E. Rehbinder M. Engelhard K. Hagen R. B. Jorgensen R. Pardo-Avellaneda A. Schnieke F. Thiele

Transcription

1 E. Rehbinder M. Engelhard K. Hagen R. B. Jorgensen R. Pardo-Avellaneda A. Schnieke F. Thiele Pharming Promises and risks of biopharmaceuticals derived from genetically modified plants and animals 4ü Springer

2 Comprehensive table of contents Preface Foreword List of abbreviations VII IX XIX 1 Introduction 1 References 7 2 The technology of pharming Recombinant pharmaceutical proteins - the advent of biotechnology Plants as a production platform for recombinant biopharmaceuticals Genetic engineering of the host plant Gene constructs Post-translational modifications Plant transformation method Transient expression using viral vectors Choice of species and site of production Leaves Cereals, legume seeds and oilseeds Fruits and vegetables Plant cell cultures and hairy root Systems Cultivation Purification of biopharmaceuticals from transgenic plants Purification of biopharmaceuticals from whole plants Purification of biopharmaceuticals from plant cell cultures and hairy root cultures Animals as a production platform for recombinant biopharmaceuticals Transgene constructs used for animal pharming 27

3 XIV Comprehensive table ofcontents Methods of producing transgenic livestock Pronudear DNA microinjection Viral gene transfer Sperm-mediated gene transfer Embryonic stemcells Embryonic germ cells Nuclear transfer Spermatogonial stem cells Adult stem cells Overview Choice of species and site of production Milk Urine Seminal fluid Blood Bird eggs Production ofproteins from transgenic animals Analysisof transgenic animals Quality and safety of the product Choice ofexpression Systems References 66 3 Risk assessment of plant pharming and animal pharming Environmental risks and co-existence of plants genetically modified for production of pharmaceuticals Legal framework and basic principles of risk assessment of GM plants Risks of pharming plants Risks of unintended exposure Transgene dispersal Horizontal gene flow The environmental risks - will pharming plants differ from the current GM plants? Concluding remarks Environmental risks of animal pharming References 95 4 The welfareof pharming animals Introduction Animal welfare risks 102

4 Comprehensive table ofcontents XV 4.3 The concept and assessment of animal welfare Animal welfare considerations in the animal pharming production phase Housing and management Protein collection and excess offspring Reproduction Effects of genotype Animal welfare considerations in the development phase Transgenesis, expression of medicinal protein, and transgene evaluation Reproductive technologies Developmental problems in somatic cell nuclear transfer (cloning) Donor animals and foster mothers Excess offspring Conclusions References Public views and attitudes to pharming Introduction Methodological considerations Attitudes to pharming in advanced societies: awareness and evaluative perspectives Awareness about pharming Evaluative perspectives Adifferentiatedlandscapeofperceptionsof pharming Ranking of biomedical and socio-economic goals and acceptance of plant pharming The specifics of the means in the acceptance of plant pharming Ranking of biomedical and social goals and acceptance of animal pharming The specifics of the means in the acceptance of animal pharming Preferences for methodsof production ofpharmaceuticals Awareness and acceptance of plant and animal pharming Elements of an explanatory model Conclusions Tables References 176

5 XVI Comprehensive table ofcontents 6 The ethical evaluation of pharming Introduction Foundations ofmoral reasoning Common moral concerns regarding pharming The moral Status of plants and animals Naturalness Integrity Aims and means of using and manipulating animals and plants for pharming Risk assessment and risk-benefit analysis References The role of patents in the development of pharming The general justification of patents The existing regulatory framework Basic rules on patentability of biological products, biological material and biological and microbiological processes Extent of protection Mandatory licenses Patents as obstacles to innovation in pharming? References Legal problems of pharming Introduction Development phase I: Protection from risks to the environment caused by the use and release of GMOs Sources of legal regulation and their scope of application Development of recombinant medicinal products with Containment Development of recombinant medicinal products without Containment Scope of application and regulatory principles ofdirective 2001/ Information requirements and risk assessment Authorization prerequisites Special issues relating to animal pharming Institutional arrangements Coexistence between experimental cultivation of GMOs and organic and conventional agriculture 237

6 Comprehensive table ofcontents XVII Waste disposal GMO-specific regulation Regulation under general waste law Disposal of excess animals and animal parts Development phase II: Animal protection Sources of regulation Animal trials: Scope of application of the relevant laws The European Convention and Directive 86/ National law Development phase III: Protection of occupational safety and health in the development of recombinant medicinal products Contained use Release without Containment General regulation of occupational safety and health Development phase IV: Regulation of development medicinal products Market authorization phase Regulation 726/2004: Objectives and scope of application Special regime for recombinant pharmaceuticals? Authorization prerequisites and procedure Labelling Institutional design Production phase Protection against risks to the environment by use and release of GMOs Coexistence between pharming and conventional and organic agriculture The problem Sources of regulation Confinement and protection measures Labelling requirements Liability Special issues in animal pharming Animal protection Production-related requirements under pharmaceuticals regulation References 283

7 XVIII Comprehensive table ofcontents 9 Conclusions and recommendations Pharming technology and its market Public attitudes and moral evaluation Attitudes Moral evaluation The assessment and management of risks associated with pharming Principles Casebycase Risk-benefit evaluation Independent risk assessment research Transparent procedures and independence of risk assessment bodies Product safety and information Measures to prevent contamination and ensure product quality New guidelines on pharming medicinal products and European Medicines Agency (EMEA) committee on pharming products Labelling and consumer information Risks to the environment and food and feed chains Experiments and cultivation with Containment, and deliberate releases Coexistence Risks to animals in pharming 300 Glossary 303 Appendix: Examples of GM pharmaceutical crops and animals 315 I. Production of molecular farmed human intrinsic factor (rhif) inpotato (Solarium tuberosum) 315 II. Production of Molecular Farmed human lactoferrin (rhlf) in rice (Oryza sativa) 316 III. Production of antithrombin in goats' (Capra hircus) milk 317 References 321 Listof authors 323 Index 329