Governing responsible nanomedical innovation – regulatory responses to emerging applications, health and environment concerns

Date: 9 & 10 September 2010
University of Twente, Enschede, Netherlands
Sabrina Lührs, Nupur Chowdhury* & Bärbel Dorbeck-Jung
Department of Legal and Economic Governance, School of Management and Governance Studies, University of Twente, Netherlands.

* Corresponding author: E-mail: n.chowdhury@utwente.nl , tel: +31 +31.53.489.5482, Fax: +31.53.489.2159, Full Mailing Address: University of Twente, School of Management and Governance, Legal and Economic Governance Studies, Ravelijn RA-2262, P.O. Box 217, NL-7500 AE Enschede.

Since the European Commission is committed to responsible nanotechnological development governance questions have been discussed intensively. At the heart of this discussion lies the problem of how to support beneficial nanotechnological development without neglecting health and environment risk concerns. Worldwide, nanomedicine is regarded as one of the most advanced sectors where high expectations on beneficial applications have been raised. Nanomedicine is a field where the University of Twente is developing high level expertise in science, product development and governance. This conference organized by Institute of Governance Studies (IGS), brought together the main stakeholders in this debate to get a perspective on nanomedical applications and their potential benefits (mainly in the field of therapeutics), health and environment concerns and their policy implications, and discuss concrete regulatory problems and lessons from European medical technology regulation. These lessons are embedded in a debate on soft regulation and governance methods that are at the forefront of nanotechnological regulation.

Nanotechnology Development and Risks: State of the Art

The conference was organized into five sessions over two days. The first session focused on setting the scene in terms of the variety of nanomedical product innovations currently underway, health and environment effects of nanoparticles and the issue of occupational health and safety. Prof. Vinod Subramaniam and Dr. Severine Le Gac, University of Twente (UT) gave an insight into the development of microfluidic devices (commonly known as lab-on-a-chip devices) in their laboratory, to be used as a platform for drug screening on membrane proteins. Following the process of protein misfolding can be useful in the early detection of Amyloid ß peptide, Alzheimer’s disease, Parkinson’s and cystic fibrosis, amongst others.

Dr. Wim de Jong, RIVM in the next presentation, underlined that safety concerns vis-à-vis nanoparticles arose, essentially given they can be of sizes similar to structures at the subcellular level and therefore (theoretically) could reach and interact with such structures. He also underlined that toxicity is calculated by multiplying dosage into exposure time – and gave the example that – even high intake of water at a short period of time could result in brain edema resulting in shock or coma. The existing problems in the safety evaluation of nanoparticles include; identification of nanomaterials (since the presence of coating and the crystal forms of the same materials), particle size and agglomeration, how do they absorb proteins and pharmacological availability (effect of nanoparticle size on tissue distribution and toxicokinetics). He underlined that there are different types of multi-walled carbon nanotubes (MWCNT) and that because it shares similar characteristics with blue or brown asbestos it does not necessarily mean that it behaves as asbestos. It is important to check for specific characteristics like rigidity, degradability and fibre length and perform proper safety evaluations to exclude this specific hazard association with a certain type of fibre. He advocated a case-by-case approach for risk assessment.

The next presentation was by Dr. Pieter van Broekhuizen, IVAM, University of Amsterdam and focused on workers safety. He stressed that non adoption of precautionary measures is accepting the state of the art – and in effect – working without a reliable risk assessment and on the other hand waiting for enough evidence is equal to a ban on development. The development of nano reference values as a tool to organizing a safe working place and the readiness in industry to use them voluntarily was discussed.

Regulatory and Ethics Governance

The second session focused on regulatory lessons from pharmaceutical and medical devices regulation and ethical aspects. Prof. Christa Altenstetter, CUNY criticized the misguided guidance for risk regulation of medical devices in the U.S. which is uncritically borrowed from drug regulation. An urgent need to develop scientific data in specific applications and device evaluation methods that are updated and transparent in their application were highlighted as missing pieces in nanomedicine regulation. The following presentation by Nupur Chowdhury, UT emphasized specific aspects of the current pharmaceutical regulatory regime in European Union – which are at crossroads owing to the development of nanomedicine. These include, the primary mode of action being the applicability criteria for determining whether a product is a medical device or a pharmaceutical, the operability of the risk-benefit balance analysis, procedures for centralized authorization or via mutual recognition. The results of the stakeholder survey suggests that, an upstream regulatory problem was a lack of definition of what constitutes nanomedicines and downstream, the lack of guidance on environmental impact assessment in the case of nanoparticles, is another problem. However a majority of stakeholders believed that there was unnecessary regulatory hype, the current evaluation criteria of risk-benefit balance were sufficient and that there was no need for a separate regulatory regime for nanomedicines. The final presentation of this session by Dr. Ineke Malsch, Malsch TechnoValuation and Dr. Kristian Hvidtfelt-Nielsen, Aarhus University, dwelt on the implications of nano-enabled human enhancement technologies for our self-understanding and concepts like health and disability.

Multiple Stakeholder Challenge

The multistakeholder panel discussion in the third session included representatives of companies, regulating bodies, European experts and civil society organizations and was chaired by Dr. Barbel Dorbeck-Jung, UT. Each speaker was invited to make a statement on the issue of regulation of nanomedicines, which was then commented by other speakers. Dr. Rob Slobbe, Philips Corporate Technologies and Dr. Richard Canady, earlier with the FDA, agreed that current regulatory regime is adequate, although there is a need for clearer standards and guidance for manufacturers. However Dr. Marga Jacobs, Leefmilieu, argued the need to examine and consider the environmental effects from the start (during the design phase of a new drug). Dr. Robert Geertsma, RIVM, contended that both the existing regulatory frameworks for medicines and medical devices is based on risk management, are perfectly adequate for nanomedical products. For borderline and combination products, the principal intended action of the product is the criterion used to decide on the relevant framework(s). In case of doubt, there will be no consequence for safety, quality, and efficacy, whichever decision is made. Dr. Brigitte Brake, BfArM and Dr. Hans Ovelgönne, Member of Committee for Advanced Therapies, EMA, agreed with this contention.

Innovative Governance Approaches

Day two started with the fourth session in which, Dr. Diana Bowman, University of Melbourne, Dr. René von Schomberg, DG Research, European Commission and Dr. Peter Hatto, Chair ISO-TC 229, CEN TC 352 and BSI NTI/1 discussed on the innovative approaches to regulatory governance of nanomedicine. She listed six kinds of regulatory triggers within the current regulatory regime viz; name (existing or new), volume, knowledge, conventional risk assessment protocols, R&D exemptions and international documents. Amendments to documents underpinning legislations – guidance and codes – should be considered as a first step. Overseeing compliance, enforcement and post-market monitoring were identified as necessary to ensure that there are no governance failures. Dr. Schomberg presented the Code of Conduct for Responsible Nanosciences and Nanotechnologies Research (CoC), adopted by the European Commission as an effective instrument for early intervention, especially in the context of knowledge deficits where legislation can be either too late or too early. The CoC is aimed at individual researchers, government bodies and organization in supporting their collective responsibility and promoting deliberation and dialogue. It is also a tool to steer innovation towards societal goals and ensure sustainability. The following presentatation by Dr. Hatto described the process of development of international standards in the ISO (International Organization for Standardization) especially with reference to workings of the Technical Committee 229 on nanotechnology standardization. He underlined that the process is based on a well established principle of consensus and these standards are primarily voluntary in nature.

Risk Regulation

In the fifth and final session, Ms. Tessa Fox (on behalf of Dr. Marjolein van Asselt and Prof. Ellen Vos, Maastricht University) and Prof. Arie Rip, UT spoke on risk regulation and governance of innovation. Ms. Fox, discussed the Collingridge dilemma of control of technology and made a plea for rethinking the role of science and expertise and the need for “uncertainty training”. Prof. Rip provided a narrative of the broader processes that resulted in the current preoccupation with risk regulation of nanotechnology. The hype about nanotechnology may be breaking down and Governments are now pushing nanoscientists to pay more attention to ‘grand challenges’ of society (health, energy, water, environment). He spoke about “waiting games” occurring in different product sectors. For instane in the nano-enabled drug delivery (“magic bullets”) is pushed by researchers but Big Pharma is not interested (or waits for further results). Organic [semi-conducting polymers] large-area electronics: interesting but unclear whether there will be a demand – because it is unclear what producers will develop (and the producers wait for signals from users). He supported, constructive technology assessment as a micro-approach to meso/macro changes in providing a breakthrough for waiting games – and allow for a variety of actors to improve strategies through interactions. In the context of nanomedicines, he suggested that it is important to disaggregate ‘nanomedicine’, avoid ‘magic bullet’ stories (as they might backfire) and link risk with innovation (not just mention benefits).

MESA+ - BIOS Visit

The conference ended with a practical insight into nanotechnology. To get a picture of work with nano particles a visit to MESA+, one of the largest nanotechnology research institutes in the world, especially to BIOS, the lab-on-a-chip group the participants were taken on a tour. The lab-on-a-chip group operates in the field of microfluidics and on lab-on-a-chip devices and it is part of MESA+. At BIOS PhD students showed their work. One works at nanowire measurement that DNA can be electrical detected. The goal of the research is the measurement of DNA hybridization on special biosensors which could be taken about 10 years when it will be successful implement on the market. BIOS is also involved in developing a platform for drug screening assays. The last shown research field was about super resolution imaging; where light is the core issue. The goal is to look at structures in more detail and to get a better image. It is done with a microscope; with this microscope a method based on repeated imaging and localization of single fluorophores can be developed.