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Regenerative medicine in Europe: political conflicts, economic biases, and legal loopholes. Alex Faulkner Centre for Global Health Policy University of Sussex firstname.lastname@example.org. Overview. Concepts Classification, stakeholders, interests
Centre for Global Health Policy
University of Sussex
-The mode of action conflicts
-The ‘ethical issues’ conflicts
CEO of World's Leading Regenerative Medicine Company, Organogenesis, Gives Keynote Address at World Congress of Regenerative Medicine in Germany.
5th annual World Stem Cells and Regenerative Medicine Conference 2010
Cloning and Regenerative Medicine News
Reprogramming a patient's eye cells may herald new treatments against degenerative disease (10/25/2009)
UK’s Life Science strategy 2011
Regulation – rules of engagement of ‘technological zones’ (A. Barry)
What does societal regulation do? - Performativity of law
- i.e. matching and linkage between a diversifying, innovative regulatable field and challenged set of regulatory frameworks and practices
R. Brownsword (2008) ‘So what does the world need now: reflections on regulating technologies’, In: R. Brownsword and K. Yeung (eds.). (2008) Regulating Technologies: Legal Futures, Regulatory Frames, and Technological Fixes.
Three dimensions of socioeconomic classification:1. confer identities on social actors (or objects), and imply social control
2. create social boundaries and signify social standing of actors (or objects)
3. involve political struggles between different interest groups; classification systems embody political power
Zhao W. (2005). Understanding classifications: Empirical evidence from the American and French wine industries. POETICS , 33, 3-4: 179-200.
- ‘Regenerative medicine clinical trials’
E.g. ‘cells as medicines’:
‘Regen: the industry responsible for cell-based therapies… universally recognised as an emerging new healthcare sector…’ C.Mason
Cell Therapy and RMAdvisory Group
138 primary firms and 49 secondary firms at the start of 2009
All allogeneic products - US firms
autologous products – all but one European.
50 firms adult stem cells, 20 hESCs
97 products - 88 skin, bone or cartilage.
European CommissionEnterprise - Biotechnology - Pharmaceuticals - Medical devices
Health & Consumers
European Parliament and committees
Council of Ministers (member states positions)
Donors; PatientsMedical professionalsCell/tissue banksScientists – developmental biology etc; scientific societiesBio-engineersHospitals, CharitiesCompanies
Human tissues and cells directive 2004 (TCD) –standards for quality & safety : supply, storage, processing, distribution..-voluntary donation
Human Tissue Authority in UK
‘regeneration of biological tissue through the use of cells, with the aid of supporting structures and/or biomolecules’ (EC SCMPMD, 2001)
autologous: national regulation
allogeneic: EU central regulation
‘the comparison of different entities according to a common metric’ (Espeland & Stevens 1998)
‘…process of making goods measurable and comparable…standardization of product categories …is a socially embedded driver of market evolution’ (Kai)
‘how the destruction of one gas in one place is made commensurate with emissions of a different gas in a different place…’ (MacKenzie – the ‘politics of market design’)
-K. Kai, Arbitrage and Commensuration as Socially Embedded Performativity. Paper presented at the American Sociological Association Annual Meeting, San Francisco, CA, August 8th, 2009.
-D. Mackenzie (2009) Making things the same: Gases, emission rights and the politics of carbon markets. Accounting, Organizations and Society 34 (3/4): 440.
Enterprise and IndustryDirectorate-General
BIO 2006 April 9-12, 2006
Genes, Cells and Tissues:
Georgette LALISDirector, European CommissionDG Enterprise & Industrygeorgette.email@example.com
The proposal does not affect the application of national legislation prohibiting or restricting the use of any specific type of human or animal cells, or the sale, supply or use of medicinal products containing, consisting of or derived from these cells.
Ref. : Article 28 of the proposal and Art. 2(1) of Dir. 2001/83/EC
Tissue engineering and cell therapy regulation mid-2000s Proposal 2.
HESCs and hybrids
Public health/medical advance
“Cells or tissues shall be considered engineered if they fulfil at least one of the following conditions:
‘… say a heart valve covered by cells. .. the main mode of action is…not the cells, it’s the valve itself. However the cells are there for a certain function but it might be secondary to the physical mode of action by the valve or by the artificial hip…’ (MHRA interview with medical device regulator, 2006).
‘what will be classed as an 'engineered' tissue, specifically the possibility that processes that have been traditionally applied to tissue allografts to render them safer, amenable to long term preservation or more biocompatible could be classed as 'engineering'’ (NBS Tissue Services–written response to EC Consultation, May 2005).
‘The Presidency has also suggested…all combined products containing viable cells or tissues should be considered ATMPs (…Members States’ positions on this): Support: Belgian, Estonian, Lithuanian, Hungarian, Portuguese and Slovenian delegations; Against: Danish, Spanish, French, Netherlands, Swedish and United Kingdomdelegations hold that the principal mode of action should be decisive.
(Health Council of Europe Working Party on Pharmaceuticals & Medical Devices, 2006)
‘(Impossible) to re-open discussion on all those different balances on … responsibilities of member states, of the Commission, related to good manufacturing practices, to Good Clinical Practice, for clinical trial conduct, to pharmacovigilance, of post-authorisation safety follow up’ (interview with EMEA, 2007).
EU’s “Advanced Therapy Medicinal Products” (ATMP) Regulation 2007 (REG/1394/2007/EC)
‘Suspension of allogeneic bone-marrow derived osteoblastic cells, intended for the treatment of non-union, delayed union or other fractures’
-Tissue engineered product, non-combined
Encapsulated cell based delivery system engineered to deliver human ciliary neurotrophic factor (CNTF) intraocularly after implantation. (reducing photoreceptor loss associated with degeneration of the cells of the retina)
Stabilising a sector / zone?
Harmonisation of states’ regulation
‘Loophole’ of hospital exemption?
Lack of incentive for hospital/academic sector
Complexity of regulatory system
A woundcare cell/TE therapy
‘This life-saving technique - taking a sample of unaffected skin, placing it on a mesh, and allowing the cells to reproduce and expand - has been in use for more than 10 years now with extremely good safety and efficacy records’
‘For us surgeons the use of human tissue engineered products has allowed us to give so many patients, over 8,000 in the last 15 years, renewed hope for a better quality of life. For regulators, however, the question was whether these products were medical devices or medicinal products..’ Wound/Burns clinician, Italy, Feb. 2013
‘it was decided to classify them under gene and cell therapy which essentially meant that the EMA would now be responsible for approving these products. The result: since that day in 2007 EMA gave more than 100 scientific advices, of which only 9 (!) resulted into a submission. Of these 9 submissions, only 2 (!) have been approved. And when it comes to my own practice, not a single one of the products that I have been using for decades with full satisfaction has been given approval. And moreover, since the 1st of January of this year, these products can no longer be made available to patients because they have not been granted approval.’ Wound/Burns surgeon, Italy, Feb. 2013 http://www.medtecheurope.org/blogposts
FDA – ‘medical device’
European Medicines Agency - ??? ATMP
“hospitals might be able to avoid complying with the provisions of the regulation, whereas industrial manufacturers of similar products would bear the obligations of compliance.., where hospitals are preparing products routinely, using an established process to create treatments for patients on a serial and routine basis, they too should have to comply with the provisions of the regulation” (Eucomed, 2006).
“To date, no stem-cell medicinal products have received marketing authorisation within the EU. However, it is still possible to gain access to stem-cell medicinal products under certain controlled conditions. These include taking part in clinical trials or compassionate-use programmes, or receiving a custom-made medicine as part of ‘hospital exemption”. (2010)
…“use of stem-cell medicinal products outside these controlled conditions may result not only in little or no benefit to patients, but could also be detrimental. This is because, outside these conditions, checks on the quality of these products may not have been carried out, and their safety and efficacy may not be properly assessed”. (EMA)
‘characterised viable autologous cartilage-forming cells expanded ex vivo expressing specific marker proteins’- classified as ‘tissue-engineered ATMP’
- Global cartilage/ACI industry
CellCoTec - A revolutionary approach to cartilage repair
Represents EU/EC/EP RM world-view:
Legislative Articles and non-legislative rationale
- Centralised ATMP route
- Orphan designation
- Compassionate use
- ‘Medical device’ – decellularised/acellular product/process
- Hospital exemption (‘a too large application of this exemption may discourage the application for marketing authorisations’).
–Cannot derive but can import hESClines(DE, IT);
–Allow procurement of hESC from supernumerary IVF embryos(CZ, DK, EL, FI, FR, NL, PT), and
–Allow somatic cell nuclear transfer(BE, ES, SE, UK);
–Embryo research legislation, not specifying hESC(HU, SI);
–No specific hESC research regulation(BG, CY, EE, IE, LU, LV, PT, RO; AT, LT, MT, PL, SK).
Source EGE Opinion 22
‘the politics of biotechnology at the EU was subordinated…to that of the member states. Basic questions about the acceptability of biotechnology’s products and the allowable forms of debate concerning them remained national in character’ (Jasanoff 2005: 280; cited in Kent,2012)
Biotechnology Directive 1998
If commercial exploitation offends ‘ordre public’ or morality – exclude from patentability:
- Cloning human beings
- Modifying germ line
- Use of human embryos for industrial or commercial purposes
-Extraction of neural precursor cells
Greenpeace challenge legality of patent 2004
- CJEU stem cells obtained at the blastocyst stage national decision
Letter of protest at Brustle case threat to stem cell funding in EU’s Horizon 2020 funding programme
“To maintain its global edge in this area of research, Europe must ensure all avenues of stem cell research continue to be financially supported, including through Horizon 2020.Europe’s strengths in this field present valuable opportunities to attract skilled scientists, biopharmaceutical companies and international investment in stem cell research to Europe, to drive the translation of basic research towards clinical benefits, and to influence the international agenda”.
Majority of Council remain in favour
Product regulation - ATMP biases, poorly aligned to sectoral interests
Property/patent regulation - material definitions (in hESC) are evolving and re-classifiable
Malleability and uncertainty of classification of RM materials, product definitions and modes of action
Political, economic and ethical struggles over boundary definitions
National and sectoral identities
- With real implications for future medicine, healthcare and global bioeconomies!
Faulkner A. (2009) Medical Technology into Healthcare and Society: a sociology of devices, innovation and governance, Basingstoke: Palgrave Macmillan.
Journal Special Issue Editorships
1.) Journal of Law and Society : Guest Editorship special issue: ‘Material Worlds: The Intersections of Law, Technology and Society’, (2012) vol 39 issue 1. (Also book by Wiley-Blackwell).
2. INNOVATION: the European Journal of Social Science Research :Guest-editorship special issue Steering Biomedicine: The Regulatory Dynamics of Therapeutic Technologies in Europe. October 2012.
Faulkner A. (2012) Commensuration and Proliferation: Similarity and Divergence in Law’s Shaping of Medical Technology.Law, Innovation and Technology, 4(2): 165–184.
Faulkner A. (2012) Law’s performativities: shaping the emergence of regenerative medicine through European Union legislation. Social Studies of Science
Faulkner, A. (2013). Medical Technology. In : Gabe J., Monaghan L. (eds.) Key Concepts in Medical Sociology, 2nd ed. Sage Publications.
Hogarth S, Hopkins M, Faulkner A. (2012) Personalized medicine: renewing the social science agenda. Personalized Medicine, 9, 2: 121-126
Mahalatchimy A, Rial-Sebbag E, Tournay V, Faulkner A. (2012) The legal landscape for Advanced Therapies: material and institutional implementation of European Union rules in France and the UK, in: Journal of Law and Society vol 39 issue 1. 131-149.Faulkner A, Lawless C, Lange B. (eds). Introduction: Material Worlds: intersections of law, science, technology and society. Journal of Law and Society, 39, 1:
Faulkner A. (2012) Tissue engineered technologies: regulatory pharmaceuticalisation in the European Union. In: Steering Biomedicine: regulatory dynamics of therapeutic technologies in Europe. Special Issue (ed. A. Faulkner) of INNOVATION: the European Journal of Social Science Research.
Faulkner A. (2011). Resisting the screening imperative: patienthood, populations and politics in prostate cancer detection technologies for the UK. Sociology of Health and Illness, Special Issue on Screening.
Salter B, Faulkner A. (2011). State strategies of governance in biomedical innovation: aligning conceptual approaches for understanding ‘Rising Powers’ in the global context. Globalization and Health, 7:3.
Faulkner, A. (2010) Trial, trial, trial again: reconstructing the gold standard in the science of prostate cancer detection. In: Will, C. & Moreira T. (eds). Medical Proofs/Social Experiments: clinical trials in context. Ashgate. pp 136-51.
Faulkner A. (2009) Regulatory policy as innovation: constructing rules of engagement of a technological zone for tissue engineering in the European Union, Research Policy, 38(4): 637-646.
Faulkner A, Geesink I, Kent, J, FitzPatrick D (2008) Tissue-engineered technologies: scientific biomedicine, frames of risk and regulatory regime-building in Europe, Science as Culture, 17, 2, 195-222.
Faulkner A, Kent J, Geesink I, Fitzpatrick D. (2006). Purity and the dangers of regenerative medicine: regulatory innovation of human tissue engineered technology. Social Science & Medicine, 63, 2277-88.
Brown, N.; Faulkner, A.; Kent, J; Michael, M. (2006). Regulating Hybrids: `Making a Mess' and `Cleaning Up' in Tissue Engineering and Transpecies Transplantation. Social Theory & Health, 4, 1, 1-24.
Kent, J., Faulkner, A., Geesink, I., & FitzPatrick, D. (2006). Towards Governance of Human Tissue Engineered Technologies in Europe: Framing the case for a new regulatory regime. Technological Forecasting and Social Change, 73, 41-60.
Kent J, Faulkner A. (2002). Regulating human implant technologies in Europe – understanding the new era in medical device regulation. Health, Risk & Society, 4,2, 190-209.
Faulkner A, Kent J. (2001). Innovation and regulation in human implant technologies: developing comparative approaches, Social Science and Medicine, 53, 895–913.