The Turkish Pharmaceuticals and Medical Devices Authority (“TİTCK“) recently published the Regulation on Clinical Trials of Pharmaceuticals, the Regulation on the Marketing Authorization of Advanced Therapy Medicinal Products, and the Regulation Amending the Regulation on Marketing Authorization of Pharmaceuticals.
Please click on the relevant link below for our specific notes regarding the recent developments.
Regulation on Clinical Trials of Pharmaceuticals
New Development
On 27 May 2023, the TİTCK published the Regulation on Clinical Trials of Pharmaceuticals. The regulation takes into account Regulation (EU) No. 536/2014 of the European Parliament and of the Council dated 16 April 2014 on Clinical Trials of Pharmaceuticals and the Commission Directive 2005/28/EC dated 8 April 2005 on Good Clinical Practice for Pharmaceuticals in Trials and on the Manufacture or Import of such Pharmaceuticals, within the framework of harmonization with the European Union legislation. In addition, the regulation repealed the Regulation on Clinical Trials of Pharmaceuticals and Biological Products dated 13 April 2013.
The regulation is available here (in Turkish).
What’s New?
Applications to be made within the scope of bioavailability and bioequivalence studies shall be reviewed by the ethics committee within 7 working days and by the TİTCK within 12 working days, provided that they are duly made and there is no deficiency in the information and documents required in the application.
If the initial application is rejected, canceled or withdrawn, the relevant application can be submitted to the TİTCK again as a new application by specifying such in the cover letter.
The interim results of clinical trials and the interim report prepared on the evaluations made in accordance with the analyses performed during the trial are relayed to the ethics committee and the TİTCK.
Data obtained from volunteers within the scope of the clinical trial protocol can be used in future scientific research, provided that it complies with the provisions of the Law No. 6698 on the Protection of Personal Data. In order to collect data in this regard, the data subject’s consent must be obtained for the use of their data other than the clinical trial protocol and the data subject must have the right to withdraw this consent at any time. Withdrawal of consent will not affect the activities already carried out and the use of data obtained based on consent before its withdrawal.
Sufficient time should be given to the volunteer or their legal representative to ask questions about the details of the trial and to decide whether or not to participate in the trial while obtaining informed voluntary consent. Additionally, if the volunteer or legal representative is unable to sign the consent form due to a medical or social reason, such as illiteracy or visual impairment, the informed consent conversation must be conducted in the presence of an independent witness who is not part of the research team.
If the child participating in the trial reaches the legal age to give consent during the conduct of the trial, informed voluntary consent must be obtained from the child.
If no volunteers have been enrolled in the clinical trial in Türkiye within 2 years from the date of notification of the permission, the permission granted by the TİTCK will be revoked unless an extension is approved upon the request of the applicant. Similarly, if a temporarily suspended clinical trial is not restarted within 2 years, the date on which this period expires or the date on which the sponsor decides not to restart the clinical trial (whichever is earlier) will be considered as the date of termination of the clinical trial. In the case of early termination, this date will be considered as the date of termination of the clinical trial.
The sponsor must notify the TİTCK and the ethics committee of the completion of the trial within 15 days of the completion of the trial in Türkiye. In addition, the trial must be reported to the TİTCK and the ethics committee within 30 days of its completion in all countries where it is conducted.
Trials that have been temporarily suspended or terminated early by the sponsor cannot be restarted unless permitted by the TİTCK. To restart the trial, an application must be made to the TİTCK with the risk and benefit assessment, the measures taken after the temporary suspension, their results, and the rationale for restarting the trial.
The sponsor must provide a trial brochure to the principal researcher and the researchers and review the trial brochure at least once a year. In addition, the trial brochure must be updated as meaningful new information becomes available, including information on safety.
Permission can be obtained from the TİTCK when necessary for the import of auxiliary pharmaceuticals to be used in trials.
If the sponsor is not resident in Türkiye, the sponsor must appoint a natural or legal person resident in Türkiye as its legal representative. The legal representative will be responsible for ensuring compliance with the sponsor’s obligations and will be the addressee for communications with the sponsor.
All financial responsibility for clinical trials belongs to the sponsor and, if applicable, its legal representative, other parties to whom duties are delegated, and the research team.
Within the scope of the regulation, a Clinical Trials Module will be established to receive applications and notifications regarding clinical trials to electronically archive and analyze the data of the trials. Meanwhile, a Clinical Trials Portal will be established to transparently disclose the information and results of the trials to the public.
Regulation on the Marketing Authorization of Advanced Therapy Medicinal Products
New Development
On 27 May 2023, the TİTCK published the Regulation on the Marketing Authorization of Advanced Therapy Medicinal Products. The regulation sets out the procedures and principles to be applied in the marketing authorization and pharmacovigilance of advanced therapeutic medicinal products and the practices regarding the advanced therapeutic medicinal products already granted marketing authorization.
The regulation is available here (in Turkish).
What’s New?
Advanced therapy medicinal products must be granted a marketing authorization in order to be placed on the market. Marketing authorization applications must be made in accordance with the Regulation on Marketing Authorization of Pharmaceuticals.
The same natural or legal person cannot use a different trade name for different strengths or routes of administration or pharmaceutical forms of advanced medicinal products with the same active substances and indications. In addition, an advanced therapy medicinal product cannot be granted a marketing authorization with the same name as a pharmaceutical, a traditional herbal medicinal product, a medical device, or a homeopathic medicinal product.
The marketing authorization can be renewed by the TİTCK 5 years after the date of grant, taking into account the balance of risk and benefit. For marketing authorizations that have been renewed once, the marketing authorization will be valid indefinitely unless the TİTCK decides to conduct an additional 5-year renewal assessment for pharmacovigilance-related reasons.
The TİTCK can suspend the marketing authorization in case of non-conformities such as the occurrence of harmful effects under normal conditions of use, the determination of no or low therapeutic effect, and production with a formula different from the formula that is the basis of the marketing authorization.
The marketing authorization holder is responsible for ensuring the availability of the advanced therapy medicinal product on the market. However, where the marketing authorization holder cannot place the product on the market, the marketing authorization holder must inform the TİTCK 30 days prior to the occurrence of the situation that the product cannot be placed on the market.
For the transfer of the marketing authorization of an advanced therapy medicinal product, an application must be made to the TİTCK with the required documents related to the transfer procedures. It is also possible to transfer the marketing authorization application.
For advanced therapy medicinal products that have been granted marketing authorization by the TİTCK and will be placed on the market for the first time, a sales authorization is required.
The short product information, package insert, and outer and inner packaging of advanced therapy medicinal products must be prepared to include the requirements specified in the regulation.
The marketing authorization holder must establish a system in line with the Regulation on Quality and Safety of Human Tissues and Cells and Related Centers in order to ensure traceability of the product. The marketing authorization holder must keep the data on the system for at least 30 years after the expiry date of the product.
Persons who applied to the TİTCK for marketing authorization for advanced therapy medicinal products before the publication of the regulation must submit updated files in accordance with the regulation by 27 August 2023.
Regulation Amending the Regulation on Marketing Authorization of Pharmaceuticals
New Development
On 27 May 2023, the TİTCK published the Regulation Amending the Regulation on Marketing Authorization of Pharmaceuticals.
The regulation is available here (in Turkish).
What’s New?
In marketing authorization applications, documents indicating that, where applicable, the intermediate product(s) used in the production process of the active substance are produced in accordance with internationally accepted good manufacturing practices, and an audit report on this (if requested by the TİTCK) must be submitted.
If the information and documents requested by the TİTCK other than the preliminary evaluation process, or the necessary explanation for the failure to submit such information and documents together with the date of submission, are not submitted to the TİTCK within 30 days at the latest, the application will be rejected procedurally. For these products for which a re-grant of marketing authorization application is made, the current file reflecting the changes approved by the TİTCK and the commitment that the changes have been reflected must be submitted in the application file.
In the marketing authorization transfer applications, the document indicating that the production site(s) based on the marketing authorization is(are) in compliance with the good manufacturing practice guidelines and the Production Site Authorization Certificate for the active substance production site(s) operating in Türkiye must also be submitted to the TİTCK. If these documents are not submitted by the marketing authorization holder, the marketing authorization can be suspended by the TİTCK.
If the TİTCK decides to revoke the conditional marketing authorization of pharmaceutical as a result of an annual evaluation, the revocation of the marketing authorization of the products in question will be carried out without any suspension of the marketing authorization.
The marketing authorization holder is obliged to notify the TİTCK of the rejection or withdrawal of the marketing authorization application in other countries where the marketing authorization application is made.
For pharmaceuticals containing an integrated medical device for which a marketing authorization application has been made or granted, a notified body opinion or CE certificate must be submitted by 31 December 2028, and marketing authorization applications made by that date must be made in accordance with the provisions of the relevant guidelines.
Conclusion
The TİTCK continues to provide guidance for companies working in the healthcare industry. Companies should carefully review the TİTCK’s announcements and guidelines and take necessary actions to ensure compliance.
