What is Biologics Drug Development?
Biologics or Biopharmaceuticals are a group of therapeutic agents manufactured from biological sources and without a single defined chemical structure or composition. Biologics may be isolated from various biological sources, such as human, animal, microorganism, and/or may be produced by modern biotechnology methods.
Biologics can be composed of proteins, nucleic acids, sugars, or complex combinations of these components, as well as include cell-based therapies, vaccines, and gene therapies.
In the past 10 years, Biopharmaceuticals have dominated new drug applications (NDAs) as compared to traditional small molecule-based drugs.
Emery Pharma has the required expertise and facilities to routinely characterize a wide variety of structural and chemical qualities in biologic compounds.
We offer an extensive array of biologics characterization services, including de novo method development and validation.
- Peptide mapping
- Intact Mass and Fragment Analyses via LC-MS
- Host Cell Proteins (HCPs)
- Post-translational modifications
- Size Exclusion Chromatography (SEC), Ion Exchange Chromatography (IEX), and other HPLC Analysis of Biologics
- Stability assessment
- Release testing
- Comparability studies
- Characterization studies
- Activity assays
- Quantitative assessment
- Impurity identification
- Bioanalyses (pharmacokinetics/toxicokinetics, biomarkers)
Challenges with Biologics Characterization
The challenges of biologics characterization are related to the complexity and size of their molecular structure(s). As compared to traditional small molecule drugs, which have a single defined structure, Biopharmaceuticals require much more involved characterization via a variety of analytical techniques such as HPLC, LC-MS, etc.
The exact characterization depends on the nature of the biologic, for monoclonal antibodies (mAbs), antibody fragments, proteins, peptide-based therapies, or Antibody-Drug Conjugates (ADCs), the following may be considered:
- The identity of the biologic molecule is determined through liquid chromatography – mass spectrometry (LC-MS) analysis of both the intact molecule and a proteolytic digest.
- The purity of the drug substance/product can be assessed with respect to the extent of aggregation via Size Exclusion Chromatography, a type of HPLC analysis (SEC-HPLC). Whereas the purity with respect to charge variants on the active pharmaceutical ingredient (API) is determined through Ion Exchange Chromatography, another type of HPLC analysis (IEX-HPLC).
- The biopharmaceutical must also be characterized for amino acid sequence and modifications including glycosylation, misincorporations, and post-translational modifications (PTMs). The observed modifications may further be isolated by preparative/semi-prep HPLC and characterized.
- For ADCs, additional analyses around drug-to-antibody ratio (DAR) are required.
At Emery Pharma, Biologics characterization is performed primarily on ultraperformance liquid chromatography (UPLC), high-field Orbitrap mass spectrometer (m/z up to 8000!), Plate readers (ligand-binding assays), etc.