Skip to main content
SpringerLink
Log in

Grundlagen der Pharmakologie biologischer Arzneimittel

Basics of the pharmacology of biopharmaceuticals

  • Leitthema
  • Published:
Der Hautarzt Aims and scope Submit manuscript

Zusammenfassung

Biologische Arzneimittel sind die Gesamtheit aller Arzneistoffe oder Präparationen aus Arzneistoffen, die biologischen Ursprungs sind oder aus biologischem Material hergestellt werden. Das Spektrum biologischer Arzneimittel ist umfangreich und schließt aus biologischem Material isolierte Stoffe, rekombinante RNA(Ribonukleinsäure)-Moleküle, Proteine sowie Vollantikörper, Antikörperfragmente oder Antikörper-Drug-Konjugate ein. Die Besonderheiten der molekularen Eigenschaften und Funktionen biologischer Arzneistoffe bedingen einen hochkomplexen, variablen Aufbau. Aufgrund der Spezifität beabsichtigter pharmakodynamischer Effekte auf ein komplexes biologisches Regulationssystem sind Besonderheiten bezüglich unerwünschter Effekte, Pharmakokinetik und Sicherheit sowohl regulatorisch als auch klinisch zu beachten.

Abstract

Biopharmaceuticals are pharmaceutical drug products or preparations of pharmaceutical drugs that are of biological origin or are manufactured from biological material. The spectrum of biological drugs is extensive and includes substances isolated from biological material, recombinant RNA molecules, proteins as well as full antibodies, antibody fragments or antibody–drug conjugates. The special features of the molecular properties and functions of biopharmaceuticals require a highly complex, variable structure. Due to the specificity of intended pharmacodynamic effects on a complex biological regulatory system, particularities regarding undesired effects, pharmacokinetics, and safety have to be considered both regulatory and clinical.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1

Literatur

  1. Heymann WR (2005) Side effects of the biologics. J Am Acad Dermatol 53:692–693

    Article  Google Scholar 

  2. Succaria F, Bhawan J (2017) Cutaneous side-effects of biologics in immune-mediated disorders: A histopathological perspective. J Dermatol 44:243–250

    Article  Google Scholar 

  3. Yao Y, Ravn Jorgensen AH, Thomsen SF (2019) Biologics for chronic inflammatory skin diseases: An update for the clinician. J Dermatolog Treat. https://doi.org/10.1080/09546634.2019.1589643

    Article  PubMed  Google Scholar 

  4. Ryckaert S, Pardon E, Steyaert J, Callewaert N (2010) Isolation of antigen-binding camelid heavy chain antibody fragments (nanobodies) from an immune library displayed on the surface of pichia pastoris. J Biotechnol 145:93–98

    Article  CAS  Google Scholar 

  5. Toleikis L, Frenzel A (2012) Cloning single-chain antibody fragments (ScFv) from hyrbidoma cells. Methods Mol Biol 907:59–71

    Article  CAS  Google Scholar 

  6. Vaks L, Benhar I (2014) Production of stabilized scfv antibody fragments in the e. Coli bacterial cytoplasm. Methods Mol Biol 1060:171–184

    Article  Google Scholar 

  7. Chapman AP (2002) Pegylated antibodies and antibody fragments for improved therapy: A review. Adv Drug Deliv Rev 54:531–545

    Article  CAS  Google Scholar 

  8. Dahlen E, Veitonmaki N, Norlen P (2018) Bispecific antibodies in cancer immunotherapy. Ther Adv Vaccines Immunother 6:3–17

    Article  CAS  Google Scholar 

  9. Wang Q, Chen Y, Park J, Liu X, Hu Y, Wang T, McFarland K, Betenbaugh MJ (2019) Design and production of bispecific antibodies. Antibodies 8:antib8030043

    Google Scholar 

  10. Pan W, Cai T, Tang S, Zhou L, Dong J (2018) Trifunctional metasurfaces: concept and characterizations. Opt Express 26:17447–17457

    Article  CAS  Google Scholar 

  11. Flemming A (2019) Trifunctional antibodies unleash nk cells. Nat Rev Cancer 19:369

    Article  CAS  Google Scholar 

  12. Hedrich WD, Fandy TE, Ashour HM, Wang H, Hassan HE (2018) Antibody-drug conjugates: pharmacokinetic/pharmacodynamic modeling, preclinical characterization, clinical studies, and lessons learned. Clin Pharmacokinet 57:687–703

    Article  CAS  Google Scholar 

  13. IQWIG-Bericht Nr. 614: Brentuximab vedotin (kutanes T‑Zell-Lymphom) Bewertung gemäß § 35a Abs. 1 Satz 11 SGB V. https://www.g-ba.de/downloads/92-975-2268/2018-01-15_Bewertung-Therapiekosten-Patientenzahlen-IQWiG_Brentuximab_Vedotin-D-340.pdf, 2018. Zugegriffen: 25.09.19

  14. O’Brien J, Hayder H, Zayed Y, Peng C (2018) Overview of microrna biogenesis, mechanisms of actions, and circulation. Front Endocrinol 9:402

    Article  Google Scholar 

  15. Hayes J, Peruzzi PP, Lawler S (2014) Micrornas in cancer: biomarkers, functions and therapy. Trends Mol Med 20:460–469

    Article  CAS  Google Scholar 

  16. Ross K (2018) Towards topical microrna-directed therapy for epidermal disorders. J Control Release 269:136–147

    Article  CAS  Google Scholar 

  17. Doevendans E, Schellekens H (2019) Immunogenicity of innovative and biosimilar monoclonal antibodies. Antibodies 8:antib8010021

    Article  Google Scholar 

  18. Hindryckx P, Novak G, Vande Casteele N, Khanna R, Laukens D, Jairath V, Feagan BG (2017) Incidence, prevention and management of anti-drug antibodies against therapeutic antibodies in inflammatory bowel disease: A practical overview. Drugs 77:363–377

    Article  CAS  Google Scholar 

  19. Thomas LW, Lee EB, Wu JJ (2019) Systematic review of anti-drug antibodies of il-17 inhibitors for psoriasis. J Dermatolog Treat 30:110–116

    Article  CAS  Google Scholar 

  20. WHO (2011) International Nonproprietary Names (INN) for biological and biotechnological substances. https://www.who.int/medicines/services/inn/BioRev2011.pdf. Zugegriffen: 25.09.19

    Google Scholar 

  21. Hayakawa T (1999) science of evaluating the characteristics, quality and safety of biotechnological products: Rdna-derived products, cell culture technology-derived products, gene therapy products, cellular therapy products, and transgenic animal-derived protein products and cellular products. Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho Hokoku 117:1–38

    CAS  Google Scholar 

  22. EEC note for guidance (1990) Production and quality control of cytokine products derived by biotechnological processes. Ad hoc working party on biotechnology/pharmacy. Pharmacol Toxicol 67:353–358

  23. Note for guidance (1991) Production and quality control of cytokine products derived by biotechnological processes. Committee for proprietary medicinal products: Ad hoc working party on biotechnology/pharmacy and working party on safety medicines. Biologicals 19:125–131

    Article  Google Scholar 

  24. International conference on harmonisation (1998) guidance on quality of biotechnological/biological products: Derivation and characterization of cell substrates used for production of biotechnological/biological products; availability. Notice. Food and drug administration, hhs. Fed Regist 63:50244–50249

  25. Quality of biotechnological products (1998) Derivation and characterisation of cell substrates used for production of biotechnological/biological products. Ich harmonised tripartite guideline. Dev Biol Stand 93:223–234

  26. Quality of biotechnological products (1998) Analysis of the expression construct in cell lines used for production of r‑DNA derived protein products. Ich harmonised tripartite guideline. Dev Biol Stand 93:205–208

  27. Quality of biotechnological products (1998) Viral safety evaluation of biotechnology products derived from cell lines of human or animal origin. Ich harmonised tripartite guideline. Dev Biol Stand 93:177–201

  28. Quality of biotechnological products (1998) Stability testing of biotechnological/biological products. Annex to the ich harmonised tripartite guideline for the stability testing of new drug substances and products. Dev Biol Stand 93:211–219

  29. van Gerven J, Bonelli M (2018) Commentary on the ema guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products. Br J Clin Pharmacol 84:1401–1409

    Article  Google Scholar 

  30. Yang Z, Wang H, Salcedo TW, Suchard SJ, Xie JH, Schneeweis LA, Fleener CA, Calore JD, Shi R, Zhang SX, Rodrigues AD, Car BD, Marathe PH, Nadler SG (2015) Integrated pharmacokinetic/pharmacodynamic analysis for determining the minimal anticipated biological effect level of a novel anti-cd28 receptor antagonist bms-931699. J Pharmacol Exp Ther 355:506–515

    Article  CAS  Google Scholar 

  31. Chavez JC, Jain MD, Kharfan-Dabaja MA (2019) Cytokine release syndrome and neurologic toxicities associated with chimeric antigen receptor t‑cell therapy: A comprehensive review of emerging grading models. Hematol Oncol Stem Cell Ther 3876. https://doi.org/10.1016/j.hemonc.2019.05.005

  32. Wohlrab J (2015) Pharmacokinetic characteristics of therapeutic antibodies. J Dtsch Dermatol Ges 13:530–534

    PubMed  Google Scholar 

  33. Toon S (1996) The relevance of pharmacokinetics in the development of biotechnology products. Eur J Drug Metab Pharmacokinet 21:93–103

    Article  CAS  Google Scholar 

  34. Petitcollin A, Bensalem A, Verdier MC, Tron C, Lemaitre F, Paintaud G, Bellissant E, Ternant D (2019) Modelling of the time-varying pharmacokinetics of therapeutic monoclonal antibodies: a literature review. Clin Pharmacokinet. https://doi.org/10.1007/s40262-019-00816-7

    Article  Google Scholar 

  35. Ryman JT, Meibohm B (2017) Pharmacokinetics of monoclonal antibodies. CPT Pharmacometrics Syst Pharmacol 6:576–588

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Universitätsklinik und Poliklinik für Dermatologie und Venerologie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Str. 40, 06097, Halle (Saale), Deutschland

    Johannes Wohlrab

  2. Institut für angewandte Dermatopharmazie, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Deutschland

    Johannes Wohlrab

Authors
  1. Johannes Wohlrab
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Johannes Wohlrab.

Ethics declarations

Interessenkonflikt

J. Wohlrab gibt an, dass er Honorare für Vorträge oder/und Beratungsleistungen bzw. Sponsoring für wissenschaftliche Projekte oder/und klinische Studien von folgenden Firmen erhalten hat, die relevante Präparate vertreiben: AbbVie, Almirall, Baxalta, Biogen, Celgene, Evolva, Galderma, GSK, Hexal, Janssen-Cilag, Leo, Lilly, Medac, MSD, Novartis, Pfizer, Sanofi, UCB.

Für diesen Beitrag wurden vom Autor keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wohlrab, J. Grundlagen der Pharmakologie biologischer Arzneimittel. Hautarzt 70, 926–933 (2019). https://doi.org/10.1007/s00105-019-04502-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00105-019-04502-4

Schlüsselwörter

Keywords

Search

Navigation