What is a Biopharmaceutical?
A biopharmaceutical, also termed a “biologic”, is a medical therapeutic (or drug) that has been synthesized or extracted from a biological source, such as a cell.
Biopharmaceuticals vs pharmaceuticals
A biopharmaceutical, also termed a “biologic”, is a medical therapeutic (or drug) that has been synthesized or extracted from a biological source, such as a cell.
The main difference between pharmaceuticals and biopharmaceuticals is that pharmaceuticals have been chemically synthesized whereas biopharmaceuticals have been made using some form of biological source or host.
From March 2020, chemically synthesized polypeptides, such as insulin, will be considered as biologics by the FDA and drug submissions will be considered according to biologics regulations.
Some examples of biopharmaceuticals include:
- Proteins, including antibodies
- Peptides
- Cells, such as stem cells
- Organs and tissues (e.g. transplants)
- Vaccines
- Gene Therapy Medicinal Products (e.g. AAV based therapeutics)
Biopharmaceutical Testing
Structural and physicochemical characterization are a crucial part of biopharmaceutical product development. These are some of the analytical methods and tests that allow drug developers to be sure that they have correctly manufactured their target drug. The FDA and EMA have set out their own guideline expectations for the protein characterization methods to be performed. Both agencies have adopted the characterization approach outlined in a regulatory document called ICH Topic Q6B.
ICH Topic Q6B provides examples of technical approaches to be considered for structural characterization and confirmation, and evaluation of physicochemical properties of the desired product, drug substance and/or drug product. The specific characterization assays employed will vary from product to product and alternative approaches may be appropriate in many cases. The guideline recognizes that new analytical technology and modifications to existing technology are continuously being developed and should be utilized when appropriate.
ICH Q6B requires data covering the following structural and physicochemical elements for the biopharmaceutical:
| Amino acid sequence | N-terminal sequencing (Edman chemistry) Mass-spectrometric sequencing | N-terminal sequencer On line LC-MS (with MSe and/or MS/MS) MALDI-MS and MS/MS |
| Amino acid composition | Amino acid analysis | Amino acid Analyzer (e.g. RP-HPLC with fluorescence detector) |
| Terminal amino acid sequence | N-terminal sequencing (Edman or mass spectrometry) Mass spectrometry based sequencing for the C-terminus | N-terminal sequencer Mass spectrometer capable of providing N- and C-terminal sequence information |
| Peptide map | Peptide mapping | On line LC-MS (with MSe and/or MS/MS) |
| Sulfydryl group(s) and disulfide bridges | Non-reduced peptide mapping | On line LC-MS (with MSe and/or MS/MS) |
| Carbohydrate structure | Monosaccharide composition analysis Oligosaccharide population analysis Linkage analysis Glycosylation site analysis | GC-MS LC and on line LC-MS (with MSe and/or MS/MS) MALDI-MS and MS/MS |
| Molecular weight or size | Intact molecular weight analysis | On line LC-MS MALDI-MS |
| Isoform pattern | IsoElectric Focusing (IEF) | Imaged Capillary IEF (icIEF) |
| Extinction coefficient | Optical density measurement and protein concentration determination | UV spectrophotometer Amino acid Analyzer (e.g. RP-HPLC with fluorescence detector) |
| Electrophoretic analysis | Charge and size based electrophoretic analysis | icIEF Capillary Gel Electrophoresis (CE-SDS) |
| Liquid Chromatography | Charge, size and hydrophilicity/hydrophobicity based chromatographic analyses | Ion-exchange chromatography (IEX) Size Exclusion Chromatography (SEC) Reversed Phase Chromatography (RP-HPLC) |
| Spectroscopic profiles | Secondary and tertiary structure analysis | NMR (1D and 2D) Circular Dichroism (CD) Fourier Transform-Infra Red (FT-IR) Fluorescence (Intrinsic and Extrinsic) |
| Analysis of truncated forms | Intact molecular weight analysis Peptide mapping Size based chromatographic and electrophoretic analysis | On line LC-MS (with MSe and/or MS/MS) MALDI-MS SEC CE-SDS |
| Analysis of other modified forms, including Post Translational Modifications (PTMs) | Intact molecular weight Peptide mapping Oligosaccharide profiling Isoform profiling | On line LC-MS (with MSe and/or MS/MS) MALDI-MS icIEF |
| Aggregation | Size based chromatography, Analytical UltraCentrifugation (AUC) | Size Exclusion Chromatography with Multi Angle Laserlight Scattering (SEC-MALS) Sedimentation Velocity-Analytical UltraCentrifugation (SV-AUC) |
Expert assessment of the structure of your product.
BioPharmaSpec scientists can accelerate the development of your product by suggesting the most efficient and effective characterization strategies.