Erik Philipp

Iron sucrose: assessing the similarity between the originator drug and its intended copies

Iron sucrose (IS) is a complex nanocolloidal intravenous suspension used in the treatment of iron‐deficiency anemia. Follow‐on IS products (iron sucrose similars (ISSs)) have obtained marketing authorization by the generic pathway, implying that identical copies of IS may be manufactured. However, recent prospective and retrospective clinical studies showed discrepancies in clinical outcomes, which might be related to differences in physicochemical properties. The aim of this work is to measure and compare the physicochemical properties of IS and three ISSs available in the market using innovative analytical procedures. The comprehensive elucidation of size, size distribution, morphology, and stability of these complex drugs revealed very significant differences between the products. This study serves to provide the basis to define critical quality attributes that may be linked to differences in clinical outcome and thus may contribute to an adequate regulatory approach for IS and its follow‐on products.

Diluting ferric carboxymaltose in sodium chloride infusion solution (0.9% w/v) in polypropylene bottles and bags: effects on chemical stability

Objectives This study was designed to assess the physicochemical stability of colloidal ferric carboxymaltose solution (Ferinject) when diluted and stored in polypropylene (PP) bottles and bags for infusion. Methods Two batches of ferric carboxymaltose solution (Ferinject) were diluted (500 mg, 200 mg and 100 mg iron in 100 mL saline) in PP bottles or bags under aseptic conditions. The diluted solutions were stored at 30°C and 75%±5% relative humidity (rH) for 72 h, and samples were withdrawn aseptically at preparation and after 24 h, 48 h and 72 h. Multiple parameters were used to test stability-related measures (pH, total iron and iron (II) content, molecular weight range determination, microbial contamination and particles count ≥10 μm). Results Overall, Ferinject diluted in 0.9% (w/v) NaCl solution and stored in PP bottles and bags was stable within the specifications for the complex and the acceptability limits set for all assays. In both containers, total iron content remained stable, within 10% of the theoretical iron content, and levels of iron (II) remained far below the threshold of acceptability. All preparations were free from sediments, particle numbers were acceptable and there was no microbial contamination. The molecular weight distribution and polydispersity index were also acceptable. Conclusions Under the tested experimental conditions, colloidal ferric carboxymaltose solution (Ferinject) diluted in saline in PP infusion bottles or bags demonstrated physical and chemical stability for up to 72 h at 30°C and 75% rH. Because of the lack of additional clinical data, when using ferric carboxymaltose, physicians/pharmacists should refer to the dilution and storing recommendations given in the products summary of product characteristics.