Project: Proof of Concept study for the development of a biosimilar monoclonal antibody using the Quality by Design (QbD) approach.

This proposal describes a Proof of Concept study that targets a timely and cost efficient development of a biosimilar monoclonal antibody (Mab) by using the Quality by Design approach (QbD). The QbD concept for Biotechnology products is outlined in the ICH guidelines (Q8 to Q10). Moreover, the research consortium will use the paper “A-Mab: a case study in bioprocess development” by the CMC Biotech Working Group (2009), as a roadmap for QbD implementation._x000D_ _x000D_ For a biosimilar monoclonal antibody, similarity to the originator product needs to be established with respect to safety, efficacy and quality. This consortium, which consists of Bioceros (CO P; NL), Pat-Consultancy (as subcontractor of Bioceros, NL), PharmaVize (BE) and Research Institute of Chromatography (RIC, BE), will focus on the development, the monitoring and the control of the quality component. It is expected that safety and efficacy studies with the biosimilar can be launched within two years after closure of this study. _x000D_ _x000D_ Crucial in this project is a very detailed characterization of the originator product. Characterization will be performed by the company RIC using high-tech analysis including state of the art mass spectrometry. RIC will also develop screening technologies for the screening and the selection of the transfected cell clones and for analysis of the samples taken from the cultures. _x000D_ _x000D_ The production of the biosimilar monoclonal antibody will be performed in the CHO-S cell line by Bioceros. The gene of interest will be transfected into the CHO cells by Bioceros using an optimized transfection regime. The choice of the ultimate clone will be based upon productivity, ease of cultivation and high-tech characterization of the secreted antibodies. The selection medium will be defined and delivered by Lonza. _x000D_ _x000D_ Cultivation of the selected clone will be developed by Bioceros in a bioreactor using a fed-batch strategy. The cultivation will be executed in the Cellution bioreactor system equiped with a specific Process Analytical Technology IT-infrastructure both for data management and for controlling the feed. The cultivation system is a CO product from the EuroTransBio project (# 08000041)._x000D_ _x000D_ Proof of Concept analyses of the biosimilar monoclonal antibody will be performed by Bioceros after single step purification by RIC._x000D_ _x000D_ Throughout the project, PharmaVize and Pat-Consultancy will manage the QbD approach, whereas PharmaVize will COly focus on the regulatory compliance of this development and on the transfer of the data obtained in licensing documentation (IMPD and CTD) and Pat-Consultancy will elaborate on the establishment of a process and product control strategy. Coen Beuvery (Pat-Consultancy) will also take full project management responsibility._x000D_

Acronym	SimiQbD (Reference Number: 5690)
Duration	01/11/2010 - 01/11/2012
Project Topic	The project proposal is dealing with the development of a biosimilar Mab up to the stage of proof of concept. We propose a typical QbD approach for the development of our biosimilar Mab as is described in the recently published ‘A-Mab: a Case Study in Bioprocess Development’.
Network	Eurostars
Call	Eurostars Cut-Off 4

Project partner

Number	Name	Role	Country
6	Bioceros BV	Coordinator	Netherlands
6	Bioceros BV	Coordinator	Netherlands
6	Lonza (Verviers)	Observer	Belgium
6	Pat-Consultancy	Observer	Netherlands
6	PharmaVize NV	Partner	Belgium
6	Research Institute for Chromatography	Partner	Belgium