Biologics differ from chemically synthesised drugs in a number of ways which impacts on their cost, manufacture and routes of administration.
The level and complexity of the testing required is dependent on two primary factors, the product indication and nature of the product more specifically the source and level of control of the raw materials, the complexity, robustness and level of control deployed during the manufacturing process, the chemical complexity of the drug substance, the chemical complexity of the drug product and the reliability and complexity of the methods used to evaluate identity, purity, and potency of the drug substance and the drug product.
Tepnel has extensive experience in lot release testing of biologics, specifically peptides, proteins, vaccines and anti-allergenics.
Small Molecules and Biologics
|Small Molecule Drugs||Biological Products|
|Generally low molecular weight||Generally high molecular weight|
|Usually organic or chemical||Made with/from live cells/organisms (inherent & contamination risk)|
|Fewer critical process steps||Many critical process steps|
|Well-characterised||Less easily characterised|
|Known structure||Structure may or may not be completely defined or known|
|Homogeneous drug substance||Heterogeneous mixtures (which may include variants)|
|Usually not immunogenic||Often Immunogenic|
Testing available for biologics:
- Pharmacopeia Monograph Tests (EP, BP, USP and the JP)
- Protein purity assay and related proteins (by HPLC and Isoelectric Focusing (IEF))
- Impurities with higher molecular masses (by Size Exclusion Chromatography (SEC))
- Gel electrophoresis (SDS-PAGE)
- Protein Concentration (A280, Bradford Assay, HPLC)
- Bacterial Endotoxins Eur Ph (2.6.14) or USP
- Sterility Testing Eur Ph
- Physico-chemico properties including appearance, colour, clarity/opalescence pH, particulates, turbidity, extractable volume, osmolality and moisture.
Forced degradation studies play a central role in the development of proteins, peptides and antibody formulations. Typical stress methods such as exposure to elevated temperatures, freeze-thawing, mechanical stress, oxidation, light, as well as various materials and devices used in the clinics during final administration need to be used to test the stability of a formulation.
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