Radiobioconjugate Targetting In Cancer In Developing Countries: Regulatory Issues

摘要

Radiobiopharmaceuticals for cancers include radiolabelled monoclonal antibodies, peptides,rnantisense nucleotides as well as intermediate molecules in pretar getting strategies. Developing countriesrnneed to consider several issues. Firstly such agents prior to radiolabelling need preparation according tornGood Manufacturing Practice. Secondly, for therapy use, since centralized distribution of a high dosernlabeled radiopharmaceutical may not be available nor feasible, logistic and economic, owing to distancesrnbetween the radiopharmaceutical manufacturers and user hospitals, high dose radiolabelling is necessitatedrnin house in the latter. This mandates understanding of hazards especially with volatile isotopes. Precautionsrninclude remote controlled pipetting and use of resins to mop up excess radiolabel .With other radiolabelsrnobtaining these at adequate specific activity and purity is sometimes difficult resulting in the need forrnconcentration Pretargetting strategies, the final agent being radiolabelled biotin/ radiolabelled chelate willrnenable centralized preparation and distribution. Thirdly availability of biological agents is hedged in byrnpatents. Developing countries thus need to manufacture centrally therapeutic molecules. Individual researchrncentres can only manufacture milligrams of an agent, whereas multicentre preclinical trials require at leastrn50 grams, needing biofermenters; mega kidney dialysis cartridge type systems, as each patient needs sayrn50-100 mg antibody per therapy course. Centralised manufacture of such quantities is estimated to bernsubstantially cheaper than the imported cost. Fourthly developing countries need appropriate regulatoryrnstandards e.g. pretesting a product for minute quantities of mouse viruses or DNA is expensive /rnunnecessary for each batch, as multiple chromatography steps for chemical purification eliminatesrnbiodangers. Fifthly some newer manufacturing techniques for biomolecules e.g. yeast based, may reducernbiohazards associated with conventional mammalian cell or bacterial manufacture. Sixthly there is anrnalarming patent trend where not only individual monoclonals but antigenic sites are restricted. Finally,rndeveloping country regulators must remember that tremendous costs in regulatory approval have led torneven developed countries sometimes being frozen in outmoded technology ,since obtaining approval forrnbetter molecules is costly, tedious and time consuming..