As the latter is an option only for generics for which the originator medicinal products already obtained marketing authorization from a centralized procedure, this option Selleck CB-5083 may receive more attention with the increasing number of medicinal products with centralized authorizations that are running off data protection and patent in the next years. With the intent to enable a consistent approach for these different routes the European Medicines Agency (EMA) issued an initiative to harmonize the data requirements throughout European Member States, i.e. EMA initiated a pro-active program “Product-specific Bioequivalence-Guidance for Generics” [15]. EMA

defines the objective of this initiative as follows: “Product specific guidance for the bioequivalence assessment of immediate release generic formulations should a priori be defined.”

Thus, applicants should be given a clear scientific guidance, how to design BE-studies and, thus, how to file generic applications. This program includes BCS-classifications for drug substances, so that a harmonized view on the BCS classification and consequently the appropriateness of a BCS-based biowaiver approach can be expected for respective products. Furthermore, the guidance provides information on the type of expected data, e.g. appropriate study population (patients or healthy volunteers), mode of administration (fasten or fed), single dose or steady state-design, appropriate dose strength and analytes, the classification

as NTID. The first wave of 16 medicinal products is dominated by anti-infectives and TKI. Dasatinib, Erlotinib, selleck products Imatinib, Sorafenib and Sunitinib are covered in this first round of harmonization [15]. From a clinician’s point of view regarding drug safety (Table 2), one could be tempted to assume that all anti-cancer Terminal deoxynucleotidyl transferase medicinal products including TKI are considered as NTID. However, this is not the case. Different definitions of NTID by different regulatory agencies do exist. US-FDA classification of narrow therapeutic ratio: → Less than a 2-fold difference in median lethal dose (LD50) and median effective dose values (ED50), -or → Less than 2-fold difference in the minimum toxic concentrations (MTC) and minimum effective concentrations (MEC) in the blood or → Safe and effective use of the drug products require careful titration and patient monitoring. In contrast to the US, for the EU no list of substances with NTID-designation is available. So far the consideration of a given substance as NTID is mainly based on national traditions. Only for a few medicinal substances (e.g. Ciclosporine, Tacrolimus) a harmonized EU decision was issued by a referral procedure. According to the draft “Product-specific Bioequivalence – Guidance for Generics” no drug is newly considered as NTID, only Tacrolimus is considered as such based on the previously finalized referral procedure.