Invasive alien marine species have garnered a negative reputation outside of their native ranges, often due to them translocating disease from their native areas to their new environment. Much of the currently available resources on the disease status of marine species is focused on species of commercial importance such as the Blue mussel Mytilus edulis, Pacific oyster Crassostrea gigas or farmed abalone species e.g., Haliotis spp. The slipper limpet Crepidula fornicata is an invasive alien species, originating from the east coast of the United States. Crepidula fornicata is now found throughout the coastal waters of southern England and Wales, U.K. Crepidula fornicata is often thought of as a pest when found in commercial shellfish areas. However, despite this negative reputation, little is known about its disease status or immunobiology. Therefore, the aim of this thesis was to study the immunobiology of C. fornicata and to understand its potential as a harbourer of infectious disease. To address the lack of information available with regards to the immunobiology of C. fornicata in Chapter 2 haemolymph (blood) was isolated and examined for the presence of the immune-enzyme phenoloxidase. The presence of laccase and catecholoxidase activities were confirmed. Importantly, it was shown that products derived from laccase and catecholoxidase activities reduced the numbers of colony- forming units of bacteria in vitro. Tissue was also examined histologically, and the presence of eumelanin-like pigments and lipofuscin was visualised in a number of regions e.g., digestive gland, connective tissues, and gills. A year-long multi-resource disease survey was carried out at two sites in South Wales, Swansea Bay, a native oyster Ostrea edulis restoration site, and Milford Haven, an area of commercial shellfish activity. In Chapters 3 & 4 a combined PCR and histological approach was taken to screen C. fornicata for the presence of diseases potentially harmful to shellfish and/or humans e.g., Vibrios, haplosporidians, microsporidians, and paramyxids. Chapter 3 found that a large proportion of individuals were PCR positive for Vibrio-like bacteria. However, it was found through a histological screen that few disease signatures could be observed, suggesting that C. fornicata are not particularly sensitive to bacteriosis at the sites surveyed. Chapter 4 found no clinical signs of C. fornicata being infected with haplosporidians, microsporidians or paramyxids. Histology revealed the presence of trematodes, turbellarians, and an apicomplexan-like parasite. The data suggested that C. fornicata are not susceptible to major parasitic infections outside of the native range. A Species Distribution Model (SDM) was constructed in Chapter 5 to aim to understand the potential future distribution of C. fornicata under predicted climate change. Areas further north in North America, Europe, and Northeast Asia were identified as areas most at risk for future introductions of C. fornicata.

A819Objectives: Patients diagnosed with rare disease face shortened life expectancy, chronic disability and a lack of viable treatment options. When effective treatments are available there are financial challenges to achieving access, highlighting the need for government subsidy. In Australia, the desire to fund rare disease therapies in the context of the legislative requirement to evaluate the cost-effectiveness of new therapies has posed significant challenges. As part of sequential reviews of the Australian Life Saving Drugs Programme and PBAC guidelines, an Industry Working Group (IWG) was established to formulate recommendations from the perspective of potential sponsors of rare disease therapies. MethOds: A multi-stage review and development process was conducted: Development of a framework for consideration of amended PBAC guidelines for rare disease therapies. An international review of health technology assessment (HTA) guidelines for rare disease therapies. Development of recommendations to Government for amending the newly revised PBAC guidelines. Results: Current challenges identified by the IWG include: obtaining appropriate advice and guidance upfront; communicating the burden of disease; reliance on lower levels of evidence; challenges in demonstrating cost-effectiveness; transparency of decision making. The IWG supported a recommendation to establish a fit-for-purpose process for evaluation of rare disease therapies. Through a review of guidelines for rare disease therapies from England, Scotland and Canada -several themes emerged: early engagement via an established pre-submission process; flexible evidence requirements and cost-effectiveness criteria; a clear decision making framework; a formalised stakeholder engagement framework; improved transparency in decision making and funding decisions. Results will inform specific recommendations to government. cOnclusiOns: There are unique challenges with assessing rare disease therapies for funding as part of a broader HTA process. Experience from Australia shows industry can partner with government and provide innovative solutions for how these challenges might be recognised as part of the evaluation framework. HealtH Care Use & PoliCy stUdies -Formulary development PHP31 WHat's NeW iN tHe GUideliNes For sUbmissioN oF dossier For listiNG iNto tHe miNistry oF HealtH mediCiNes FormUlary (moHmF) ?