Are regulators up to speed to address the challenges of biotechnological m edicinal products? The CAT W ork program m e 2 0 1 0 -2 0 1 5 Regulatory Science: Are regulators leaders or follow ers? European Medicines Agency 1 5 Decem ber 2 0 1 0 Dr Christian K Schneider, MD Committee for Advanced Therapies (CAT), EMA, London Committee for Medicinal Products for Human Use (CHMP), EMA, London Paul-Ehrlich-Institut (PEI), Germany An agency of the European Union
Starting with thanks… Lucia D‘Apote, PhD (EMA) Patrick Celis, PhD (EMA) Olga Oliver-Diaz (EMA) 2 Christian Schneider - CAT workprogramme- CHMP December 2010
Complexity of biotechnological products Insulin Aspirin 5 700 Daltons 180 Daltons Monoclonal antibody 150 000 Daltons Coagulation Factor VIII 280 000 Daltons 3 Christian Schneider - CAT workprogramme- CHMP December 2010 www.laborjournal.de www.wikipedia.org
Advanced therapies and their challenges Somatic cell therapy Tissue engineering Gene therapy medicinal products products medicinal products Genetically modified cells www.heartandmetabolism.org http://www.cbte.group.shef.ac.uk/ Nat Biotechnol 2005, 23(7) 4 Christian Schneider - CAT workprogramme- CHMP December 2010
Complexity of Advanced Therapies monoclonal antibody 5 Christian Schneider - CAT workprogramme- CHMP December 2010 B cell budding viruses www.aecom.yu.edu/aif/gallery/sem/sem.htm
Intracellular MAPK signaling signaling pathways Intracellular MAPK pathways stress factors mitogens Enviroment factors, inflammatory cytokines, UV-light, stimuli Cell adhesion, growth and oxidative stress, osmolarity shock differentiation factors P Ras P G protein cytoplasm MAPKKK MEKK Raf-1 TAK 1 1-3 Thr P MAPKK Ser P Thr MEK 1 P Thr Thr MKK 4 MKK 3 P P MEK 2 Ser P Ser Ser MKK 7 MKK 6 P P Thr P MAPK Tyr P ERK 1 Thr SAPK α P / JNK 1 Thr Thr P P p38 ERK 2 Tyr P SAPK β / JNK 2 Tyr P Tyr P Thr P Transcription factors Ser P nucleus biological responsive cellular genes 6 Christian Schneider - CAT workprogramme- CHMP December 2010 response E. Flory, PEI
Complexity of signalling Overlap and location of positive and negative modulators of NFk-B signalling identified in a cell-based screen within the T-cell receptor signaling pathway Halsey et al, Genome Biology 2007 7 Christian Schneider - CAT workprogramme- CHMP December 2010
Challenges with cell-based products Cells are complex systems • Cells are dependent on their (micro-) environment • Cells are reactive to their environment • Cell cultures can become heterogeneous • Cells might de-differentiate (e.g. during longer cell culture) • Cells might migrate („biodistribution“) • Cells are fragile and (sometimes) mortal => Regulatory consequences: √ Need for adequate characterization √ but also necessity to accept limitations 8 Christian Schneider - CAT workprogramme- CHMP December 2010
The ATMP Regulation Com m ittee for for Advanced Advanced Therapies Therapies Com m ittee � New Scientific Arena � Expertise � Beyond Traditional � Research ► Lack of funds and costly investments ► Market (specific and small) ► Regulatory barriers 9 9 Christian Schneider - CAT workprogramme- CHMP December 2010
Com m ittee for for Advanced Advanced Therapies Therapies Com m ittee W hy a w ork program m e? EMA is a key player in the successful im plem entation of ATMP legislation ► A shared vision to address challenges of ATMPs ► Being empowered to take decisions means taking responsibilities and learn balance 10 Christian Schneider - CAT workprogramme- CHMP December 2010
Com m ittee for for Advanced Advanced Therapies Therapies Com m ittee W hy a w ork program m e? ► Understand the environment ► Provide adequate tools to overcome barriers to translation ► Guidelines in line with scientific progress Is it the product that has to stretch to the guideline or is it the guideline that has to be realistic for the product? 11 Christian Schneider - CAT workprogramme- CHMP December 2010
Challenge: Products legally on the market 12 Christian Schneider - CAT workprogramme- CHMP December 2010
„I n God w e trust, the rest bring data!“ W. Edwards Deming Pioneer in Quality Philosophy, W. Edwards Deming is widely held to have been one of the leaders who helped create the Total Quality Movement . Deming’s 14 points and his book “Out of the Crisis” are key documents in the development of Quality Systems for Business management. Dr. Deming is best known for his revolution in the quality and economic productions in Japan where from 1950 onward he taught top management and engineers, methods for management of quality. These teachings dramatically altered the economy of Japan. In recognition of his contributions the Union of Japanese Science and Engineering (JUSE) instituted the annual Deming prizes for achievement in quality and dependability of product. http://www.resourcesystemsconsulting.com/blog/reference/glossary 13 Christian Schneider - CAT workprogramme- CHMP December 2010
Efficacy data (Marketing ≠ Efficacy!) („Experience“ ≠ Proof of efficacy!) Which data can be used? How to deal with claims like „No reports on serious adverse events so far, so a very well tolerated and safe product“? 14 Christian Schneider - CAT workprogramme- CHMP December 2010
Objective 1 ► To successfully respond to im plem entation of the provisions of Article 2 9 of Regulation ( EC) 1 3 9 4 / 2 0 0 7 : assessm ent of products legally on the EU m arket Know the num ber and kind of products legally on EU m arket CAT Reflect on the criteria for MAA assessm ent Proactive dialogue w ith potential applicants and MSs Developers Report on the experience to EC and MSs in 2 0 1 0 -2 0 1 1 15 Christian Schneider - CAT workprogramme- CHMP December 2010
Objective 2 ► To facilitate developm ent of ATMP and access to registration procedure B) Strengthen dialogue w ith stakeholders: • Draft a structured work programme tailor-made for the specific needs of CAT different parties (industry, SMEs, Academia, research groups, patients’ groups). • Increase the list of CAT I nterested Parties • Engage in dialogue with charity foundations and trusts concerning products they are developing . Developers • Organise a joint conference on ATMPs involving EMA/ CAT, EFPIA, EBE, EUROPABIO, Learned Societies to share clinical, scientific and regulatory expertise in the field for the benefit of all stakeholders 16 16 Christian Schneider - CAT workprogramme- CHMP December 2010
Objective 3 ► Prom ote the use of available regulatory procedures and introduce potential im provem ents Provide regular tutorial training/ w orkshop for all stakeholders ( including assessors, inspectors) CAT Developing an European training and education platform for SMEs and Academ ia Dedicated assistance for ATMP certification subm issions Developers 17 Christian Schneider - CAT workprogramme- CHMP December 2010
Objective 4 ► To explore possibilities offered by the regulatory procedures to the ATMP field ( by im proving existing procedures and reflecting on alternative procedures) Fast track evaluation? Extend incentives for SMEs to academ ia, hospitals, trusts and sm all research groups? CAT Because the science is evolving fast, on regular basis to screen system to identify potential changes required ( and then engage in dialogue w ith the European Com m ission) Developers Appropriate use of follow -up efficacy system 18 Christian Schneider - CAT workprogramme- CHMP December 2010
Objective 5 ► Foster innovation Dialogue w ith EC DG Research CAT Prom ote allocation of funds for ATMP research Reinforce contact w ith Developers leaders of EU projects on ATMP 19 Christian Schneider - CAT workprogramme- CHMP December 2010
Objective 6 ► Prom ote access and availability to ATMP for EU patients Cooperation w ith CTFG CAT Dialogue w ith NCA on ‘hospital exem ption’ Encourage developm ent of ATMPs for unm et m edical needs w ithout alternative treatm ents. Developers 20 Christian Schneider - CAT workprogramme- CHMP December 2010
The CAT as an open-minded scientific player Lancet 376(9740):514 Nat Rev Drug Discov 9(3):195-201. 21 Christian Schneider - CAT workprogramme- CHMP December 2010
Holistic view: Step back and look at the entire picture Francis Bacon Francis Bacon Self portrait Portrait (1971) (1979) 22 Christian Schneider - CAT workprogramme- CHMP December 2010
…and closing w ith thanks CAT Developers Yes, w e are up to speed to address the challenges of Advanced therapies m edicinal products – the EMA has created an innovative environm ent! 23 Christian Schneider - CAT workprogramme- CHMP December 2010
Recommend
More recommend
