The Turkish Medicines and Medical Devices Agency ("Agency") published the new Guidelines for Drug Supply and Use from Abroad ("Guidelines") on 23 October 2021.
The Guidelines regulate the procedure of drug supply from abroad for drugs that are not authorized in Turkey or authorized but not available in the market for various reasons. The Guidelines were first published in 2014, updated in 2015, 2017, and 2020 and finally, the final version was published on 23 October 2021.
The most significant amendments made in the Guidelines are on the suppliers, supply conditions, and terms that regulate the removal of a product from the "Foreign Drug List" ("the List").
Following this amendment, the Agency published an announcement on 24 November 2021, which lists the products that will be removed from the List.
1. New Suppliers
The Guidelines preserved the following institutions' authority to supply drugs from abroad; the Turkish Pharmacists' Association, the Social Security Institution İbn-i Sina Pharmaceutical Warehouse, and Uluslararası Sağlık Hizmetleri A.Ş.
However, the Guidelines also regulated that the public institutions and organizations that are deemed appropriate for the foreign drug supply by the Agency can also be authorized as suppliers.
No explanation or Agency announcement has been published regarding the new suppliers deemed appropriate by the Agency.
2. New Supply Conditions
The previous version of the Guidelines regulated that drugs could be supplied if they were authorized by FDA/EMA or PIC/s member countries.
However, the Guidelines removed this provision, and the new one states that products which have been authorized by the following authorities and placed on the market in the relevant countries:
- ICH (International Council for Harmonization) founding or permanent member competent authorities
- MHRA (Competent Authority of United Kingdom) or
- TGA (Competent Authority of Australia)
by proving their scientifically acceptable effectiveness, quality, and safety, can be supplied primarily.
ICH founding and permanent members are EU Countries, USA, Japan, Brazil, Singapore, Korean Republic, China, Saudi Arabia, and Turkey.
- If the drug that is requested to be supplied has not been authorized and placed on the market in one of these countries; the Agency can decide to supply the drug on the condition that it is manufactured in the facilities that received a certificate of conformity with the Good Manufacturing Practices (GMP) inspection made by the Agency, ICH founding or permanent member competent authorities, MHRA or TGA, and that the drug is available on the market in the country in which it will be supplied from.
- If the drug requested to be supplied has not been authorized and placed on the market in these countries and has not been subject to the Good Manufacturing Practices (GMP) inspection by the authorities of the countries listed; it has been regulated that the Foreign Drug Evaluation Commission will decide to conduct a product-based Good Manufacturing Practices (GMP) inspection.
The Guidelines have also regulated supply conditions for the generics of the products that are in the List.
For the applications on product groups where at most one generic can be supplied, the generic must be on the market in the country/countries that have a population greater than the population of Turkey independently or in total, and the results of the studies showing bioavailability, bioequivalence or bio-similarity in accordance with the product should be presented to the Agency.
If it is challenging to supply drugs in the List for any reason, an application can be made to the Agency on condition that the relevant application is for at most one additional generic or biosimilar product of the drugs in the List.
3. Regulations on Delivery
Documents that need to be received from the product owner by the suppliers have been regulated in detail. It is mandatory to receive the following documents during the delivery of the product:
- Certificate of Origin,
- for every batch, Certificate of Analysis approved by the technical manager of the production facility
- Certificate of Batch Release, in applicable situations for every batch.
Annex- 5, which regulates the suppliers' rules, has been updated according to this provision in the Guidelines.
4. Regulations on Removal from the List
Products that are not compliant with the supply conditions have been removed from the List as of the Guidelines' publication date. Within this context, it has been stated that, for products excluded from the List, an application can be made to the Agency within 30 days to include the products to the List again, and those deemed appropriate will be included in the List again.
The provision regulating that the suppliers shall send the trade names, box numbers, and box prices of the supplied drugs every three months via e-mail and official letter in excel format (provided that information of how many boxes were supplied to how many patients is available) to the Department of Economic Assessments and Drug Supply Management, has been preserved in the Guidelines.
According to the data sent to the Agency, it is also regulated that products that have not been supplied for the last year shall be removed from the List upon the necessary order/stock controls are completed.
5. Products that Completed their Three Years of Listing and Products that Have 6 Months Left to Complete the 3 Year-Period
On 05 December 2018, a provision had been introduced on Law No. 984 on Commercial Pharmaceutical Warehouses and Shops that Sell Poisonous Chemical Substances Used in Arts and Agriculture ("Law on Warehouses"). This new provision stated that it is mandatory to apply for marketing authorization within three years from entry into the Foreign Drug List. It is also compulsory to obtain marketing authorization within two years from the date of application for marketing authorization. After completing the given duration, the President of the Republic is authorized to decide on the continuation of the supply of drugs that did not obtain a marketing authorization or for which no marketing authorization application is filed.
For the products supplied from abroad before the entry into force of the provision, which is 05 December 2018, the application period for marketing authorization and for the products that were previously applied for marketing authorization, the period to obtain a marketing authorization began on 05 December 2018. It has been regulated that the Agency announces the products included to the List, on six months left to complete their three year period starting from their date of entry to the List.
Therefore, when the said article entered into force on 05 December 2018, the 3-year marketing authorization application period started for the products already been on the List. In this regard, an announcement on products that do not have a marketing authorization application was expected to be published on 05 June 2021.
However, the Agency published the products to be included in this evaluation on 24 November 2021. The Foreign Drug Evaluation Commission will now evaluate these products and submit the products they deem suitable to remain on the List for Presidential approval.
Neither the Law on Warehouses nor the Guidelines specify the criteria that the products should meet to be submitted to the President's approval in the evaluation of the Foreign Drug Evaluation Commission and for the review to be carried out by the Presidency.
The amendments show that the efficacy, quality, and safety elements of the products supplied will be scrutinized more strictly by the Agency. As of the publication date of this Guidelines, products that do not comply with the supply conditions were removed from the List, countries that products can be supplied from have been limited with countries that have robust marketing authorization inspection mechanisms, and provisions have been implemented to allow making decisions taking into account product safety based on the country or the product.
The amendments aim to ensure reliable product supply. In this context, generics of many products were excluded from the List upon publication of the Guidelines.
It is expected that the President will evaluate the products that have completed three years on the List, and a decision on these products will be made soon. Whether the products removed from the List upon the President's decision will be re-listed and whether the 3-year period for obtaining marketing authorization for products that will remain on the List will start again is yet to be seen.