A Groundbreaking Achievement from Atabay: 100% Domestic ‘From Seed to Shelf’ Herbal Medicine Production! The pharmaceutical sector is one of a country’s strategic domains.

To date, no original product has been successfully commercialized in our country. Although numerous projects have received financial support from public institutions such as TÜBİTAK and TÜSEB, they have not progressed to full development. While there are many reasons for this, the most significant can be summarized as follows: the know-how required for scale-up has not been sufficiently developed domestically; the process of obtaining marketing authorization directly from the EMA is highly demanding; and projects backed by long-term government procurement guarantees have failed to connect with merit-based manufacturers capable of collaborative development. The pharmaceutical sector is one of a country’s strategic domains. During the COVID-19 period, we observed how the entirety of industrial and national operations came to a halt as a result of the pandemic.

Dependence on foreign sources for chemical raw materials, and the complexity of the marketing authorization process for biosimilar products, constitute the primary obstacles standing in the way of our country’s independence in the pharmaceutical sector. The Traditional Herbal Medicinal Product (THMP) platform — developed under the regulatory framework of the Turkish Medicines and Medical Devices Agency (TİTCK), affiliated with the Ministry of Health — has provided our country with a significant and new opportunity.

Herbal treatment methods that appear on the Ministry of Health’s approved list, whose therapeutic efficacy has been established among the population over a period of 30 years — representing, in a sense, a completed Phase IV study — will be eligible for commercialization under MEDICINAL PRODUCT status (not to be confused with the food supplement pathway) when developed in accordance with the scientific drug development processes prescribed by the applicable regulation. The requirements of such a process encompass infrastructure necessitating multi-million dollar investments, including: Good Agricultural Practice (GAP) and its verification, Good Storage Practice (GSP) and its verification, Good Laboratory Practice (GLP), and Good Manufacturing Practice (GMP) and its auditing.

This entire process can be implemented and executed under 100% domestic control within our country. Another critical point is that the majority of the plant species required for this process are native to the Anatolian geography. As the intersection of three distinct plant zones, the Anatolian geography harbors a greater diversity of taxa than the entirety of the European continent.

The Story of RUSCUS ACULEATUS

A Public-Private Collaboration Project

In March 2017, in collaboration with TÜBİTAK MAM and TİTCK, the project titled “TÜBİTAK 1009 – Bringing Traditional Herbal Medicinal Products of Anatolian Culture into the Service of Modern Medicine, and Production of Standardized Ruscus aculeatus L. Root and Rhizome Extract” was launched. Plants were collected under supervision in Antalya; their active parts were separated, cleaned, and their conformity was determined through analytical studies.

Following this, within the scope of the project, a pilot Standardized Extraction facility was established at the TÜBİTAK MAM campus and received GMP approval from the Ministry of Health. Upon completion of the R&D for the production of Ruscus aculeatus L. root and rhizome extract, reproducible manufacturing processes (in-process control) were developed. Once the targeted yield, quality, and purity levels were achieved, the process was locked and scale-up phases commenced, culminating in the preparation of a Drug Master File (DMF) document ready for commercial submission. The project was carried out by TİTCK President of the period Hakkı Gürsoy, THMP Manager Handan Öztunca, TÜBİTAK MAM President İbrahim Kılıçaslan, Project Leader Murat Bardakçı, pharmacognosy luminary Prof. Dr. İrem Çankaya, Senior Expert Researcher Ceyda Şener — responsible for GMP facility establishment and standardized extraction — and Senior Expert Dr. Burak Dürüs.

In September 2019, TÜBİTAK MAM invited pharmaceutical companies to a workshop for the project titled ‘TÜBİTAK 1009 — Bringing Traditional Herbal Medicinal Products of Anatolian Culture to the Service of Modern Medicine and the Production of Standardized Ruscus aculeatus L. Root and Rhizome Extract’, with the aim of encouraging the industry to take ownership of the project and support its commercialization.

We were the sole representative from the sector to express interest in the project. There are three primary reasons why this project was of significance to Atabay:

1. To transfer Atabay’s 40 years of knowledge and experience in standardized plant extraction to younger generations.
2. To ensure the continuity of projects to which significant public budgets have been allocated.
3. To identify the THMP pathway as one of the viable routes to achieving 100% domestic pharmaceutical production, and to establish a sustainable infrastructure in this field.