The sensitive political nature of healthcare and pharmaceuticals has made this sector one of the most heavily regulated in Turkey. Parallel with scientific developments in pharmaceuticals, the relevant legislation has been amended and updated to embrace the new realities. The central piece of legislation on licensing pharmaceuticals is the Regulation on Licensing Medicinal Products for Human Use1 ("Regulation"). On 22 April 2009, several amendments were made to the Regulation, and in this article we will review them and examine implementation of the Regulation.
There is a new concept introduced by the Regulation under the "Definitions" section, and that is "co-marketing," allowing identical products manufactured in the same release batch – with the same qualitative and quantitative composition and the same pharmaceutical form – to be marketed under different trade names. Another amendment made under "Definitions" relates to the generic product. Although the definition of a generic product was not changed, Article 4 of the Regulation has clarified that as long as the different salts, esters, ethers, isomers, enantiomers, mixes, complexes or derivatives of isomers of an active material are not significantly different with regard to properties of safety and/or efficiency, they will be treated as the same active material.
According to the "License Applications" under Article 5 of the Regulation, the license holder should inform the Ministry of Health when the product is introduced into the market, and the Ministry of Health will inform the license holder within five (5) business days at the latest that this information has been recorded. The same Article further stipulates that if the efficiency and safety of radiopharmaceuticals prepared as a magistery are proven in the world or Turkey and routinely used, and relevant literature evidencing this fact is submitted to the Ministry of Health, no license is required, provided that the use of those radiopharmaceuticals is regulated by the relevant health institution.
Article 8 of the Regulation stipulates the information and documentation required for the license application, and features certain amendments.
- In applying for a license, certain analyses, tests and controls may be discarded in accordance with the approval of the Ministry of Health, provided that they do not affect the safety and quality of the product.
- For the import or licensed manufacture of a product that has been licensed abroad, the applicant should undertake that the Summary of Product Characteristics ("SPC") is updated. In addition to the SPC, operating manual and sample packages, a translation of these documents should be submitted.
- If the product to be manufactured under license, imported or manufactured in Turkey is to be co-marketed, in addition to current requirements the written approval of the natural persons or legal entities that will co-market the product, as well as information on Module-1, will be required.
- Within the framework of pharmacovigilance practices, address, telephone, fax number, job description and resume of the person responsible for product safety and the description of the scientific service, as well as the address, telephone and fax number of the scientific service, will be required.
In compliance with Article 15 of the Regulation, the Ministry of Health will finalize the license application within 210 days. However, if the product is innovative and will reduce public health expenses, the application will be finalized within 180 days at the latest. If the product is to be co-marketed and the license application of the reference product has been made, but the production is not licensed yet, the applications for both products will be reviewed concurrently. If the reference product is licensed in Turkey, the Ministry of Health will only review the information on Module-1 and finalize the application within 90 days.
Articles 22 and 23 of the Regulation provide that in case the license of a product is suspended or cancelled, manufacture and importation of that product will cease. The previous version of the Regulation only provided for the cessation of manufacture.
The amendments under Article 25 of the Regulation regarding change of license holder are noteworthy. Upon transfer of license, the SPC to be submitted should be "updated." In the former version of Article 25 of the Regulation, it was stipulated that the company of origin may "unilaterally" change the real or legal person authorized to license and sell the product in Turkey. However, the word "unilaterally" has been removed from that Article in the new version, meaning that the manufacturer can no longer unilaterally change the existing authorized natural person/legal entity. This amendment will prevent foreign manufacturers from unilaterally changing their licensed local distributors.
Additional documents are required for changing the existing authorized natural person/legal entity. These are either the letter from the existing license holder stating that the original license has been returned, or the court order stating that the existing license holder is no longer authorized. With regard to license transfers before a notary public, there are documents to be submitted to the Ministry of Health: (i) an undertaking letter prepared by the company that will be new license holder, stating that no modification has been made to the product during the transfer application, and (ii) an undertaking letter prepared by the company that will be the new license holder, stating that all modifications and updates mandated for the product by the Ministry of Health will be made after the transfer.
If all documentation and information in the license transfer application made before the notary public is complete, the Ministry of Health will finalize the application within 30 days, in contrast to the 60-day period for this process in the previous version of the Regulation. It is noteworthy that another amendment of Article 25 of the Regulation provides for the license applicant's transfer of his/her rights arising out of that application to another natural person or legal entity fulfilling the requirements set out in Article 25 of the Regulation.
Finally, Article 26 of the Regulation pertaining to sales authorization has been abrogated. Prior to this abrogation, obtaining sales authorization was required before a licensed product could be marketed, in compliance with this Article.
As license applications for medicinal products are crucial, the amendments introduced by the Regulation will undoubtedly affect practice in this area. However, in view of the nature of these amendments, we expect a smoother, clearer license application process.
1. Published in the Official Gazette dated 19 January 2005 and numbered 25705.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.