309 KB46 KB199820252017Doljak, BojanJurca, SabinaKragelj Lapanja, NevenkaToplak Časar, Renataštevilka:1letnik:64str. 1-14ISSN:1318-0207COBISSID_HOST:4393841URN:URN:NBN:SI:doc-IQYTO3F1enSlovensko kemijsko društvoActa chimica slovenicaFarmacevtska industrijagenotoksične nečistotemutagene nečistotezdravilne učinkovineTheoretical purge factor determination as a control strategy for potential mutagenic impurities in the synthesis of drug substances|Mutagenic impurities (MIs) are of serious concern for pharmaceutical industry, regulatory agencies and public health. The first guideline addressing the control of genotoxic impurities (GTIs) dates back to 2006. Since then there have been several updates and refinements, which eventually resulted in the guideline, published by the International Conference on Harmonisation (ICH) in June 2014. The ICH M7 guideline, compared to previous ones, offers greater flexibility in terms of control strategies for GTIs in drug substances. More specifically, it describes a control strategy that relies on process controls in lieu of analytical testing which is based on understanding the process chemistry and process parameters that impact the levels of GTIs. This principle is adopted in the theoretical purge factor determination tool proposed by Teasdale et al. Several case studies applying the proposed theoretical purge factor determination tool were published in recent years. The results confirm the tool%s good predictability of the extent to which the impurity is removed by the process. Hopefully, this approach will soon be released as an in-silico tool, generally accepted by the regulatory agenciesMutagene nečistote predstavljajo velik problem za farmacevtsko industrijo, regulatorne oblasti in javno zdravje. Prva regulatorna smernica, ki je obravnavala nadzor genotoksičnih nečistot je bila izdana leta 2006, sledile pa so številne dopolnitve in izboljšave. Junija 2014 je bila s strani mednarodne konference o harmonizaciji zahtev izdana smernica ICH M7, ki v primerjavi s prvotnimi smernicami ponuja bolj pragmatične možnosti za nadzor genotoksičnih nečistot v zdravilnih učinkovinah. Poleg analitskega spremljanja genotoksičnih nečistot ima sedaj farmacevtska industrija preko smernice ICH M7 možnost kontrolne strategije, ki sloni na razumevanju procesa sinteze in na oceni vpliva procesnih parametrov na nivo pridobljenih in nastalih nečistot. Ta pristop je predlagal in prvi opisal A. Teasdale s sodelavci. Predlagani pristop izračuna teoretičnih faktorjev očiščenja je bil v zadnjih letih uporabljen na številnih praktičnih primerih. Objavljeni rezultati kažejo na to, da lahko s tem pristopom precej dobro napovemo sposobnost očiščenja nečistot skozi proces. Upati velja, da bo omenjeni pristop kmalu na voljo v obliki računalniškega orodja, ki bo splošno sprejemljiv s strani regulatornih oblastiTEXTznanstveno časopisjejournalsSlovenian National E-content AggregatorNational and University Library of SloveniaSlovensko kemijsko društvo