Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Regulatory Framework and Challenges for Approval of "Generic" Non-biological Complex Drugs (NBCDs) ***

Dr. Karin Geßele (Abschlußjahr: 2018)

Summary
Language: English
In the recent years a new category of medicinal products, the so-called non-biological complex drugs (NBCDs) have received increasing attention. This diverse group contains medicinal products of chemical origin, which may be even more complex than biological products. Unlike for small-molecule generics and biosimilars, there is no dedicated regulatory pathway available for the approval of follow-on (“generic”) NBCDs. In the past, this caused controversial discussions on the required scientific data for applications and resulted in lengthy approval procedures.
In this thesis, the approval history of three examples of NBCD follow-on products for iron sucrose, glatiramer acetate and the low molecular heparin enoxaparin in Europe and the United States are compared. Since the approval of the first iron sucrose similars with questionable equivalence, much progress has been made. Within each jurisdiction, there seems to be consensus on the legal basis for the regulatory approval. Product-specific guidance documents for some follow-on NBCDs were developed, which help applicants to identify the expected data required for approval.
In Europe, NBCD follow-on products are usually approved under the Article 10(3) legal basis. As with biosimilars, NBCD comparability is assessed in a stepwise approach, starting with a comprehensive characterisation of the quality parameters, followed by non-clinical and clinical studies. The extent of the non-clinical and clinical studies depends on the weight of evidence obtained in the previous steps and therefore is determined on a case-by-case basis.
In the United States, the NBCD follow-on products are filed as abbreviated new drug applications (ANDAs). The U.S. FDA puts great emphasis on demonstration of active ingredient sameness and applies very stringent quality equivalence criteria, up to equivalent manufacturing procedures, to avoid the need for clinical efficacy studies. However, this approach may prevent the development of similar products with minor quality differences without clinical relevance.
Despite the different regulatory procedures and standards between Europe and the United States there seems to be a progress towards harmonized scientific requirements across jurisdictions. An overarching European guidance document, outlining the general principles for approval of NBCD-similars, could provide further guidance and help applicants in the development of these products.
Pages: 60