Biologics Drug Development

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.

Benjah-bmm27, Public domain, via Wikimedia Commons

Emw, CC BY-SA 3.0, via Wikimedia Commons

Emw, CC BY-SA 3.0, via Wikimedia Commons

Our Solutions

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
  • N-Glycosylation
  • Host Cell Proteins (HCPs)
  • Post-translational modifications
  • Size Exclusion Chromatography (SEC), Ion Exchange Chromatography (IEX), and other HPLC Analysis of Biologics
  • Misincorporations
  • 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.