**EPC CONFERENCE**

***Emerging biotechnology applications: EU, US and global regulatory
perspectives***

4-5 December 2005

Lille (France)

**[REPORT]{.underline}**

**[1. Background]{.smallcaps}**

In collaboration with the US Mission to the European Union and the
European Commission, the European Policy Centre organised a two-day
conference on *"Emerging biotechnology applications: EU, US, and global
regulatory perspectives"* on 4 and 5 December 2005 in Lille, France.

Within the framework of its Better Regulation Programme, the EPC has
contributed to increasing the level of convergence of regulations at the
international level in general, and between the EU and US in particular.
This conference was part of this programme and aimed to promote
transatlantic regulatory convergence.

The conference was chaired by Stanley Crossick, Founding Chairman of the
EPC, and this report was written by Richard Meads, the Rapporteur of the
EPC's Risk Forum. The event was held under Chatham House Rules.

**[2. Objectives]{.smallcaps}**

The conference focused on managing the risks and benefits from new and
emerging applications of modern biotechnology in the EU and US. Its
principal objectives were:

-   To improve mutual understanding of the regulatory treatment of new
    and emerging biotechnology in the EU and US;

-   To identify areas where approaches are similar and where they are
    different;

-   To explore forward-looking options for enhanced regulatory
    convergence in the main biotechnology sectors ('white', 'red', and
    'green').

**[3. Participants]{.smallcaps}**

Nearly 50 experts from Europe and the US attended the conference. A wide
range of organisations were represented, including government services,
businesses, non-governmental organisations (NGOs), academia, and related
professions. The attendance list is included as an annex to this report.

**[4. Welcome to the Conference]{.smallcaps}**

In his opening remarks, EPC Founding Chairman **Stanley Crossick**
highlighted the importance of the objectives of the event and the extent
of the EPC's support for transatlantic regulatory convergence. Over a
period of nearly ten years, the EPC has organised 15 conferences on this
issue.

This event built on the 2004 EU-US conference on biotechnology organised
by the EPC, which was held in Perugia, Italy, and identified a number of
issues of relevance to the future regulation of biotechnology in the US
and EU. Specifically:

-   Differences in regulatory approach are strongly influenced by
    different constitutional and regulatory cultures;

-   The US is characterised by high levels of public trust in regulators
    but a lighter touch for federal government, leaving more to market
    forces and the courts to enforce compliance;

-   Traditions and histories influence regulatory approaches, especially
    in relation to food, agriculture, and the food chain;

-   In Europe, citizens may, in some areas, be more fearful of change
    than in the US;

-   Amongst citizens in the Atlantic area, but especially in the EU,
    there is a lack of understanding of the nature of risk and that a
    risk-free society is not possible;

-   All stakeholders need to communicate responsibly and citizens should
    have the opportunity to make informed choices, whenever possible;

-   The politicisation of science should be avoided.

**[5.]{.smallcaps} Keynote speeches**

**Robert Madelin**, Director-General, Health and Consumer Protection
Directorate-General, European Commission, argued that there is a need to
connect the regulatory framework for biotechnology with wider regulatory
trends, and to try to avoid seeing biotechnology as being unique.

Moreover, it is essential to recognise that promoting the development
and diffusion of modern biotechnology depends on more than the design of
the regulatory framework. Action is also needed to overcome the lack of
risk capital for biotechnology investments in Europe and to ensure
adequate public support for relevant science. In recognition of this
more complex policy challenge, there has been an EU-wide strategy for
biotechnology since 2002. A wide range of policy initiatives have also
been initiated by the EU's Member States in the last ten years.

However, alongside these initiatives, Member States have also created
regulatory barriers, most notably through decisions by a number of them
to reject recommendations from the Commission and its agencies to
approve "green biotechnology" (agricultural) products. Mr.Madelin
explained that this was not a problem confined solely to biotechnology.
Member States had, through the EU's comitology process, also rejected
Commission recommendations in other areas, such as food additives.

The Director-General remained sceptical about the extent to which the
Union could be characterised as being "anti-science" or the US as
"pro-science", arguing that most EU Member States were attempting to
build up science-based regulatory systems.

He said there were a number of things that regulators and stakeholders
could do to establish more effective and credible science-based
regulatory systems. Science should be transparent and its findings made
more understandable to citizens. Issues need to be addressed
holistically and all concerns (including ethics, science, and economics)
understood. This is of particular importance for "green biotechnology".
Industry too has a role to play. It needs to recognise the concerns of
citizens and take these into account in its investment decisions. Risk
management decisions take a wide range of factors into account, and are
not solely determined by science.

Finally, Mr. Madelin identified a number of steps that could be taken to
strengthen regulatory convergence between the EU and the US. Better
links are needed at the operational level, including the creation of a
network of risk assessors. This could help foster greater transatlantic
understanding of risk assessment methodologies.

**Madelyn Spirnak**, Senior Advisor for Biotechnology, US Department of
State, highlighted the benefits that modern biotechnology has brought to
agriculture. After nearly ten years of commercial planting, more than
eight million farmers in 17 countries grow biotech crops on over 200
million acres. Whilst the US remains the largest grower, 90% of users of
agricultural biotechnology are in developing countries. This growth has
been achieved, argued Ms. Spirnak, without any reliable documented harm
to human or animal health. Indeed, the use of biotech crop has cut
pesticide use, reduced greenhouse gases and created additional income
for farmers.

In the US, the regulatory system is science-based and makes use of
rigorous risk assessment. It focuses on risk rather than technologies,
and assumes that biotechnology does not pose any intrinsic risks. This
facilitates the development and use of agricultural biotechnology,
protects citizens and creates consumer confidence. Today, more than 25%
of all processed foods consumed in the US contain ingredients from
transgenic crops.

Ms. Spirnak explained how the US was sharing its knowledge of
agricultural biotechnology with developing countries. There is growing
regional cooperation through organisations such as the APEC High-level
Dialogue on Agricultural Biotechnology.\
The US government also supports policy-makers in developing countries
through capacity- building programmes. Some internationally-led NGOs
have opposed this, but their attempts to persuade African governments to
adopt a more precautionary approach have been rejected, because of the
importance of agriculture in many African economies.

There is, Ms. Spirnak argued, considerable convergence between the EU
and US policies for supporting the use of biotechnology in developing
countries. The two, for example, have a shared understanding of the
potential economic gains from the adoption of transgenic crops in
developing countries. But there are also differences in approach. She
said the EU needed to recognise the potential negative impact on
developing countries of the perceived resistance of EU consumers and
regulators to transgenic crops.

Only five agricultural biotechnology products have been approved by the
EU since the mid-1990s, and Member States remain able to ban them
despite the evidence of scientific risk assessments and European Court
of Justice decisions. There is a risk that this will, over time, make
the EU a less attractive location for investments in biotechnology, as
well as leading to higher prices for meat and processed foods.

**Discussion**

Participants considered that public trust in regulators was a critical
pre-condition for building consumer confidence in biotechnology, and
argued that more effort was needed to improve risk communication.

Biotechnology in general, and agricultural biotechnology in particular,
highlight important structural characteristics of the EU's approach
towards implementing framework legislation.

Final implementation decisions about individual products or their uses
are made using the comitology process. This is the risk management phase
and normally takes place after a science-based risk assessment, often
undertaken by one of the EU's new science-based agencies. Comitology
involves the Member States meeting together to make the final decision
and, as such, is a political process. This weakens the link between
science and regulatory outcome and, because differing views amongst
Member States sometimes produce unpredictable outcomes, leads to a lack
of regulatory certainty. Over time, investors take account of such
uncertainty and make changes in the allocation of capital. Lack of
regulatory predictability increases the risks involved in developing new
biotechnology products because it raises the overall risk profile of a
project at a point when other factors (such as market potential and
science) have become less uncertain.

Participants suggested the EU's comitology process could be reformed in
a number of ways. More powers could be delegated to the Member States or
to the Commission. Greater delegation to Member States could help
increase transparency and accountability, but would fragment the Single
Market. They also agreed that public concern about transgenic crops is a
reality in the EU and must be recognised by investors. One cause is the
lack of recognisable benefits for consumers; another is the association
with food.

**[6.]{.smallcaps} Regulating "red" biotechnology: maximising benefits
and managing safety for new biomedical developments and applications**

**Background**

Modern biotechnology is one of the most important enabling technologies
used by the global pharmaceutical industry. Known as "red
biotechnology", it provides the basis for new and improved therapeutic
products, and is used extensively in drug development, drug production
and diagnostics.

More than 160 biopharmaceutical products have already been approved to
treat or help prevent heart attacks, strokes, multiple sclerosis,
leukaemia, hepatitis, rheumatoid arthritis, breast cancer, diabetes,
congestive heart failure, lymphoma, kidney cancer, cystic fibrosis, and
other diseases. Over 250 million patients worldwide have benefited from
bio-pharmaceutical products, and modern biotechnology provides more than
half of the new compounds now in clinical trials.

Future application of modern biotechnology in the pharmaceutical sector
may have the potential to meet unmet needs, to tailor medical
treatments, and to prevent and better diagnose disease. However, ethical
and safety concerns surround some new applications.

**Professor Christopher-Paul Milne**, Assistant Director, Tufts Center
for the Study of Drug Development, Tufts University, USA, who moderated
this session, highlighted the growing importance of biotechnology in
drug development. Much of the investment in these technologies came, he
explained from large pharmaceutical companies ("big pharma"), especially
in the US. At the same time, the drug discovery 'productivity' of large
pharmaceutical companies has fallen.

The reasons for this are unclear. One explanation is that this has been
a temporary phenomenon: others see the trend as structural, and caused,
in part, by the US regulatory system failing to keep up with drug
discovery technologies. Another concern is that the 'promise' of
biotechnology has not been met, with its impact primarily confined to
improvements in the R&D process.

There are, Professor Milne explained, emerging concerns about the
potential safety of new pharmaceuticals. There has been a slight upward
trend in product withdrawals and, more importantly, because of biotech
and other improvements in drug discovery techniques, companies have more
clinical targets but fewer references for each target.

**European perspective**

**Dr. Nils Behrndt**, Deputy Head of Unit, Enterprise and Industry
Directorate-General, European Commission, argued that there are two
sides to the debate about future applications of biotechnology to human
health. On one side, there are ideas that promise major improvements in
quality of life and reductions in disease and premature deaths. But
these are counter-balanced by concerns about safety and ethics. The
future evolution of 'red' biotechnology in the Union will, he suggested,
be influenced by the actions of wide range of actors, including
industry, EU institutions, citizens and the Member States. A key concern
at EU-level is striking an appropriate balance between promoting
competitiveness and protecting public health. Ideally, these goals
should not be antithetical.

Concerns about the safety of future biotech-based pharmaceuticals can be
overcome, Dr. Behrndt argued, through a number of different strategies.
One option (a passive approach) is to increase the number of clinical
trials; another (more 'active') strategy involves greater use of new
technologies such as pharmaco-genetics.

The EU's legal framework for 'red' biotechnology has its origins in the
1960s, although major improvements have been made in the last decade.
Recent changes include improved new pre-market authorisation processes
('centralised' process and the European Medicines Agency - EMEA -- an EU
agency for science-based risk assessment of new pharmaceuticals);
improved intellectual property protection; an Orphan Drug regulation;
new proposals to regulate advanced therapies; and guidelines for the
development and testing of bio-similars (generic-type copies of
bio-pharmaceuticals). In many respects, these changes mirror those that
have occurred in the US, although the EU's guidelines for bio-similars
are more developed than those in the US.

The EU's Orphan Drug rules, for example, are similar to those in place
in the US and provide incentives to develop products for small markets.
More than 300 products have been designated as 'orphan' products, over
20 authorisations have been granted and there has been an increase in
relevant R&D.

An emerging issue in the EU is the regulation of advanced therapies.
Many of these are, as Dr. Behrndt explained, based on modern biotech,
and include technologies such as tissue-engineered products, gene and
cell therapies. Ethical concerns surround some applications, and there
are gaps and inconsistencies in the EU's regulatory framework.

Dr Behrndt argued that there was a "regulatory gap" that threatened to
undermine public confidence and investment. In response, the Union has
developed new legislation providing a stable, clear, transparent
procedure, involving the EMEA, centralised\
pre-market assessment, and post-marketing controls. But, in a change
from the EU's traditional approach, Member States will retain the right
to refuse community marketing authorisations if they have ethical
concerns - a political compromise that recognises the importance of
ethical issues in this area.

**US perspective**

**Dr. Eric Flamm**, Senior Science Policy Advisor, Office of the
Commissioner, US Food and Drug Administration (FDA), explained that in
the US there is, generally, no special regulatory focus on
biotechnology. As a general rule, US regulators focus solely on science
and risks, rather than technologies.

Within the FDA, there is recognition of declining drug company
productivity, falling numbers of new products, and the need to exploit
changes in drug development technologies. Hence the decision to set up
the Critical Path Initiative (CPI). This programme attempts to modernise
the techniques and methods used to evaluate safety, efficacy and quality
of medical products as they move from product selection and design to
mass manufacture. CPI aims to make use of biomedical discoveries, and
focuses on clinical trials and manufacturing.

New regulatory approaches are also being developed to assess the risks
of gene therapy. Threats to safety posed by these technologies have been
highlighted by a number of\
well-known incidents. So far, the FDA has examined each new gene therapy
on its merits, although a range of special safety and ethical
considerations have been identified. These include toxicity risks,
potential for uncontrolled heritable changes, and possible spread into
the environment. New risk evaluation procedures have been developed. The
greater consideration of ethical factors in this area illustrates some
convergence with the approach taken by the EU to regulate similar
technologies.

Finally, Dr. Flamm explained the US approach to regulating
"bio-similars". Unlike the EMEA, the FDA has yet to issue guidelines for
assessing these products. It is unclear, argued Dr. Flamm, whether safe
bio-similars can be placed on the market if they have not passed through
a complete set of clinical trials and there are major concerns about the
complexity of production of such products.

**Discussion**

Participants recognised the global lead taken by the EMEA to provide a
regulatory framework for licensing bio-similars. The new guidelines
provide for a case-by-case assessment and enable assessors to call for
additional safety or efficacy data if appropriate.

It is, however, misleading to describe bio-similars as generics: the
production of biopharmaceuticals poses safety and efficacy questions
because of the complexities of the manufacturing processes. In the US,
the FDA will not grant generic status to a product unless it can
demonstrate equivalence.

Use of pharmaco-genomics will permit the development of drugs targeted
at small\
sub-groups within the wider population. This could pose ethical issues,
especially if such groups are defined on the basis of characteristics
such as race. Evidence from the US and the EU suggests ethical issues
are becoming increasingly important in influencing the overall
regulatory framework for "red" biotechnology.

Trust issues will also become more important for regulators on both
sides of the Atlantic as biotech-based technologies create new
opportunities and concerns in healthcare. Public concerns about ethics
and safety are important determinants of trust and the regulatory
framework. Public officials and companies need to become more aware of
the causes of negative risk perception, including issues such as
'outrage', 'dread', and stigma'. One way of improving public trust could
be to increase investment in post-marketing surveillance. Business, it
was pointed out, can help in this area.

Perceptions of the risk-benefit balance of different biotech
applications appear to have an impact on the political response to new
technologies by the EU's Member States. So far, it was suggested,
life-saving medicines have been regarded, in general, as having a
positive balance, whereas GM foods have not. This typology may change as
ethical concerns become more important. Negative views about "green"
biotechnology in some EU Member States may erode public support for new
biotechnology applications in human healthcare.

7\. Regulating "white" biotechnology: industrial applications,
processes, product performance, and environmental clean-up

# Background

"White" biotechnology, also known as industrial biotechnology, describes
the use of micro-organisms and enzymes to produce goods and services,
and to remediate environmental damage. It is the application of modern
biotechnology for the sustainable and eco-efficient industrial
production of chemicals, materials, and energy. It encompasses the use
of biorenewables for feedstocks; the application of bioprocesses for
production; and the development of bioproducts for markets.

Although successfully established in areas as diverse as antibiotics,
vitamins, animal feed, starch, food and drink, and detergents, the use
of industrial biotechnology is still in its infancy. Future applications
could transform conventional processes and improve\
eco-efficiency in sectors such as energy, pulp and paper, chemicals,
textiles, leather, metals, minerals, and waste treatment. White
biotechnology provides the basis for cutting energy inputs, reducing
waste and improving cost efficiency, quality and yields. It can also
facilitate the use of a wide range of sustainable raw materials.

But there are also concerns about the use of these technologies. There
are fears that, in some cases, using genetically-modified (GM) enzymes
in production may lead to GM materials being present in final products,
for example. It is also argued that the products of GM-based processing
aids or GM-enhanced production processes should be clearly labelled, so
as to enhance consumer choice.

**Professor Wim Soetart**, Laboratory for Industrial Microbiology and
Biocatalysis, Department of Biochemical and Microbial Technology, Ghent
University, Belgium, moderated this session.

**European Perspective**

**Mark Cantley,** Adviser for Biotechnology, Agriculture and Food,
Research Directorate-General, European Commission, said the Commission
supports the increased use of "white" biotechnology and is aware of its
potential environmental benefits. There are, he argued, a wide range of
potential applications of these new technologies, including improved
crops, enhanced production processes and bio-refineries. A biorefinery,
for example, offers the potential to utilise a portfolio of chemical,
thermal and biological processing tools to convert whole crops into
fuels, chemicals, and materials.

Mr. Cantley argued that current and future regulation of "white"
biotechnology in the EU is likely to be influenced by a range of
factors. These include the EU's existing biotechnology-relevant
legislation, its Precautionary Principle and the nature of the
application. Under existing EU rules, for example, regulation could be
greatest for uses that involve modified crops or the food chain, because
of the EU's biotech-specific deliberate release, and traceability and
labelling legislation. Uses that are confined to processing plants and
that do not involve food could be subject to fewer rules, although they
would need to comply with the EU's contained release legislation.

The Union, in its life sciences and biotechnology strategy issued in
2002, recognised the need to update its biotech-specific regulatory
framework. Possible areas for improvement identified include procedures
for authorising the deliberate release of GMOs.

Yet the future application of EU regulation for "white" biotechnology
remains unclear. In part, this is due to evolution of technology. But it
is also linked to the potential future application of the EU's
Precautionary Principle.

In 2000, the Commission set out guidelines for the application of the
Precautionary Principle, a risk management principle embedded in the EU
Treaty. These guidelines require measures based on the precautionary
principle to be proportional,\
non-discriminatory, consistent, based on an examination of potential
benefits and costs, and subject to review. Moreover, measures should be
capable of assigning responsibility for producing the scientific
evidence necessary for a more comprehensive risk assessment. However,
said Mr. Cantley, the guidelines have not been followed in all cases,
leading to uncertainty about future application.

He also reminded participants that debates about the regulation of
biotechnology take place within a global context. Recent global
initiatives include, for example, the Biodiversity Convention and
Cartagena Protocol. These too will influence the EU's future regulation
of "white" biotech applications.

Finally, the regulation of "white" biotechnology applications in the EU
will be influenced by a wide range of non-scientific factors. There are
several communities in public policy - including scientific, legal,
economic, political and ethical communities - and each of these will
play in role in shaping the regulation of "white" biotechnology in the
EU.

**US perspective**

**Dr. Flora Chow**, Senior Chemist, Office of Pollution Prevention and
Toxics, US Environmental Protection Agency (EPA), said that in the US,
the EPA manages the risks posed by new micro-organisms (a form of
"white" biotechnology) through the provisions of the Toxic Substances
Control Act (TSCA).

Uses of biotech regulated under the TSCA include the development and
release of new GM industrial or speciality enzymes, and bioremediation.
The development of new\
micro-organisms must be notified to the EPA using the procedures
established for new chemical substances. These include exemptions on the
basis of risk or if uses remain experimental.

The EPA has nearly ten years experience of regulating micro-organisms,
and, as a result, has built up an understanding of the risks they pose.
These include toxigenicity, pathogenicity, fugitive releases from closed
systems, unintended release and gene transfer from environmental
releases. In response, the EPA assesses the risks posed by new
micro-organisms on a case-by-case basis and, where necessary, takes
action to limit their use. The EPA will also consider taking action if
petitioned by stakeholders. Restrictions have, for example, been
introduced to protect vulnerable population groups.

Dr. Chow said the EPA had also become aware of some of the "risk-risk"
issues that surround applications of "white" biotechnology.
Increasingly, regulatory decision-making seeks to take these factors
into account. In a recent example, a new GM enzyme posed unknown risks
to human health and the environment, but provided major opportunities to
reduce the use of traditional chemicals in oil recovery operations.
Regulators faced the need to consider reduction of a known risk
(exposure to chemicals) with possible new, additional risks. This is a
more complex decision-making environment for risk managers.

Reforms to the regulatory requirements for "white" biotechnology are
being considered by the EPA. More micro-organisms may be included within
the exemptions set out in TSCA, but manufacturers will be required to
demonstrate that the new materials "will not present" an unreasonable
risk, and that conditions for physical containment and\
record-keeping will be met. Dr. Chow said these changes would, if
introduced, protect public health whilst also strengthening incentives
for the greater use of "white" biotechnology in the US.

**Discussion**

Participants highlighted a number of differences between the US and EU
approach to the regulation of "white" biotechnology.

In the US, enzymes and micro-organisms are regulated as chemicals; there
is no biotech-specific regulation. The focus is on risk, not technology.
This provides a high level of regulatory predictability. In contrast,
the EU has focused on developing technology-specific regulations. This
leads, potentially, to problems for users of "white" biotechnology.

Within the EU, the greatest restrictions are placed on deliberate
release of "white" biotech or uses in food production. Whilst the
contained release controls appear to work well, there are considerable
concerns about the potential application of the deliberate release, and
food-related, biotech directives to "white" biotech. Boundaries between
'contained' and 'deliberate' release are, for example, difficult to
define, and implementation of the relevant EU directives takes place at
Member-State level, leading to uncertainty and inconsistency. The
Union's existing "technology-specific" approach may, it was pointed out,
provide a framework for further restrictions on the use of "white"
biotechnology.

Despite regulatory problems, there is evidence that some EU farmers are
beginning to try to make use of "white" biotechnology to create added
value crops. In some instances, it can produce products with the same
performance as traditionally produced ones, but without any price
advantages. Governments need to provide financial incentives for users
to switch away from traditionally produced products. In the US, this can
be achieved through federal government action; in the EU, competence
remains with Member States.

Because of its potential to create cleaner, less harmful products, good
regulation of "white" biotechnology requires decision-makers to consider
both costs and benefits. In the US, this is possible because the TSCA is
a risk-benefit statute: regulators are allowed to consider costs and
benefits of decisions. In contrast, the focus in the EU is primarily on
assessing and reducing risks to human health or the environment.
Benefits can, however, be considered implicitly during the risk
management decision-making process, although in most biotech-specific
regulations there is no explicit recognition of this. An exception is
the EU's legislation on food and animal feed, which expressly allows
regulators to consider "other legitimate factors" when making risk
management decisions.

Negative attitudes to non-pharmaceutical uses of GM technologies in the
EU could lead to stigmatisation of processes or materials that make use
of modern biotechnology. In turn, this could persuade industrial users
to limit investments in "white" biotechnology. Stigmatisation may also
trigger the introduction by regulators of additional restrictions on
uses of "white" biotechnology. There are, for example, continuing
concerns in the EU about the use of unmodified enzymes produced using GM
technologies in a wide range of production processes. So far, these have
been considered to be processing aids so long as they do not form part
of the final product.

8\. Regulations and non-food GM crops and cross-overs between "white",
"green" and "red" biotechnology

**Background**

"Green biotechnology", or the use of GM technology in the agricultural
sector, is no longer confined to food crops. A range of sectors are
beginning to make use of genetically modified, non-food outputs from the
agricultural sector. Today, the most important non-food GM crop is
cotton. Worldwide 7.2 million hectares were grown in 2003, including 30%
of production in India and 75% in the US.

Researchers are developing new, non-food GM crops for a wide range of
sectors, including "red" and white" uses of biotechnology. In the
pharmaceutical sector, for example, alfalfa plants are being developed
that can produce vaccine for foot and mouth disease. Known as
"bio-pharming", this may also include transgenic animals capable of
producing inputs for pharmaceuticals. Other applications in development
include GM potatoes, trees for the pulp and paper industry, and GM
modified oilseed rape for use in the speciality chemical sector. GM
technology is also being applied to the development of modified forms of
biomass as a sustainable input for the energy sector.

These developments have raised considerable concerns about issues such
as\
cross-contamination, animal welfare, ethics, choice, environmental
damage, and threats to human health and public safety.

**Dr. Jennifer Kuzma**, Associate Director of the Center for Science,
Technology, and Public Policy at the University of Minnesota, USA, who
moderated the session, highlighted examples of the use of 'green'
biotechnology for industrial and healthcare applications, noting that
proteins could be produced in goat milk and inputs for vaccines could be
provided by GM tomatoes.

In the US, the regulatory framework to manage the possible risks to
human health and the environment posed by these new applications is
already in place. It is based on a\
coordinated framework involving all relevant federal agencies and was
established in the mid-1980s. It focuses on the potential risks posed by
products rather than the technologies used to create them. As a result,
no new biotech-specific legislation has been put in place in the US,
although additional test guidelines have been established where
appropriate. There are specific guidelines established by federal
agencies to manage potential risks posed by field trials of new GM
crops.

However, the development of non-food GM crops was not considered when
the original regulatory framework was put in place in the US. There is a
need, argued Dr. Kuzma, for US policy-makers to create stronger
oversight mechanisms to ensure that all risks and concerns are
considered fully and ensure coordination and coherence between different
federal agencies. Better post-market monitoring of non-food GM crops is
also needed.

Dr. Kuzma argued that future regulation of the potential risks and
benefits posed by non-food GM crops needed to consider:

-   Concerns about the possible impact of cross-pollination;

-   A more complex risk-benefit distribution, including the wider social
    benefits of non-food GM crops, such as environmental gains, and
    impacts on the developing world;

-   Public perceptions;

-   Non-scientific factors, such as animal welfare and ethics.

**European perspective**

**Dr. Paola Testori Coggi**, Director, Health and Consumer Protection
Directorate-General, European Commission, said that in the EU, "green"
biotechnology is focused predominantly on improving the agronomic traits
of crops, rather than providing consumer benefits or producing inputs
for other sectors, such as healthcare or industry.

Moreover, only a small number of "green" biotech crops have been
approved for use in the EU, and some sections of public opinion have yet
to be convinced that such products offer any net benefit to society,
even after taking into account possible benefits\
to farmers.

The Commission is, however, aware that future "green" biotech
applications could provide inputs for "white" or "red" applications.
Recently, the EU received an application to market a GM potato capable
of providing starch to the pulp and paper industry.

Non-food GM crops may pose new challenges for risk assessors, including
additional safety, nutritional, and environmental considerations. They
may also create difficulties for risk managers in the EU, not least in
determining what legislation applies in addition to the Union's
biotech-specific legislation.

On the basis of the EU's current regulatory framework, non-food GM crops
must comply with the requirements of two groups of regulations: the EU's
biotech-specific legislation, especially laws dealing with deliberate
release of GMOs, traceability and labelling, and planting
(co-existence); and sector-specific risk management legislation covering
areas such as medicinal products, food, pesticides and biocides. Some
exceptions might be possible, so long as relevant sectoral laws require
risk assessments that meet the requirements set out in the main
biotech-specific directives.

It was also possible that further new risk management requirements might
be needed, such as new containment measures for plants used as
'factories' for pharmaceutical production or for transgenic animals.

**US perspective**

**Dr. John Turner**, Director, Policy Co-ordination Division, APHIS, US
Department of Agriculture (USDA), said relevant US regulatory agencies
had examined the risks posed by non-food GM crops and put in place
appropriate regulatory guidelines for field trials. It is recognised
that there is considerable interest in such crops because of their
potential economic benefits, although only a small number are, as yet,
in commercial production.

Since the late 1980s, the US has had stringent, science-based safety
controls to manage the risks posed by all GM crops during field trials.
Guidelines apply to all forms of GM crops and cover permits, separation
distances, land use, segregation of equipment and facilities, training,
testing and inspections. There is also a high level of transparency,
with details of all permits publicly available.

Specific regulatory requirements are, however, determined on a
case-by-case basis. This enables regulators to establish larger
separation distances where appropriate, and this approach has been used
in a number of cases involving non-GM crops.

Dr. Turner explained that the overall framework has been used to manage
more than 11,000 field trials, involving over 100 species of plants and
micro-organisms at nearly 50,000 locations.

Crops can only be planted commercially when it can be demonstrated that
that they meet the safety standards of other similar non-GM crops. Once
this has been achieved, then segregation, containment and other
restrictions are removed. This is, Dr. Turner argued, a science-based
approach that focuses on regulating risks rather than technologies.

Dr. Turner said this framework has been used successfully to manage the
risks posed by GM food crops in the US. However, he recognised that
non-food GM crops may pose additional challenges, especially if they are
not intended for the food chain. In this case, safety standards may need
to be established by other relevant regulations.

**Discussion**

Participants pointed out that in the EU, field trial approvals and
conditions are determined by Member States. EU-level regulators are not
involved and there is little consistency of approach across the Union.

Despite the rigorous and expensive conditions imposed by US regulators,
the overall number of field trials carried out in the EU is likely to be
substantially less than in the US, it was argued. In fact, US measures
to control possible risks posed by field trials may exceed those used in
the Union.

Regulatory controls on the commercialisation of non-food GM crops are
significantly greater in the EU than in the US. In the US, such crops
must comply with stringent controls on field trials and demonstrate that
they meet the safety standards required of similar products produced
using other technologies. After this has been achieved, there are no
additional, biotech-specific regulatory costs. In contrast, non-food GM
crops must meet the safety standards imposed by biotech-specific and
sectoral laws, as well as the costs imposed by national co-existence
guidelines. This final group of requirements limits available acreage,
and raises production costs. In the EU, all commercial planting of\
non-food GM crops will be required to observe co-existence rules.

Non-food GM crops and the use of transgenic animals pose major risk
perception issues for both US and EU policy-makers. Indeed, some
scientists are still concerned about potential unintended consequences
for the environment and human health of such technologies. There are
also ethical concerns. Regulators, industry, and other stakeholders need
to discuss these and other concerns, through a process of dialogue. Used
well, this could help identify emerging issues, build trust and shape
future regulatory frameworks.

Market forces may also play a role in 'regulating' the potential risks
posed by non-food GM crops. Some participants suggested that in the US,
major food producers and retailers may require farmers to introduce
containment and segregation measures, so as to avoid possible liability
claims.

9\. Biotechnology and Ethics: research choices, trade-offs and impacts
on public welfare and developing countries

**Background**

In a growing number of cases, ethical and related regulatory factors
influence biomedical research and the exploitation of biotechnology by
developing countries.

Regulation of the development and exploitation of "red" biotechnology'
is increasingly influenced by ethical factors in a number of areas.
These include using information about people including genetic data,
demographic data, clinical records, and human tissues; carrying out new
forms of research (stem cells, human embryos, and cloning); exploiting
the results through, for example, patenting and other forms of
Intellectual Property Rights (IPR); and carrying out clinical trials in
developing countries

Public policy action to support, or hinder, the use of GM crops in
developing countries has also become, in part, an issue influenced by
ethical concerns. There are ethical and social issues involved in making
GM crops readily and economically available to people in developing
countries who want them. Access to relevant agricultural biotech is
influenced by regulatory frameworks in the EU and the US, including
IPR**,** market access, labelling and traceability rules.

Whilst many of the ethical and social issues are currently limited to
the exploitation of GM food crops, similar problems are likely to be
encountered once developing countries begin large-scale exploitation of
non-food GM crops in "red" and "white" applications.

EU and US regulators need increasingly to consider the worldwide
distribution of harms and benefits from "green" uses of biotechnology,
as well as considering the impact of ethical factors on the exploitation
of all forms of biotechnology by developing countries.

**Professor Derek Burke**, Vice-Chancellor, University of East Anglia,
UK, who moderated the bioethics session observed that in Britain,
regulators first become aware of bioethics when transgenic animals were
developed for food production. This was seen by some influential groups
as morally unacceptable, especially if it involved human genes. It was,
moreover, seen as 'unnatural': an offence against nature. But not all
groups share these concerns, said Professor Burke. There is, he argued,
a clash of values and attitudes: a conflict between moralistic and
utilitarian beliefs, for example.

Policy-makers recognise that these concerns create new challenges for
risk managers. Decisions about the best way to protect citizens and the
environment from some risks faced challenges from citizens and potential
loss of legitimacy, unless ethical factors are recognised and
understood.

The bioethics debate has become more complex in recent years, as
policy-makers and opinion-formers (such as the Nuffield Council for
Bioethics, based in the UK) have begun to assess its scope and
implications more rigorously. More emphasis is being placed on
developing countries. Biotechnology, argued Professor Burke, has the
potential to help developing countries solve fundamental problems, and
there is a moral obligation for human beings in richer countries to help
those in poorer ones.

**EU perspective**

An EU perspective on bioethics and "red" biotechnology, and the ethical
issues surrounding biotech and developing countries was provided by
**Professor Julian Kinderlerer,** Department of Law, University of
Sheffield, UK, who chairs the European Group on Ethics (EGE), an
advisory group to the European Commission President.

He identified a number of ethical issues that are likely to influence
the regulation of "red" biotechnology in the EU, with three main areas
of current concern: data privacy, clinical trials and developing
countries, and stem cell research. He also outlined some of the ethical
concerns surrounding test data and privacy.

Biotech advances make it possible for tests to be carried out that
identify genetic disposition to certain diseases or conditions. Such
tests are generally undertaken by individuals. But the results could
have negative outcomes for other family members, even though they have
not been involved in the tests. The freedoms of one group are
potentially restricted without the exercise of choice, through the
freely taken actions of others. It is possible that this problem may be
resolved through existing law. EU data protection legislation does not,
as a general rule, permit disclosure of data.

Another ethical problem facing EU regulators is the use of data from
clinical trials in developing countries. In the Union, and other
Organisation for Economic Cooperation and Development (OECD) countries,
clinical trials are carried out within a highly regulated context, with
a strong emphasis on informed consent.

In many developing countries, systems for ensuring informed consent of
participants are sometimes poor or inadequate. Regulators, researchers
and pharmaceutical companies need to consider, said Professor
Kinderlerer, whether it is acceptable ethically to use clinical trials
data obtained from countries that fail to meet standards of informed
consent demanded in wealthy countries. No EU legislation currently deals
with this issue.

The use of embryonic stem cells in research also poses ethical problems
for EU regulators. Some Member States believe, principally on moral
grounds, that it is immoral to use data obtained from stem cells. Others
reject this but have, in most cases, created rigorous regulatory regimes
to control relevant research. In the UK, for example, all research
involving stem cells must be licensed. For the EU, there remains a major
ethical problem: is it acceptable ethically for data produced from stem
cell research to be used in countries that prohibit this activity? As
yet, this problem has not been resolved.

There is an international legal framework to address the ethical issues
surrounding the use of biotechnology by developing countries, based on
the Biodiversity Treaty and Cartegena Protocol. Unlike the US approach
to biotechnology, this framework focuses on technology rather than risk.

This, argued the Professor, has the potential to stigmatise
biotechnology, despite its potential to alleviate hunger, disease and
poverty. Already, there is evidence that some developing countries are
reluctant to use agricultural biotech or to accept food aid from
countries that grow GM crops. This is due to fears about long-term
health risks, and concerns about access to EU markets for agricultural
products.

Professor Kinderlerer expressed concern about the ethics of this
approach. Continued starvation and poverty were, he argued, the most
likely consequences for developing countries of taking a 'precautionary'
approach to the use of agricultural biotechnology. In poor countries,
the costs of inaction were likely to be significantly greater than the
theoretical risks posed by agricultural biotechnology.

Finally, the problem of stigmatisation of agricultural biotechnology in
the EU is becoming more complex because of the impact of market forces.
Evidence from a number of leading food retailers suggests that
'voluntary' bans on the use of GM technology in the food chain are
becoming more common. These have been established by retailers, in their
role as 'gatekeepers', and represent a real barrier to trade between the
EU and developing countries, said Professor Kinderlerer.

**US perspective**

**Professor Robert Cook-Deegan**, Director, Center for Genome Ethics,
Law and Policy, Duke University, USA, focused on ethics within a policy
context.

The US accounts for more than 40% of global spend by governments and
not-for-profit organisations on biotech R&D. Governments and private
companies in the eight largest industrial nations are the dominant
investors in this area and own most biotech patents.

Although biotech Intellectual Property (IP) and research spending are
concentrated in developed countries, biotech offers developing countries
major opportunities, argued the Professor. Genomics has, for example,
provided information that may facilitate the development of effective
vaccines against malaria. New patent laws and a lack of restrictions on
stem cell research offer scientists in India the opportunity to develop
new products for diseases. Antibody technologies offer developing
countries the possibility of producing low-cost field detectors for a
wide range of diseases.

Within this context, policy-makers in wealthy countries face a number of
ethical issues, argued Professor Cook-Deegan. Specifically:

-   Research priorities and the needs of developing countries;

-   IP-related obstacles to the use of biotech by researchers in
    developing countries;

-   Concentration of ownership of IP in wealthy countries and concerns
    about "distributive justice";

-   Incentives for researchers in wealthy countries to create IP for use
    in developing countries;

-   Global access to research carried out in developing countries;

-   Misuse of bio-technologies and the threat of bio-terrorism

**Discussion**

Participants pointed out that international bodies like the EU face
difficulties when seeking to address ethical issues. Ethical values and
philosophies frequently differ between nation states, because they are
often rooted in social attitudes, beliefs and experiences.

A well-known typology of ethics identifies four different forms:
utilitarian, fundamental rights, institutional, and intrinsic or moral.
There are also different philosophical traditions. In the US, for
example, there has been a strong utilitarian tradition, although this is
now being challenged, in some states, by religious or moral values. In
contrast, the UK has been more pragmatic, considering issues on a
case-by-case basis. These differences make it difficult for
international bodies to use ethical factors to make decisions that will
be widely-accepted.

A potential problem for the EU is that the legal requirement to consider
ethical factors may act to delay or obstruct the development of new
products. Additional debates, and the introduction of non-scientific
factors into risk management decision-making processes, create
additional costs, slow down time to market and create uncertainty. This
in turn reduces incentives for innovation, causes capital to be
re-allocated, and limits the availability of socio-economic benefits
from biotechnology to Europeans. Because of the nature of many of the
potential benefits from new biotech applications, this is an ethical
problem. There are, therefore, "ethics of delay".

Some environmental activists in the industrial world have contributed to
creating obstacles to biotechnology use in developing world, it was
suggested. They have made decisions about the desirability of
biotechnology on the basis of Western values and circumstances, without
explicitly considering the problems facing developing countries.

EU policy-makers need to ensure that ethical debates about biotechnology
are rigorous and "balanced". To do this effectively, they need to
consider its benefits as well as the risks. Too often, it was suggested,
EU legislation focuses solely on managing risks rather than achieving a
proper balance of risk and benefit. Potential beneficiaries of biotech
include patients, developing countries and the environment. Agricultural
biotechnology could, for example, to help developing countries alleviate
starvation, poverty and disease. Used well, however, ethical advice can
help policy-makers formulate additional relevant questions and highlight
important 'hidden' benefits and the potential dangers of using a
precautionary approach to the exploitation of new, enabling
technologies.

10\. Concluding Round Table on "Regulatory frameworks for emerging
biotechnology applications: ways ahead"

**European perspective**

**Professor Derek Burke** of the University of East Anglia, UK, said
there were important difference between the way in which the EU and the
US have chosen to regulate biotechnology. This has led to trade
frictions and, because the EU approach stigmatises and creates
technology-specific regulatory obstacles, limits the availability to
Europeans of the socio-economic benefits from biotech.

It is important to understand why different policies have been pursued
and to consider whether differences of approach to regulating the risks
posed by biotech will persist. The Professor suggested that the problems
lie in the regulatory policies pursued in the EU and in the US, and not
in science.

The EU has focused on regulating the use of the technology itself,
whereas the US does not use a biotech-specific approach. Instead, US
regulators make use of existing laws to manage risks. Moreover, the US
approach is flexible and appears to accommodate changes in technology
easily. Extensive use of guidelines within a well-established,
science-based framework has, argued Professor Burke, created a
regulatory context in the US that has encouraged innovation and
investment, whilst ensuring high standards of protection for human
health and the environment.

However, the regulation of biotechnology in the US and the EU also
needed to be seen within a wider context. In the US, considerable
emphasis is placed on the 'ex post' management of risks through personal
responsibility of citizens, market mechanisms and the courts. This
complements the 'ex ante' regulations put in place by Federal or State
governments. In contrast, the EU focuses principally on 'ex ante' risk
management by governments. These different approaches are the result of
major differences in cultural, legal, and constitutional traditions
between the EU and the US, argued Professor Burke.

Whilst these factors are important for understanding some of the
differences between the US and EU approach to regulating biotechnology,
they do not provide a complete explanation. EU legislation is, he
suggested, less science-based and more risk-averse, than in the US. This
is the result of the interaction of a number of different issues.

Throughout the 1990s, the EU experienced a series of "regulatory
failures" (such as BSE). These undermined public trust in scientific
evidence and regulators, and contributed to increased risk aversion. At
the same time, activists carefully exploited concerns surrounding the
use of agricultural biotechnology. There were fears about contamination
of the food chain, lack of choice, interfering with nature, and ethics.
Taken together, these two groups of issues influenced the evolution of
the EU's approach to regulating biotechnology.

As a result, argued the Professor, the EU has created a regulatory
framework for managing risks that potentially stigmatises the use of
biotechnology and creates additional regulatory costs for innovators.
This is a structural challenge facing EU policy-makers as they seek to
manage the risks and benefits posed by emerging biotechnology
applications.

**US perspective**

**Dr. Murray Lumpkin**, Deputy Commissioner, US Food and Drug
Administration (FDA), outlined the transatlantic differences in risk
tolerance and shifting perspectives within the FDA.

The FDA has begun to move away from focusing solely on protecting the
public to also promoting health. To achieve this, he said, more emphasis
needs to be placed on understanding the willingness of patients to
accept risk. In part, this change in policy was influenced by the HIV
debate in general, and concerns about access to new, innovative
treatments in particular. In the US, this shift in emphasis has been
achieved through changes within the regulatory framework; new primary
legislation has not been required.

Achieving a greater understanding of patients' risk tolerance has also
been helped by the greater use of advisory committees. Federal law
requires all agencies to have such committees. Representatives of
consumers and patients sit on all FDA committees. Meetings are open to
the public, and this helps to strengthen transparency and trust.

Advisory committees have also provided officials with an opportunity to
gain greater insights into ethical concerns. One specific example
involved the use of drugs in children, which was seen as unethical
unless the same drugs had been tested on children. In this case, a
specific advisory committee was set up to help inform the regulatory
guidelines.

Finally, the FDA works closely with the EU's EMEA and the international
**ICH** initiative to strengthen technical links between regulators and
risk assessors. Advances in biotechnology, argued Dr. Lumpkin, provide
opportunities to speed up drug development through less emphasis on
trial and error, and the provision of better, faster data.

**[Participation list]{.underline}**

Nils Behrndt European Commission (DG ENTR)

Thomas Bols AMGEN

Derek Burke University of East Anglia

Mark Cantley European Commission (DG RTD)

Flora Chow US Environmental Protection Agency

Stan Cohen US Mission to the EU

Robert Cook-Deegan Duke University

Elisabeth Cramaussel US Mission to the EU

Stanley Crossick European Policy Centre

Michèle Dastin-van Rijn US Mission to the EU

Ignace Debuyne American Soybean Association

Dominique Dejonckheere Copa-Cogeca

Günther Eberz Bayer AG

Trevor Evans US Embassy to the United Kingdom

Eric Flamm US Food and Drug Administration

Christopher Friend Genetic Interest Group

Benjamin Gannon Johnson & Johnson

Iain Gillespie OECD

Peter Grosser US Mission to the EU

Wills Hughes-Wilson Genzyme

Lynn Johnson Langer John Hopkins University

Josephine Johnston The Hastings Center

Kristen Katzer US Embassy to France

Julian Kinderlerer Sheffield Institute of Biotech Law & Ethics

Jennifer Kuzma University of Minnesota

Murray Lumpkin US Food and Drug Administration

Robert Madelin European Commission (DG SANCO)

Hervé Martin European Commission (DG ENV)

Richard Meads European Policy Centre

Xavier Mennig US Mission to the EU

Christopher-Paul Milne Tufts University

Alison Morton European Policy Centre

Daniel Nelki The Wellcome Trust

Katja Neubauer European Commission (DG SANCO)

Patricia Pellier Serono International SA

Jonathan Ramsay Monsanto

Paul Rohrlich US Embassy to Belgium

Caroline Ruggiere Emerging Biotechnology Enterprises

Harald Schmidt Nuffield Council on Bioethics

Wim Soetaert University of Ghent

Madelyn Spirnak US Department of State

Peter Stonier US Mission to the EU

Claudia Stuckmann BASF AG

Paola Testori Coggi European Commission (DG SANCO)

John Turner US Department for Agriculture (APHIS)

Johann Vanhemelrijck EuropaBio

Etienne Vervaecke Eurasanté

Paul Von Hoegen The Weinberg Group

Christina Vozzi Serono International SA