Biological drugs are products that manufacture or extract the active substance from biological sources, not from chemical syntheses. In the production processes, characterization experiments are carried out utilizing a range of physicochemical and biological measures that will be adopted in terms of quality standards. These products are;
• Immunological products
• Blood products
• Products obtained by controlled expression of coding genes in prokaryotic and eukaryotic cells, including transformed mammalian cells with recombinant DNA technology and hybridoma and monoclonal antibody methods,
• Advanced medical treatment products
• Reagents from which the active substance is not directly derived, culture medium, veal fetus serum, additives, chromatography, etc.
Where the product is protein, banks are created from living organisms (bacteria, mammalian cells, etc.) that will produce the target product using recombinant DNA technology. The first step is to locate the DNA sequence (gene) that will encode the required recombinant protein into the desired organism for this product to be generated. A pool with many cells that contain the desired gene is obtained at the end of the process. The best cells are chosen here, in consideration of the targeted product quality and production capacity. The selected cell shall be replicated and stored for further use in production under appropriate cold conditions (such as < -70 ° C). Such cells are cell banks specifically designed for that product. It does not include any identified pathogens and should be able to process the protein optimally and in quantities suitable for mass production.
Protein development starts with the melting of stored frozen cells and their growth under a suitable environment and ambient conditions. The cultures that are produced by growing the cells at different production levels are distilled using similar segregation methods. The mechanisms through which cell banks receive pure protein are called bioprocesses. The product formulation processes are completed and then transformed into finished products by filling them under aseptic conditions in proper packages (syringes, cartridges, vials, etc.)
Biosimilar is a drug similar to a licensed biologic (reference drug) drug. It is a similar product that is developed after the biological reference product’s patent expiry. The comparative quality of a biosimilar drug, derived from specific trials similar to the reference product, should be illustrated by non-clinical and clinical results.
Developing a biosimilar drug is more difficult and takes longer than generic medications since the active ingredients are more complex. Health agencies (Turkish Medicines and Medical Devices Agency, FDA, EMA, etc.) are investigating the control of the similarity of biosimilar products to the reference biologic medicines. Comparability studies will be able to demonstrate whether the quality, effectiveness, and health of the biosimilar medication are comparable to the reference / original product. For this reason, biosimilar and biological reference drugs are generally used with the same effectiveness for treating the same disease.
Toksöz Group started its investments in biological medicine production in 2007. Arven Pharmaceuticals, with its qualified researchers experienced in biosimilar product development in Turkey, who are withholding graduate and doctoral degrees, has been working to serve the public health by enriched biosimilar product development infrastructure and production capacity day by day.
Arven Pharmaceuticals, as a result of investments in biotechnology, achieved the success of licensing the first biosimilar product which is developed and produced by Turkey’s domestic pharmaceutical industry.
The high technology products production facility for Arven Pharmaceuticals which has 28,000 square meters of indoor space in Kırklareli Organized Industrial Zone, which is one of the investments of the Toksöz group, has started production by obtaining GMP approval as of 2017.
The Arven R&D facility located in Selimpaşa / Istanbul continues its project development activities without interruption by gaining the status of the R&D center in 2017.
Biological drugs used in cases where treatment with conventional drugs is not possible such as cancer, autoimmune diseases are expensive. They impose an economic burden on both the patient and health systems. Therefore, it is important to produce biosimilars that can be an alternative in the treatment process in our country. Our company’s biggest goal is to develop biosimilars of overpriced biological medications at the quality level the authorities require. Employment of young people of our country who have graduated from related disciplines (such as Molecular Biology and Genetics, Physics, Bioengineering) for this purpose, is also a significant benefit for our country.
In the biosimilar development process, guidelines published by the World Health Organization, the European Medicines Agency, and the US Food and Drug Administration are followed. Such guides demonstrate the development process that the biosimilar product must go through and are acknowledged in the international platform as the golden reference. For Arven Pharmaceuticals, “The product is the process.” approach, and the importance of quality during this process is essential. Arven Pharmaceuticals performs a large portion of the structural and functional analyses with its existing infrastructure and applicable industry capabilities as outlined in international guidelines. Probably the most important step in the development process is the implementation of production methods to commercial requirements without compromising product quality, which is an indispensable task for Arven Pharmaceuticals in the field of public health.
1. A guide to biosimilar medicinal products. Ministry of Health, Turkey Pharmaceuticals, and Medical Devices Agency
2. ICH Topic Q 5 D: Quality of Biotechnological Products: Derivation and Characterization of Cell Substrates Used for Production of Biotechnological / Biological Products
3. ICH Topic Q 5 A (R1): Quality of Biotechnological Products: Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin
4. European Medicines Agency. Guideline on similar biological medicinal products
5. European Medicines Agency. Questions and answers on biosimilar medicines (similar biological medicinal products)
6. European Medicines Agency. Similar biological medicinal products containingbiotechnology-derived proteins as active substance: quality issues.
7. European Medicines Agency. Similar biological medicinal products containingbiotechnology-derived proteins as active substance: non-clinical and clinical issues.
8. FDA Guidance for Industry; Scientific Considerations in Demonstrating Biosimilarity to a Reference Product.
9. FDA Guidance for Industry; Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product
10. FDA Guidance for Industry; Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product
11. Biosimilars. Alper B. İSKİT XXXVIII. National Hematology Congress
12. Biosimilar competition: lessons from Europe. Henry Grabowski, Rahul Guha and Maria Salgado, Nature Reviews, Drug Discovery 2014 (13) 99-100