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.

Differences between
Small Molecules and Biologics

Small Molecule DrugsBiological Products
Generally low molecular weightGenerally high molecular weight
Usually organic or chemicalMade with/from live cells/organisms (inherent & contamination risk)
Fewer critical process stepsMany critical process steps​
Well-characterisedLess easily characterised
Known structureStructure may or may not be completely defined or known
Homogeneous drug substanceHeterogeneous mixtures (which may include variants)
Usually not immunogenicOften 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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Lot and Batch Release Testing

Formulations for Inhalation

Oral Dosage Formulations