The Pharma Legal Handbook: Turkey

Istanbul’s First Instance IP Court recently dismissed a negative declaratory action (the “Case”) against our client citing the plaintiff’s lack of standing because the pharmaceutical at issue was unlicensed as of the when the action was started. The ruling is noteworthy because it appears to confirm the precedential force of similar Court of Appeal decisions.

 

For pharmaceuticals in particular, negative declaratory relief is considered as an effective market-clearing tool. Anyone with an interest in a pharmaceutical product sufficient to confer standing, may petition a competent court for a declaratory ruling that current and future use of the product is, or, as the case may be, is not, infringement. These actions are initiated both by pharmaceutical and non-pharmaceutical entities as a means of avoiding prospective infringement actions and, concomitantly, of securing rights before entering a market.

 

As illustrated by the Case, timing of the petition is crucial. This is particularly so for pharmaceuticals both in light of the process for bringing a drug, particularly a competing generic, to market; and of Article 85/3-c of the Turkish Industrial Property Law numbered 6769, referred to colloquially as the Bolar exemption, which provides a safe harbor for non-rights holders to use patented pharmaceuticals for clinical trials without infringing on the patent owner’s rights.

 

The Bolar exemption is interpreted and applied without uniformity by Turkey’s intellectual and industrial property courts. Accordingly, pharmaceutical companies and IP lawyers have lacked the clarity of a unifying pronouncement of the limits of the Bolar exemption. However, the Court of Appeal has consistently held that an unlicensed pharmaceutical is not subject to IP enforcement.

 

Under Turkey’s Code of Civil Procedure numbered 6100, standing to file an action requires a sufficient legal interest. Where standing is lacking courts must, ex-officio or upon motion, dismiss the case. In the Case, negative declaratory relief was sought against our client’s registered patent rights. We argued that dismissal was required under the Bolar exemption because the product in question was not licensed and, therefore, the plaintiff lacked standing, and, because the product license dossier might change during the licensing process, it would be impossible, prior to licensing, for the court to rule on the merits of the claim.

 

The court ruled in favour of the patent holder and dismissed the case. It is reasonable, then, in light of the outcome of the Case, to consider the question of timing settled in accord with the Court of Appeal.

 

The Case confirms the settled practice of the Court of Appeal and according to the settled practice, in case of negative declaratory actions, timing is important, as the actions might be refused due to lack of legal interest. Considering this settled approach, it is advisable to file a negative declaratory action close to the anticipated time of the pharmaceutical license approval to avoid dismissal of the case.

Also from this Legal Handbook

The shockwaves from the UK’s exit from the European Union have resounded across the continent, including in Turkey, where the country’s pharmaceutical and medical devices regulator has had to adjust its guidance on CE-mark certified devices. Leading lawyers from top Turkish law firm and PharmaBoardroom legal partner Moroğlu Arseven explain the current situation.

 

CE Certificate Requirement in Turkey

The Regulation on CE Marking, published in the Official Gazette on, and effective as of, 23 February 2012 (the “Regulation”) governs the use of the CE Mark in Turkey. Medical devices covered by the Regulation must bear the CE mark to legally enter the Turkish market. Within Turkey, the CE Mark is symbolic of CE certification by a notified body authorized to conduct product conformity assessments.[1] In addition, the Customs Union Agreement between Turkey and the European Union (the “EU”), to bear a CE Mark a medical device must be CE certified by a notified body within Turkey or the EU.

 

TMMDA’s Response to Brexit

Upon Brexit, the United Kingdom (the “UK”) has dropped out of the EU, its notified bodies have dissolved, and CE certificates issued by them have been invalidated. Accordingly, medical devices marketed in Turkey and bearing a CE Mark pursuant to a CE certificate issued by a former UK notified body, have been decertified.

The Turkish Medicines and Medical Devices Agency (the “TMMDA”) addressed certain Brexit related CE certification matters in published announcements about a post-Brexit transition period (the “Transition Period”); within which affected devices marketed in Turkey with CE certification from a former UK notified body can become compliant.

To take advantage of the Transition Period, a medical device manufacturer, or its local representative or distributor had to, in a timely manner, file with the TMMDA a confirmation letter from the associated notified body stating that the assessment is in process; and, thereupon, the TMMDA would grant an automatic 120 day extension of CE certification during which a new CE certificate for the device had to be uploaded to the TMMDA’s online registration system.

The TMMDA has sought to minimize the impact of Brexit both on domestic consumers and global producers of medical devices marketed in Turkey.

 

Implementation of Post Brexit Plan

The Transition Period concluded on 31.12.2020. On 01.01.2021, all CE certifications obtained from former UK notified bodies were invalidated.

The TMMDA announced the following new post-Brexit rules for devices CE certified by a former UK notified body:

• The expiration of all CE certificates issued by former UK notified bodies, even if facially valid beyond 31.12.2020, are accelerated, and all such certifications are deemed expired as of 31.12.2020. No extension is available.
• CE certificates issued by a former UK notified body and facially valid beyond 31.12.2020, and with respect to which the 120 day extension period granted by the TMMDA has lapsed, are deemed expired as of 31.12.2020. No extension is available.
• CE certificates issued by former UK notified bodies which expired naturally on or before 31.12.2020 are deemed expired. No extension is available.

 

Conclusion

The global ramifications of Brexit cannot be underestimated. We have had several opportunities to communicate both with TMMDA and the TR Ministry of Health about their position on post-Brexit CE certification. Both insist on maintaining Turkey’s formal CE certification process. Nevertheless, both remain open to considering exceptional cases, substantiated by official documentation from authorized national or international authorities, where a necessary medical device not yet CE certified may require an exemption from certain regulatory requirements due, in whole or in part, to issues arising from the COVID-19 pandemic, or for other reasons deemed, in its discretion, satisfactory by the TMMDA.

 

[1] A notified body is an organization accredited by at least one EU Member State to conduct conformity assessments under relevant EU Directives, and based thereupon, issue CE certificates. After certification, a manufacturer may legally affix a CE Mark to the certified product.

Also from this Legal Handbook

The COVID-19 pandemic continues to spread rapidly across the globe amid critical supply shortages of medical devices and medicines. The rapid spread of the virus, on the one hand, threatens supply chains and causes shortages, on the other hand, it also strengthens global solidarity.

 

Brands from different sectors make an effort towards helping in the fight against the pandemic. Fashion brands are manufacturing masks, luxury cosmetic brands are supporting disinfectant manufactures, the entrepreneur ecosystem swept into seeking alternative ways to support healthcare heroes who are facing the growing shortage of personal protective gear. News keeps coming from the technology industry, 3D printing of protective gears ramps up, people even have started using their personal printers for such purpose. Furthermore, pharmaceutical companies across the world are diligently working to develop vaccines and antivirals.

Not surprisingly, all these developments raise questions about compulsory licensing. Intellectual property rights, patents primarily, are protected to support and secure future inventions and developments. Because the main purpose is to support the actors who have contributed to the field to ensure continuous and stable development. Disclosing the invention to the public and making it available for others are also required for that purpose. In this sense, there is always a delicate balance between those who should use existing inventions and the inventors who need support for future inventions. In some exceptional cases, compulsory licensing mechanism comes along with patent protection, to maintain this balance.

The Agreement on Trade-Related Aspects of Intellectual Property Rights (“TRIPS”) is one of the main sources of the World Trade Organization (“WTO”) members regarding legislative purposes of intellectual property rights. TRIPS covers the patent protection and exceptional limitations to be imposed. Accordingly, WTO members, including Turkey, are expected to implement those into their law systems.

In Turkey, IP Law protects inventors by enabling them to patent their inventions and exercise their rights. Basically, the patent is an exclusionary right that permits the patent right holder to prevent others from making, using or selling the patented invention for a limited period. This exclusionary right is subject to exemptions, as well. Compulsory licensing mechanisms are one of the exemptions.

The exclusionary status of patent rights makes the compulsory licensing mechanisms very rare and exceptional. Since the very beginning of the patent protection in Turkey, there has been only one case for compulsory license requests which had been concluded with a settlement without a court decision.

Even though, the compulsory license may not be required as we are all together in this fight against the outbreak, the current trend on the rapid raises of the shortages indicates that this mechanism might be triggered soon.

 

COMPULSORY LICENCE PROCEEDINGS IN TURKEY

The IP Law sets certain conditions for granting Compulsory Licence (“CL”) in Turkish practice and regulates the following CL request/grant proceedings respectively:

• In case of non-use arguments: – The courts are entitled to handle these requests.
• In case of interdependency of the subjects of the patents – The courts are entitled to handle these requests.
• In cases where plant breeders cannot develop a new type of plant without infringing on a preceding patent.
• In cases where patent holders engage in activities that prevent, distort or restrict competition while using the patent. – Turkish Competition Authority is entitled to handle these requests.
• To meet requirements of the Doha Declaration (The export of pharmaceutical products to foreign countries experiencing public health problems.) – The courts are entitled to handle these requests.
• In the interest of public order – Turkey’s Ministry of Health and the Ministry of National Defence are entitled to request these CLs and the President decides on the granting.

 

THE CL PROCEEDINGS IN THE INTEREST OF PUBLIC ORDER

The IP Law regulates that where public health or national security is at stake, at the request of the Ministry of Health and the Ministry of National Defence, the President of Turkish Republic is entitled to grant a compulsory license.

In accordance with their exclusionary nature, such rights are protected with patents and aimed to be protected as strong as possible. Due to this nature, compulsory licensing is exceptional for them.

However, at some point, this protection might upset the market balance. The non-use status of the patent or the activities of the patent holder which are not compatible with competition rules is relatively common ways of compulsory license granting mechanisms. On the other hand, the licenses granted by the President of the Turkish Republic are rarely seen in this exceptional situation. The granting mechanism – the procedural steps that need to be followed are relatively straightforward in comparison with the other compulsory license types. This is not surprising given that this license type can only be granted in cases of a national emergency and/or extreme urgency regarding public health or national security.

 

EXPORT/IMPORT STATUS OF THE PHARMACEUTICALS PRODUCED UNDER A COMPULSORY LICENCE:

Today, we are experiencing a global outbreak, COVID-19 is a true example of “extreme urgency”. Therefore, it comes as no surprise in case this mechanism is triggered in Turkey in case of need.

The compulsory license mechanism brings the questions on whether licensee will be entitled to the export and import of the pharmaceuticals that are produced under a compulsory license.

In principle, the nature of the CL does not allow the licensee the right of the exportation/importation. It is only granted for producing the generics “predominantly for the supply of the domestic market”, not for export purposes. Also, the product must be produced in the market, not be imported This principle leads to two primary consequences:

• Limiting the exportation amount when the pharmaceuticals are manufactured under the CL.,
• Effecting the countries with insufficient manufacturing capacity. These countries will face difficulties when supplying their needs.

The first exception to this principle is CL proceedings for the exportation of the pharmaceutical goods manufactured under the CL.  Levels of the spread of the virus and severity vary from country to country, and each has its own weaknesses and strengths. On the other hand, each country has different level of manufacturing facilities, capacities, technologies or stocks on chemicals or active ingredients. Therefore, a country in the near future might be in need of pharmaceuticals products which it is not capable of manufacturing it. In such a case, the exportation of the products from a country where the products are being manufactured will be possible under the compulsory license.

With Doha Declaration and relevant amendments, Turkey has agreed to import the pharmaceutical products manufactured under CL only in a national emergency or other circumstances of extreme urgency, which forms the second exception. Considering the extreme urgency of maintaining fast and uninterrupted access to these vital pharmaceutical products, in case a need arises while granting such compulsory license, the Presidency can grant the right of importation to the licensee. This authority must be limited to the need and must be granted temporarily.

In Turkey the applicable law provides the basis to act either as exporters or as importers, or as both. Regarding the COVID-19 outbreak, it is very gripping to follow the developments to see whether CL proceedings is going to be applied ever.

 

REFERENCES

• https://www.wto.org/english/news_e/pres03_e/pr350_e.htm
• https://www.wto.org/english/tratop_e/trips_e/pharmpatent_e.htm
• https://www.wto.org/english/thewto_e/glossary_e/paragraph6_e.htm
• https://www.wto.org/english/res_e/reser_e/ersd201507_e.htm
• https://www.wto.org/english/news_e/pres03_e/pr350_e.htm
• https://www.resmigazete.gov.tr/eskiler/2014/03/20140315-4-1.pdf
• https://www.wto.org/english/docs_e/legal_e/27-trips_04c_e.htm

 

This article was originally published on April 20th 2020 here

Also from this Legal Handbook

The low-down on the situation regarding biosimilars & biologics in Turkey. Prepared in association with Moroğlu Arseven, a leading Turkish law firm, this is an extract from The Pharma Legal Handbook: Turkey, available to purchase here for GBP 75.

 

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

Generic medicines include identical molecules with the original reference product, and these molecules are small and chemically stable molecules produced through chemical synthesis. However, biosimilar is the name of medicine, which is similar (not identical) with the reference licensed biological medicine.

The active ingredient of a biosimilar is only the similar of the reference medicine. Generics are different than biosimilars because they are considered equivalents and includes the same active ingredient. Biosimilar and reference biological medicines are used to treat the same illness with the same effect.

Since every biologic has a unique manufacturing process, it is impossible to produce the perfect identical of a biologic. A biosimilar’s active ingredient should be highly similar to the active ingredient of the reference biological medicine in terms of molecules and biology. The active ingredients of the biologic and biosimilars are basically similar, yet they have different cell lines and a different manufacturing process.

As generics are chemical-based, and the active ingredients of the original and the generic is the same, they are only different in terms of packaging and trademarks.

 

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

The patents are regulated under the Industrial Property Rights Law numbered 6769 (“IP Law”).

According to the IP Law, in order to be patentable, an invention must be novel, include an inventive step and be industrially applicable.

According to the Intellectual Property Law, the following are considered non-inventions:

• scientific discoveries and theories;
• mathematical methods;
• schemes, methods and rules for performing mental acts, playing games and doing business;
• computer programs;
• literary, scientific and aesthetic works or creations; and
• presentations of information.

Further, under the Intellectual Property Law, the following inventions are considered non-patentable:

• inventions that are contrary to public order or morality;
• inventions concerning plant or animal varieties or essentially biological processes for the production of plants or animals, excluding the microbiological processes or the products thereof;
• diagnostic methods that are practiced on humans or animals and all such treatment methods, including surgical methods;
• the human body at various stages of its formation and development and the discovery of one of its elements, including the sequence or partial sequence of a gene; and
• the use of human embryos for industrial or commercial purposes, including processes for:
  o cloning human beings;
  o modifying the germline or genetic identity of human beings; and
  o modifying the genetic identity of animals in ways that are likely to cause them suffering without any substantial medical benefit to humans or animals.

However, the IP Law notably lacks an explicit definition of ‘biotechnological inventions’, as outlined by Article 52 of the European Patent Convention (“EPC”) and Rules 27 and 29 of the Implementing Regulations. As a result, each patent is evaluated individually, and as long as they meet the general criterion of novelty, an inventive step and are applicable to the industry, such inventions may also be patented.

 

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?

In general, the identification of biologics is considered harder than the identification of the chemical derivatives. Three-dimensional structure, the amount of acid-base variations or glycosylation profiles may change drastically due to “minor” changes in the production process. Therefore, for biosimilar products, the approach for the generics are not suitable, and thus further comparability studies for quality, safety and efficiency is required.

TMMDA under MoH has published the “Guideline on Biosimilar Medicinal Products” (“Guideline”) in 2009. There are several issues set forth in the Guideline specifically addressing the marketing authorization process for biosimilars.

 

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 general, there are several data, which is required for all types of pharmaceuticals, for their application for marketing authorization. For biosimilars, the Guideline underlines that the following should be met:

• All requirements for quality, efficiency and safety related data for all types of pharmaceuticals should be met including criteria in the monographs of European Pharmacopoeia, in updated guidelines of Committee for Human Medicinal Products and International Committee for Harmonization
• The pharmaceutical form, power and application form of the biosimilar should be the same with the referenced biologic. In this case, additional data should be submitted in terms of comparative studies.
• Any difference between the biosimilar and the referenced biologic should be evaluated through suitable studies for each case.
• Due to different varieties of biologics, additional data required should be determined considering the special features of the specific biologic. If the referenced biologic addresses more than one indication, the efficiency and safety of the biosimilar should be proven for each indication.

In this context, the following are generally required:

• For quality
  o Detailed comparison of the features of the products
• For Pre-clinical Phase:
  o Depending on the complexity of the molecule, sub chronic toxicity test,
  o Local tolerance testing,
  o Pharmacokinetics and pharmacodynamics studies
• For Clinical Phase:
  o Phase 1 pharmacokinetics and pharmacodynamics studies
  o Phase 3 studies for each indication
  o Risk Management Plans

 

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

The choice of the reference comparator product should be a licensed pharmaceutical, whose application has been made to the relevant authority in another country including all data for administrative, quality and clinical data.

 

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

Yes. See Question 5 above.

Biosimilars themselves cannot be referenced. Moreover, the reference biologic should get licensed with a full file. The tradename, pharmaceutical form, formulation, production date, and expiry date of the referenced pharmaceutical that shall be used for the comparative study, should be clearly indicated.

The reference standards in the pharmacopoeia, cannot be cited as referenced pharmaceutical. If the referenced pharmaceutical has different strengths, the same strengths should also be chosen for the comparison of the subject biosimilar.

 

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

In Turkey, the pricing of biosimilars is regulated under the Communiqué on Pricing of Pharmaceutical Products for Human Use (“Communiqué”). According to Article 9/g of the Communiqué, biosimilars’ prices are determined as 100% of its reference price (Reference price means the sale prices to warehouseman. This price is the lowest price of the reference product). If this is not available, the price of a biosimilar is the 100% of the reference price of the referenced original biologic. If the biosimilar of a biologic enters to the market, the reference price of the reference original biologic does not change.

 

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

According to the Communiqué on Health Practices published by the SSI, the financing of treatments and health services which are reimbursed by the SSI is determined under the lists annexed to the Communiqué on SSI’s Health Application. Within these lists, the SSI should evaluate the diagnostics and treatment and confirm that it’s appropriate due to the Communiqué on SSI’s Health Application.

Accordingly, the Commission shall determine the reimbursement to be made by the SSI. There are not specific regulations on the reimbursement of biosimilars, however, there are several biosimilar currently being reimbursed in Turkey.

 

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

As explained in Question 7, the reference price of the referenced biologic does not change as a biosimilar enters into the market. Because every biologic product, including the biosimilar is deemed to be a separate product. Neither the reimbursement policy changes with the biosimilar’s market entry. However, considering new market conditions and new competition caused by the launch of the biosimilar and high prices of the biologics, we observe that a voluntary discount can be applied to biologics by the marketing authorization holder to maintain the reimbursement status.

 

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?

There is not any specific regulation in Turkey for prescribing or dispensing biosimilars. Thus, there are not any differences between biologics and biosimilar in this context.

In general, according to the Regulation on the Classification of Human Medicinal Products, pharmaceuticals are classified only as prescription and nonprescription pharmaceuticals. Both prescription and nonprescription pharmaceuticals are allowed be sold at pharmacies and pharma-organizations only (such as pharmaceutical warehouses) (Article 1, Law on Pharmaceuticals and Medical Preparations). The Turkish legislation prohibits the sale of pharmaceuticals via the Internet or any other electronic medium (Article 24, Law on Pharmacists and Pharmacies).

 

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

No, there are not any regulation on the interchangeability of the biosimilars with biologics. In general, physicians have discretion to prescribe the biologic or biosimilar versions, where applicable.

The Turkish Law does not regulate interchangeability specifically, the subject is only examined with respect to reimbursement policies. Meaning that pharmacists are entitled to offer patients to switch from a biologic and dispense the biosimilar versions.

In the light of this fact, the reference biologic manufacturer needs to preserve its spot in the reimbursement mechanism and maintain its market share, therefore in order to stay as reimbursed, the referenced biologic companies voluntarily offer further discount around 20%. It is important to underline that such discount does not derive from legal obligations and such decision is only based on marketing strategies. The companies may not choose to offer such discount considering its profitability.

 

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

No, there are not any specific regulations for biosimilars. However, as stated in the Guideline, Risk Management Plans shall be submitted to the MoH. Moreover, as it is the same for all pharmaceuticals, post-approval safety studies should be conducted, all measures be taken to minimize the risks and the regular risk-benefit reports be prepared.

 

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?

There are not any specific requirements for labelling biosimilar products in the event of second medical use patents.

 

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)

As the patent protection for many biologics expires in 2019 and 2020 in Turkey, there are many preparations in the market to launch upon the expiry date, including the support of the government. Therefore, we expect many lawsuits and other developments in the sector with the launch of new biosimilars.

 

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?

A draft Guideline on Biosimilar Medical Products was released on 30 May 2017 by the TMMDA. However, there is no indication as to the possible date of entry into force of the draft.

 

Also from this Legal Handbook

The ins and outs of localization in Turkey. Prepared in association with Moroğlu Arseven, a leading Turkish law firm, this is an extract from The Pharma Legal Handbook: Turkey, available to purchase here for GBP 75.

 

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?

Localization is a developing and ongoing plan in Turkey. Increasing employment, attracting foreign investment, and maintaining the quality reached in the Turkish pharmaceutical industry encouraged localization in our Turkey. Thus, localization was first announced/proposed in the Action Plan of the 64th Government for the Year 2016 (“Action Plan”). In the meantime, follow-up announcements were also made within this framework by both the Turkish Medicines and Medical Devices Agency (“TMMDA”) and Social Security Institution (“SSI”) on their official websites.

Action 46 of the Action Plan is to enhance the medical equipment and the process of reimbursement, pricing, authorization of strategical and domestic drugs. It has been stated in the Action Plan that “The imported drugs, which will be removed from the list of reimbursement, will be determined, provided that the required security for providing a proper treatment is ensured.” In this regard, the number of sales of the products, which have an import license with more than one generic, has been reviewed as per this Action Plan.

In addition, TMMDA’s announcement mentions that, in light of the negotiations and discussions with the relevant association, union and firms, a time plan is prepared regarding localization of the products, whose rate in manufacturing is more than 50%, as a first step, in order to prevent any supply problem in the market. The announcement is available in Turkish on TMMDA’s website at https://www.titck.gov.tr/duyuru/2521.

Furthermore, within the scope of the localization, a new Commission on Transferring from Import to Produced has been established with the participation of the representatives of the TMMDA, SSI, Turkish Ministry of Development, Ministry of Finance, Ministry of Economy, Undersecreteriat of the Treasury. In this regard, all process in relation thereto will be followed by this commission accordingly.

 

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

N/A

 

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)?

According to the announcement made by TMMDA and the time plan referred to above, it was planned to commence with the process of localization of the equivalent groups determined as of 4 April 2016. In this regard, it has been also stated in the abovementioned announcement that relevant firms shall provide their undertaking for the domestic production to the Directorate of Drug Licensing of the TMMDA as of 22 March 2016. If such firms cannot or did not provide the undertaking regarding localization for the products, then the reasoning in relation thereto shall be provided as of 22 March 2016.

In addition, it has been stated in the Action Plan that the drugs, which are applied to be produced in Turkey, will be licensed expeditiously by the MoH.

 

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)?

N/A

 

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 Action Plan states that the reimbursement policies of the drugs, which are applied to be produced in Turkey, will be considered and reviewed. The SSI shall accelerate the evaluation process in order to add the medical products produced in Turkey to the list of reimbursement and by making required regulations in the legislation. The imported drugs, which will be removed from the list of reimbursement, will also be determined, provided that the required security for providing a proper treatment is ensured.

In this regard, TMMDA’s announcement has mentioned that the Action Plan in relation thereto does not aim to remove the imported products from the list of reimbursement but aims to promote/encourage the domestic production within predictable time.

 

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)?

N/A

 

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?

N/A

 

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

N/A

 

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?

N/A

 

Also from this Legal Handbook

Keen to learn more about orphan drugs & rare diseases in Turkey? Read on! Prepared in association with Moroğlu Arseven, a leading Turkish law firm, this is an extract from The Pharma Legal Handbook: Turkey, available to purchase here for GBP 75.

 

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

There is no definition of rare diseases in Turkey.

 

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

There was a provision regarding the orphan drugs in the Turkish Ministry of Health’s (“MoH”) Communiqué on Pricing of Pharmaceutical Products published on 11.12.2015. In this communiqué, the orphan drugs are defined based on a quantitative criterion, as “pharmaceuticals used for diseases with an incidence of less than 1/100.000 people in a country, and which are precisely defined”.

However, this communique is no longer in force and was replaced by the Communiqué on Pricing of Human Medicinal Product (“Communiqué”), which was published on the 29.09.2017 in the Official Gazette, and the definition of orphan drugs is not regulated under the Communiqué. In other words, there is no official definition of orphan drugs in Turkey.

 

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?)

Although orphan drugs are regulated in many countries at a national level and by European Commission with specific regulations, there is no specific independent regulation in Turkey for orphan drugs in terms of marketing authorizations, promotion activities, incentives or otherwise. Consequently, obtaining marketing authorization for orphan drugs requires the same procedure as regular drugs.

 

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

N/A

 

5. Is there an expedited pathway for Orphan Drugs?

According to Article 4.3 of the Social Security Institution’s (“SSI”) Health Implementation Communiqué published on 24.03.2015 in the Official Gazette, the drugs, which cannot be obtained in the national market and are required for the people who benefit from the medical care of the SSI, can be obtained from abroad, only if the MoH gives permission for the drug supply by approving the fact that such drugs do not exist in the national market and must be taken by relevant patients. In line with this purpose, a protocol between Turkish Pharmacists Organization (“TEB”) and the SSI was executed on 01.04.2016 and is still in force. Therefore, the orphan drugs may also be obtained through this process.

 

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

In principle, selling pharmaceutical products in Turkey is possible only with a marketing authorization. However, it is possible to sell orphan products to Turkish patients through TEB when requested by the patient having the necessary prescription as explained under Question 5. Otherwise, those who sell pharmaceutical products in Turkey without marketing authorization will have penal, administrative and civil liabilities.

The penal liability for selling pharmaceutical products without a marketing authorization (out of the scope of exception of selling through TEB) is defined as a criminal act under Article 187 of the Turkish Criminal Law, as follows:

Making or Selling Drugs in a Way to Endanger People’s Life and Health
Article 187 – (1) Those who make or sell drugs in a way to endanger people’s life and health shall be condemned to imprisonment from one to five years and a monetary penalty.
(2) In the event that this act is committed by a medical doctor or pharmacist or within the scope of a profession carried out by official permission, the penalty shall be aggravated by 1/3.

Marketing pharmaceutical products without a marketing authorization is considered within the scope of the article referred above.

 

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

Yes, however, there is no regulation specific to orphan drugs in the reimbursement legislation.

Furthermore, please note that if orphan drugs are obtained through the process explained under Question 5 and are indicated in the “Foreign Drug Pricing List”, which is annexed to the Health Implementation Communique of the SSI as Annex-4/C, then such drugs can be reimbursed.

 

8. How are the prices of Orphan Drugs regulated?

In general, all drugs are based on a reference pricing method in Turkey. Pursuant to Article 9/e of the Communiqué, orphan products can be priced up to 100% of the reference price. In other words, orphan product prices are set based on the reference price stated in the official documentation from their country of import and manufacture. Prices for these drugs are annually reviewed and revised in parallel with the annual sales volume.

Additionally, the pricing can be determined according to the cost card for the orphan products produced in Turkey. (The cost card is prepared and approved by the applicant and the certified public accountant and shows the cost of the product, which is the basis of determining the sale price of the product, and other expenses.) In this case, however, the price requested on the cost card cannot exceed 15% of the reference product price and if exceeded, such claims will be evaluated by the Price Evaluation Commission (consisting of representatives of the Ministry of Finance, Ministry of Development, Undersecretariat of Treasury and Directorate of Social Security Institution)

 

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

In line with our answer to Question 8, the reference price, which is used for the pricing of the orphan products, is based on countries with a basket of 5 members of the European Union. Pursuant to Article 4/1 of the Communiqué, these countries are France, Spain, Italy, Portugal, and Greece.

 

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

The Turkish Pharmaceutical Industry Strategy Document and Action Plan (“Plan”) for the years between 2015 – 2018 has been published by the Turkish Ministry of Industry and Technology, General Directorate for Industry. According to this Plan, the following has been proposed and planned to be implemented latest at the end of 2018; however, they are not yet implemented in Turkey:

• A detailed analysis for the status and analyses will be made regarding rare diseases. As per the results of such analysis, an orphan drug policy will be established.
• With regard to rare diseases, an inventory record system and headquarters, where such rare diseases can be determined, will be established in Turkey. The connection will be made between the current global reference network systems for rare diseases and the national reference system. New policies will be issued to develop and produce the medicines required for rare diseases in Turkey.

 

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?

No reform or significant changes regarding regulation of orphan drugs exist or are expected in Turkey in the near future.

 

Also from this Legal Handbook

The legal framework for regulatory reforms in Turkey. Prepared in association with Moroğlu Arseven, a leading Turkish law firm, this is an extract from The Pharma Legal Handbook: Turkey, available to purchase here for GBP 75.

 

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

No proposals for reform exist or are expected in the short term. However, minor amendments of existing laws and regulations may occur.

The Draft Regulation on the Registration, Surveillance and Tracking of Medical Devices covers procedures and principles for registration, traceability and follow-up of devices covered by:

• The Regulation on Medical Devices,
• The Regulation of Active Medical Devices on the Body,
• The In Vitro Medical Diagnostic Devices Regulation.

A Draft Guideline on Biosimilar Medical Products was released on 30 May 2017 by the Pharmaceutical Product and Medical Device Institution and the revised draft guideline was released on 11 November 2020.

 

2. When are they likely to come into force?

Product Safety and Technical Regulation is expected to be published on 12 March 2021.

 

Also from this Legal Handbook

Patents and trademarks in Turkey – an overview. Prepared in association with Moroğlu Arseven, a leading Turkish law firm, this is an extract from The Pharma Legal Handbook: Turkey, available to purchase here for GBP 75.

 

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

Both patents and trademarks are regulated under the Industrial Property Rights Law numbered 6769 entered into force on 10 January 2017 (“IP Law”). Any sign, including words, shapes, colours, letters, numbers, sounds and packaging form, which meets the following can be registered as a trademark (Article 4, IP Law):

• Can be graphically represented,
• Is capable of distinguishing an entity’s goods or services from those belonging to others.

 

Protection can be granted to inventions which are (Article 82, IP Law):

• Novel,
• Involve an inventive step,
• Applicable to industry,
• Not within the scope of non-patentable inventions – as explained under Question 3.

 

2. What agencies or bodies regulate patents and trademarks?

The Turkish Patent and Trademark Office (“TPTO”) receives applications and registers both patents and trademarks.

 

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

TRADEMARKS:

There are absolute and relative grounds for the refusal of trademarks. Any signs can be registered if they are not refused on these grounds. The TPTO examines absolute grounds for refusal ex-officio, while relative grounds should be raised by third parties through an opposition. An opposition should be filed within two months of the subject trademark application being published in the Official Trademark Bulletin.

Absolute grounds for refusal include where a sign:

• Does not have distinctive character,
• Refers to type, characteristics, quality, intended purpose, value, production time/period or origin of the covered goods or services,
• Is identical (or almost identical) to earlier registered trademarks and covers the identical or same type of goods and services,
• Is used by everyone in trade or used to identify a certain occupational group,
• Is compulsory to use to define and identify the goods’ shape, other characteristics or to achieve a technical result,
• Is misleading as to the nature, quality and geographical origin of the goods and services,
• Concerns the public and possesses historical and cultural value due to their incorporation of coats of arms, emblems, or hallmarks, without the consent of the competent authorities (except for those within the scope of Article 6ter of the Paris Convention, which are also refused on absolute grounds),
• Contains religious terms, symbols, names of religious officials, holy words and so on,
• Is contrary to public policy or accepted principles of morality,
• Is the same with a registered geographical indication.

 

Relative grounds for opposition are:

• The application is the same, similar, covers the same or similar goods and services, and creates the likelihood of confusion with:
  • An earlier registered trademark,
  • An earlier registered trademark application,
  • An unregistered trademark which was in use in Turkey before the application date,
  • A guarantee or collective marks (this argument can be claimed up to three years after the basis trademark’s expiry date),
  • An expired trademark (this argument can be claimed within two years after the basis trademark’s expiry date),
• Unauthorized filings by an agent or commercial representative,
• Dilution of a well-known trademark (the opposition may target different goods and services),
• Infringement of the rights arising from a name, photograph, copyrighted work, or any other industrial property rights owned by a third party,
• Made in bad faith by the applicant.

 

PATENTS:

All inventions regarding a product or process can be protected through patents, provided they meet the legislative criteria.

The following are accepted as being outside the scope of patentability:

• Discoveries, scientific theories, and mathematical methods,
• Plans, methods, schemes/rules for performing mental acts, for conducting business/trading activity, and for playing games,
• Computer programmes
• Literary and artistic works, scientific works, creations having an aesthetic characteristic, and computer programs,
• Presenting information.

The following are not granted patent registration:

• Inventions that are contrary to public order and morality,
• Plant and animal varieties/species, or processes for breeding/plant or animal varieties/species, which are based mainly on biological grounds, except products derived from microbiological processes,
• All methods of diagnosis, therapy, and surgery applying to humans or animals,
• The ‘simple discovery’ of any element of the human body at any stage of its formation and development (including full or partial gene sequencing),
• Processes for cloning human beings, modifying the germ-line genetic identity of human beings, use of human embryos for industrial or commercial purposes,
• Processes for modifying the genetic identity of animals which are likely to cause them suffering without any substantial medical benefit to man or animal (as well as animals resulting from such processes).

 

4. How can patents and trademarks be revoked?

Trademarks:

Cancellation of a trademark can only occur in Turkey through a decision made by the authorized courts. Claimants can seek trademark cancellation in Turkey on the following grounds:

• Breach of absolute grounds for refusal,
• Breach of relative grounds for refusal.

Trademark cancellation actions must be filed within five years following the date on which the prior right holder becomes aware of the use of the subject trademark. The non-use grace period for a trademark in Turkey is five years, starting from the trademark’s registration date. Third parties can only initiate non-use actions after the fifth year of a trademark’s registration.

Whereas the effect of a cancellation decision is retrospective, the invalidation of a trademark is prospective. Invalidation grounds for trademarks are as follows:

• Non-use of the subject trademark,
• The trademark has become generic in respect of the goods or services resulting from trademark’s owner,
• As a result of the trademark owner’s use (or a person authorized by the owner), the trademark has become misleading for the public as to the nature, quality, place of production, or geographical origin of the goods or services which the subject trademark is registered for,
• Use of a guarantee mark which is contrary to the technical specification.

Invalidation actions are handled by the authorized first instance courts. However, by 2022, this authority will be transferred to the TPTO.

 

Patents:

The IP Law introduced a post-grant opposition system, whereby third parties can now oppose a patent within six months of the TPTO publishing its decision to grant the patent.

The grounds for such a patent opposition are:

• The patent does not meet the patentability criteria,
• The invention is not disclosed in a sufficient manner,
• The patent exceeds the scope of the initial application.

The Re-examination and Evaluation Board (“Board”) will refuse the opposition if it examines the opposition and finds that the patent conforms with the IP Law. If the Board concludes that the patent partially conforms with the IP law, it will confirm partial validity. The Board will inform the patent owner accordingly, requesting the patent be amended in line with a partial approval. The patent will be invalidated if no amendments are filed (or the amendments are not approved).

Otherwise, patents can be revoked through legal actions before the first instance courts on the following grounds:

• The invention’s subject matter does not meet the patentability criteria,
• The invention’s subject matter has not been described in a sufficiently explicit and comprehensive manner so as to enable a person skilled in the technical field concerned to re-create the invention,
• The patent’s subject matter exceeds the scope of the application,
• The patent holder does not have the right to a patent.

 

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

Turkey is party to a range of international agreements related to patents and trademarks:

• The Paris Convention for the Protection of Industrial Property since 1925 when it became a signatory to the London text, and later the Stockholm Text (1995),
• The Patent Cooperation Treaty, since 1 January 1996,
• The European Patent Convention, since 29 January 2000,
• The Protocol Relating to the Madrid Agreement Concerning the International Registration of Marks, since 1 January 1999.

Therefore, all foreign patents and trademarks registered within the scope of any of these above-mentioned agreements are recognized in Turkey.

 

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

Turkey introduced a legislative data exclusivity regime in January 2005 in the Regulation on Licensing of Human Medicinal Products. Under this regime, data exclusivity exists for six years after the first marketing authorization application date of a new pharmaceutical in a country which is a member of the European Union Customs Union.

A pharmaceutical product for human use cannot be marketed in Turkey unless it is authorized by the Ministry. In granting a marketing authorization, the Ministry requires drug producers to submit the results of their pharmaceutical products’ safety and efficacy tests, along with other documents regarding the product. Data exclusivity provides original drug producers with protection for the information gathered from their clinical trials and studies. During the data exclusivity period, no other firm can apply for marketing authorization from the Ministry by referring to the clinical data related to the new pharmaceutical, without specific permission.

Under Turkish law, the data exclusivity period is linked to the patent protection period (if the pharmaceutical is also subject to a patent). Original pharmaceutical products which have been licensed in a country which is a member of the European Union Customs Union are subject to a data exclusivity period of six years (Article 9, Regulation on Licensing of Human Medicinal Products). The six-year term starts from the first marketing authorization of the original product in any of the Customs Union Member States. If a Turkish patent exists, the data exclusivity will end when the Turkish patent expires, even if this is earlier than six years. Therefore, the period of data exclusivity depends on the term of any Turkish patent which covers the active substance of the biological reference product. To determine the data exclusivity period in Turkey, it is important to know whether patent protection exists or not.

The Regulation on Licensing of Human Medicinal Products applies to:

• Original pharmaceuticals which apply for marketing authorization after 1 January 2005 in countries which are members of the European Union Customs Union,
• Original medicinal products which apply for marketing authorization after 1 January 2001 in countries which are members of the European Union Customs Union, provided that no applications have been made for marketing authorization relating to generic pharmaceuticals before 1 January 2005.

Marketing exclusivity is not regulated in Turkey. Therefore, once the data exclusivity term expires, generic companies are entitled to apply for marketing authorization by referring to the clinical data which was previously protected by data exclusivity, as well as to launch their product on the market. In practice, the Ministry tends to accept marketing authorization applications during data exclusivity term and process them. However, such products cannot enter into the market while the data exclusivity period remains active.

 

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

No, there are no restrictions to any type of medicines or devices that can be granted patent and trademark protection besides the restrictions set forth under Question 3.

 

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

Registering a license is not compulsory. However, it is common and good practice for industrial rights licensees to register their licenses with the TPTO in order to claim their rights against bona fide third parties. For example, if the owner of intellectual property rights transfers its rights to a third party, the licensee cannot claim its right against the bona fide third party who acquired the intellectual property rights, if the license is not registered before the TPTO.

 

Also from this Legal Handbook

An insight about product liability in Turkish Pharma. Prepared in association with Moroğlu Arseven, a leading Turkish law firm, this is an extract from The Pharma Legal Handbook: Turkey, available to purchase here for GBP 75.

 

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

Medicinal product liability arises from the Code of Obligations as tort liability and contractual liability, as well as from the Consumer Protection Law.

To claim under tort law, the claimant must prove the existence of an unlawful act, fault by the perpetrator, damage and causal link between the act and damage (Article 49, Code of Obligations).

Contractual liability can arise from a breach of contract (typically concluded between the consumer and the retailer), or from a product defect (Article 219, Code of Obligations).

The Code of Obligations also recognizes the liability of the proprietor or manager of an enterprise exposing imminent danger and of the principal for misconduct by auxiliary persons in the exercise of his duties.

Product liability currently falls under the Regulation on the Liability of Damages Raised from Defective Products. However, if the Draft Code on Product Safety and Technical Regulation enters into force, the conditions will become less strict.

 

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

These types of liabilities apply to the manufacturers of medicines and devices under the Code of Obligations and Consumer Protection Law. Under the Code of Obligations, these types of liabilities can be reflected as tort liability by the lack of contractual relationship between the consumer and the manufacturer. This kind of an action in tort can be based on risk liability where only the manufacturer is liable or on auxiliary person liability where the manufacturer is deemed liable for damages caused by its employees or other auxiliary persons during their employment or business (Article 66, Code of Obligations).

The manufacturer is also liable towards consumers for the repair or exchange of the defective product (Article 11/2, Consumer Protection Law).

If the Draft Code on Product Safety and Technical Regulation comes into force, the product’s manufacturer or importer will be deemed responsible for any loss and damage by product liability.

Physicians can also be pursued through malpractice lawsuits.

 

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

Potential liability also extends to distributors and retailers. Distributors can have liability towards consumers under the Consumer Protection Law where the distributor/seller fails to deliver the goods in conformity with the agreement (Article 9, Consumer Protection Law). In other words, delivers defective products.

Distributors may also face product liability on other grounds if the Draft Code on Product Safety and Technical Regulation enters into force in its current form.

Retailers can face liability under both contract law and consumer law. The sale contract between the consumer and the retailer prevents consumers from suing manufacturers because of the lack of a direct contractual relationship. Therefore, the consumer can pursue product defect claims, as outlined in the sales contract, or as foreseen under the Code of Obligations (if there is no provision in the contract).

The retailer’s liability continues even if it is unaware of the defects.

 

4. How can a liability claim be brought?

For tort liability claims which includes auxiliary person liability and risk liability, a two-year limitation period applies, beginning from when the claimant becomes aware of both the damage and identity of the person who caused the damage (Article 72, Code of Obligations) and in any case 10 years at most.

A two-year limitation period applies for contractual liability raising from defective products (Article 231, Code of Obligations), unless the seller accepts a longer period. However, if the product was sold with a gross fault, the two-year limitation period does not apply.

Under the Consumer Protection Law, a two-year limitation period applies from the date the consumer received the defective product. However, a longer term can be agreed. No limitation applies if the defect was hidden via gross fault or fraud.

 

5. What defences are available?

Various defences exist against product liability claims. Generally, in those cases, claimants fail to establish causation. Therefore, this is an important point for defendants to focus on. Equally, the statute of limitations often acts as a bar to claimants.

 

Also from this Legal Handbook

The lowdown on the situation regarding traditional medicines and OTC products in Turkey. Prepared in association with Moroğlu Arseven, a leading Turkish law firm, this is an extract from The Pharma Legal Handbook: Turkey, available to purchase here for GBP 75.

 

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

Traditional herbal medicinal products are pharmaceutical preparations which have specific indications for use, which are specifically administered according to the specified dose and posology, and which are administered either orally, externally or via inhalation. In relation to the composition and intended use, traditional herbal medicinal products are designed with the intent to be used without the physicians’ diagnostic monitoring, prescription, nor therapeutic monitoring. There must be sound justification by bibliographic data that the medical herbs within the product’s composition have been used within Turkey or the European Union for at least fifteen years, or for at least thirty years within other countries, prior to applying for a marketing authorization. Such products can be provided from pharmacies via warehouses.

Marketing authorization procedures for traditional herbal medicinal products are regulated under Regulation on Traditional Herbal Medicinal Products. Food supplements, herbal cosmetic products or herbal devices are not included in the scope of this Regulation.

TİTCK supervises license application. The requirements for traditional, herbal, complementary, or alternative medicines and devices are defined as follows:

• The manufacturing site where herbal medicine is produced must have the Certificate of Good Manufacturing Practices,
• Applicants must be resident in Turkey,
• Real person applicants must have graduated from one of the higher education institutions providing education in the fields of pharmacy or medical science and they must practice their profession in Turkey,
• Legal Person applicants must employ a representative who was graduated from one of the higher education institutions that provide education in the fields of pharmacy or medical science and they must practice their profession in Turkey (Article 6, Regulation on Traditional Herbal Medicinal Products),
• A separate file must be prepared for each pharmaceutical dosage form according to the information and documents specified in this Regulation,
• Applications must be made in the Common Technical Document format.

The Regulation on Traditional Herbal Medicinal Products lists the required documents, such as the product’s name, pharmaceutical dosage form, application route, amount in the unit package and the product’s qualitative as well as quantitative composition.

 

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

The Regulation on Promotional Activities of Medical Products for Human Use shall be applicable for advertising activities of traditional, herbal, complementary, or alternative products (Article 29, Regulation on Traditional Herbal Medicinal Products). Rules, restrictions and procedures for advertising medicinal products for human use are the same for traditional, herbal, complementary, or alternative products.

Please see the Marketing, Manufacturing, Packaging & Labelling, Advertising overview.

 

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

Penalties regarding obligations arising from the traditional, herbal, complementary, or alternative products are not regulated under a specific regulation. Procedures of the claims to be made under this Regulation shall be same with the human medicinal products and regulated under Pharmaceutical and Medical Preparations Law and Turkish Criminal Code.

 

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

In Turkey, OTC products are defined as drugs that have been found to be safe and appropriate for use without supervision from a health care professional, such as a physician. Therefore, consumers can purchase OTC products without a prescription. OTC products which are accepted as effective and safe for the disclosed indications are used to treat simple diseases which are commonly encountered in daily life.

According to the Regulation on the Classification of Human Medicinal Products, pharmaceuticals are classified only as prescription and non-prescription pharmaceuticals. A pharmaceutical is classified as a prescription pharmaceutical if it meets any of these criteria (Article 6):

• Using the pharmaceutical under medical supervision causes direct or indirect danger to health, even if the pharmaceutical is applied correctly,
• Using the pharmaceutical poses a risk to human health due to frequent and common misuse of the pharmaceutical,
• With respect to preparing the active substance or formulation, the activity and/or adverse effects need further research,
• The pharmaceutical is applied via parenteral methods.

If a product is not classified as prescribed, it is deemed to be a non-prescription pharmaceutical. Turkey does not define OTC products, nor regulate requirements for advertisement or specific sale channels. Therefore, under Turkish regulations, non-prescription pharmaceuticals are effectively equivalent to OTC products. As a result, general Turkish regulations regarding pharmaceuticals apply for non-prescription OTC products, including advertising bans.

 

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

In Turkey, sales channels of all kinds of medicinal products are strictly regulated. Pharmacists are liable for ensuring non-prescription products are supplied in a safe and rational manner that is appropriate to the needs of the patient and the pharmacists must provide counselling in this regard (Article 7/1-ç, Regulation on the Pharmacists and Pharmacies). Accordingly, OTC products can only be sold in the pharmacies, the same as for prescription drugs.

 

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

Turkish law makes no strict distinction between OTC products and prescription drugs regarding product claims. Please see the Product Liability overview.

 

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

There is no strict distinction between OTC and prescription pharmaceuticals in Turkish pharmaceutical legislation for marketing and advertisement. However, preparations which must be sold under prescriptions may only be advertised in medical publications (Article 13, Pharmaceutical and Medical Preparations Law). Regulations distinguish between OTC and prescription pharmaceuticals. Therefore, arguably OTC products can be marketed or advertised directly to the public, without being subject to any restriction. However, rules, restrictions and procedures for the advertisement of medicinal products for human use apply for OTC products too.

Pursuant to the Article 11/3 of the Establishment of Radio and Television Enterprises and their Media Services Law numbered 6112 published in the Turkish Official Gazette dated 3 March 2011 and numbered 27863 (“Radyo ve Televizyonların Kuruluş ve Yayın Hizmetleri Hakkında Kanun”), “Advertisements for pharmaceuticals and medical treatments that are not subject to prescription shall be prepared under the principle of integrity, and in such manner that they will comprise elements that reflect the truth and can be verified.” The same article can be found in the Article 12/b of the Regulation on Broadcast Service Procedures and Principles published in the Turkish Official Gazette dated 2 November 2011 and numbered 28103 (“Yayın Hizmeti Usul ve Esasları Hakkında Yönetmelik”)

 

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

The Ministry re-examines the classification of pharmaceutical products for human use when it renews medicine licenses, or where it is notified regarding the new product developments (Article 10, Regulation on Classification of Human Medicinal Products). The Ministry will convert an OTC product into a prescription-only product whether:

• Using the pharmaceutical under medical supervision causes direct or indirect danger to health, even if the pharmaceutical is applied correctly,
• Using the pharmaceutical poses a risk to human health due to frequent and common misuse of the pharmaceutical,
• With respect to preparing the active substance or formulation, the activity and/or adverse effects need further research,
• The pharmaceutical is applied via parenteral methods.

 

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

There is no distinction between importing traditional medicines, OTC products, or prescription pharmaceutical. There are three ways to import pharmaceuticals:

• Market consumption of licensed products:

The most common method. The Turkish Pharmaceutical and Medical Device Institution and the Ministry grant a license to pharmaceutical products. The Licensing Regulation on Human Medicinal Products includes the necessary information and documents to obtain the license. This license includes the permission to import the traditional medicines or OTC products.

• Patient Sales / Named Patient Program:

This method is especially for pharmaceuticals for treating serious or rare diseases. According to a guideline published by the Ministry, to use this method, the product must be either unlicensed in Turkey, not produced in Turkey, or the product cannot be found in the Turkish market.

• Compassionate Use Program:

The compassionate use program is a strict method. This method provides pharmaceuticals to patients whose treatment have failed with existing licensed products, who suffer from a serious or urgent life-threatening disease and who have not been included in the scope of clinical trials. These pharmaceuticals are not registered in Turkey.

 

Also from this Legal Handbook

Hot-button legal issues around marketing, manufacturing, packaging & labelling and advertising in Turkish pharma. Prepared in association with Moroğlu Arseven, a leading Turkish law firm, this is an extract from The Pharma Legal Handbook: Turkey, available to purchase here for GBP 75.

 

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

Under Turkish laws and regulations, a registration process is required for a drug, biologic medicinal product, over-the-counter medications and any other medicinal products that are used to treat, diagnose, and prevent diseases to be released at the market. The registration process is outlined under the Regulation on the Registration of Medicinal Products for Human Use. Unlicensed or unregistered drugs and other medicinal products cannot be released or marketed (Article 5, Licensing Regulation on Human Medicinal Products).

Real and legal entities of Turkish residency must apply to the Ministry for authorization with additional forms and documents (Article 6, Licensing Regulation on Human Medicinal Products). Applicants may be required to fulfil certain criteria to apply for registration.

Applications undergo a preliminary examination by the Ministry regarding fulfilment of requirements (Article 13, Licensing Regulation on Human Medicinal Products). License applications which meet preliminary requirements will then be subject to a broader examination which takes approximately 210 days.

If the application is found satisfactory, marketing authorization is granted for the concerned product and the applicant will be notified. Products which the Ministry approves are then published in the Official Gazette along with the name and surname of the marketing authorization holder and the authorization number.

The rules and principles regarding the marketing and advertisement of medical devices are regulated under Regulation on the Sales, Advertisement and Publicity of Medicinal Devices.

To be authorized as a medical device sales centre, real and legal entities must submit a petition to the relevant Provincial Directorate of Health (“Directorate”) providing their commercial information. The Directorate reviews the petition within 15 business days of the application (Regulation on the Sales, Advertisement and Publicity for Medicinal Devices. If the application documents are complete, it will conduct an on-site examination at the intended sales centre within 45 business days of the application. The Directorate issues a certificate of authorization if the sales centre meets the required conditions. The Directorate will notify the applicant if its on-site examination reveals failures to meet the necessary conditions. The applicant may correct the deficiencies and apply for the authorization certification within 45 business days of the notification.

Medical devices that are required to be used or operated by health care professionals cannot be advertised through any means of public media and communication tools (Article 15, Regulation on the Sales, Advertisement and Publicity of Medicinal Devices).

The Directorate inspects sales centres every two years. The Directorate can order a centre to immediately cease or terminate all sales activities, promotion and advertisement. If the unlawful or inappropriate situation is not remedied by the centre within given times, activities can be ceased altogether. (Article 27, Regulation on the Sales, Advertisement and Publicity of Medicinal Devices).

 

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

A shortened authorization process exists for generic versions of already licensed original drugs if the original product’s data exclusivity period has expired (Article 9(3), Licensing Regulation on Human Medicinal Products). A registration application for a generic product does not constitute a violation of the original authorization holder’s patent right. For generic products, applicants are exempt from conducting and providing the results for mandatory toxicological and pharmacological tests and clinical research. The data exclusivity period for original products is six years for products which were either:

• Granted authorization for the first time after 1 January 2001 from a Turkish Customs Union country and no generic registration application were filed in Turkey before 1 January 2005; or
• Granted authorization for the first time after 1 January 2005 from a Turkish Customs Union country.

 

3. What are the typical fees for marketing approval?

Applicants for drug or other medicinal product licenses must pay various fees, such as analysis, scientific research and assessment fees. The amount of each fee differs annually, with the tariffs announced on the Turkish Medicines and Medical Devices Agency website.

2020 tariffs can be found here (in Turkish): https://www.titck.gov.tr/dinamikmodul/70

The authorization process for a medical device sales centre requires applicants to pay several different fees:

• Medical device sales centre certificate of authorization fee (TRY 381, as of 8 December 2020),
• Additional fees for permits regarding directors and special personnel.

 

Detailed information regarding authorization and renewal fees of medical device sales centres can be found on the Provincial Directorate of Health website (in Turkish): http://istanbulism.saglik.gov.tr/

 

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

The registration process is outlined in the Licensing Regulation on Human Medicinal Products. Accordingly, the Ministry conducts a preliminary investigation within 30 days of receiving an application. If the Ministry finds that the application does not meet requirements, the applicant is given an additional 30 days to fulfil the requirements. The Ministry conducts a second preliminary investigation within 30 days of receiving a revised application.

After the preliminary investigation, applications fulfilling all the requirements set under this Regulation are proceeded by the Ministry for further investigation which shall not exceed 210 days.

If the Ministry rejects the application, the applicant can object to the decision in writing within 30 days of receiving the rejection. The Ministry must consider the objection within 90 days.

Licenses are renewed every five years (Article 21, Licensing Regulation on Human Medicinal Products). License holders must submit documents and information regarding changes and pharmacovigilance data to the Ministry at least three months before the end of the fifth year.

 

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

Marketing authorization holders have an ongoing responsibility to monitor the effects of their products and to assure the safety of their customers after obtaining marketing authorization and releasing the product to the market. The responsibilities of market authorization holders regarding their authorized medicinal product are outlined in detail (Article 24, Licensing Regulation on Human Medicinal Products).

Marketing authorization holders’ responsibilities in relation to the safety of their products are also outlined in detail (Article 5, Regulation on the Safety of Medicinal Products).

Detailed and technical information can be found in English here: https://www.titck.gov.tr/PortalAdmin/Uploads/UnitPageAttachment/lWcsQPio.pdf

 

6. Are foreign marketing authorizations recognized?

Foreign marketing authorizations are not recognised in Turkey. If a medicinal product is licensed abroad and is imported or manufactured in Turkey, a Turkish marketing authorization is still required. Applicants for marketing authorization must submit original and up to date copies of a medicinal product’s (Article 8, Licensing Regulation on Human Medicinal Products):

• Summary of characteristics,
• Patient information leaflet and packaging samples (with Turkish translation).

 

7. Are parallel imports of medicines or devices allowed?

Imports of medicinal product are strictly regulated in Turkey and parallel imports of medicinal products are not allowed. The Code on Pharmaceutical and Drugs regulates importing, exporting and manufacturing medicinal products, including penalties for non-compliant products or activities.

Marketing authorization must be obtained from the Ministry before a medicinal product is (Article 3, Code on Pharmaceutical and Drugs):

• Released into the Turkish market (products manufactured in Turkey); or
• Imported or exported (products manufactured outside Turkey).

An importer must have marketing authorization to import medicinal products into Turkey.

In principle, marketing authorization for a particular medicinal product can be held by only one entity. However, two or more companies may agree to market and sell the same medicinal product under two different brand names by entering into a co-marketing agreement. Therefore, a product can be subject to co-marketing if the authorized company gives authorization to another company.

Accordingly, parallel imports of medicinal products are legally impossible. Importing medicinal products into Turkey without local market authorization constitutes smuggling (Article 19, Code on Pharmaceutical and Drugs) which is subject to imprisonment for between one and five years.

 

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?

MEDICAL DEVICES

The Regulation on Sales, Marketing and Promotion of Medical Devices outlines restrictions, clear rules, and procedures for marketing medical devices in Turkey:

• Medical devices cannot be advertised to the public if they can only be operated by healthcare professionals or by parties on the Social Security Institution’s reimbursement list. Promotion of these medical devices can only be made to healthcare professionals and technical personnel who work for medical devices in the healthcare institutions and organizations.
• Promotion can be made through brochures, symposiums, meetings, or personal visits. Regulation on Sales, Marketing and Promotion of Medical Devices outlines detailed rules on permitted promotional activities.
• The value of promotional materials must be worth less than 2.5% of the monthly minimum wage in Turkey.
• An authorized sales centre (“Sales Centre”) is a centre for distribution and sale of medical devices. To become an authorized medical device sales centre, an applicant must submit the documents listed in the Medical Device Marketing and Sales Regulation to the local health authorities. If a Sales Centre wishes to sponsor a healthcare professional or medical device personnel to attend a scientific event or meeting, it must provide details to the Authority. No such event or meeting can be held or sponsored at coastal or ski centres during high-season, except for international congresses regularly held in different countries. Sponsorship of participation in scientific events or meetings is subject to certain conditions (from 15 May 2015 onwards):

• • • Meetings must only target healthcare professionals’ or medical device personnel’s areas of expertise;
    • Healthcare professionals and medical device personnel can be sponsored for a maximum of three events per year, two events by the same sales centre per year, or two events outside Turkey per year;
    • Sponsorship must go directly to the hosting organisations, not to the healthcare professional or medical device personnel.

• • • It is prohibited to give benefits or incentives to healthcare professionals or medical device personnel with the intention of incentivising prescription, use, purchase or recommendation of a particular medical device.
    • Donations can be made to healthcare professionals. A Sales Centre can donate to public or non-profit healthcare institutions if several conditions are met. These include prior approval from the authorities and properly recording the donation in the Sales Centre’s accounts and records. The donation must not influence decisions on public tenders or constitute unethical behaviour regarding the sale of medical devices.
    • Donations must be intended for general use by the recipient entity, not a specific individual.
• Free samples of medical devices are permitted, provided they meet certain technical requirements, including:

• • • Packaging must include the phrase “free promotional sample, not for sale”; and
    • The sample’s value cannot exceed 2% of the medical device’s turnover for the previous year (not applicable for the first year which a product enters the market).

MEDICINAL PRODUCTS

The Regulation on Promotion of Medicinal Products for Human Use regulates promotion of medicinal products for human use. It generally includes similar provisions to the Regulation on Sales, Advertising and Promotion of Medical Devices.

The Regulation on Promotion of Medicinal Products governs the relationship between pharmaceutical companies and healthcare professionals:

• Promotion of the medicinal products can only be made to the physicians, dentists and pharmacists. Promotion to the healthcare professionals is made by (Article 5, Regulation on Promotion of Medicinal Products for Human Use):
  • Using the promotion materials to the physicians, dentists and pharmacists,
  • Organizing scientific meetings and product promotion meetings,
  • Visiting physicians, dentists and pharmacists through the product promotion representatives.
• Companies must not promote prescription of their products by offering any kind of benefit to healthcare professionals (Article 6/10(c), Regulation on Promotion of Medicinal Products for Human Use).
• The value of gifts given by companies to healthcare professionals is restricted to 2.5% of the monthly minimum wage in Turkey (Article 8, Regulation on Promotion of Medicinal Products for Human Use).
• Healthcare professionals are prohibited from asking for benefits (Article 6, Regulation on Promotion of Medicinal Products for Human Use).

Restrictions also apply to marketing practices for healthcare organizations and individual medical practitioners within the context of media and broadcasting. Commercial broadcastings of pharmaceuticals and prescription medical treatments are banned according to:

• Article 11/2 of the Establishment of Radio and Television Enterprises and their Media Services Law numbered 6112, published in the Turkish Official Gazette dated 3 March 2011 and numbered 27863 (“Radyo ve Televizyonların Kuruluş ve Yayın Hizmetleri Hakkında Kanun”),
• Article 12/b of the Regulation on Broadcast Service Procedures and Principles published in the Turkish Official Gazette dated 2 November 2011 and numbered 28103 (“Yayın Hizmeti Usul ve Esasları Hakkında Yönetmelik”).

The Public Servants Law numbered 657 (“Devlet Memurları Kanunu”) prohibits public servants from receiving or requesting gifts or credits from those for whom they perform their duties, with the purpose of taking advantage of their duties (Article 29). All employees working in the public sector are deemed to be public servants, including employees of public hospitals.

According to the Turkish Criminal Code numbered 5237, bribery is a crime. The Criminal Code defines bribery as occurring where any person secures directly (or through other persons) an undue advantage to a public official such as an employee of the Ministry (or another person indicated by the public official) to perform or not to perform a task related to his or her duty (Article 252, Criminal Code).

The Turkish Criminal Code equally punishes public official who receives the bribe and the person who provides the bribe. If a legal entity receives an unfair advantage as a result of bribery, the legal entity is also subject to, for example, cancellation of official authorizations (such as marketing authorization), seizure of property, or seizure of proceeds of crime. Turkish laws in this respect still apply if a Turkish citizen commits bribery outside Turkey. Therefore, healthcare professionals involved in illegal promotion of pharmaceuticals abroad will still be subject to the sanctions indicated in the Turkish Criminal Code.

 

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

According to the Regulation on the Manufacturing Plants of Human Medicinal Products, natural and legal entities must apply to TİTCK, with the necessary information and documents. The applicant will be granted a manufacturing place permission document after supervisors make an inspection. Since Turkey is a member of Pharmaceutical Inspection Co-operation Scheme (PIC/S), applicants must hold a Good Manufacturing Practice Certificate (GMP) / Manufacturing License.

 

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

According to current legislation, almost all specifications required for local manufacturing are compatible with the European Medicines Agency, as regulated under the Regulation on the Manufacturing Plants of Human Medicinal Products. It was drafted in accordance with the legislation of the European Union by taking into account the:

• Directive No. 2011/83/ EC on human medicinal products,
• Directive No. 2001/94/ EC on the principles and guidelines for Good Manufacturing Practices of human medicinal products and clinical research products,
• Directive No. 2011/62 on preventing the entry of counterfeit medicinal products into the legal supply chain.

 

11. What is the inspection regime for manufacturing facilities?

Manufacturers which are within the scope of the Regulation on the Manufacturing Plants of Human Medicinal Products are subject to inspections by TİTCK, which may occur with or without prior notice. TİTCK may take samples of medicinal products for human use and active substances. TİTCK can also inspect a manufacturing site before granting the manufacturing permit, or at any later time it deems necessary, without being required to provide prior notice. Any documents or records related to manufacturing, quality control, or quality assurance can be examined during the inspection. TİTCK prepares a report indicating whether the site complies with the Regulation on Manufacturing of Medicinal Products’ requirements.

Manufacturers, laboratories that provide contractual analysis services for human medicinal products, and importers are subject to routine inspections within TİTCK’s risk-based evaluation program. Where necessary or due to a suspicion of any non-conformity, TİTCK will carry out inspections of imported active substances and of manufacturing facilities of auxiliary substances or of storage and distribution places.

The manufacturing permit or the responsible manager’s authority can be partly or completely cancelled or suspended (on a temporary or permanent basis) if the site fails to comply with the Regulation on Manufacturing of Medicinal Products’ requirements.

Administrative fines range from TRY 10,000 to 500,000 for manufacturing, selling, and supplying non-compliant products (Article 18, Code on Pharmaceutical and Drugs). Breaches of advertising restrictions attract administrative fines (starting at TRY 100,000), as well as potential sanctions from the Information and Communication Technologies Authority (for online advertising). Administrative fines double for repeat offences.

Persons who manufacture drugs which endanger human life or health are also subject to imprisonment of between one and five years, as well as punitive fines (Article 187, Criminal Code numbered 5237). Sanctions increase by one third where the crime is committed by a physician, pharmacist, or within the scope of performing a profession subject to public authority permission.

 

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

Turkey became a member of the Pharmaceutical Inspection Co-operation (“PIC/S”) on 1 January 2018. PIC/S has conducted several inspections in Turkey to evaluate and approve the country’s membership application. However, PIC/S does not inspect pharmaceutical companies and does not certify companies.

 

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

The Ministry’s Regulation on the Labelling, Package Leaflet and Tracing of Human Medicinal Products outlines the requirements for storage, packaging and handling of medicines and what information must be inserted on the inner and outer packages of medicinal products. It also lists the minimum requirements for usage instructions and labels for medicinal products.

Packaging of medicinal products which contain radionuclides must be labelled in accordance with the regulation regarding the Turkish Atomic Energy Agency, as well as other relevant international legislation.

Please see below Question 14 for mandatory labelling content.

 

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

Labels should include (Article 5, Implementing Regulation on the Labelling, Package Leaflet and Tracing of Human Medicinal Products):

• The product’s name, dosage and pharmaceutical form,
• If the product contains up to three active substances, the international non-proprietary name (INN), or common name (if no INN exists),
• Whether the product is intended for babies, children, or adults (if applicable),
• The unit amounts or administration routes and the weight or volume amounts of the active substance’s pharmaceutical form (indicated by the INN or common name),
• The number of units in the package, such as number of tablets, ampoules, or bottles,
• The volume, weight, or dose number of active substances in pharmaceutical form (if these cannot be regarded as net content),
• Excipients such as colourings, preservatives, antioxidants, flavouring substances, and alcohol must be indicated by name,
• Excipients known to have an apparent effect must be presented as a list (qualifying excipients are specified in the Packaging and Labelling Regulation on Medicinal Products). However, all excipients must be indicated if the product is injectable, applied locally, or is an ocular preparation,
• Method of use and route of administration (if necessary) must be indicated,
• Other special warnings relating to the product must be indicated (where applicable),
• Storage conditions and special storage conditions for the product (if any),
• Special warnings relating to the disposal of unused products or waste of products and, where necessary, the appropriate collection system must be indicated,
• Packaging must include the recyclable symbol, number, and abbreviation of the package type,
• The registration or permit holder’s name and address,
• The name of the company marketing the product which has been authorized to represent the registration or permit holder (optional),
• Manufacturer’s name and address,
• The product’s registration or permit number,
• The product’s batch number,
• The product’s expiry date,
• Instructions for users (if the product is used for self-medication purposes),
• Warnings stating:

• • • “keep out of reach of children”;
    • “do not purchase packages that have been cut or opened”;
    • “read the package insert before use”;
    • “consult your physician if any undesirable effects appear”;
    • other warnings issued by the Ministry.
• Information about whether the product requires a prescription or not,
• A two-dimensional barcode (as a secondary identifier) and legible information relating to the content of the barcode,
• The product’s barcode (optional),
• The product’s price (optional).

Where a product has both inner and outer packaging, most of the information listed must also be included on the inner packaging. Additionally, all the information above must be displayed in a readable, easily understandable and non-deletable way. Information must be in Turkish on the outer and inner packages, as well as in the instructions for use. In addition to the mandatory Turkish information, information can also be presented in any official language used by EU member countries.

Labelling is not required on transparent outer packages. However, for such packaging arrangements, all the information required to be on the outer package (listed above), must be included on the inner package instead.

 

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

Along with the mandatory information mentioned in Question 14, some non-compulsory elements are permitted for the label, such as the firm’s logo, or the label/logo of the marketing firm. The product’s barcode can also be displayed. The pricing list for the medicine can also be put on the label. The label can also include logo or symbols of the above mentioned information that make understanding easy for the consumer.

 

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

Any logo that might confuse consumers, or which mimics “CE”, must not be included on the device (Article 18, Regulation on the Medical Devices). On the other hand, although it is not explicitly stated, it is understood that packaging must not include any logo, mark or symbol that would lead the consumer to use more of a medicine or use the medicine without any need. Accordingly, labels must not include anything that would mislead the consumer in terms of substances or way of usage.

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

The Regulation on Promotion of Medicinal Products for Human Use regulates the marketing and advertising of human medicines. The Regulation on Sale, Advertising and Promotion of Medical Devices regulates the marketing and advertising of medical devices.

Promotion of medicinal products can only be made to physicians, dentists and pharmacists via (Article 5, Regulation on Promotion of Medicinal Products for Human Use):

• Using the promotion materials to the physicians, dentists and pharmacists,
• Organizing scientific meetings and product promotion meetings,
• Visiting physicians, dentists and pharmacists through the product promotion representatives.

Medical devices cannot be advertised to the public if they can only be operated by healthcare professionals, or by parties on the Social Security Institution’s reimbursement list. These medical devices can only be promoted to healthcare professionals and technical personnel who work for medical devices in the healthcare institutions and organizations. Promotion can be done through brochures, symposiums, meetings, or personal visits. The Regulation on Sales, Advertising and Promotion of Medical Devices outlines detailed rules on permitted promotional activities.

No monetary advantage can be gained from the advertisements of the medical devices to the physicians, dentists or medical staff; proposals relying on monetary advantages shall not be made as regards to the medical samples or advertisement activities. Advertising activities cannot include information or visuals that promote excessive use of the medicine (Article 6, Regulation on Promotion of Medicinal Products for Human Use).

Medical products cannot be marketed directly to the consumers.

Pharmacies cannot use advertisement labels or posters to promote products in their windows (Article 25/3, Regulation on Pharmacists and Pharmacies).

 

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

Pharmacies have sole authority to sell medicine in Turkey. All medicine (prescribed or not), licensed herbal medicines, homoeopathical products (which are subject to TİTCK approval) must only be sold in pharmacies (Article 42/1, Regulation on Pharmacists and Pharmacies).

Pharmacies can also sell food supplements, medicine, chemicals and other medical products used in pharmacies and agriculture, veterinary medical products and cosmetics. The medicine sold in pharmacies cannot be sold on any other channel or online. Pharmacies cannot have their own websites to sell medicine, nor sell or deliver medicine via post. However, in 2016 Social Security Institution and Post and Telegraph Organization (“PTT”) executed a protocol regarding the delivery of the medicines via post. Turkish Employer Pharmacists Union (“TEİS”) made an objection against this protocol before the Council of State, claiming that this procedure will be explicitly against the laws and will promote unawareness among the patients. Additionally, TEİS states that the delivery of some drugs requires special transportation and storage conditions and that PTT does not have such expert and knowledge to conduct the transportation of these medicines. The Council of State decided to stay enforcement of the protocol, so currently the delivery of the medicines cannot be conducted via postal services until this case is resolved.

Medicine cannot be marketed directly or indirectly on internet, social media or any other communication form that is publicly available, such as movies, TV shows, or news.

 

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

Medicine cannot be marketed directly or indirectly on internet, social media or any other communication form that is publicly available, such as movies, TV shows, or news.

Accordingly, online publication regarding use of products can only be done with TİTCK’s permission and only on websites permitted by TİTCK. No advertising or informational activity can be made on websites which aren’t permitted by TİTCK. Advertisements to promote and introduce a new medicine to medical staff in magazines or newspapers which are permitted by TİTCK are exempted from this prohibition.

 

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

In case of an epidemic or vaccinations which are crucial to public health, informative activities for the public can be directly conducted via designated channels (Article 6/1, Regulation on Promotion of Medicinal Products for Human Use). In such case, advertising must be made in accordance with limits laid down by the Ministry.

Prescription medicines cannot be directly purchased by patients. Rather, these can only be sold with a valid and up-to-date prescription, issued by a physician.

Medical devices can be advertised to the public, except for devices which can only be operated by healthcare professionals or which are in the Social Security Institution’s reimbursement list (Article 15/2, Regulation on Sales, Marketing and Promotion of Medical Devices).

 

21. How is compliance monitored?

The Regulation on Safety of Drugs regulates medicinal product safety in Turkey. It outlines responsibilities for marketing authorization holders, healthcare providers, health institutions and organisations, as well as for the Authority itself.

The Authority reviews all data scientifically through pharmacovigilance systems. It must track the results of precautions taken within the scope of risk management plans prepared by marketing authorization holders, as well as evaluate updates in risk management plans.

The Authority can give marketing authorization holders time to rectify failures to comply with the Regulation on Safety of Drugs. Depending on the nature of the breach, the period can range between 15 days and three months. Marketing authorization will be suspended if the breach is not rectified within the period.

A medicinal product’s effectiveness and safety must be maintained following market entry. The product must also bear the appropriate technical and pharmaceutical specifications.

If the marketing authorization holder fails to comply with the related regulations, the Ministry can suspend its marketing authorization (Article 22, Licensing Regulation on Human Medicinal Products). If a medicinal product’s marketing authorization is suspended, manufacturing and import of this product must also cease (Article 22, Licensing Regulation on Human Medicinal Products). The marketing authorization holder is allowed six months to submit rebuttal documents to the Ministry regarding the suspension. If the marketing authorization holder fails to do so, the authorization will be cancelled.

Samples of advertisements must be approved in advance by the Ministry. Films prepared concerning the scientific properties of a preparation may be screened by the permit from the Ministry and at the places indicated by the Ministry.

 

22. What are the potential penalties for noncompliance?

As per Article 18 of Law on Pharmaceutical and Medical Preparation, an administrative penalty up to five times of the previous year’s total annual sales of non-compliant product (minimum 100,000 Turkish Lira) applies for those who:

• Promote or sell preparations contrary to the obligations set forth in the legislation,
• Sell off these products beyond their scope of certified indications,
• Encourage writing prescription in this manner.

If promotion or sales are made over the internet, the Ministry shall immediately conclude to block access to these websites. This decision will be notified to the Information and Communications Authority for implementation. Administrative penalty of between 20,000 and 300,000 Turkish Lira will be given to those who promote or sell a product using a health declaration, without the permission of the competent authority or contrary to given permission.

 

Also from this Legal Handbook

Preclinical and clinical trial requirements in Turkey – a legal guide. Prepared in association with Moroğlu Arseven, a leading Turkish law firm, this is an extract from The Pharma Legal Handbook: Turkey, available to purchase here for GBP 75.

 

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

Clinical trials for drugs are regulated by the Regulation on Clinical Trials of Drugs and Biological Products. Clinical trials for medical devices are regulated by the Regulation on Clinical Trials of Medical Devices.

Both regulations are based on:

• Fundamental Healthcare Services Law,
• EU directives on good clinical practices.

The Good Clinical Practice Guideline is based on the World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects 1964 (Helsinki Declaration). It is endorsed as a premise for human subject protection policy in Turkey and involves internationally recognised ethical and scientific quality standards for researchers. These standards address designing, performing, recording and reporting clinical studies involving human subjects.

Clinical trial applications for both medicinal products and medical devices are made to TİTCK.

Clinical trial applications must be prepared in accordance with the Clinical Practice Guideline and other applicable guidelines (Article 12, Regulation on Clinical Trials of Drugs; Article 13, Regulation on Clinical Trials of Medical Devices).

Clinical studies must first be performed in a non-human in vitro environment, or on a sufficient number of test animals (Article 5(1)(a), Regulation on Clinical Trials of Drugs; Article 5(1)(a), Regulation on Clinical Trials of Medical Devices).

Clinical trials in Turkey can only be conducted at (Article 11, Clinical Trials Regulation on Clinical Trials of Drugs; Article 12, Regulation on Clinical Trials of Medical Devices):

• Centres for health practice and research established in universities,
• Approved centres for research and development in universities,
• The Ministry’s teaching and research hospitals,
• Gülhane Military Medical Academy,
• Military teaching and research hospitals.

Clinical trials must be performed at locations dedicated to clinical research which have appropriate staff, equipment, and laboratory facilities, to ensure:

• Safety and monitoring of the clinical trial,
• Access to research subjects,
• Proper conduct of appropriate emergency care.

Insurance which meets minimum regulatory requirements must be provided to clinical trial subjects during clinical trials for medicinal products (Article 5(1)(l), Regulation on Clinical Trials of Drugs). Observational drug studies and Phase IV clinical studies are excluded from this requirement (Article 10, Regulation on Clinical Trials of Drugs).

Phase IV is the stage of clinical research involving a large number of patients where (Article 10(ç), Regulation on Clinical Trials of Drugs):

• Products authorised in Turkey are further investigated in terms of their approved indications, posology and method of administration,
• Products permitted in Turkey are further investigated for their safety and efficacy characteristics against their recommended use, or these are compared with other established treatments, products or procedures.

TİTCK has discretion to make audits with or without notification regarding (Article 22(1), Regulation on Clinical Trials of Drugs):

• Research conducted in and outside the country,
• The places where such research is conducted,
• Sponsor and contracted research institutions,
• Places where researched products are produced,
• Laboratories in which the relevant analysis is made,
• Ethical committees in terms of compliance with the Regulation and other relevant legislation.

Clinical trials aren’t required to be conducted locally.

 

2. How are clinical trials funded?

For clinical trial applications regarding medicinal products and medical devices, the clinical trial’s sponsor must first apply to TİTCK and an Ethics Committee. The Ethics Committee’s role is to provide an independent opinion on:

• The methods and documents used to inform volunteers,
• Necessary consents,
• Other relevant issues to protect the rights, safety and well-being of the clinical trial volunteers.

The sponsor can also appoint a contract research organisation (CRO) domiciled in Turkey to make the application. If the sponsor has no representative in Turkey, the clinical trial application must be submitted through a CRO which is domiciled in Turkey (Article 12, Regulation on Clinical Trials of Drugs; Article 13, Regulation on Clinical Trials of Medical Devices).

The sponsor must cover the costs of all kind of research products used in the research, as well as equipment and materials for using such products, relevant examinations, investigations, analyses and treatments. Volunteers or social security institutions cannot be forced to pay such amounts. (Article 23, Regulation on Clinical Trials of Drugs)

 

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

Applications for a clinical trial must be prepared in accordance with the Clinical Practice Guideline and other applicable guidelines (Article 12, Regulation on Clinical Trials of Drugs; Article 13, Regulation on Clinical Trials of Medical Devices). The application form and its appendixes are available in Turkish on TİTCK’s website, at https://www.titck.gov.tr/faaliyetalanlari/ilac/klinik-arastirmalar

 

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

Subjects must be insured for clinical trials of medical devices. However, no insurance is required during clinical trials conducted on medical devices bearing the CE mark and conducted in line with the purposes of use determined by the producer of such medical devices, provided the Ethics Committee deems it appropriate after taking the risk-benefit ratio into account (Article 5(l), Regulation on Clinical Trials of Medical Devices).

Before participating in a clinical trial for both medicinal products and medical devices, a volunteer (subject), or their legal representatives, must provide written consent stating they participate in the trial of their own free will (Article 5(1)(i), Regulation on Clinical Trials of Drugs; Article 5(1)(i), Regulation on Clinical Trials of Medical Devices).

The subject must be informed of the study’s (Article 5(1)(ı), Regulation on Clinical Trials of Drugs; Article 5(1)(ı), Regulation on Clinical Trials of Medical Devices):

• Objective,
• Methodology,
• Expected benefits,
• Foreseeable risks, challenges, and any aspects unfavourable to the subject’s health or personal characteristics,
• Conditions under which the study will be conducted and carried out.

The written consent must include reference to the information noted above.

 

5. May participants in clinical trials be compensated?

Other than insurance coverage, no type of convincing or financial incentive can be presented to the volunteer or to her/his legal representative in return for participating in the research or continuing to participate. However, the decrease in income resulting from the missed working days for volunteers who participate in the research is specified in the research budget and it is covered from this budget. (Article 5(1)(m) and Article 23, Regulation on Clinical Trials of Drugs)

 

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

Clinical trials must be conducted by a team appropriate to the nature of the study, led by a principal investigator (Article 13(3)(a), Regulation on Clinical Trials of Drugs; Article 14(3)(a), Regulation on Clinical Trials of Medical Devices).

If new circumstances emerge during the clinical trial or investigation product which may impact on subjects’ safety, urgent safety measures must be taken. Responsibility for these safety measures can rest with the sponsor, principal investigator, or investigators who are physicians or dental practitioners (Article 13(3)(b), Regulation on Clinical Trials of Drugs; Article 14(3)(b), Regulation on Clinical Trials of Medical Devices).

The principal investigator or an investigator appointed by the principal investigator must immediately report adverse events to the sponsor (Article 18, Regulation on Clinical Trials of Drugs; Article 19, Regulation on Clinical Trials of Medical Devices). Reporting is not required for events specified in the research protocol, the investigator’s brochure, or those deemed not to require immediate reporting.

If serious adverse reactions occur during the clinical trial, the sponsor must inform the Ethics Committee and the Authority within seven days of receiving such information (Article 19, Regulation on Clinical Trials of Drugs; Article 20, Regulation on Clinical Trials of Medical Devices).

Subjects must be insured for clinical trials of medical devices. However, no insurance is required during clinical trials conducted on medical devices bearing the CE mark and conducted in line with the purposes of use determined by the producer of such medical devices, provided the Ethics Committee deems it appropriate after taking the risk-benefit ratio into account (Article 5(l), Regulation on Clinical Trials of Medical Devices).

If damage occurs due to the clinical trial, volunteer participants must be compensated. The fact that a volunteer’s informed consent form has been provided does not lift the volunteer’s right to compensation if they have suffered due to the clinical trial.

 

Also from this Legal Handbook

An intro to the legal situation for regulatory, pricing and reimbursement in Turkey. Prepared in association with Moroğlu Arseven, a leading Turkish law firm, this is an extract from The Pharma Legal Handbook: Turkey, available to purchase here for GBP 75.

 

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

Turkey’s Ministry of Health (“Ministry”) is the main regulatory and responsible authority for drugs, biologicals and medical devices.

Regulatory authorities with jurisdiction over drugs, biologicals and medical devices in Turkey are the:

• Ministry of Health,
• Turkish Medicines and Medical Devices Agency (“TİTCK” – “Türkiye İlaç ve Tıbbi Cihaz Kurumu”).
• Social Security Institution.

 

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

There are various regulations on authorization, pricing and reimbursement of drugs, biologicals and medical devices in Turkey. In general, these are based on the Law on Pharmaceutical and Medical Preparations numbered 1262 published in the Turkish Official Gazette dated 26 May 1928 and numbered 898 (İspençiyari ve Tıbbi Müstahzarlar Kanunu).

In addition to the main law, other regulations in this area include:

• Law on the Pharmacists and Pharmacies numbered 6197 published in the Turkish Official Gazette dated 24 December 1953 and numbered 8591 (Eczacılar ve Eczaneler Hakkında Kanun),
• Main Law on Medical Services numbered 3359 published in the Official Gazette dated 15 May 1987 and numbered 19461 (Sağlık Hizmetleri Temel Kanunu),
• Regulation on the Safety of Medicinal Product published in the Turkish Official Gazette dated 15 April 2014 and numbered 28973 (İlaçların Güvenliliği Hakkında Yönetmelik),
• Regulation on Pharmacists and Pharmacies published in the Turkish Official Gazette dated 12 April 2014 and numbered 28970 (Eczacılar ve Eczaneler Hakkında Yönetmelik),
• Council of Ministers Decree on the Pricing of Human Medicinal Products published in the Turkish Official Gazette dated 24 February 2017 and numbered 29989 (Beşeri Ürünlerin Fiyatlandırılmasına Dair Karar),
• Regulation on Manufacturing Plants for Human Medicinal Products published in the Turkish Official Gazette dated 21 October 2017 and numbered 30217 (Beşeri Tıbbi Ürünler İmalathaneleri Yönetmeliği),
• Implementing Regulation for Labelling, Package Leaflet and Tracing of Human Medicinal Products published in the Turkish Official Gazette dated 25 April 2017 and numbered 30048 (Beşeri Tıbbi Ürünlerin Ambalaj Bilgileri, Kullanma Talimatı ve Takibi Yönetmeliği),
• Regulation on the Licensing of Human Medicinal Products published in the Turkish Official Gazette dated 19 January 2005 and numbered 25705 (Beşeri Tıbbi Ürünler Ruhsatlandırma Yönetmeliği),
• Regulation on the Surveillance and Examination of Human Medicinal Products published in the Turkish Official Gazette dated 22 March 2005 and numbered 25763 (Beşeri Tıbbi Ürünlerin Güvenliğinin İzlenmesi ve Değerlendirilmesi Hakkında Yönetmelik),
• Communiqué on the Pricing of Human Medicinal Products published in the Turkish Official Gazette dated 29 September 2017 and numbered 30195 (Beşeri Tıbbi Ürünlerin Fiyatlandırılması Hakkında Tebliğ),
• Regulation on Promotion of Medicinal Products for Human Use published in the Turkish Official Gazette dated 3 July 2015 and numbered 29405 (Beşeri Tıbbi Ürünlerin Tanıtım Faaliyetleri Hakkında Yönetmelik),
• Guidelines for the Labelling, Instructions and Tracing of Human Medicinal Products issued by Ministry of Health (Beşeri Tıbbi Ürünlerin Ambalaj Bilgileri ve Kullanma Talimatına İlişkin Kılavuzlar),
• Regulation on Clinical Research for Medication and Biological Products published in the Turkish Official Gazette dated 13 April 2013 and numbered 28617 (İlaç ve Biyolojik Ürünlerin Klinik Araştırmaları Hakkında Yönetmelik),
• Regulation on Traditional Herbal Medical Products published in the Turkish Official Gazette dated 6 October 2010 and numbered 27721 (Geleneksel Bitkisel Tıbbi Ürünler Yönetmeliği),
• Regulation on Clinical Research for Medical Devices published in the Turkish Official Gazette dated 6 September 2014 and numbered 29111 (Tıbbi Cihaz Klinik Araştırmaları Yönetmeliği),
• Regulation on Sales, Advertisement and Promotion of Medicinal Devices published in the Turkish Official Gazette dated 15 May 2014 and numbered 29001 (Tıbbi Cihaz Satış, Reklam ve Tanıtım Yönetmeliği),
• Regulation on Medical Devices published in the Turkish Official Gazette dated 7 June 2011 and numbered 27957 (Tıbbi Cihazlar Yönetmeliği),
• Regulation on Test, Control and Calibration of Medical Devices published in the Turkish Official Gazette dated 25 May 2015 and numbered 29397 (Tıbbi Cihazların Test, Kontrol ve Kalibrasyonu Hakkında Yönetmelik).
• Guideline on Good Pharmacovigilance Practices issued by Turkish Medicines and Medical Devices Agency (İyi Farmakovijilans Uygulamaları Kılavuzu)

Turkish texts and unofficial translations for some of these can be found at TİTCK’s official website: https://www.titck.gov.tr/mevzuat

 

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

Developing a medicinal product takes considerable time in Turkey. The Ministry requires strict criteria for each step during this process (testing, licensing or marketing).

The authorization process generally involves:

• Preliminary examination,
• Evaluation of application,
• Approval or denial of application,
• Receiving the authorization of sale.

Pharmaceutical products cannot be launched on the market before obtaining a license, which is granted by the Ministry. To obtain a license, an application must be made to the Ministry by submitting the documents listed under the Licensing Regulation on Medicinal Products.

Before submitting a license application, the applicant must conduct toxicological and pharmacological tests, as well as clinical trials. The Regulation on Clinical Research outlines the procedure for conducting clinical trials. The application procedure begins with submitting a clinical trial dossier simultaneously to both TİTCK and the Ethics Committee (appointed by the Ministry). The Ethics Committee submits its review and assessments to TİTCK. he approval process takes approximately 7 to 15 days. Following the Ethics Committee’s assessment, TİTCK delivers a report to the Ministry within 30 days for administrative evaluation and approval.

Subsequently, to distribute the drug, the applicant must obtain marketing authorization, which is regulated under the Licensing Regulation on Medicinal Products. TİTCK is the responsible administrative body. To obtain marketing authorization, real persons or legal entities who are resident in Turkey must file an application to the Ministry, including the documents listed under the Licensing Regulation on Medicinal Products. When granting marketing authorizations, the Ministry considers whether (Article 16, Licensing Regulation on Medicinal Products):

• Efficacy of the envisaged usage conditions have been proved,
• The pharmaceutical’s reliability has been proved,
• Adequate technical and pharmaceutical properties exist.

The Ministry has discretion to waive some of these criteria on the basis of public health. Such a decision can be given with regard to pharmaco-economic data.

Real person(s) applying for marketing authorization must be graduates from pharmacy, medicine, or chemistry faculties, and be entitled to operate in these disciplines in Turkey. Legal person(s) applying for marketing authorization must employ a person who meets these criteria (Article 7, Licensing Regulation on Medicinal Products).

If a medicinal product will be imported into Turkey, the following certificates (issued by the license owner of the medicinal product) must be obtained from the local marketing authorities abroad and submitted to TİTCK with Turkish translations (Article 8, Licensing Regulation on Medicinal Products):

• Certificate showing that the importer is the sole representative authorized to manufacture and/or sell the medicinal product in Turkey.
• If co-marketing occurs:

• • A certificate showing that a real person or legal entity other than the sole authorized representative in Turkey is also authorised for the purpose of co-marketing,
  • Written consent from real persons or legal entities who will be engaged in co-marketing activities.

 

4. What are the approximate fees for each authorization?

The costs for obtaining authorization vary depending on the type of the medicine or the medical product. These are updated annually. Some of the 2020 fees include:

• Drug License Fee (Medicines produced abroad): TRY 5,407
• Drug License Fee (Medicines produced in Turkey): TRY 3,605
• License Application Fee (Medicines produced abroad): TRY 69,445
• License Application Fee (Medicines produced in Turkey): TRY 34,723
• Scientific Review Cost: TRY 75,834
• License Renewal Fee: TRY 2,072
• Pharmaceutical Warehouse License Fee: TRY 4,570
• Pricing Commission Application Fee: TRY 1,516

For further fees and costs please see this link: https://www.titck.gov.tr/dinamikmodul/70

 

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

Marketing authorizations are valid for five years (Article 21, Regulation on the Registration of Medicinal Products for Humans). To renew a marketing authorization, it should be presented to the Ministry with necessary pharmacovigilance data, along with data on quality, safety and efficacy which outlines all changes which have occurred since the authorization was issued. The renewal application must be made no later than three months before the five-year authorization period expires.

 

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

The toxicological, pharmacological tests and pre-clinical, clinical trials contained in the original medicinal product’s dossier do not necessarily have to be provided to evaluate the generic product’s application. Article 9 of the Regulation on the Registration of Medicinal Products for Humans regulates the abridged application for numerous clauses and some exceptional cases related to the generic products.

Pharmaceutical products owned by both local and foreign manufacturers cannot be launched on the market in Turkey before obtaining a license from the Ministry (Article 5, Regulation on the Registration of Medicinal Products for Humans; Article 3, Pharmaceutical and Medical Preparations Law). To obtain a manufacturing site permit from the Authority, applicants must:

• Employ a responsible manager meeting the requirements under the Regulation on Manufacturing of Medicinal Products,
• Employ a quality assurance and quality control manager,
• Establish a quality control unit,
• Ensure the manufacturing facility complies with the guidelines of good manufacturing for the medicinal products,
• Submit an original or certified copy of a non-sanitary enterprise certificate,
• Present an environmental impact assessment report (if required).

Importers of pharmaceutical products must also obtain a certificate of control from the Ministry that is Audited by the Ministry (Communiqué on Import of Certain Products; Communiqué No: 2012/20). 

 

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

Biological medicinal products are defined as products where the active substance is a biological substance (First Annex, Article 3.2.1.1(b), Licensing Regulation on Medicinal Products). Biological products are regulated in detail under the Biosimilar Medicinal Products Guidelines (Product Guidelines).

Accordingly, a biological medicinal product is a product made from a biological source (or extracted), where a combination of physicochemical biological tests together with the production process, and review are required to determine the quality of its active substance (Article 4.1, Product Guidelines).

Applications for marketing authorization for combination products are regulated under Article 9(a)(3) of the Licensing Regulation on Medicinal Products.

 

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?

The European Medicines Agency’s compliance system has three stages:

• Research and development – Including:
  • Good Laboratory Practice (GLP),
  • Good Clinical Practice (GCP),
  • Good Manufacturing Practice (GMP).
• Marketing authorization application – Focused on pharmacovigilance inspections and sampling and testing.
• Post-authorization – Including monitoring via Good Distribution Practice (GDP) and product defects

The U.S. Food and Drug Administration (FDA) follows a similar route for monitoring compliance to the European system. The FDA observes pre-manufacturing, manufacturing and post-manufacturing phases with distinguished bodies and procedures.

TİTCK conducts checks on the development, manufacturing, storage and distribution phases until the drugs reach the end user. All processes related to compliance are carried out by the Drug Control Department. Under TİTCK’s review system, GLP, GCP, GMP and GDP mechanisms are accompanied by complaints. A mechanism called Good Pharmacovigilance Practices (GPvP) also exists, whereby license holders and contracted pharmacovigilance service organizations are audited.

 

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

Administrative fines can range up to TRY 1,000,000 and five years of imprisonment (Article 18, 19 and 20, Pharmaceutical and Medical Preparations Law). The range of penalties is quite wide, including different administrative penalties and prison sentences. For instance, the minimum penalty limit for making promotions and sales contrary to the Law is TRY 100,000 (Article 18(2)), whereas to import a product without permission is deemed to be smuggling and imposed to a penalty of 1 to 5 years of imprisonment and judicial fine of up to 10.000 days, which is regulated by Anti-Smuggling Law numbered 5607 published in the Official Gazette numbered 26479 and dated 31 March 2007 (“Kaçakçılıkla Mücadele Kanunu”).

 

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

The state is responsible for organising and regulating the healthcare system, as well as for procurement of public healthcare services, taking into account Article 60 of the Constitution. The Ministry is responsible for operating protective and remedial healthcare services. However, healthcare services are also carried out by other ministries, universities, and private institutions, as permitted by legislation.

The national healthcare service is primarily financed by the state budget, revolving funds, fund incomes, and taxes. Social security premiums (public and private health insurance). Other private payments (for example, donations) support the public healthcare system’s funding.

 

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

The Code on Fundamental Health Services numbered 3359 published in the Official Gazette numbered 19461 and dated 15 May 1987 (“Sağlık Hizmetleri Temel Kanunu”) aims for every person living in Turkey to have access to an equal healthcare system.

The Ministry is responsible for establishing hospitals and public health institutions to provide medical services to the public. Both public and foundation universities with medical faculties in their incorporation may also establish hospitals as per the Higher Education Code numbered 2547 published in the Official Gazette numbered 17506 and dated 6 November 1981 (“Yükseköğretim Kanunu”).

Private hospitals have become very common in Turkey in recent years. The establishment and operational principles for private hospitals are regulated under Regulation on Private Hospitals published in the Official Gazette numbered 24708 and dated 27 March 2002 (“Özel Hastaneler Yönetmeliği”).

Health services provided by both public, institutional and private sector corporations are supervised by the Ministry.

Most health services provided by public health institutions are covered under General Health Insurance (Article 63 and 64, Law on Social Insurance and General Health Insurance published in Official Gazette numbered 5510 and dated 31 May 2006; “Sosyal Sigortalar ve Genel Sağlık Sigortası Kanunu”).

Health services provided by private health institutions might be covered by General Health Insurance according to the contracts between the Social Security Institution and provider.

 

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

The Ministry of Health sets the maximum prices and invokes pricing measures to ensure that medical products are made available to consumers on proper terms, to ensure a more efficient and sustainable healthcare system.

Turkey adopts a reference pricing system whereby pharmaceutical prices are determined based on the reference prices from five reference countries (among European Union countries) determined by the Ministry of Health.

The reference price refers to the lowest warehouse sales price for original and licensed products (exclusive of discount) in the reference countries. However, if a country where the product is produced or imported from is not one of the reference countries, but the warehouse sales price of the relevant product is lower than the reference prices in the reference countries, the lower price will be considered as the reference price.

The Ministry of Health has discretion to change reference countries, provided it makes an announcement at least two months before. In this pricing method, equivalent of 1 (one) Euro in TRY is used, upon multiplying with the adaptation co-efficient designated as 70 percent of the average annual Euro value to be calculated upon taking into basis the daily indicative Euro foreign exchange sales rate realizations of the Central Bank of the Republic of Turkey declared in the Turkish Official Gazette of the previous year.

The pricing procedure timeline is as follows:

• The Price Evaluation Commission (consisting of representatives of the Ministry of Finance, Ministry of Development, Undersecreteriat of Treasury and Directorate of Social Security Organization) sets a meeting within the first six months of each year to evaluate drug prices.

• A license holder applies to the Ministry of Health, including the price declaration form and supporting documents indicating the determination process of the price.

• Applications for receiving an initial price are concluded within 90 days.

• Price-related applications other than the initial pricing must be finalized within ten days.

 

During the determination process, the Ministry of Health considers information provided by the license holder which is liable for the accuracy of the information provided to the Ministry of Health.

The licence holder must inform the Ministry of Health about price fluctuations. Its liability in this respect will continue beyond completing the application.

The Ministry of Health has discretion to check the accuracy of information and documentation through national or international data bases, as well as via official inquiries.

Drug prices cannot be determined in foreign currency. Price determination is solely made in TRY.

The limits on profit rates vis-à-vis the drug’s retail price are as follows:

Warehouse Sale Price	Warehouse Profit	Pharmacy Profit
Up to TRY 10 (inclusive)	9%	25%
Between TRY 10 and 50 (TRY 50 included)	8%	25%
Between TRY 50 and 100 (TRY 100 included)	7%	25%
Between TRY 100 and 200 (TRY 200 included)	4%	16%
More than TRY 200	2%	12%

 

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

The Social Security Institution is a public organization for private sector and blue-collar public-sector workers in Turkey. It allocates a global budget to reimburse healthcare services offered in public hospitals, subject to conditions determined annually. It finances several drugs and devices.

The Social Security Institution has two commissions for financing drugs and devices:

• The Drug Reimbursement Commission,
• The Medical and Economic Evaluation Commission.

These commissions determine which drugs and devices will be covered by and paid from General Health Insurance.

Retired persons receive a 90% deduction from the purchase price for drugs, while active insured members receive an 80% deduction

If a device or drug is not covered by the General Health Insurance, patients must pay for it themselves.

Some Private Health Insurers may also pay for drugs and devices which are not financed by the Social Security Institution, according to the agreement between insurance company and consumer.

 

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

Drugs can only be sold in licensed drugstores or drug trade houses (Article 1, Law on Pharmaceuticals and Medicinal Preparations). Title of pharmacists is a debatable issue in Turkey, as per the Turkish Commercial Code and Supreme Court’s decisions, pharmacists are deemed to conduct their business operations as “merchants”.

Regardless of whether a pharmaceutical is prescription or nonprescription, it can only be sold at pharmacies and pharma-organizations (such as pharmaceutical warehouses) (Article 1, Law on Pharmaceuticals and Medical Preparations). Turkish legislation prohibits the sale of pharmaceuticals via the internet or any other electronic medium (Article 24, Law on Pharmacists and Pharmacies).

 

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?

Pharmacists are the sole entities authorized to dispense drugs. A valid degree from the pharmacy faculty of a foundation university or a public university is required. Pharmacists’ duties, obligations and liabilities are regulated in detail by the Code on Pharmacists and Pharmacies.

Pharmacists are prohibited from carrying out wholesale drug transactions or taking part in biddings. Additionally, pharmacists cannot enter agreements with institutions, physicians or organizations or any other third parties about promoting prescriptions, promising benefits, nor offer prizes or bonuses. Pharmacists will be held personally liable for breaches and administrative fines of between TRY 5,000 and 50,000 will apply. Penalties can be doubled for repeat offences.

Any person who produces, stores or sells products containing toxic substances which are subject to license without obtaining necessary permissions is liable for imprisonment ranging from two months to one year (Article 193, Turkish Criminal Code).

Within the scope of patient care and safety, pharmacists have the obligation to duly and accurately inform consumers under the Consumer Protection Law. Instructions, directions and adverse effects must be provided to the consumers, accordingly necessary steps should also be taken about the feedbacks from the consumers with regards to a drug’s adverse effects and symptoms.

Under the Data Protection Law, pharmacists must take necessary measurements to protect consumers’ personal data.