Masterarbeit
Regulatory requirements and actual data outcomes from EPARs on the Non-clinical Studies of ATMPs (Covering Gene Therapy, Somatic Cell Therapy), and Recombinant Proteins other than Monoclonal Antibodies based on Review of EPARs (12/2009-12/2019) ***
Dr. Poonam Balani (2020)
Summary
Language: English
EPARs provide comprehensive information on the studies submitted for the process of evaluation of a dossier submitted for marketing authorization and provide valuable insights into the studies that are critical from the point of view of the assessors. EPARs can also be used as a reference for the design of a non-clinical program for future applications for marketing authorisations.
In the present work, the non-clinical requirements of advanced therapy medicinal products (ATMPs) and recombinant proteins have been analysed for the MPs authorised in the EU through centralised procedure in the last decade.
The aim of the non-clinical program for ATMPs is to provide basic studies for the demonstration of a positive benefit risk balance, so as to enable moving into the clinical phase. Therefore, flexibility in the design of studies on a case by case basis, and a risk-based approach is adopted for the non-clinical program. For the ATMPs analysed in the present work, the studies conducted are often limited due to unavailability of suitable animal model systems representative of the human conditions. Therefore, a risk-based strategy along with the implementation of post- authorisation measures and risk mitigation practices is followed to better understand the safety and efficacy of ATMPs.
In case of novel recombinant proteins, comprehensive non-clinical program is expected for the assessment of efficacy and safety relevant aspects, based on the ICH S6 (R1). On the other hand, the design of non-clinical program for biosimilars is often abridged, based on the guidelines on biosimilar medicinal products and product-class specific guidelines.
EPARs are a secondary source of information and represent an abridged version of all the studies conducted on the part of the applicant to demonstrate the efficacy and safety of the potential medicinal product. It is observed that not all EPARs elaborate all the sections of the studies and often lack justifications for omission of studies from the point of the assessors. Therefore, especially in cases where the EPARs do not carry sufficient information on subsections, it does not necessarily imply that the studies were not conducted. In conclusion, while the data analysis provides information on the trends and the adherence/deviations to the guidelines specific to product class regarding non-clinical aspects, any conclusions derived on the basis of EPAR data alone should be dealt with caution.
Pages: 66
Annexes: 48 (XLVIII ), Pages: 82