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is possible not only to emphasise the exemplary safety record of genetic modification but also to obtain for our techniques and engineered products much more univer- sal acceptance.

By being open and informing interested parties the industry may also avoid seeing the whole of Europe being dragged down the route of the most restrictive and constrained practices available because of mis- informed pressure from activists in particular member states.

Proposed changes to the Contained Use Directive and Regulations will ease the administrative burden by simplifying the notification and consent requirements for the lower category organisms which are essentially safe.

For example, the original Annex I1 of the CU Direc- tive was criticised as being over complex without iden- tifying clear boundaries between the groups and that too many inherently safe organisms were ending up in the higher (Group 11) category. Proposals in Appendix 3 of the HSC document to replace the central test of ‘non- pathogenicity’ and details in Directive 94/51/EC and Commission Decision 9 1/448/EC will hopefully clarify the situation and lead to a simpler organism classi- fication. This may then lead to a reduced number of notifications. and therefore reduce costs and delays.

Despite the different groups and agencies that are involved in legislating on GM work a reasonable liaison has been established, however informally, between gov- ernment departments and users and this is clearly a benefit. The UK regulators in general appear to be more pragmatic than some EU partners and this, plus their support to industry in interpretation of legislation, is invaluable.

There is general acceptance that overtight controls were initially exercised on GM work. At the time the measures appeared necessary and with the limited knowledge of the time were wholly appropriate.

With approximately 30 years of experience and accu- mulated knowledge it is encouraging to see, with the current reviews of both European and national legisla- tion, that there is a trend towards controlled deregu- lation particularly at lower containment categories where inherently safe GMOs are being used. It is important that the distinction is made between essen- tially safe organisms, constructs and modifications and the higher category, high risk work, which should remain highly regulated.

In summary, regulations that are scientifically sound and objective but that are flexible, easily implemented, easily enforceable and a guide rather than a straight- jacket are beginning to emerge. Hopefully they will lead to a system where containment measures appropriate to the risk can be implemented rather than a compulsory list of measures at each containment level. These regula- tions must also be consistent and preferably universal as the cost of developing products from GMOs is high and

the economic risks are greater if their regulation is uncertain. It is this uncertainty that is a concern. We do not want products and processes that have been under development for a long time jeopardised by uncertainty.

The Impact of the GMO Regulations on a UK Pharmaceutical Company

Paul Burke

Zeneca Pharmaceuticals, Mereside, Alderley Park. Macclesfield, Cheshire SKlO 4TG, UK

Introduction

Modern biotechnology offers important opportunities for economic growth in the health care, chemical, agri- cultural and food sectors. In 1993 the free world market for pharmaceutical products approached f 160 billion. However, the present pharmaceutical market is more competitive than ever with increased pressure on growth and profits. It is essential for the future pros- perity of all concerned that as many of these products as possible are researched, developed and manufactured by UK industry.

Biotechnology is a fast moving area of research which provides a unique set of tools to aid the invention of new drugs, agrochemicals or the breeding of new plant varieties. These challenges require, more than ever, a molecular insight into the functioning of genes, cells and tissues. Our ability to transfer genetic material between different species (genetic modification) and the ability of these genetically modified organisms (GMOs) to self- replicate is often cited as a cause of concern, for example that man will inadvertently create new patho- gens or weeds. We find arguments that genetic modifi- cation is inherently safe are as unhelpful as arguments that all genetic modification is dangerous and should be stopped. What society needs is a science-based regula- tory system that is strictly enforced by a regulatory authority. Such a system would encourage research and investment and would help develop the confidence of the public.

The impact of genetic modification legislation

Until the late 1980s the UK was developing a regula- tory system that protected both man and the environ- ment while encouraging investment in research and industry. The regulatory framework and guidance developed in a planned and deliberate manner- alongside the technology. Over nearly 20 years, genetic modification in the UK and world-wide has had an exemplary safety record. However, the implementation in the UK of European Directives 90/219 (Contained

308 Extended Summaries-Biotechnology Group

Use) and 90/220 (Deliberate Release) has impeded the conduct of research and development in both academic and industrial sectors and there is no evidence that safety has been increased. The Directives appear to be based on the concept that genetic modification per se poses unique risks to man and the environment and therefore must be controlled in a unique manner.

In the UK the Regulations which implement the Directives had to undergo extensive modification after the first round of consultation because of their inap- propriate and grossly convoluted format. The complex- ity of the new safety legislation surrounding GMOs has made its implementation difficult for Zeneca as well as other UK companies. Many managers and scientific staff see the new Regulations as excessively bureaucratic and not risk-based. The text of the G M (Contained Use) Regulations is amplified by additonal guidance provid- ed in a set of 11 separate documents (ACGM/HSE/DoE Notes 1-1 1) drafted jointly by the Advisory Committee on Genetic Modification (ACGM) and the Health and Safety Executive (HSE). However, despite the large amount of data available it is not clear what a research scientist wishing to perform a genetic modification experiment must actually do to meet the requirements. Nor is it obvious how to set up an internal procedure to ensure that the correct information is supplied to mana- gers and scientific staff and that all implications of the work are considered; for example, the G M Contained Use Regulations highlight over 50 detailed points related to safety, health and environmental consider- ations of work with GMOs.

The cornerstone of the Regulations is the risk assess- ment procedure as this will establish the type of con- trols needed. The risk assessment procedure for contained use is complex and depends on the character- istics of the host, vector and DNA insert and must take into account health and safety and environmental con- siderations. All institutions wishing to conduct activities involving GMOs must form a local safety committee as laid out in ACGM/HSE/DoE Note 11. The practice at Zeneca Pharmaceuticals is to ensure that applications for GM experiments must be seen and approved by members of the Committee. This has been a costly exer- cise, requiring that Committee members should each receive copies of GM submissions and that they period- ically meet to debate applications, listen to justifications and give their approval. It is then the responsibility of the Committee to make notifications to the HSE and keep records of applications. Risk assessments must be kept for ten years. This form of ‘peer review’ and approval of a given risk assessment does not occur in any other form of UK legislation.

Additional local changes included the need to develop a training programme to enable managers and scientific staff to have a clear understanding of the process as well as tutoring in the new approach to risk assessment. In addition, a computer-based risk assess-

ment system was developed to take the scientist through the risk assessment process in a logical manner. Elec- tronic form filling provides the opportunity to include context sensitive help texts, e.g. on the Regulations and ACGM guidance material that amplify the questions asked in a way that would be costly in terms of time under a paper-based risk assessment system.

It is interesting to note that new legislation updating the COSHH Regulations which came into force in January 1995 includes special provisions relating to the control of biological agents, i.e. pathogens. These are less restrictive than the new Genetically Modified Organisms (Contained Use) Regulations despite the fact that genetic modification work is normally based on non-pathogenic micro-organisms and known gene sequences of known properties.

The consequences of the regulatory regime on competitiveness

Zeneca Pharmaceuticals currently estimates that its genetic modification safety costs have risen by approx- imately 50% to meet the new Regulations. Additional capital expenditure of between 5 and 10% is required for normal research activities, while this will rise to 25-30% for certain larger scale activities. Similar cost- ings are predicted by the other Zeneca businesses. A survey of over 500 members of the Chartered Institute of Management Accountants (CIMA)’ found that nearly 70% of financial directors believed that health and safety costs rose faster than average over 1993. The main reason given for the increase is the enforcement of stricter regulations. Whilst 90% agree that it is right for health and safety regulations to be tightened, these costs are seen as a burden and reflect a belief that other EC Member States pay only lip service to compliance with EC legislation.

At the present time, Zeneca Pharmaceuticals is producing all material for clinical and preclinical testing within the UK either in-house or through contractual arrangements. Where Zeneca will manufacture in the future has not been decided. It is, however, clear that the evolving regulatory climate and attitudes in the European Community will make a contribution to this decision. In the biotechnology area the UK has a com- mendable record of both research and industrial achievement. From the above paragraphs it is clear that we have serious concerns that the costs associated with over-bureaucratic regulations in the UK and Europe will damage research. This will make the UK a less attractive prospect in the future for companies wishing to use biotechnology to bring pharmaceutical products to the marketplace.

Biotechnology will not be used by British industry if society or the consumer does not want the resulting produrts. In order to encourage public confidence there

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is a need for a focused campaign aimed at explaining to the public in honest, non-scientific terms the tech- nology, the regulatory safeguards and the benefits arising from each sector of biotechnology. Regulation has a critical function to perform in this context. The right level of regulation will reassure the public but inappropriate regulation would not satisfy public con- fidence and would severely damage the efforts and pro- spects of those industries where biotechnology is an ever-increasingly important tool.

Reference

1 . Chartered Institute of Management Accountants, Costs of Business Survey. CIMA, 63 Portland Place, London W1N 4AB. 1994.

Consumer Views on GMOs

Richard Shepherd, L. J. Frewer and P. Sparks

Institute of Food Research, Earley Gate, Whiteknights Road, Reading RG6 682. UK

Biotechnology, and particularly genetic modification, offers enormous potential in a number of fields, includ- ing medicine, pharmaceuticals and the production of foods. The implementation of this technology is cru- cially dependent on public acceptance but at present we do not have a good understanding of what public views are now or what they are likely to be in the future.

Studies in the risk perception literature have shown risks to be perceived by the public in terms of their per- ceived severity, how well known the risks are seen to be and the number of people believed to be exposed to the hazards. In a study specifically of food-related hazards, genetic modification was found to be extreme in terms of being unknown (both by science and by those exposured) but to be of only moderate severity.’

In a more detailed series of studies of public views on genetic modification, the general picture to emerge is one of low public awareness and knowledge and poorly- formed attitudes towards the application of genetic modification. In one study, the technology was described in different ways to different groups of con- sumers (genetic engineering, genetic modification, genetic manipulation or gene technology) but there were few differences in rated risks or benefits.’

Applications to medicine are generally viewed more positively than those to agriculture or food production. The genetic engineering of animals is viewed less favourably than that of plants or micro-organisms and surprisingly the transfer between different types of organisms (e.g. between animals and plants) is not viewed more negatively than the transfer between the

same type of organisms (e.g. between animals and animals).

People rate themselves at less risk from a large number of hazards than are other people, a phenome- non known as ‘optimistic bias’. This is particularly true for hazards such as alcohol or fat intake where people feel that they have a very high degree of personal contr01.~ However, optimistic bias is also shown, although to a lesser extent for genetic modification. When dsked about control in this context people see control as lying at the level of society rather than them- selves or other individuals. The issue of perceived control and trust in the regulatory system are likely to be key issues in the acceptance or rejection of the tech- nology.

Ethical concerns are not only said to be important by the public but also have an important effect on atti- tudes, independent of perceived costs and benefits of the technology. However, closer questioning reveals many of the ethical concerns to be potentially addressable, such as issues of animal welfare and potential effects on human health.

The media are the major channels through which the public learns about new technologies. An examination of coverage of different food-related hazards over one year (from February 1992) in the quality British press showed fewer articles on biotechnology than either microbiological risks or additives but that because these tended to be longer articles the number of relevant words on biotechnology was second only to microbio- logical risks.4 Whereas microbiological risks were reported with some limited information about the mag- nitude of the risks, reporting the biotechnology issues centred on the issues of conflict and different actors in the debate (e.g. government and pressure groups).

Trust in information sources has been included in a number of surveys and, in general, consumer organis- ations are rated as highly trusted, whereas government departments and industry spokespersons come out as less trusted.’ However, when real information is attrib- uted to different sources that information appears to be trusted equally. Individual differences in trust in sources of information, and in risk perceptions, are identifiable based upon characterising different world-views among individuals. The effects of trust, information content and individual differences on communication are currently being investigated.

A major problem in assessing public attitudes towards products of genetic modification is that, in the food area, there are few products on the market and hence most studies have asked questions at the level of general attitudes or if specific applications have been considered these have been presented as hypothetical examples. When people are confronted with real pro- ducts they may react differently once these products are seen not to be radically different from conventional pro- ducts and might offer some consumer benefits. A pre-