Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Registration of antibody based medicinal products ***

Dr. Manfred Kurz (Abschlußjahr: 2006)

Language: English
 
The present thesis relates to the therapeutic use of antibodies.
Antibodies are complex, Y-shaped serum glycoproteins. They are produced by antigen stimulated B-cells which divide, enlarge and differentiate to antibody secreting plasma cells. Their ability to bind to targets (antigens) with high specificity and affinity has been utilised for the development of therapeutic medicinal products by means of targeting disease related antigens. This concept was first recognised by Paul Ehrlich at the beginning of the 20th century when he envisioned the use of antibodies/drugs as “magic bullets” for the treatment of infectious diseases.

This document describes general characteristics of different types of antibodies, registration pathways, authorisation criteria and antibody discovery.

Furthermore it provides an overview on medicinal products containing either natural, polyclonal antibodies derived from the body liquid of living organisms (animals/humans) or monoclonal antibodies generated by the hybridoma method and manufactured either in vivo (mouse ascites) or in vitro (cell culture). Basic principles for the in vitro construction of recombinant antibody fragments are also addressed.

More particularly, this thesis reviews requirements for the registration of

• animal derived immunosera
• human plasma derived immunoglobulins
• monoclonal antibodies
• transgenic animal derived immunoglobulins

In each case the manufacture, pharmacotoxicological and clinical regulatory requirements are outlined. Registration relevant information is supplemented and illustrated by case studies against the background that antibody derived medicinal products may not be sujected to standard nonclinical/clinical development programmes but rather require individualised testing regimes.

Knowledge of filing information is primarily extracted and integrated from European legislation. In addition, national (German) laws as well as FDA and WHO guidance documents are referenced. Moreover other regulatory intelligence (e.g. EPARs, SBAs, monographs, publications, patents, SPCs) is taken into account. Key guidelines are listed.

Overall, the consolidation of quality, safety and efficacy related information supports the drafting of CTD documents for the quality, nonclinical and clinical documentation of marketing authorisation applications. Furthermore, general recommendations and principles for the compilation of CTD documents are provided.

Pages: 94 Annex: 1 Pages: 4