors by the Act on Pharmaceuticals.
Distribution of medical devices may only be conducted by distributors who are registered with the Institute. To be registered, a distributor must notify the Institute of its operation prior to the commencement of the distribution service. The Act on Medical Devices does not stipulate any additional requirements regarding the registration of distributors of medicinal products.xi Classification of products
Medicinal products are classified under the Act on Pharmaceuticals into the following categories; the classification of a particular medicinal product is carried out by the Institute as part of the marketing authorisation procedure:
- medicinal products that are subject to medical prescription;
- medicinal products that are subject to restricted medical prescription;
- medicinal products that may be dispensed without the (restricted) medical prescription (i.e., over-the-counter medicines);
- medicinal products that may be dispensed without the (restricted) medical prescription with restrictions; and
- selected medicinal products (i.e., medicines that may be dispensed without a medical prescription outside pharmacies).
Generally speaking, a medicinal product must be dispensed with a medical prescription if it might jeopardise, whether directly or indirectly, the health of the patient. When classifying a medicinal product as prescription-only, the Institute should consider, for example, whether it contains a substance classified as a narcotic or psychotropic or whether it may lead to addiction or be misused for illegal purposes. In certain cases, the Institute can stipulate in the marketing authorisation that the medicinal product concerned is to be dispensed on a restricted medical prescription, which means that the product may only be prescribed by a specialist or a doctor with a professional qualification under supervision of the specialist based on his or her written authorisation. Medicinal products will usually fall within the restricted-prescription-only category where the supervision of a specialist is required during treatment or where the medicinal product is intended for treatment that may only be conducted at an inpatient healthcare facility. Similarly, in the case of over-the-counter medicines, the Institute can stipulate in the marketing authorisation that the medicinal product concerned is to be dispensed with restrictions. In this case, a medicinal product may only be dispensed to persons for whom it is intended and, therefore, the provider authorised to dispense the product is obliged to maintain records of who it has been dispensed to. The restriction may represent, in particular, specification of the dose for individual administration or specification of an age limit in relation to persons asking to be given the medicinal product.
As regards 'selected medicinal products', these may be used without expert consultation and are mainly used to cover the acute needs of the patient (e.g., medical products intended for treatment of mild pain). Rules of good practice for the retailers of selected medicinal products are laid down in Ministerial Decree No. 106/2008 Coll.
As of 1 January 2018, medicinal products should be prescribed on a medical prescription in electronic form (making a medical prescription in paper form is allowed only in limited cases).
The Act on Medical Devices provides in respect of medical devices classification a non-exhaustive list of medical devices, including, for example, an active implantable medical device, an in vitro diagnostic medical device or a custom-made medical device. However, this classification does not affect prescription or sale of the medical devices. In addition, medical devices may be classified into risk classes I, IIa, IIb or III in ascending order by the degree of risk corresponding to the use of the medical device concerned.xii Imports and exports
Under the Act on Pharmaceuticals, a manufacturing authorisation is required for importation of medicinal products from third countries. The person who oversees the import from a third country must have at his or her disposal a certificate of quality control drawn up in compliance with the marketing authorisation for each batch of the medicinal product.
Importation of medical devices is to be conducted by an importer registered with the Institute, and the imported medical devices may only be supplied to a distributor, a healthcare service provider, a dispenser or a seller. As regards custom-made medical devices, only those medical devices in respect of which a declaration of conformity has been issued and which has been CE-marked may be imported. For the purposes of exporting a medical device outside the EU Member States, the manufacturer of a notified medical device established in the Czech Republic has to apply for a free-sale certificate, which is a public document certifying that the medical device has met the conditions for being placed on the market.xiii Controlled substances
Controlled substances, such as narcotics and psychotropics, are governed by the Act on Addictive Substances, which regulates, inter alia, the handling of addictive substances (i.e., narcotics and psychotropics as defined by the Governmental Regulation on Lists of Addictive Substances), their import and export, and transition operations therewith. Every individual export operation of an addictive substance is subject to an authorisation by the Ministry of Health, except for the exporting of mass-produced medicinal products containing certain categories of addictive substances. The export authorisation may only be issued after submission of an import authorisation issued by the country where the export is to take place or, if an import authorisation is not required, the approval of a relevant authority in the importing country. Similarly, imports of addictive substances to the Czech Republic must be authorised by the Ministry of Health.xiv Enforcement
As stated above, the Institute is responsible for enforcement of medicinal products and medical devices legislation. The aim of an inspection is to check compliance with statutory requirements. The Institute is authorised, in particular, to suspend the validity of marketing or manufacturing authorisations that have been issued pursuant to the Act on Pharmaceuticals. In the event of an administrative offence, a fine of up to 20 million Czech koruna or a ban on operations for a period of up to two years may be imposed.
As regards inspections relating to medical devices, the Institute is entitled to require the suspension or termination of use of a medical device if it decides that use of the device may result in imminent danger of harm to the health of patients. All costs associated with the Institute's decision are to be borne by the healthcare service provider. As regards administrative offences, the level of fines that may be imposed for non-compliance with the Act on Medical Devices are significantly lower than those stipulated in the Act on Pharmaceuticals; the maximum fine is 2 million Czech koruna.