Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Comparison of Biosimilar Registrations for the Swiss and the German Market or What CMC Can Tell Us

Dr. Urs Dominik Hobom (Abschlußjahr: 2015)

Summary
Language: American English
Biologicals are an important class of medicines and early examples include hormones and chemokines that normally occur in nature. The advent of recombinant DNA technology has allowed the synthesis of these compounds in living cells, replacing some earlier cumbersome extraction methods. In the last decade, the first of these protein drugs have slipped out of market exclusivity provisions, necessitating a legal pathway for the authorization of ‘bio-generics’, highly similar copy versions of protein therapeutics, that, on a molecular level, are less stringently defined and display sub-molar side chain microheterogeneity.
The reverse-engineering of a Follow-on Biologic requires the definition of an analytical Quality Target Product Profile as a narrow gauge for achieving a pharmaceutically, immunologically, and clinically equivalent version of the originator drug substance. Lessons learned from past hGH, EPO, and G-CSF filings have sensitized regulators to the limitations of pre-authorization preclinical and clinical data that are considered the gold standard in providing the so-called “biocomparability and biosimilarity exercise”. At the heart of the biosimilar application, the Module 3 quality data are more extensive than for a full Marketing Authorization Application, requiring a separate section for a physico-chemical and biological head-to-head comparison with the reference biologic. Time is now set for a new wave of biosimilar applications as the fusion protein and monoclonal antibody class of protein products with huge blockbuster drugs in immunology and oncology indications approaches patent expiry in Germany and Switzerland.
Recombinant DNA technology-derived products automatically fall under the responsibility of the EU Centralized Authorization Procedure but it has to be kept in mind that Switzerland,  although in the heart of Europe, is neither a member of the European Union nor of the European Economic Area. Its Regulatory Body, Swissmedic, independently reaches its decisions, as stipulated by national law. Nonetheless, as especially biosimilars are considered known active substances in Bern, special provisions are in place that effectively limit Swissmedic’s assessment to a review of the EPAR, where it is available, and rapid and aligned decisions are very supposable. Swissmedic also provides an example that in the absence of a mandatory preclocked time schedule decisions can be reached more rapidly, with the same predictability.
Barriers to global biosimilar development are the often strict requirements with regards to the reference product which must be the nationally authorized originator product even in the case of economies of the size of Switzerland. Provisions have recently been  implemented that would allow also non-EEA or non-Swiss comparator products, although these come with the obligation to then also present a bridging study between the biosimilar, the national reference product, and the comparator product used. A lot of myths are still circulating in this evolving field of biosimilar versions of marketed biologics and the at least ‘unclear’ situation with regards to automatic substitution at the pharmacy/INN level  has perhaps been the single most critical variable that makes biosimilar development for highly regulated markets a risky endeavor.
Pages: 75