Legal & Regulatory > Turkey > Preclinical and Clinical Trial Requirements

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.