This article was first published in the Journal for Clinical Studies, Aug 2014
To a lot of Europeans, Turkey is — let’s face it — tucked away past the Balkans, out on the eastern edge. It’s a great place to go on holiday, has lovely beaches and some interesting archaeology, and then there’s that song about Istanbul (not Constantinople) that remains a pop culture fixture. But if that’s all that comes to mind when you think about Turkey, then you really are missing the point.
The country was a founding member of the UN and belongs to NATO, the OECD and the Council of Europe. It is one of the G20 economies, is an associate member of the EU, and is fully part of the EU Customs Union. The first application to join the EU as a full member was made in 1999 and ongoing negotiations started in 2005.
As a bridge between Europe and the Middle East and Asia, Turkey occupies a unique position, with a population of around 75 million, nearly three-quarters of whom live in towns and cities. Most are considered to be ethnically Turkish, but there are also people of Armenian, Greek and Jewish origins, with minority ethnic groupings of Abkhazians, Albanians, Arabs, Assyrians, Bosniaks, Circassians, Georgians, Hamshenis, Laz, Crimean Tatars, Bulgarians, Pomaks and Roma.1
From a pharmaceutical R&D perspective, this wide diversity offers a great opportunity for data spread within a clinical trial—all while dealing with one administration, the Turkish Medicines and Medical Devices Agency (TMMDA). The Turkish regulations are completely in line with EC Directives (EC 2001/20 and EC 2005/28), so adding the country to a trial running within EU countries should not require significant additional work, following ethics approval.
To date, over 1500 trials have taken place in Turkey.2 The Middle East and North Africa region as a whole accounts for only around 1% of the distribution of clinical trials, so this low density of trials offers significant opportunities for growth.
What Does the Trial Environment Look Like?
Turkey has a highly-centralised healthcare system and many world-class healthcare facilities, following a significant reform programme introduced in 2003. In 2012, there were 129,772 physicians treating an average of 583 patients each.3 Doctors are interested in participating in clinical trials, and speak good English. Turkey is considered to have a unique patient base, especially for studies in hepatitis, and genetic diseases.
The Clinical Trials Department of the TMMDA reviews clinical trials in Turkey. Its staff numbers have grown exponentially in recent years. Under the Clinical Trials Department, there are a phase evaluation unit, bioequivalence/bioavailability evaluation unit, and a post-marketing surveillance evaluation unit. The department has a programme working to standardise ethics approvals and improve on time from submission to approval. The goal is to reach targets of 30-day approvals for ethics and 30-day approvals for the Turkish Ministry of Health, which monitors the timing taken by ethics committees and has taken more of a performance-based approach.
|YEAR||PHASE I||PHASE II||PHASE II||PHASE IV||BA/BE*||PMS**|
**PMS: Observational studies with drugs.
Numbers of clinical trials from 1997-20124
Trying to pull together all the requirements for paperwork for a study application can be a challenge. The sponsor’s legal entity must deal with insurance, as well as contract and budget forms. Each ethics committee will have slightly different needs and diversified requirements depending on the nature of the sites/institutions (type of documents required, different format/forms, meeting schedules). The ethics committee at a site usually deals with every type of application, and a lack of specialisation can delay the application.
Shipping into Turkey
An import permit issued by the Turkish Ministry of Health is needed to send in supplies, and the consignee should always apply for the import permit before the arrival of the shipment, as it normally takes about a week for the permit to be issued. A copy of the invoice must be provided in the application. Permits are normally issued on a per-shipment basis, but sometimes they can cover all the shipments in a given period for the same study and contents, same shipper and same consignee.
Access to the shipment is not always permitted during the clearance process, so adding dry ice or changing gel packs might not be an option. As a result, temperature-controlled shipments could be severely jeopardised by delays caused by permit issues. In some cases, an application can be made for a customs broker to receive access, but this cannot be relied upon.
- ORIGINAL invoice required, signed and/or stamped with blue ink by shipper/exporter.
- Zero value is not accepted
- Must be customs invoice or commercial invoice (proforma not accepted)
- Must show a unique invoice number
- Must show customs tariff code(s)
- Non-compliance will result in serious clearance delays as customs may refuse any statement provided afterwards.
Government institutions must use their own broker to clear shipments and are not allowed to give a power of attorney to another customs broker. They are then dependent on the speed at which the broker works and the number of other shipments under their control. Because of the Turkish customs regulations, importation can only be handled by a consignee appointed customs broker.
Temperature-controlled Storage in Istanbul
All airline handlers offer +2°C to +8°C and -20°C storage. Airlines do not provide temperature reading of their storage facilitates. By experience, World Courier advises that temperatures have been fairly stable in the past. Please note that all perishables (food, biologics, and pharmaceuticals) are stored in the same area. There is limited controlled ambient storage — and it is only available to certain airlines — so routing and airline choice can become extremely important, depending on shipment requirements.
In its Vision 2023, Turkey has outlined a series of goals for the country to achieve by the 100th anniversary of the founding of the Republic of Turkey. The goals specifically recognise R&D investment in pharmaceuticals as a critical growth area and offers substantial incentives for sponsors. Turkey offers a stable platform and growth potential for clinical trials. Turkish investigators are well educated and connected to the clinical trials arena. The authorities are much more responsive and put in a concerted effort to attract more trials to Turkey. With all these factors in place, consensus opinion points to an increase in the number of trials in Turkey over the next 3-5 years. It’s no stretch to say that for clinical trials, it could indeed be a Turkish delight.