A product which requires a manufacturing procedure and control, together with a combination of physicochemical biological tests for the determination of the quality of the active substance and which is produced or extracted from a biological source.

These products are:

·         Immunological products,

·         Blood products,

·         Products obtained through the recombinant DNA technology in prokaryotic and eukaryotic cells, the controlled expression of genes coding in the biologically active proteins, including also transformed mammal cells, hybridoma and monoclonal antibody methods,

·         Advanced Medical Treatment Products,

·         Reagents not derived directly from the active substance; culture medium, bovine fetus serum, additives, chromatography, etc.

 

            The name given to drugs showing similarity to a licensed biological reference drug.

Biosimilar drugs are only different from biological reference drugs based on trade name, appearance and packaging features.

The identification of biological drugs is generally more difficult than the identification of chemically derived products. In addition, there is molecular complexity interval between the various products in this group (recombinant DNA, blood or plasma products, immunological products, gene and cell therapy, etc.). Furthermore, post-translation modifications such as three dimensional structure, acid-base variants amount or glycolization profile, may change significantly with changes which may be considered “minor” at the beginning of the production process. In this context the safety and efficacy profiles of the said products depends on them being sufficient in terms of quality and monitoring.

 

Within this scope:

 

·         Standard generic approach (evidencing bioequivalence with reference medicinal product by using appropriate bioavailability studies) is normally applied to chemically produced products.

Depending on the complexity of the biological/biotechnological products a generic approach is not appropriate in biosimilar products. In this case comparability studies have to be made in terms of quality safety and efficacy.

 

·         In terms of the data regarding the evidencing of quality, efficacy and safety the biosimilar product should meet all requirements identified in Appendix 1 of the Medicinal Products for Human Use and also meet technical requirements included in the Monographs of the European Pharmacopeia and any additional requirement identified in the CHMP (Committee for Medicinal Products for Human Use) and ICH (International Conference on Harmonization) current guides related to general and products.

 

·         The active substance of a biosimilar product should show molecular and biological similarity to the active substance of the reference medicinal product.

 

·         The pharmaceutical form, strength and route of administration of the biosimilar medicinal product should be same with the reference product.

 

·         In case the pharmaceutical form, strength and route of administration are not the same additional data should be presented within the scope of comparability studies.

 

·         Any difference between the biosimilar medicinal product and the reference medicinal product should be evaluated with appropriate studies per case.

In case a registration application is made by a separate application holder for a biologic medicinal product referenced to an original medicinal product having received registration in Turkey and defined in paragraph 3.2 of Section 1 attached to the Registration Regulation the following issues are valid.

The information to be presented should not be restricted to Common Technical Document (CTD) Module 1, 2, 3. In addition toxicological non-clinical and related clinical data to be presented for each product should conform to the related scientific guide.

Due to the variety of biological medicinal products the additional studies foreseen in the Common Technical Document (CTD) Module 4 and Module 5 should be determined by considering the specific features of each biological medicinal product. If the original medicinal product has more than one indication, the efficacy and safety of the medicinal product claimed to be biosimilar should be justified and if necessary proved for each claimed indication.

 

 

·        Selected Reference Medicinal Product should be a registered product whose complete application including administrative, quality, pre-clinical and clinical data has been made to the related authority abroad.

 

·         During the development process of the biosimilar medicinal product for registration, all comparison trials (similar to the related biological reference product and those made to evidence that it is as safe and efficient as this product) performed on the quality, safety and efficacy are performed with the reference biological drug. The aim of this trial is to evidence that there are no significant differences in terms of quality, safety or efficacy between the biosimilar and related reference biological drug.

·         Biosimilar products cannot be launched for sale during the data privilege. In case the related products present not required additional studies for registration, they will be exempt from the data privilege period.