The development of microbial pest control products for control of arthropods: a critical evaluation and a roadmap to success ______________________ Willem Ravensberg Thesis committee Thesis supervisor Prof. dr. J.C. van Lenteren Professor of Entomology, Wageningen University Other members Prof. dr. ir. J. Bakker, Wageningen University Prof. dr. ir. R.H. Wijffels, Wageningen University Dr. M.M. van Oers, Wageningen University Dr. J.W.A. Scheepmaker, National Institute for Public Health and the Enviroment, Bilthoven This research was conducted under the auspices of the Graduate School of Production Ecology and Resource Conservation Willem Ravensberg The development of microbial pest control products for control of arthropods: a critical evaluation and a roadmap to success ______________________ Thesis submitted in fulfilment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. dr. M.J. Kropff, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Tuesday 7 September 2010 at 11.00 a.m. in the Aula. Ravensberg, W.J. (2010) The development of microbial pest control products for control of arthropods: a critical evaluation and a roadmap to success PhD Thesis Wageningen University, Wageningen, NL (2010) With references, with a summary in English ISBN 978-90-8585-678-8 to my late parents Contents ___________________________________________________________________________ Contents List of Acronyms and Abbreviations ix-x Chapter 1 General introduction and outline 1 Chapter 2 Selection of a new microbial pest control agent 17 Chapter 3 Mass production and product development of a microbial pest control agent 45 Chapter 4 Quality control 99 Chapter 5 Registration of microbial pest control agents and products and other related regulations 133 Chapter 6 Implementation of a microbial pest control product in an integrated pest management programme 181 Chapter 7 Critical factors in the successful commercialization of microbial pest control products 225 Chapter 8 Roadmap to success and future perspective 275 References 293 Summary 337 Acknowledgement 341 Curriculum vitae 343 List of publications 345 vii viii Acronyms and Abbreviations ___________________________________________________________________________ List of Acronyms and Abbreviations ABIM - Annual Biocontrol Industry Meeting ABS - Access and Benefit Sharing ATCC - American Type Culture Collection BCA - Biological Control Agent BIPESCO - Biocontrol of Important Soil Dwelling Pests by improving the Efficacy of Insect Pathogenic Fungi (EU research project) BPIA - Biopesticide Industry Alliance (USA) BPPD - Biopesticides and Pollution Prevention Division (of the US-EPA) BPSG - BioPesticides Steering Group (OECD) BVL - Bundesamt für Verbraucherschutz und Lebensmittelsicherheit (The Federal Office for Consumer Protection and Food Supply), Germany CABI - Commonwealth Agricultural Bureau International CBD - Convention on Biological Diversity CBS - Centraal Bureau voor Schimmelcultures (Fungal Biodiversity Centre) CFU - Colony Forming Unit CIPAC - Collaborative International Pesticides Analytical Council COST - Cooperation in Science and Technology (EU projects) CRD - Chemicals Regulation Directorate (United Kingdom) CRO - Contract Research Organization CTB - College voor de Toelating van Bestrijdingsmiddelen (the Netherlands) CTGB - College voor de Toelating van Gewasbeschermingsmiddelen en Biociden (Board for the Authorisation of Plant Protection Products and Biocides (the Netherlands) DAR - Draft Assessment Report DG SANCO - Directorate-General for Health and Consumers (EU) DG ENVI - Directorate-General Environment (EU) DJ - Dauer Juvenile (of entomopathogenic nematode) DSMZ - Deutsche Sammlung von Mikroorganismen und Zellkulturen (German Collection of Microorganisms and Cell Cultures) EC - European Commission ECS - European Committee for Standardization EFSA - European Food Safety Authority EPA - Environmental Protection Agency (USA) EPC - European Patent Convention EPN - Entomopathogenic Nematode EPO - European Patent Office EPPO - European Plant Protection Organisation ERA - Environmental Risk Assessment EU - European Union EUROSTAT - Statistical Office of the European Communities FAO - Food and Agriculture Organization (United Nations) GEP - Good Experimental Practices GLP - Good Laboratory Practices ix Acronyms and Abbreviations __________________________________________________________________________ GMO - Genetically Modified Organisms GMP - Good Manufacturing Practices GV - Granuloviruses HACCP - Hazard Analysis and Critical Control Points IBCA - Invertebrate Biological Control Agent IBMA - International Biocontrol Manufacturers Association IGR - Insect Growth Regulator IOBC - International Organization for Biological and Integrated Control of Noxious Animals and Plants IOBC/EPS - IOBC East Palaearctic Section IOBC/WPRS - IOBC West Palaearctic Regional Section IP(R) - Intellectual Property (Rights) IPM - Integrated Pest Management ISO - International Organization for Standardization ISPM - International Standards for Phytosanitary Measures (FAO) LSF - Liquid State Fermentation MPCA - M icrobial Pest Control Agent MPCP - Microbial Pest Control Product MSDS - Material and Safety Data Sheet MRL - Maximum Residue Level MS - Member State of the European Union NPV - Nucleopolyhedroviruses OB - Occlusion Bodies OECD - Organisation for Economic Co-operation and Development PCT - Patent Cooperation Treaty PIB - Polyhedral Inclusion Bodies PMRA - Pest Management Regulatory Agency (Canada) PSD - Pesticide Safety Directorate (United Kingdom) PPP - Plant Protection Product QC - Quality Control RAFBCA - Risk Assessment of Fungal BioControl Agents (EU research project) REBECA - Regulation of Biological Control Agents (EU research project) RMS - Rapporteur Member State SIP - Society for Invertebrate Pathology SSF - Solid State Fermentation TGAI - Technical Grade Active Ingredient TQC - Total Quality Control USDA - United States Department of Agriculture VWA - Voedsel en Waren Autoriteit (in Dutch) (Food and Consumer Product Safety Authority) WHO - World Health Organization (United Nations) x General introduction and outline ___________________________________________________________________________ Chapter 1 General introduction and outline Contents Abstract ...................................................................................................................................... 1 Introduction .............................................................................................................................. 2 Microbial pest control products ............................................................................................ 2 The early history of microbial control.................................................................................. 2 The first microbial pest control products.............................................................................. 3 The rise and struggle of the biopesticide industry................................................................ 3 Hurdles and constraints ........................................................................................................ 3 The need for a roadmap for the development of a microbial pest control product ............ 5 Insect pathogens as microbial control agents ........................................................................ 7 Bacteria.................................................................................................................................. 7 Fungi...................................................................................................................................... 7 Viruses ................................................................................................................................... 8 Protozoa and Microsporidia.................................................................................................. 8 Nematodes.............................................................................................................................. 8 Aim of this thesis ...................................................................................................................... 9 Outline of this thesis............................................................................................................... 10 Appendix: Terminology and definitions .............................................................................. 13 Microbial pest control agents and products ....................................................................... 13 Biological control and microbial control ........................................................................... 14 Biocontrol strategies............................................................................................................ 15 Taxonomy ............................................................................................................................ 15 Abstract Microbial pesticides have been developed for a hundred years, but many of these crop protection products have not been successful in the market. The history of microbial pest control products is summarized, the companies involved are reviewed, and the reasons for failure in obtaining success are briefly described. The need for a model that facilitates the development and commercialization of these products is recognized. The entomopathogenic bacteria, fungi, viruses