Check GAD antibody positivity with the Diamyd anti-GAD RIA plate*

Diamyd’s Commercial Development of a GAD VaccineJohn RobertsonDiamyd Medical has been pioneering both the evaluation of clinical safetyand clinical efficacy of GAD – with a view to its potential use as a vaccine toprevent autoimmune diabetes. Both these achievements were made possibleby Diamyd’s early definition of a manufacturing process – capable ofproviding the quantity and quality of GAD required for different stages ofcommercial drug development.Our manufacturing process relies on the expression ofrecombinant human GAD65 in an insect cell line -grown under special conditions – after infection withan insect specific baculovirus containing the GADcDNA (our “baculoGAD” recombinant clone). This is referred to asthe baculovirus/insect cell expression system (or BVES). Both thequantity and quality of GAD manufactured by our BVES processhave proven appropriate up to the current stage of development – andseem likely to meet our future requirements up to market introduction.While currently at the 50 litre scale (with each 50L batch providingsufficient GAD for thousands of vaccinations) we have alreadyfound that our process can readily be scaled-up to 500 litres (providingtens of thousands of vaccinations per batch). So, pending thesuccessful outcome of our Phase II, our manufacturing process seemscapable of producing sufficient GAD for further clinical developmentand market introduction.Apart from its suitability for manufacturing active GAD, theBVES also has inherent safety advantages – as a non-mammalianexpression system modified to avoid contact with any mammaliancomponents. This implies the low risk of contamination of our vaccineby harmful viruses. Moreover, because the vast majority of humanviruses are not able to grow in the insect cells used, the likelihood ofthese inadvertently being propagated during manufacture and contaminatingour vaccine is considerably reduced. Similarly, because the“baculoGAD” recombinant clone is an insect-specific virus (that cannot infect mammalian cells) the risk imposed by possible residual tracesof residual virus in our vaccine is greatly reduced.A final attribute of our GAD therapeutic strategy has recentlySf9InsectcellsDiamyd - cGMP manufacturerhGAD65 Bulk Drug50LfermenterExtract/PurifyrhGA D65Bulk DrugDiamydGADrecombinantbaculovirusFormulationDiamydFormulation/FillAlumDiamyd Vaccinebecome apparent. Despite only one (or a few) small regions (ca. 12amino acids) of GAD being thought as likely to be active, we madethe decision at the outset (now 9 years ago) that we would not riskpage 42 dmccad june 2003