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Characterisation of non- biological complex drugs

Due to their heterogeneity, each NBCD requires its own toolbox for specific characterisation and this article provides an overview of different methods that have been used successfully to characterise and compare this class of drugs

Julia Schnorr Peter Langguth PhD Institute of Pharmacy and Biochemistry, Department of Pharmaceutical Technology and Biopharmaceutics, Johannes Gutenberg University, Mainz, Germany

A rising number of newly approved drugs is more complex and differ in terms of structure from most small, single-molecular drugs. Furthermore, they are most commonly administered by injection or infusion. One group has been termed non-biological complex drugs (NBCDs). This class is not represented by members having similar pharmacological effects, but rather analogies in their structure and similarity in manufacturing and characterisation. In contrast to biologicals, which are synthesised by biological sources, NBCDs are synthetic drugs such as drug-bearing liposomes (for example, AmBisome®

, Caelyx® ), glatiramoids (for example, Copaxone® NBCDs can be )

and iron carbohydrate complexes for parenteral use. According to a definition provided previously, 1

characterised by four key attributes: 1. They consist of a multitude of closely related nanoscopic structures;

2. The whole complex is responsible for the pharmacological effect;

3. Their activity cannot be fully characterised by physicochemical methods, and;

4. Their manufacturing process is especially crucial for a reproducible performing product.


A long time before the scientific community recognised the issue of

NBCDs, iron carbohydrate complexes have been used in clinical practice 2

later 9, 10 . All

colloidal iron preparations contain iron oxide hydroxide nanoparticles (FeOOH) and a varying carbohydrate, for example, dextrane, saccharate, gluconate or isomaltoside. Although all complexes contain iron as the putative active ingredient, these complexes show differences in clinical 3, 4

studies. 5– 8 In 2009, FerMed®

and non-clinical (iron

sucrose) was marketed in Germany as a generic product of Venofer®


performing any comparative tissue distribution studies. Reports published

raised doubts about the

biosimilarity between the two products. These discoveries go hand in hand with De Vlieger’s definition for NBCDs 1


which states that it is not possible to fully predict the pharmacological activity of NBCDs using physicochemical methods alone. Additional in vitro and in vivo analyses are therefore mandatory to obtain a deeper understanding of the complex structure and make scientifically justified statements about similarities and therapeutic equivalence of NBCDs and thus their substitution. Despite similar ingredients, a different

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