Table 2.

European public assessment reports comparison—filgrastim

	Zarzio/filgrastim hexal	Biograstim/filgrastim ratiopharm/ratiograstim/tevagrastim (XM02)	Nivestim
Product characteristics
Produced	E. Coli	E. Coli	E. Coli
Strength	Two strengths: 30 MU/0.5 ml and 48 MU/0.5 ml.	Two strengths: 30 or 48 MIU (corresponding to 300 and 480 μg respectively).	Three strengths: 120 μg/0.2 ml, 300 μg/0.5 ml and 480 μg/0.5 ml.
Medicinal product	Product composition of Zarzio and Neupogen® are quantitatively identical except the buffer system, glutamate for Zarzio and acetate for Neupogen®	Buffered with acetate. Differs from Neupogen® only in pH and in the concentration of filgrastim and polysorbate 80.	Buffered with acetate.
Pre-clinical data
Studies	6 primary PD studies (4 in vitro); 3 toxicology studies (comparative repeat-dose toxicity, toxicokinetics, local tolerance; no single-dose toxicity study); no secondary PD studies; no safety pharmacology studies; no PK studies	6 primary PD studies (3 in vitro); 1 secondary PD study (in vitro); 3 safety pharmacology studies; 2 PK studies; 6 toxicology studies (repeat dose toxicity study non-comparative)	Primary PD studies: PD response was determined in a neutropenic rat model, as well as in healthy rat in a repeat-dose toxicity study; no secondary PD studies; no safety pharmacology studies; PK assessed as part of the repeat-dose toxicity study; no single-dose toxicity study
Clinical data
Phase I (PK/PD) studies	4 PK/PD studies in healthy volunteers	2 PK/PD studies in healthy volunteers	2 PK/PD studies in healthy voluteers
Phase III studies	1 non-controlled study in patients with breast cancer	3 RCTS (patients with breast cancer, lung cancer, NHL)	1 RCT in patients with breast cancer
Efficacy data	Similar to Neupogen® The comparability of the efficacy based on a PPD study in healthy volunteers (absolute neutrophile and CS34+ cell counts) was considered acceptable by the CHMP.	Similar to Neupogen® There were no statistically significant differences between XM02 and Neupogen® with regard to the mean ANC nadir and with regard to time to ANC recovery in the studies.	Similar to Neupogen® There was therapeutic equivalence between the two products in terms of efficacy with regard to the mean ANC nadir and with regard to time to ANC recovery.
Safety data	Similar to Neupogen®	Similar to Neupogen®	Similar to Neupogen®