NBCD Characterization
THE PROCESS IS THE PRODUCT – Proof of a consistent, carefully controlled manufacturing process
In contrast to small molecule characterization, nanoparticulated non-biological complex drugs (NBCD’s) cannot be fully characterized by physico-chemical analytical methods.
However, the similarity of many physico-chemical properties like e.g. particle size, size distribution, molar ratios of selected components and other special analytical methodologies, can be used to demonstrate and ensure that a manufacturing process is consistently planned and performed carefully.
Furthermore, the more all-encompassing such a characterization is, the better a physico-chemical similarity between e.g. a generic NBCD and a reference listed drug can be elucidated.
Suisse TP offers a sound experience in NBCD characterization, especially in nanoparticulated iron carbohydrate complexes.
For such iron-based nano-colloidal products Health and Regulatory Authorities like EMA and FDA have published draft guidances. These list three main quality attributes that may have a major impact on efficacy and safety. Therefore, these attributes should be investigated extensively:
- The stability of the iron-carbohydrate complex
- The physico-chemical properties of the carbohydrate matrix
- The physico-chemical properties of the iron core and the whole iron-carbohydrate particle
Based on the example of iron-based nano-colloidal products, Suisse Tp offers the following physico-chemical characterization methods:
Whole Particle
Overall particle Size
- Molecular weight (MW) - GPC
- Polydispersity Index - GPC
- Particle Size - DLS
Ferrous iron content (Fe2+)
- Ferrous iron content (Fe2+) - Cerimetric titration
- Ferrozin Assay - UV Spectrometry
Reductive degradation kinetics
- Complex Stability as "acid soluble iron" by determination of t0.5 - UV Spectrometry
Na content
- ICP-OES
- AAS
Total iron
- Iron assay
- ICP-OES
- Complexometric titration with EDTA
Free iron (or "dialysable iron" or "low molecular weight iron")
- Free iron (or dialyzable iron) - Ultrafiltration, ICP-MS
- under physiological conditions (in human serum) - Ferrozine, Bleomycin or other assays
Metal impurities
- ICP-MS
Total carbon
- C/S - Analyzer
Iron Core
Size & Morphology of Iron Core
- Diameter and Morphology - TEM
Carbohydrate Shell
Composition
- decomposition pattern - FT-IR
- water loss - 1H and/or 13C NMR
- degradation - TGA
- melting of the complex - DSC
Particle Size Changes under dilution and/or dialysis
- Particle Size Changes under dilution and/or dialysis
- DLS
Surface Charge
- Zeta Potential by Dynamic light Scattering
- DLS
Method development
Appropriate analysis methods need to be developed for new products and for the qualitative and quantitative determination of unknown substances. The experienced analysts of Suisse TP develop optimized and therefore cost-effective analysis methods. If required we develop those methods according to ICH guidline Q2(R2)/Q14 EWG – “Analytical Procedure Development and Revision of Q2 (R1) Analytical Validation”
a few examples of typical applications are
- Development of release-relevant analysis methods for APIs
- Development of analytical methods for the cleaning validation
- Creation of complete analysis packages for the monitoring of chemical production processes
- Development of routine analyses according to customer requirements
- …
