Access to Orphan Drugs in Türkiye: A Guide for Foreign Pharmaceutical Companies

Introduction

As the global pharmaceutical industry continues to expand its reach, Türkiye presents a unique opportunity for foreign pharma companies yet it still has improvement areas particularly focusing on orphan drugs. Orphan drugs, designed to treat rare diseases affecting a small percentage of the population, face distinct regulatory challenges in Türkiye. Unlike the European Union and the United States, Türkiye currently lacks specific legislation for orphan drugs. However, there are pathways through which patients in Türkiye can access these critical medicines, primarily via the Named Patient Program and the Compassionate Use Program. This article aims to provide a comprehensive overview of these mechanisms, offering essential insights for foreign pharmaceutical companies seeking to enter the Turkish market for orphan drugs.

The European Union defines rare diseases as those affecting no more than one in 2,000 people, with life-threatening or disabling consequences. Orphan drugs, used for the diagnosis, prevention, or treatment of rare diseases, play a critical role in addressing the unmet medical needs of patients with such conditions. While the European Union and the United States have well-defined regulations for orphan drugs, Türkiye's regulatory framework is still evolving.

Patients in Türkiye have access to 151 out of 416 medicines that have been granted orphan drug status by the FDA or EMEA, but only 76 of these are licensed locally.[1] As a result, Turkish patients rely on alternative pathways to access these vital medicines, namely through the Named Patient Program, and the Compassionate Use Program. This article provides an overview of alternative pathways to licensing and offers recommendations for foreign pharmaceutical companies seeking to enter the Turkish market with orphan drugs.

Named Patient Program: An Exceptional Importation Regime

The Named Patient Program (“NPP”) allows the importation of unlicensed medicines into Türkiye for patients who have exhausted all licensed treatment options or for whom such options are unavailable. The NPP is governed by the Regulation on Supply of Medicines from Abroad ("NPP Regulation") and the accompanying Guideline on the Supply of Pharmaceuticals from Abroad ("NPP Guideline"). The program aims to ensure that patients can access life-saving treatments that are not available in the Turkish market.

Key Aspects of the NPP:

• Initial Medicine Use Application: To initiate the process, the patient’s consulting physician must submit an "Initial Medicine Use Application" to the Turkish Medicines and Medical Devices Agency (“TMMDA” or the “Agency”), supported by a council decision from at least three specialized physicians.

• Requirements for Imported Medicines: Medicines imported under the NPP must meet stringent quality, efficacy, and safety standards, including Good Manufacturing Practices (“GMP”) and Good Clinical Practices (“GCP”). They must also be approved by recognized international regulatory authorities.

• Foreign Medicine Supply Source: The medicines must be sourced from authorized manufacturers or pharmaceutical warehouses that meet specific regulatory criteria. A Turkish representative must be appointed to fulfill the obligations of the foreign supplier.

Compassionate Use Program: Early Access to Unlicensed Medicines

The Compassionate Use Program (“CUP”) provides a pathway for patients with life-threatening diseases to access unlicensed medicines that have completed at least Phase-II clinical trials and are not yet available in Türkiye. This program is intended for patients who have no other treatment options and cannot participate in clinical trials.

Implementation of the CUP:

• Program Initiation: The program is initiated by a sponsor or a contracted research organization that applies to the TMMDA, specifying the indication and the patient population for the medicine.

• Inclusion Criteria: Patients eligible for the CUP include those with life-threatening conditions that cannot be treated with available medicines in Türkiye or those for whom the expected benefit from the unlicensed drug is high.

• Program Termination: The program can only be terminated based on medical evidence indicating that the drug is no longer beneficial or poses safety risks to the patient. The sponsor is obliged to supply the medicine until it is licensed and available in Türkiye.

Access Through the Social Security Institution and Turkish Pharmacists’ Association

In Türkiye, the Social Security Institution (“SSI”) and the Turkish Pharmacists’ Association (“TPA”) play crucial roles in facilitating access to orphan drugs.

• Social Security Institution

The SSI, as the primary public payer, provides reimbursement for medicines, including orphan drugs, under certain conditions. For orphan drugs to be reimbursed by the SSI, they must be included in the SSI's reimbursement list, which requires a detailed application process. The application must include clinical evidence supporting the drug's efficacy and safety, as well as a justification for its use in the specific patient population.

Once the drug is included in the reimbursement list, patients can access it through hospitals or pharmacies, with the cost covered by the SSI. However, if the drug is not on the list, patients or healthcare providers may need to apply for an individual reimbursement decision, which requires approval from the SSI.

• Turkish Pharmacists’ Association

The TPA is authorized to procure medicines from abroad that are not available in Türkiye. This includes orphan drugs that are necessary for the treatment of rare diseases. The TPA works in collaboration with the Ministry of Health and the SSI to facilitate the importation and distribution of these medicines.

The TPA follows strict procedures to ensure that the imported medicines meet the required standards of quality, safety, and efficacy. The process involves obtaining necessary approvals from the TMMDA and coordinating with foreign suppliers to ensure timely delivery of the medicines to patients in need.

Adverse Event Management

Effective pharmacovigilance is crucial for both the Named Patient Program and the Compassionate Use Program. The management of adverse events is governed by the guidelines provided by the TMMDA.

• For Named Patient Program:

Under the NPP, adverse reactions reported to foreign medicine suppliers must be submitted to the TMMDA within fifteen days of receipt. Additionally, any follow-up information must also be provided within fifteen days. This includes monitoring scientific and medical literature for adverse reactions and reporting any that occur in Türkiye.

• For Compassionate Use Program:

In the CUP, adverse events that occur during treatment must be reported to the TMMDA using the Adverse Event Reporting Form provided in the guidelines. Serious adverse events, particularly those resulting in death or significant harm, must be reported within seven days. Ongoing treatment effectiveness and adverse events must be reported to the Agency every six months.

Conclusion

Access to orphan drugs in Türkiye is facilitated through the Named Patient Program and Compassionate Use Program, providing a lifeline for patients with rare, life-threatening diseases. However, the regulatory landscape is complex, and challenges such as limited availability, reimbursement issues, and the absence of specific legislation need to be addressed. Foreign pharmaceutical companies can play a vital role in improving access to orphan drugs by engaging with local authorities, utilizing early access programs, and advocating for legislative changes. By effectively navigating the existing frameworks, these companies can broaden access to their life-saving drugs, ensuring they reach more patients in Türkiye.

[1] Ertok, Ö., Akbil, Ş., & Cebeci, Z. (2023). Orphan Diseases in Türkiye (Only in Turkish). Retrieved from Association of Research-Based Pharmaceutical Companies: https://www.aifd.org.tr/nadirhastaliklarraporu/tr.pdf