Healthcare & Life Sciences Newsletter

The Turkish Pharmaceuticals and Medical Devices Authority (“TİTCK”) recently published the Regulation on the Duties, Authorities and Responsibilities of the National Control Laboratory of the Turkish Pharmaceuticals and Medical Devices Authority Guideline on the Pharmacovigilance System, an announcement regarding European Union (EU) Implementing Regulations No. 2022/2346 and No. 2022/2347 and an announcement on Medical Device Clinical Trials. Moreover, the TİTCK has amended (i) the Decree on the Pricing of Medicinal Products for Human Use (ii) Regulation on the Marketing Authorization of Medicinal Products for Human Use; (iii) Regulation on Private Health Institutions for Outpatient Diagnosis and Treatment; (iv) Regulation on Private Hospitals; (v) Guideline on the Implementation of the Regulation on Quality Conformity and Quality Control Tests of Diagnostic Radiology, Nuclear Medicine and Radiotherapy Group Medical Devices; (vi) Guideline on Applications for Good Manufacturing Practices (GMP) Inspection of Overseas Production Facilities; and (vii) Communiqué on Pricing of Medicinal Products for Human Use. Lastly, the TİTCK announced the annulment of the Decision on the Extension of the Approval Periods for the Use of Off-Indication/ International Medicinal Products.

Regulation on the Duties, Authorities and Responsibilities of the National Control Laboratory of the Turkish Pharmaceuticals and Medical Devices Authority

The Regulation on the Duties, Authorities and Responsibilities of the National Control Laboratory of the Turkish Pharmaceuticals and Medical Devices Authority was published by the TİTCK on 30 November 2022 and entered into force through its publication. In this regard, the Regulation sets out the duties, authorities and responsibilities and working procedures and principles of the National Control Laboratory, where the analysis activities of the substances and products falling under the duties and responsibilities of the TİTCK and the serial release activities regarding the vaccines and immune serums filled and/or produced in Türkiye are carried out.

According to the said Regulation, it should be ensured that the laboratories have appropriate equipment related to the relevant fields of activity, necessary measures should be taken to ensure that the equipment used and the results of the analysis are not affected by environmental conditions. In addition, the environment should be protected from adverse conditions such as dust, humidity, steam, vibration, electromagnetic factors and harmful creatures. In addition, appropriate measures such as an emergency body and eye shower should be taken in easily accessible suitable places to be used in case of danger in the laboratory.

The Regulation is available here (in Turkish).

Guideline on the Pharmacovigilance System

The TİTCK published the Guideline on Pharmacovigilance System on 30 November 2022. The Guideline is prepared to explain the structure of the pharmacovigilance system established within the TİTCK. In this regard, the Guideline provides guidance on many issues such as the pharmacovigilance system of the TİTCK, data and records management, the duties of the TİTCK related to pharmacovigilance and the distribution of duties by units, and the duties of the Turkish Pharmacovigilance Center (TÜFAM).

The Guideline provides information on the mission and organizational structure of the TİTCK and discusses in detail the core values and functioning of the pharmacovigilance system.

The pharmacovigilance-related duties of the TİTCK are carried out by the Department of Pharmacovigilance and Controlled Substances in line with the Regulation on the Safety of Pharmaceuticals and the current Circular on Unintended Effects After Vaccination (ASIE) of the General Directorate of Public Health and Circular No. 2022/2 dated 28 September 2022. The relevant Department consists of two sub-departments, namely the TÜFAM, where pharmacovigilance activities are carried out, and Pharmacovigilance Risk Management Unit. While the TÜFAM carries out studies on adverse events, the Pharmacovigilance Risk Management Unit is more focused on the drug safety of foreign pharmaceutical authorities. According to the Guideline, the duties and responsibilities of both departments are set out in detail.

The Guideline is available here (in Turkish).

Decree on the Pricing of Medicinal Products for Human Use

On 14 December 2022, the Presidency published the Decree Amending the Decree on the Pricing of Medicinal Products for Human Use. The main amendments introduced by the Decree are as follows:

• The effective date of the actual source price or sales price changes made in accordance with the Communiqué on the Pricing of Medicinal Products for Human Use was set as the publication date of the Decree for 2022, i.e. 14 December 2022.
• The value of one Euro in TRY to be used in the pricing of medicinal products for human use was increased by 36.77%, effective from 15 December 2022. The calculated increase will continue to be applied for the next year and a new Euro value will not be announced during 2023.
• The thresholds in the Decree have been updated in line with the change in the value of the Euro. They have been increased to TRY 37.10 for price protected products and TRY 19.39 for other products.

This update is effective as of 15 December 2022.

The Decree is available here (in Turkish).

Regulation on the Marketing Authorization of Medicinal Products for Human Use

On 14 December 2022, the TİTCK published the Regulation Amending the Regulation on the Marketing Authorization of Medicinal Products for Human Use, which became effective retrospectively, as of 11 December 2022. The main amendments introduced by the Regulation are as follows:

• If any of the nonconformities listed in the Regulation occur, the TİTCK should make an assessment including the safety of the nonconformity before suspending the marketing authorization. The marketing authorization may be suspended according to the results of this assessment.
• The deadline for the completion of the marketing authorization process for (i) radionuclide generators, kits, radionuclide precursor radiopharmaceuticals, industrially prepared radiopharmaceuticals placed on the market with a registration certificate and for which a marketing authorization application has been submitted; and for (ii) blood products and immunological medicinal products for human use placed on the market with an import permit and for which a marketing authorization application has been submitted, has been postponed to 31 December 2023.

The Regulation is available here (in Turkish).

Annulment of the Decision on the Extension of the Approval Periods for the Use of Off-Indication/International Medicinal Products

The TİTCK previously extended the expiry date of all off-label drug use approvals granted by the TİTCK for pharmaceuticals holding marketing authorization and pharmaceuticals without marketing authorization imported from abroad by specifying the relevant active substance on a patient basis, or approvals for the use of pharmaceuticals abroad, which expired as of 1 January 2020. On 15 December 2022, the TİTCK announced that it had annulled this decision, effective as of 31 December 2022. In this regard, it is necessary to apply to the TİTCK to continue using the pharmaceuticals after 31 December 2022.

The Announcement is available here (in Turkish).

Implementing Regulations (EU) No. 2022/2346 and (EU) No. 2022/2347

On 16 December 2022, the TİTCK published an announcement regarding the EU Commission’s Implementing Regulations (EU) No. 2022/2346 and (EU) No. 2022/2347 on product groups listed in Annex XVI of the EU Medical Device Regulation (e.g. contact lenses, equipment intended for use to reduce adipose tissue such as liposuction, etc.).

Implementing Regulation No. 2022/2346 sets out common specifications addressing the implementation of risk management as set out in the general safety and performance requirements for non-medical product groups listed in Annex XVI of the (EU) Medical Device Regulation. The Implementing Regulation entered into force on 22 December 2022 and will be applicable in all EU Member States and Türkiye as of the effective date of Article 2/3 and the remaining provisions as of 23 June 2023.

In addition, Implementing Regulation No. 2022/2347 reclassifies certain product groups listed in Annex XVI of the (EU) Medical Device Regulation to ensure a conformity assessment consistent with their inherent risks prior to placing on the market of certain groups of active non-medical products. This Implementing Regulation entered into force on 22 December 2022.

In this regard, manufacturers wishing to place products listed in Annex XVI of the (EU) Medical Device Regulation on the market are required to fulfill the requirements of the Commission’s Implementing Regulations No. 2022/2347 and No. 2022/2346, complete the conformity assessment process, which involves a notified body that is competent in the relevant field, and obtain a CE certificate for their products.

The Announcement is available here(in Turkish).

Regulation on Private Health Institutions for Outpatient Diagnosis and Treatment

On 17 December 2022 and 7 January 2023, the Ministry of Health published the Regulations Amending the Regulation on Private Health Institutions for Outpatient Diagnosis and Treatment. The main amendments introduced by the Regulation are as follows:

• If it is determined that a violation of patient rights has been committed, the activities of the relevant unit will be temporarily suspended by the Governorship upon the decision of the Ministry of Health until appropriate conditions are provided, without disrupting the diagnosis and treatment process of patients outside the unit in question. Administrative and legal action will be taken against the related persons in accordance with the legislation. However, if the unit in question is of vital importance in patient diagnosis and treatment, such as emergency, medical laboratory and imaging, it will be ensured that the unit operates under the supervision of a commission to be determined by the Provincial or District Health Directorate.
• If a deficiency is detected in any unit or part of the health institution that will adversely affect the treatment of patients, the activities of the relevant unit will be suspended by the Governorship upon the decision of the Ministry of Health until the deficiency is eliminated, and if there are situations that are deemed to adversely affect the health of society or the health service recipients, the activities of the relevant unit will be suspended by the Governorship until this situation is eliminated.
• Doctors who have a clinic may perform the treatment of patients who apply to their clinic in licensed health institutions by making an annual contract. Health institutions may enter into contracts with these doctors, provided that the number of the contracted doctors does not exceed onethird of the total number of staff in the relevant specialty.
• Doctors who have a clinic prior to 7 January 2023 will be exempt from the abovementioned limitations concerning the staff number in the health institutions with which they will enter into a contract.

The Regulation dated 17 December 2022 is available here (in Turkish); the Regulation dated 7 January 2023 is available here (in Turkish).

Regulation on Private Hospitals

On 17 December 2022 and 7 January 2023, the Ministry of Health published the Regulation Amending the Regulation on Private Hospitals. In this regard, a number of amendments were made in line with the amendments introduced by the Regulation on Private Health Institutions for Outpatient Diagnosis and Treatment. The main amendments introduced by the Regulation are as follows:

• If a deficiency is detected in any unit or part of the hospital that will adversely affect the treatment of patients, the activities of the relevant unit or the entire private hospital will be suspended by the Governorship until the deficiency is eliminated, and if situations that are deemed to adversely affect the health of society or the health service recipients arise, the activities of the relevant unit or the entire private hospital will be suspended by the Governorship until this situation is resolved.
• If it is determined that a violation of patient rights has been committed, the activities of the relevant unit will be temporarily suspended by the Governorship upon the decision of the Ministry of Health until appropriate conditions are provided, without disrupting the diagnosis and treatment process of patients outside the unit in question. Administrative and legal action will be taken against the related persons in accordance with the legislation. However, if the unit in question is of vital importance in patient diagnosis and treatment, such as emergency, medical laboratory and imaging, it will be ensured that the unit operates under the supervision of a commission to be determined by the Provincial or District Health Directorate.
• Doctors who have a clinic may perform the treatment of patients who apply to their clinic in licensed private hospitals by making an annual contract. Private hospitals may enter into contracts with these doctors, provided that the number of the contracted doctors does not exceed one third of the total number of staff in the relevant specialty.
• Doctors who have a clinic prior to 7 January 2023 will be exempt from the abovementioned limitations concerning the staff number in the hospitals with which they will enter into a contract.

The Regulation dated 17 December 2022 is available here (in Turkish); the Regulation dated 7 January 2023 is available here (in Turkish).

Guideline on the Implementation of the Regulation on Quality Conformity and Quality Control Tests of Diagnostic Radiology, Nuclear Medicine and Radiotherapy Group Medical Devices

On 22 December 2022, the TİTCK updated the Guideline on the Implementation of the Regulation on Quality Conformity and Quality Control Tests of Diagnostic Radiology, Nuclear Medicine and Radiotherapy Group Medical Devices. In this regard, amendments have been introduced to allow applications to the TİTCK to be made electronically. The main amendments introduced by the Guideline are as follows:

• The following works and procedures are described: (i) medical physicist quality control work certificate and medical physicist quality conformity letter applications to be made electronically via e-Government Gateway, (ii) quality control and quality conformity tests to be performed on diagnostic radiology, nuclear medicine and radiotherapy group medical devices, and (iii) quality conformity body applications to be submitted electronically to the TİTCK.
• The content of the report to be issued after quality control and quality conformity tests has been added.

The Guideline is available here (in Turkish).

Guideline on Applications for GMP Inspection of Overseas Manufacturing Facilities

On 27 December 2022, the TİTCK updated the Guideline on Applications for GMP Inspections of Overseas Production Facilities as part of its efforts tonbecome one of the regulatory authorities listed by the World Health Organization. The main amendments introduced by the Guideline are as follows:

• As the impact of the pandemic decreases, the TİTCK will plan on-site GMP inspections at overseas production facilities based on risk-based assessments.
• Within the framework of the provisions of the Guideline, the validity periods of GMP certificates for (i) products for which a risk-based inspection (renewal) application has been made before the expiry of the GMP certificate validity period and an on-site inspection decision has been made as a result of the evaluation, and (ii) products that do not have the right to apply for renewal for the third time in accordance with the Guideline and products for which GMP certificates were previously issued by the TİTCK through an inspection on file (exemption) application made with reference to these products have been extended until 1 June 2024.
• If there is a change in the scope of the GMP certificate of the products whose certificate periods have been extended, the importer companies must apply in accordance with the Guideline.
• Existing GMP certificates that have not been evaluated by the TİTCK and for which there is no on-site inspection decision have not been extended. In this regard, for products with GMP certificates, except for products whose validity period has not been extended by the TİTCK and products for which GMP certificates have been issued in accordance with the announcement titled “Additional Measures to be Implemented During the Pandemic Process Regarding GMP Inspections and Certification Processes Overseas”, risk-based and file-based inspection applications should be made in accordance with the Guideline before the expiration of the certificate validity period.
• The existing GMP certificate validity periods of the products produced in the facilities where on-site inspections will be carried out will be evaluated according to the results of the inspection.

The Guideline is available here (in Turkish) and the Announcement is available here (in Turkish).

Communiqué on Pricing of Medicinal Products for Human Use

On 31 December 2022, the TİTCK published the Communiqué Amending the Communiqué on the Pricing of Medicinal Products for Human Use. The main amendments introduced by the Communiqué are as follows:

• For products that are priced according to the cost card, the price up to 15% more than the sum of the costs specified on the card will be determined as the sale price to the warehouse.
• For imported allergy products for which the actual source price cannot be determined, a price can be given through a document issued and approved by the applicant and a certified public accountant, valid for one year, in which the costs are presented in Turkish Lira. Concerning allergy products manufactured in Türkiye for which the actual source price cannot be determined, a price can be given according to the cost card.
• For traditional herbal medicinal products, medicinal teas, homeopathic medicinal products and medicinal products used in aromatherapy, prices can be given according to the declaration of the applicants.
• In terms of increases calculated with the cost card, no increase can be made more than 50% of the current sales price to the warehouse keeper.
• Concerning imported non-refundable products, an application for price change can be made by submitting their own real source prices during the real source price change period. If imported generic non-refundable products do not have their own price, the real source price of the non-refundable reference product will be determined as the real source price.

The Communiqué is available here (in Turkish).

Announcement on the Medical Device Clinical Trials

On 11 January 2023, the TİTCK announced that it has updated the medical device clinical trial application forms. In this regard, the new form must be used for first applications to be made as of 1 January 2023.

The Announcement is available here (in Turkish).  

Conclusion

The TİTCK continues to provide guidance for companies working in the healthcare industry. Companies should carefully review the TİTCK’s announcements and take necessary actions to ensure compliance.

To read the Turkish version of this newsletter, please visit Sağlık ve Yaşam Bilimleri Bülteni

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