Öz
Biyolojik tıbbi ürünler, konvansiyonel tedavilere cevap vermeyen çeşitli hastalıkların tedavisinde yeni
tedavi seçenekleri olarak karşımıza çıkmaktadır. Biyobenzer tıbbi ürünler, ruhsatlı bir biyolojik tıbbi
ürüne (referans tıbbi ürün) yüksek düzeyde benzerlik gösteren ürünlerdir. Biyobenzer tıbbi ürünler,
referans tıbbi ürünlere kalite özellikleri, biyolojik aktivite, güvenlilik ve etkililik açısından benzer olmalı
ve benzerlik karşılaştırılabilirlik çalışmaları ile gösterilmelidir. Hedef Ürün Kalite Profili (HÜKP) ve
molekül özellikleri referans tıbbi ürünle karşılaştırılabilir olmalıdır. Biyobenzer tıbbi ürünler referans
tıbbi ürünler ile aynı gen dizisine sahip olmalarına rağmen; farklı klonlama vektörü, konakçı hücre,
fermentasyon koşulları, kültür ortamı, saflaştırma işlemleri ve formülasyon nedeniyle üretim süreci
sonunda farklı biyofiziksel özelliklere sahip biyobenzer ürün elde edilir. Üretim sürecinin herhangi bir
aşamasında meydana gelebilecek değişiklikler üründe farklılıklara neden olarak ürünün kalitesini,
güvenliliğini ve etkililiğini değiştirebilmektedir. Ürün ya da üretim işlemi kaynaklı safsızlıklar,
translasyon sonrası modifikasyonlar, üretim, taşıma, saklama ve hasta kullanımı sırasında meydana
gelebilecek stres koşulları, ürünün stabilitesini, biyoaktivitesini ve immünojenisitesini değiştirebilir. Bu
farklılıkların ürünün güvenlilik ve etkililiğini değiştirmediği preklinik ve klinik çalışmalarla gösterilmelidir.
Anahtar Kelimeler
Biyobenzer tıbbi ürün üretim süreci kalite güvenlilik etkililik
Kaynakça
- Demir-Dora D. Biyofarmasötik Ürünlerin Geliştirilmesinde Biyobelirteçler. Turkiye Klinikleri J PharmacolSpecial Topics 2017; 5 (2):75-83.
- T.C. Sağlık Bakanlığı Türkiye İlaç ve Tıbbi Cihaz Kurumu, Biyobenzer Tıbbi Ürünlere İlişkin Kılavuz. 07.08 2008.
- T.C. Sağlık Bakanlığı Türkiye İlaç ve Tıbbi Cihaz Kurumu, Biyobenzer Tıbbi Ürünler Hakkında Kılavuz Taslağı. 30.05.2017, https://www.titck.gov.tr/mevzuat/biyobenzer-tibbi-urunler-hakkinda-kilavuzu-taslagi27122018173016 (Erişim: 20.11.2019)
- European Medicines Agency and the European Commission. Biosimilars in the EU-Information guide for healthcare professionals. 29.10.2019. https://www.ema.europa.eu/en/documents/leaflet/biosimilars-euinformation-guide-healthcare-professionals_en.pdf (Erişim: 20.11.2019)
- European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP). Guideline on similar biological medicinal products (CHMP/437/04 Rev 1), 23 October 2014.
- European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP). Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (EMA/CHMP/BWP/247713/2012 Rev1), 22 May 2014.
- European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP). Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: nonclinical and clinical issues (EMEA/CHMP/BMWP/42832/2005 Rev1), 18 December 2014.
- U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER). Scientific Considerations in Demonstrating Biosimilarity to a Reference Product, Guidance for Industry. April 2015.
- Özdem S, Çiçin İ, Demir-Dora D, Korucu-Nazlı C. Sorularla Biyoteknolojik ve Biyobenzer İlaçlar. Ed: İrfan Çiçin, Güneş Tıp Kitapevleri 2017. ISBN: 978-975-277-697-5.
- T.C. Sağlık Bakanlığı Türkiye İlaç ve Tıbbi Cihaz Kurumu, Beşeri ve Tıbbi Ürünler İmalathaneleri İyi İmalat Uygulamaları (GMP) Kılavuzu, 05.05.2016.
- European Medicines Agency (EMA). ICH Topic Q5D: Quality of Biotechnological Products: Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/Biological Products (CPMP/ICH/294/95). 1998.
- European Pharmacopoeia 8.0, 5.14. Gene transfer medicinal products for human use, 705-716.
- Werner RG, Noe W, Kopp K, Schulter M. Appropriate mammalian expression systems for biopharmaceuticals. Drug Res 1998; 48: 870-880.
- Adrio JL, Demain AL. Recombinant organisms for production of industrial products. Bioeng Bugs 2010; 1: 116–131.
- Wurm FM. Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 2004; 22: 1393–1398.
- Larrick JW, Thomas DW. Producing proteins in transgenic plant and animals. Curr Opin Biotechnol 2001; 12: 411-418.82 Ege Tıp Dergisi / Ege Journal of Medicine
- Winder R. Biomanufacturing, Cell culture changes gear. Chem Ind 2005; 20: 18–20.
- Walsh G. Post-translational modification of protein pharmaceuticals. Drug Discov Today 2010;15(17-18):773- 780.
- Walsh G, Jefferies R. Post-translational modifications in the context of therapeutic proteins. Nat Biotechnol 2006; 24: 1241–1252.
- Stanbury PF, Whitaker A, Hall SJ. Principles of Fermentation Technology, 2nd ed., Butterworth-Heinemann, Elsevier Science Oxford, 2003: 167-214.
- Kontoravdi C, Samsatli NJ, Shah N. Development and design of bio-pharmaceutical processes. Curr Opin Chem Eng 2013; 2: 435–441.
- Gronemeyer P, Ditz R and Strube J. Trends in Upstream and Downstream Process Development for Antibody Manufacturing, Bioengineering 2014; 1 (4), 188- 212.
- Cramer SM, Holstein MA. Downstream bioprocessing: recent advances and future promise. Curr Opin Chem Eng 2011; 1: 27–37.
- Hanke AT, Ottens M. Purifying biopharmaceuticals: knowledge-based chromatographic process development. Trends Biotechnol 2014; 32 (4):210-220.
- Tamizi E, Jouyban A, Forced degradation studies of biopharmaceuticals: selection of stres conditions, Eur J Pharm Biopharm 2016; 98: 26–46.
- Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharm Res 2010; 27 (4): 544–75.
- Samir Mitragotri S, Burke PA, Langer R. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nat Rev. Drug Discov 2004; 13: 655–672.
- Arsiccio A, Paladini A, Pattarino F, Pisano R. Designing the Optimal Formulation for Biopharmaceuticals: A New Approach Combining Molecular Dynamics and Experiments. J Pharm Sci 2019; 108: 431-438.
- Sharma B. Immunogenicity of therapeutic proteins. Part 2: impact of container closures. Biotechnol Adv 2007; 25: 318-24.
- Wang W, Singh SK., Li N, Toler ML, King KR, Nema S. Immunogenicity of protein aggregates-concern and realities. Int J Pharm 2012; 431:1-11.
- Kessler M, Goldsmith D, Schellekens H. Immunogenicity of biotherapeuticals. Nephrol Dial Transplant 2006; 21: 9-12.
- Barbosa M. Immunogenicity of biotherapeutics in the context of developing biosimilars and biobetters. Drug Discov Today 2011; 16: 7-8.
- Committee for Medicinal Products for Human Use (CHMP), Guideline on Immunogenicity Assessment of Biotechnology-Derived Therapeutic Proteins (EMEA/CHMP/BMWP/14327/2006), 13 December 2007.
- Ebbers HC, Crow SA, Vulvo AG, Schellekens H. Interchangeability, immunogenicity and biosimilars. Nat Biotechnol 2012; 30: 1186-1190.
- Korucu FC, Nazlı H, Gedik G, Çiçin İ. Biyobenzer ürünlerde klinik uygulamada karşılaşılabilecek sorunlar. Marmara Pharm J 2016; 20: 44-51.
- Parr MK, Montacira O, Montacir H. Physicochemical characterization of biopharmaceuticals. J Pharm Biomed Anal 2016; 130: 366–389.
- Chirino AJ, Mire-Sluis A. Characterizing biological products and assessing comparability following manufacturing changes. Nat Biotechnol 2004; 22: 1383–1391.
- Planinc A, Bones J, Dejaegher B, Antwerpen PV, Delporte C. Glycan characterization of biopharmaceuticals. Updates and Perspectives Anal Chim Acta 2016; 921: 13-27.
- Büyükköroğlu G, Demir-Dora D, Özdemir F, Hızel C. Techniques for Protein Analysis. In: Debmalya Barh, Vasco Azevedo (eds). Omics Technologies and Bio-engineering Volume 1: Towards Improving Quality of Life, Elsevier Inc, Chennai: Academic Press, pp.317-352, 2017.
- Shintani H. Development of Test Method for Pharmaceutical and BioPharmaceutical Products. Pharm Anal Acta 2013; 4:258.
- European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP). Biotechnological/biological products subject to changes in their manufacturing process: comparability of biotechnological/biological products (CPMP/ICH/5721/03), 01 June 2005.
The effect of manufacturing process and quality of biosimilar medicinal products on safety and efficacy
Öz
Biological medicinal products are emerging as new treatment options for the treatment of various
diseases that do not respond to conventional treatments. Biosimilar medicinal products are biological
medicinal products that are highly similar to an already authorized original biological medicinal
products (reference medicinal product). Biosimilar medicinal products should be similar to reference
medicinal products in terms of quality characteristics, biological activity, safety and efficacy and
biosimilarity should be demonstrated by comparability studies. The quality target product profile
(QTPP) and molecular properties should be comparable to the reference medicinal product. Although
biosimilar medicinal products have the same gene sequence as reference medicinal products; due to
the different cloning vector, host cell, fermentation conditions, purification processes and formulation, a
biosimilar product with different biophysical properties is obtained at the end of the manufacturing
process. Changes that may occur at any stage of the manufacturing process change the quality,
safety and efficacy causing differences in the product. Product or process related impurities, posttranslational modifications, stress conditions that may occur during production, handling, storage and
patient use may alter the stability, bioactivity and immunogenicity of the product. It should be
demonstrated by preclinical and clinical studies that these differences do not change the safety and
efficacy of the product.
Anahtar Kelimeler
Biosimilar medicinal product manufacturing process, quality safety efficacy
Kaynakça
- Demir-Dora D. Biyofarmasötik Ürünlerin Geliştirilmesinde Biyobelirteçler. Turkiye Klinikleri J PharmacolSpecial Topics 2017; 5 (2):75-83.
- T.C. Sağlık Bakanlığı Türkiye İlaç ve Tıbbi Cihaz Kurumu, Biyobenzer Tıbbi Ürünlere İlişkin Kılavuz. 07.08 2008.
- T.C. Sağlık Bakanlığı Türkiye İlaç ve Tıbbi Cihaz Kurumu, Biyobenzer Tıbbi Ürünler Hakkında Kılavuz Taslağı. 30.05.2017, https://www.titck.gov.tr/mevzuat/biyobenzer-tibbi-urunler-hakkinda-kilavuzu-taslagi27122018173016 (Erişim: 20.11.2019)
- European Medicines Agency and the European Commission. Biosimilars in the EU-Information guide for healthcare professionals. 29.10.2019. https://www.ema.europa.eu/en/documents/leaflet/biosimilars-euinformation-guide-healthcare-professionals_en.pdf (Erişim: 20.11.2019)
- European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP). Guideline on similar biological medicinal products (CHMP/437/04 Rev 1), 23 October 2014.
- European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP). Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues (EMA/CHMP/BWP/247713/2012 Rev1), 22 May 2014.
- European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP). Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: nonclinical and clinical issues (EMEA/CHMP/BMWP/42832/2005 Rev1), 18 December 2014.
- U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER). Scientific Considerations in Demonstrating Biosimilarity to a Reference Product, Guidance for Industry. April 2015.
- Özdem S, Çiçin İ, Demir-Dora D, Korucu-Nazlı C. Sorularla Biyoteknolojik ve Biyobenzer İlaçlar. Ed: İrfan Çiçin, Güneş Tıp Kitapevleri 2017. ISBN: 978-975-277-697-5.
- T.C. Sağlık Bakanlığı Türkiye İlaç ve Tıbbi Cihaz Kurumu, Beşeri ve Tıbbi Ürünler İmalathaneleri İyi İmalat Uygulamaları (GMP) Kılavuzu, 05.05.2016.
- European Medicines Agency (EMA). ICH Topic Q5D: Quality of Biotechnological Products: Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/Biological Products (CPMP/ICH/294/95). 1998.
- European Pharmacopoeia 8.0, 5.14. Gene transfer medicinal products for human use, 705-716.
- Werner RG, Noe W, Kopp K, Schulter M. Appropriate mammalian expression systems for biopharmaceuticals. Drug Res 1998; 48: 870-880.
- Adrio JL, Demain AL. Recombinant organisms for production of industrial products. Bioeng Bugs 2010; 1: 116–131.
- Wurm FM. Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 2004; 22: 1393–1398.
- Larrick JW, Thomas DW. Producing proteins in transgenic plant and animals. Curr Opin Biotechnol 2001; 12: 411-418.82 Ege Tıp Dergisi / Ege Journal of Medicine
- Winder R. Biomanufacturing, Cell culture changes gear. Chem Ind 2005; 20: 18–20.
- Walsh G. Post-translational modification of protein pharmaceuticals. Drug Discov Today 2010;15(17-18):773- 780.
- Walsh G, Jefferies R. Post-translational modifications in the context of therapeutic proteins. Nat Biotechnol 2006; 24: 1241–1252.
- Stanbury PF, Whitaker A, Hall SJ. Principles of Fermentation Technology, 2nd ed., Butterworth-Heinemann, Elsevier Science Oxford, 2003: 167-214.
- Kontoravdi C, Samsatli NJ, Shah N. Development and design of bio-pharmaceutical processes. Curr Opin Chem Eng 2013; 2: 435–441.
- Gronemeyer P, Ditz R and Strube J. Trends in Upstream and Downstream Process Development for Antibody Manufacturing, Bioengineering 2014; 1 (4), 188- 212.
- Cramer SM, Holstein MA. Downstream bioprocessing: recent advances and future promise. Curr Opin Chem Eng 2011; 1: 27–37.
- Hanke AT, Ottens M. Purifying biopharmaceuticals: knowledge-based chromatographic process development. Trends Biotechnol 2014; 32 (4):210-220.
- Tamizi E, Jouyban A, Forced degradation studies of biopharmaceuticals: selection of stres conditions, Eur J Pharm Biopharm 2016; 98: 26–46.
- Manning MC, Chou DK, Murphy BM, Payne RW, Katayama DS. Stability of protein pharmaceuticals: an update. Pharm Res 2010; 27 (4): 544–75.
- Samir Mitragotri S, Burke PA, Langer R. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nat Rev. Drug Discov 2004; 13: 655–672.
- Arsiccio A, Paladini A, Pattarino F, Pisano R. Designing the Optimal Formulation for Biopharmaceuticals: A New Approach Combining Molecular Dynamics and Experiments. J Pharm Sci 2019; 108: 431-438.
- Sharma B. Immunogenicity of therapeutic proteins. Part 2: impact of container closures. Biotechnol Adv 2007; 25: 318-24.
- Wang W, Singh SK., Li N, Toler ML, King KR, Nema S. Immunogenicity of protein aggregates-concern and realities. Int J Pharm 2012; 431:1-11.
- Kessler M, Goldsmith D, Schellekens H. Immunogenicity of biotherapeuticals. Nephrol Dial Transplant 2006; 21: 9-12.
- Barbosa M. Immunogenicity of biotherapeutics in the context of developing biosimilars and biobetters. Drug Discov Today 2011; 16: 7-8.
- Committee for Medicinal Products for Human Use (CHMP), Guideline on Immunogenicity Assessment of Biotechnology-Derived Therapeutic Proteins (EMEA/CHMP/BMWP/14327/2006), 13 December 2007.
- Ebbers HC, Crow SA, Vulvo AG, Schellekens H. Interchangeability, immunogenicity and biosimilars. Nat Biotechnol 2012; 30: 1186-1190.
- Korucu FC, Nazlı H, Gedik G, Çiçin İ. Biyobenzer ürünlerde klinik uygulamada karşılaşılabilecek sorunlar. Marmara Pharm J 2016; 20: 44-51.
- Parr MK, Montacira O, Montacir H. Physicochemical characterization of biopharmaceuticals. J Pharm Biomed Anal 2016; 130: 366–389.
- Chirino AJ, Mire-Sluis A. Characterizing biological products and assessing comparability following manufacturing changes. Nat Biotechnol 2004; 22: 1383–1391.
- Planinc A, Bones J, Dejaegher B, Antwerpen PV, Delporte C. Glycan characterization of biopharmaceuticals. Updates and Perspectives Anal Chim Acta 2016; 921: 13-27.
- Büyükköroğlu G, Demir-Dora D, Özdemir F, Hızel C. Techniques for Protein Analysis. In: Debmalya Barh, Vasco Azevedo (eds). Omics Technologies and Bio-engineering Volume 1: Towards Improving Quality of Life, Elsevier Inc, Chennai: Academic Press, pp.317-352, 2017.
- Shintani H. Development of Test Method for Pharmaceutical and BioPharmaceutical Products. Pharm Anal Acta 2013; 4:258.
- European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP). Biotechnological/biological products subject to changes in their manufacturing process: comparability of biotechnological/biological products (CPMP/ICH/5721/03), 01 June 2005.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Olgu Sunumu |
| Yazarlar | |
| Yayımlanma Tarihi | 20 Ocak 2021 |
| Gönderilme Tarihi | 6 Nisan 2020 |
| Yayımlandığı Sayı | Yıl 2021Cilt: 60 Özel Sayı:1 (Romatoloji) |
