药物BCS分类系统.ppt

World Health Organization Biopharmaceutical Classification System (BCS) Background What is a problem? What is WHO doing and planning to do? What resources are available? Conclusions What is the key for multisource (generic) pharmaceutical products? New medicines – applicant has to prove quality, safety and efficacy Multisource (generic) pharmaceutical products – applicant has to prove quality, in case of safety and efficacy it refers to the originator product The key is THERAPEUTIC INTERCHANGEABILITY It is assumed that if the concentration pattern in the blood is essentially the same then the safety and efficacy profile must be essentially the same Therapeutic interchangeability: prerequisites Constant and reproducible quality of MPPs Manufactured under GMP Compliance with all quality specifications Variations control No constant and reproducible quality, no need for proving interchangeability as it is meaningless (all batches different anyhow…) Options to show therapeutic interchangeability of multisource pharmaceutical products (MPP) The in vitro approach refers to the Biopharmaceutics Classification System (BCS) In Vitro Approaches/Biowaiver options The possibility of ‘in vitro documentation of bioequivalence’ for ‘certain medicines and dosage forms’ is specified in Section 9 of the WHO guidance document [1]. If the drug substance in question is highly soluble and highly permeable (BCS class I) and is manufactured as an immediate release dosage form, exemption from an in vivo pharmacokinetic bioequivalence study may be considered provided that relevant dissolution requirements are fulfilled. Principles The solubility is not meant to be the absolute solubility here. In contrast high solubility refers to the highest single unit dose to be completely soluble in 250 ml aqueous buffer medium within the pH range of 1.2 to 6.8 without any stability problems. As another related physicochemical characteristic high permeability should be demonstrated for the pa