EMA s role & responsibility for the development of modern/advanced therapies Agenda Current regulatory picture Overall Regulatory framework New Committee at EMA Current Activities & Challenges Egbert Flory Section Tissue-Engineering & Somatic Cell Therapeutics 63225 Langen, Germany E-mail: floeg@pei.de Paul-Ehrlich-Institut Federal Agency for Vaccines & Biomedicines
Current overall regulatory picture (e.g. bioreactors Matrices, Scaffolds) Medicinal Products integrate Advanced Therapy Medicinal Products (ATMP) Tissue Engineering Cell Therapy Gene Therapy Cell-Based Medicinal Products (CBMP)
Advanced Therapy Medicinal Products Interdisciplinary medicinal products of high complexity, especially when combined with biomolecules/materials & chemical substances Highly science-driven & innovative manufacturing processes Often individualized and patient-specific medicinal products Usually developed by micro, small & medium-sized enterprises, universities and hospitals Limited market and high financial pressure Increasing number of these products are being tested in clinical trials
3Q 2010: EudraCT Clinical Trial Applications Somatic cell therapy MPs 3Q 2005 3Q 2006 3Q 2007 3Q 2008 3Q 2009 3Q 2010 cancer immunotherapy 3 23 45 70 92 112 cardio-vascular 4 17 31 44 47 54 skin/liver/lung/eye/diabetes/ intestine/bone TE 5 12 28 48 63 92 neurological 1 4 5 6 6 7 lymphohistiocytosis (HLH) 1 1 1 1 1 AIDS 1 1 1 1 1 infertility 1 1 1 1 1 vaccines 1 overall products (trials) 13 (25) 59 (73) 112 (132) 171 (213) 236 (329) 269 (375)
3Q 2010: EudraCT Clinical Trial Applications Gene therapy MPs 3Q 2005 3Q 2006 3Q 2007 3Q 2008 3Q 2009 3Q 2010 cancer 4 13 20 29 35 42 cardio-vascular 2 3 4 6 7 7 metabolic diseases 1 1 3 autoimmune diseases 1 2 2 4 6 7 HIV vaccine 2 2 2 7 7 7 infectious disease (HPV, chronic Hepatitis C) 1 2 5 6 neuronal 1 3 5 5 7 vaccines (monovalent, combi-) 2 3 5 6 6 overall products (trials) 9 (19) 23 (51) 35 (69) 59 (124) 75 (161) 85 (173)
ATMP Clinical Trial Applications within EU & Germany 3Q 2005 to 3Q 2010 trials 400 350 300 250 200 150 100 50 0 Gene Ther. EU Cell Ther. EU Gene Ther. DE Cell Ther. DE 2005 2006 2007 2008 2009 2010
Cell-based Medicinal Products (CBMP) 1) Isolation of target viable human cells (autologous oder allogeneic) allogeneic cell 2) Human cells undergoing a manufacturing process or used for not same essential function autologous cell 3) Re-Infusion of viable human cells, may be associated with non-cellular components biomolecules, chemical substances or combined with structural materials
Cell-based Medicinal Products CBMP are very heterogenous with regard to - origin & type of the cells - complexity of the product These products combine various aspects of medicine, cell and molecular biology, material science for the purpose of regenerating, repairing or replacing tissues Legislation of Advanced Therapies (EC1394/2007) is classifying most of these CBMP as Tissue-Engineered Products
Tissue-Engineered Products Cartilage repair Autologous chondrocyte transplantation (ACT) 1st & 2nd & 3 rd generation products Skin regeneration Different skin cells (keratinocytes, fibroblasts) in combination with a sheet-like matrices/scaffolds Acute wounds, diabetic foot skin ulcers Bone regeneration Osteoblasts or bone-marrow-derived stem cells combined with ceramic-based scaffolds or biomaterials Cardiovascular regeneration Stem cells for heart regeneration Engineered autologous/allogeneic blood vessels or heart valves Complete organ engineering Artificial liver Artificial engineered trachea
Tissue-Engineered Trachea The transplanted trachea. (Credit: Image courtesy of University of Bristol) Stem-cell seeded trachea Lancet (Nov. 2008) A patient who had severe tuberculosis: A team of researchers from European universities took a trachea from a deceased donor, removed its cells, leaving behind the extracellular structure, and re-seeded it utilising the patient's own mesenchymal stem cells. The bioengineered trachea provided the patient with a normally functioning airway.
Cell-Therapy Medicinal Products Liver repair Allogenic liver cell suspension for treatment of acute sepsis or inherited metabolic liver failure Immunotherapeutics CTLs or NK cell transfer for adoptive immuntherapy Cell-based therapeutic Vaccines Peptide-loaded DC used as tumor vaccines to induce immunity towards tumor-associated antigens Fused Tumor/DC hybrid cells
Agenda Current regulatory picture Overall Regulatory framework New Committee Current Activities & Challenges
The Regulatory framework Legislation relevant for all medicinal products Legislation relevant for all cell-based MP Technical Requirements Guidelines
The Regulatory framework Legislation relevant for all medicinal products Directive 2001/83/EC (Nov 2001) amended by 2009/120/EC (Jun 2009) Community code relating to all medicinal products for human use Requirements with a view to MA Regulation 726/2004 (Mar 2004) Centralized MA procedure via EMA Legislation relevant for all cell-based MP Technical Requirements Guidelines
The Regulatory framework Legislation relevant for all medicinal products Legislation relevant for all cell-based MP Directive 2001/83/EC (Nov 2001) amended by 2009/120/EC (Jun 2009) Community code relating to all medicinal products for human use Requirements with a view to MA Regulation 726/2004 (Mar 2004) Centralized MA procedure via EMA Regulation 1394/2007 on Advanced Therapy Medicinal Products Central licensing and requirements for ATMPs Directive 2004/23/EC (Mar 2004) Standards of quality and safety for donation, procurement, testing, processing, preservation, storage and distribution of human tissues/cells Technical Requirements Guidelines
The Regulatory framework Legislation relevant for all medicinal products Legislation relevant for all cell-based MP Directive 2001/83/EC (Nov 2001) amended by 2009/120/EC (Jun 2009) Community code relating to all medicinal products for human use Requirements with a view to MA Regulation 726/2004 (Mar 2004) Centralized MA procedure via EMA Regulation 1394/2007 on Advanced Therapy Medicinal Products Central licensing and requirements for ATMPs Directive 2004/23/EC (Mar 2004) Standards of quality and safety for donation, procurement, testing, processing, preservation, storage and distribution of human tissues/cells Technical Requirements Directive 2006/17/EC (Feb 2006) technical requirements for donation, procurement testing Directive 2006/86/EC (Oct 2006) traceability, notification of serious adverse reactions and events, technical requirements for coding, processing, preservation, storage distribution Guidelines
The Regulatory framework Legislation relevant for all medicinal products Legislation relevant for all cell-based MP Directive 2001/83/EC (Nov 2001) amended by 2009/120/EC (Jun 2009) Community code relating to all medicinal products for human use Requirements with a view to MA Regulation 726/2004 (Mar 2004) Centralized procedure via EMA Regulation 1394/2007 on Advanced Therapy Medicinal Products Central licensing and requirements for ATMPs Directive 2004/23/EC (Mar 2004) Standards of quality and safety for donation, procurement, testing, processing, preservation, storage and distribution of human tissues/cells Technical Requirements Directive 2006/17/EC (Feb 2006) technical requirements for donation, procurement testing Directive 2006/86/EC (Oct 2006) traceability, notification of serious adverse reactions and events, technical requirements for coding, processing, preservation, storage distribution Guidelines Guideline on human cell-based MPs (Sept. 2008) Contains quality, non-clinical, clinical aspects Concept paper on Risk-based approach for ATMP (2010) Reflection paper on human stem cells including HSC, MSC, ips and embryonic (2011)
Agenda Current regulatory picture Overall Regulatory framework New Committee (CAT) Current Activities & Challenges
THE CAT
WHY the CAT Evaluation of ATMPs requires very specific expertise - Beyond traditional pharmaceutical field - Covers areas bordering biotechnology - Medical device Composition shall ensure coverage of all relevant scientific areas
CAT Expertise Ethics 8% PhVig 5% Med Dev 5% surgery 1% Gene Therapy 19% Biotech Biotech 24% 24% Tissue Engineering 17% Cell Therapy 21%
Committee for Advanced Therapies (CAT) BWP SAWP CPWP 2 Representatives of Clinicians GTWP 22 Experts from national CA PhVWP PgWP CHMP CAT VWP EWP QWP 5 double members 2 Representatives of patient organisations BPWP SWP BMWP
CAT-CHMP assessment teams for ATMPs Two extended assessment teams responsible for review of ATMP MAA CAT Rapporteur CAT Co-Rapporteur CHMP Co-ordinator CHMP Co-ordinator Q/S/E/Phvg/ERA (ATMPs) experts Q/S/E/Phvg/ERA (ATMPs) experts
TASKS of CAT Draft opinion to CHMP on marketing authorisation of ATMPs Classification procedure: is a product an ATMP? Scientific recommendation from CAT Assist scientifically to develop guidelines on ATMPs Actively involved in all SA for ATMP (via SAWP) Certification procedure: Q/N-C review, for ATMP only CAT opinion EMA certification
Objective of Certification Procedure Stand alone evaluation procedure Not directly binding for future MAA or Clinical trial application (CTA) Certificate will not replace any data to be submitted in MAA or CTA
SCOPE of Certification Procedure Scientific evaluation of manufacturing / non-clinical data generated by an SME during the development of an ATMP But not on a full Module 3 / 4 CAT evaluates compliance with scientific and technical requirements of Annex I Resulting in a Certificate Only certification of those parts / studies that are performed/finalised in line with scientific standards for MAA
SCOPE of Certification Procedure No assessment of benefit/risk No statements on appropriateness to enter into clinical trials No prospective statements pertaining to the further development of the product (that is the role of Scientific Advice) Timing of submission: Applicant can submit at any stage of development
Agenda Current regulatory picture Overall Regulatory framework New Committee (CAT) Current Activities & Challenges
Reflection paper on stem cell-based medicinal products Concept paper on the development of a guideline on the risk-based approach
CAT Statement April 2010
Thank you for your attention Paul-Ehrlich-Institut Federal Agency for Vaccines & Biomedicines