Time frame
How long does it take, in general, to obtain an authorisation from application to grant, what fees are payable and what is the normal period of validity of the authorisation?
According to the Licensing Regulation, in principle, an application must be reviewed and concluded by MoH within 210 days of submission. However, MoH does not follow this regulatory rule strictly, and completion of a marketing authorisation process may take approximately two to three years, depending on deficiencies in the dossier.
Fees for obtaining marketing authorisation vary depending on the status and type of the authorisation and product.
Pursuant to the Licensing Regulation, an application for the renewal of a marketing authorisation must be submitted to the TMMDA at least three months before the end of the first five years of the marketing authorisation’s issuance, together with the pharmacovigilance data and information regarding quality, security and operation of the marketing authorisation and details of all changes that have occurred. Marketing authorisations must be renewed every five years accordingly.
Protecting research data
What protection or exclusivities apply to the data submitted by originators to gain initial approval and, on variation or new application, to add indications or pharmaceutical forms?
The Licensing Regulation limits the data exclusivity period to six years, and this period starts from the first registration in the EU-Turkey Customs Union area. The data exclusivity period shall apply to original products:
for which no generic registration application was submitted in Turkey before 1 January 2005, among the original products registered for the first time after 1 January 2001 in one of the countries within the Customs Union area; and
that are registered after 1 January 2005 in one of the countries within the Customs Union area.
For products enjoying patent protection in Turkey, the implementation of the six-year data exclusivity period shall be limited by the patent period of the relevant product. The nature of the regulatory data exclusivity is an administrative protection measure. It does not grant any civil proprietary right nor limit any such rights. The MoH’s regulatory data exclusivity provision in the Licensing Regulation provides for an administrative measure by not allowing third parties to use or benefit from data. However, according to established court precedent, filing an abridged licence application to obtain a marketing authorisation for a generic product does not violate data exclusivity.
Under the Licensing Regulation, the granting of marketing authorisation does not affect the expiry of the patent period. Additionally, supplementary protection certificates are not recognised under Turkish law. Nevertheless, the Bolar provision (under which, clinical trials for generics and biosimilars are exempt from infringement) is still recognised under Industrial Property Law No. 6769 enacted in 2017.
Freedom of information
To what extent and when can third parties make freedom of information applications for copies of research data submitted by applicants for authorisation to market medicinal products or medical devices?
Under Turkish law, there is a general freedom of information regime mainly regulated by the Law on the Right to Information (No. 4982) and the Regulation on Implementation Principles and Procedures Regarding the Law on the Right to Information. Such Law and Regulation mainly regulate that everyone, subject to certain conditions for foreigners, has a right to request information from public bodies and institutions due to democratic and transparent governance principles. However, there are certain exceptions provided by the Law, including trade secrets, among others.
The Licensing Regulation explicitly stipulates that the marketing authorisation submission to be made to the MoH is classified and shall have its confidentiality maintained by the MoH. If any third party requests any information within the dossier from the MoH, the MoH will refuse such request due to the confidentiality obligation. Therefore, it is not possible for any generic or other competitor company to obtain any information including, but not limited to, clinical trial data or manufacturing data from the drug approval file (marketing authorisation dossier) of an original product by requesting such information from the MoH.
However, there is a possibility that a court may issue a court order to the MoH to send the marketing authorisation dossier to a court, if such dossier is required to be viewed with respect to a patent law-related dispute. Even in cases where it is necessary for the dossier to be reviewed during court proceedings, both the MoH and courts take very strict precautions to ensure confidentiality of the dossiers.
Per a State Counsel decision, limited information, such as the marketing authorisation application number of an abridged application, based on freedom of information under advocacy law, should be disclosed to the MA holder of the original product to which the MA application is abridged.
Regulation of specific medicinal products
Are there specific rules for approval, and rewards or incentives for approval, of particular types of medicinal products, such as traditional herbal and homeopathic products, biologicals and biosimilars, controlled drugs, orphan drugs and those for paediatric use?
There are certain specific regulations providing rules and requirements regarding these particular types of medicinal products in Turkish law.
Traditional herbal products are regulated within the Regulation on Herbal Medicinal Products dated 2010. The products must be manufactured in accordance with GMP conditions by the natural or legal person resident within the borders of Turkey, in a production site that fulfils the requirements listed in the Regulation. The licence application must include necessary information and documents as a separate file for each pharmaceutical dosage form, and must be made in a common technical document. Within the application:
the qualitative or quantitative composition of the product must be disclosed;
data on conventional use must be sufficient; in particular, regarding pharmacological effects and efficacy on the basis of long-term use and experience; and
pharmaceutical quality must be documented adequately.
Additionally, the product must not be harmful under normal use. Turkish law provides limited references to orphan drugs, and, although a detailed regulation in relation to orphan drugs has been on the MoH’s agenda for a long time now, there is still no specific regulation. Orphan drugs are subject to almost the same rules as conventional medicinal products, and most orphan drugs have entered the country under named-patient programmes, but the MoH enacted a new provision in 2018 requiring marketing authorisation for those products offered to the market on a named-patient basis.
What pharmacovigilance or device vigilance obligations apply to the holder of a relevant authorisation once the product is placed on the market?
The Regulation on the Safety of Medicinal Products provides certain procedures for pharmacovigilance, and requires adverse effects of pharmaceutical products to be effectively monitored to ensure the safe use of medicinal products for human use. This Regulation requires the marketing authorisation holder to employ a qualified physician or pharmacist to provide necessary notifications to the MoH regarding the safety of the medicinal product. The marketing authorisation holder may prefer to outsource on the basis of an agreement. However, the ultimate responsibility in this regard belongs to the marketing authorisation holder.
The medical device vigilance procedure is operated under a risk-management system in accordance with the Communiqué on the Rules and Procedures for the Safety Reporting of Medical Devices. The Communiqué provides that the manufacturer, authorised agent, importer or the legal or natural person responsible for placing the medical device on the market must notify the MoH of any defect, side effect or recall of a medical device. In addition to the notification obligation, such persons shall also be severally responsible to:
carry out the necessary investigation, including risk analysis;
identify and implement corrective actions to ensure device safety;
send an information letter to users and the MoH, explaining the adverse event originating from the device and measures that can be taken by users, including the relevant company’s contact details;
inform the MoH immediately of any failure to fulfil the responsibilities arising from the Communiqué; and
notify the MoH of all damages directly or indirectly arising from the use of in vitro medical diagnostic devices.
Other authorisations
What authorisations are required to manufacture, import, export or conduct wholesale distribution and storage of medicinal products and medical devices? What type of information needs to be provided to the authorities with an application, what are the fees, and what is the normal period of validity?
To obtain a manufacturing site licence for manufacturing of medicinal products, any real or legal entity satisfying the general conditions (ie, employing a responsible manager with a degree in pharmacy, medicine or chemistry, employing certain other personnel, documenting that the facility satisfies technical requirements and compliance with GMP requirements) and possessing the required documents (ie, documents relating to employees, buildings, workflow, equipment, workplace opening permits and environmental assessment reports) under the Manufacturing Regulation can apply to the provincial directorates of the MoH.
Considering that the issuance of a GMP certificate for the relevant manufacturing site by the TMMDA is one of the most important conditions for the issuance of a marketing authorisation, manufacturing practices in Turkey are quite robust. Moreover, a GMP certificate issued by an EU authority is not by itself acceptable for most imported products, since the TMMDA inspects manufacturing facilities in Turkey and abroad. This condition also reveals the robust application of GMP in Turkey. The TMMDA will inspect the manufacturing site and, if it determines that the features of the manufacturing site are sufficient and proper, will issue the authorisation. According to the legislation enacted in 2017, warehouses providing secondary packaging services shall be evaluated as manufacturing facilities and further procedural requirements will be applied to these services as well. Besides, to carry out serial release activities and release medicinal products to the Turkish market, it is also required for the marketing authorisation holder to obtain a licence for serial release activities and a qualified person certificate for the serial release site.
The import and export of medicine is subject to general import and export provisions with some additional requirements. If the medicines contain narcotic or psychotropic substances, special authorisation is required from the MoH. If they do not contain any of these substances, written confirmation of this fact from the MoH will be required. For the import of medicines, a licence and certificate of analysis (control (import) certificate) are needed. A control certificate is issued for a duration of 12 months. For exports, a certificate of analysis and the documents needed for the licensing of the product in the destination country are required.
The wholesale distribution and storage is conducted by warehouses in Turkey, of which there are two types. The first is warehouses that will make secondary packaging, which need to obtain a manufacturing site licence, as explained above. The second is called a pharmaceutical warehouse, which does not make secondary packaging, but only stores and sells pharmaceuticals to pharmacies or other wholesalers. To obtain a pharmaceutical warehouse licence, any real or legal entity satisfying the general conditions (ie, employing a responsible manager with a degree in pharmacy, medicine or chemistry, employing certain other personnel, documenting that the facility satisfies technical requirements and compliance with good distribution practice requirements) and possessing the required documents (ie, documents relating to buildings, fire safety, workplace opening permits and, for legal entities, a trade registry certificate and articles of association of the company approved by the provincial directorates of the MoH) under the Regulation on Pharmaceutical Warehouses and Products in Pharmaceutical Warehouses can apply to the provincial directorates of the MoH.
The fee for obtaining authorisation varies depending on the type of authorisation. There is no explicit provision regulating the validity period of authorisations, if it is not specifically stipulated; hence, authorisations are routinely controlled and updated by the MoH after issuance.
Sanctions
What civil, administrative or criminal sanctions can authorities impose on entities or their directors and officers for breach of the requirements concerning controlled activities?
Depending on the issue, life sciences regulations provide enforcement provisions of a different nature. The most common enforcement measures are administrative and financial sanctions, such as suspending marketing authorisations, banning promotional activities or imposing financial fines. The breach of compliance may also result in civil and criminal sanctions, such as personal liability, including the liability arising from bribery. The authority may also order the publication of the decision regarding the unsafe product by publicly announcing details of the unsafe product and the relevant measures imposed by the authority.
Exemptions
What, if any, manufacture and supply of medicinal products is exempt from the requirement to obtain an approval to market?
Medicinal products prescribed by a physician specifically for an individual patient and prepared according to this formula in a pharmacy (magistral medicines) are exempt from the requirement of obtaining an approval to market.
Parallel trade
Are imports allowed into your jurisdiction of finished products already authorised in another jurisdiction, without the importer having to provide the full particulars normally required to obtain an authorisation to market? What are the requirements?
Parallel import is a legitimate practice in Turkey, but since only the marketing authorisation holder can import medicinal products, the parallel import of medicinal product is not technically possible. Regarding parallel export, the MoH published a circular in 2014 stating that it may prevent the export of medicines imported into Turkey from abroad if Turkish patients need such medicines. Accordingly, the MoH is expected to take measures to prevent parallel exports under certain circumstances; however, the technical preparations for the establishment of an efficient system for this purpose remain unclear. The Competition Board had carried out investigations related to parallel export restrictions. In a very recent case, it was decided by the Board that direct or indirect export bans for pharmaceuticals are not violating Turkish competition law, although the export ban provisions are, in principle, against the competition rules in general, since the effects of these export bans are not seen in the Turkish market.
Firstly published in Lexology on 10.12.2019.