Release & Stability

• Compendial Tests

  Standardized tests for common quality attributes

   

  • Appearance

    • Documentary Standards (USP-NF)

      <1> Injections And Implanted Drug Products (Parenterals)—product Quality Tests

      <697> Container Content For Injections

  • Clarity

    • Documentary Standards (USP-NF)

      <855> Nephelometry and Turbidimetry

      <1430.7> Analytical Methodologies Based on Scattering Phenomena—Nephelometery and Turbidimetry

  • Color

    • Documentary Standards (USP-NF)

      <631> Color and Achromicity

  • pH

    • Documentary Standards (USP-NF)

      <791> pH

  • Osmolality

    • Documentary Standards (USP-NF)

      <785> Osmolality and Osmolarity

  • Particulates

    • Reference Standards

      1500502: Particle Count Set

       

      Documentary Standards (USP-NF)

      <787> Subvisible Particulate Matter in Therapeutic Protein Injections

      <790> Visible Particulates in Injections

      <1787> Measurement of Subvisible Particulate Matter in Therapeutic Protein Injections

      <1788> Methods for the Determination of Subvisible Particulate Matter

      <1788.1> Light Obscuration Method for the Determination of Subvisible Particulate Matter

      <1788.2> Membrane Microscope Method for the Determination of Subvisible Particulate Matter

      <1788.3> Flow Imaging Method for the Determination of Subvisible Particulate Matter

      <1790> Visual Inspection Of Injections

       

      USP Educational Content

      Monitoring Impurities in Biologics

      Determining Particulate Matter in Liquids Parenteral and Ophthalmic Products

       

      Other Resources

      • Stimuli: Visual Inspection and Visible Particle Testing

      • Stimuli: Particles in the Submicrometer Size Domain

• Size Variants

  Tests for protein aggregates and fragments that may form during manufacturing or storage

   

  • Intact Mass

    • Reference Standards

      1076192: BSA for Protein Quantitation

      1445539: USP mAb 001, monoclonal IgG1

      1445547: USP mAb 002, monoclonal IgG1

      1445595: USP mAb 003, monoclonal IgG1

       

      Documentary Standards (USP-NF)

      <736> Mass Spectrometry

      <1736> Applications of Mass Spectrometry

       

      Other Resources

      Poster: USP mAb Ref Stds, High Resolution Mass Spectroscopy

  • SEC-MALS

    (Multi-Angle Light Scattering)

    • Documentary Standards (USP-NF)

      <129> Analytical Procedures for Recombinant Therapeutic Monoclonal Antibodies

      <1430> Analytical Methodologies Based on Scattering Phenomena - General

      <1430.1> Analytical Methodologies Based on Scattering Phenomena-Static Light Scattering

  • Size Exclusion

    (SEC-HPLC, SEC-UPLC)

    • Reference Standards

      1445550: Monoclonal IgG System Suitability

      1445539: USP mAb 001, monoclonal IgG1

      1445547: USP mAb 002, monoclonal IgG1

      1445595: USP mAb 003, monoclonal IgG1

       

      Documentary Standards (USP-NF)

      <129> Analytical Procedures for Recombinant Therapeutic Monoclonal Antibodies

      <621> Chromatography

  • CE-SDS

    (Reduced and Non-Reduced)

    • Reference Standards

      1445550: Monoclonal IgG System Suitability

      1445539: USP mAb 001, monoclonal IgG1

      1445547: USP mAb 002, monoclonal IgG1

      1445595: USP mAb 003, monoclonal IgG1

       

      Documentary Standards (USP-NF)

      <129> Analytical procedures for recombinant therapeutic monoclonal antibodies

      <1053> Capillary Electrophoresis

  • SDS-PAGE

    (Reduced and Non-Reduced)

    • Reference Standards

      1445550: Monoclonal IgG System Suitability

      1445539: USP mAb 001, monoclonal IgG1

      1445547: USP mAb 002, monoclonal IgG1

      1445595: USP mAb 003, monoclonal IgG1

       

      Documentary Standards (USP-NF)

      <129> Analytical procedures for recombinant therapeutic monoclonal antibodies

      <1056> Biotechnology-Derived Articles—Polyacrylamide Gel Electrophoresis

• Charge Variants

  Tests for acidic and basic variants which may be caused by deamidation or oxidation

   

  • Ion Exchange Chromatography

    (IEX)

    • Documentary Standards (USP-NF)

      <621> Chromatography

      <1065> Ion Chromatography

       

      USP Educational Content

      Analysis of charge variants in biologics

       

      Other Resources

      Presentation: Reference Standards, Analysis of Charge Variants

      Poster: Standards for Cation Exchange Chromatography

  • Isoelectric focusing

    (cIEF/iCIEF)

    • Reference Standards

      1445539: USP mAb 001, monoclonal IgG1

      1445547: USP mAb 002, monoclonal IgG1

      1445595: USP mAb 003, monoclonal IgG1

       

      USP Educational Content

      Analysis of charge variants in biologics

       

      Documentary Standards (USP-NF)

      <1053> Capillary Electrophoresis

      <1054> Biotechnology-Derived Articles—Isoelectric Focusing

       

      Other Resources

      Tech Note: Charge Variant Analysis of USP mAb Standards

      Presentation: Reference Standards, Analysis of Charge Variants

  • Peptide Mapping

    • Documentary Standards (USP-NF)

      <621> Chromatography

      <1055> Biotechnology-Derived Articles—Peptide Mapping

       

      Other Resources

      Tech Note: Charge Variant Analysis of USP mAb Standards

      Presentation: Reference Standards, Analysis of Charge Variants

• Glycosylation

  Tests for covalently attached sugars that can modulate biological activity

   

  • N-Linked Glycan Profiling

    • Reference Standards

      1478210: Oligosaccharide System Suitability Mixture A

      1478221: Oligosaccharide System Suitability Mixture B

      1478232 Oligosaccharide System Suitability Mixture C

      1478243 Oligosaccharide System Suitability Mixture D

       

      Documentary Standards (USP-NF)

      <129> Analytical Procedures for Recombinant Therapeutic Monoclonal Antibodies

      <212> Oligosaccharide Analysis

      <1084> Glycoprotein and Glycan Analysis-General Considerations

       

      Other Resources

      Manuscript: USP mAb Ref Stds: Tools to Verify Glycan Structure

      Manuscript: Comprehensive Stds for Monitoring Glycosylation

      Manuscript: Macro- and Micro-heterogeneity of Glycosylation

      Poster: USP mAb Ref Stds, High Resolution Mass Spectroscopy

  • Monosaccharide Analysis

    • Reference Standards

      1612619: N-Acetylneuraminic Acid

      1294284: N-Glycolylneuraminic Acid

       

      Documentary Standards (USP-NF)

      <210> Monosaccharide Analysis

  • Mass Spectrometry

    • Reference Standards

      1445539: USP mAb 001, monoclonal IgG1

      1445547: USP mAb 002, monoclonal IgG1

      1445595: USP mAb 003, monoclonal IgG1

       

      Documentary Standards (USP-NF)

      <736> Mass Spectrometry

      <1736> Applications of Mass Spectrometry

       

      Other Resources

      Manuscript: Macro- and Micro-heterogeneity of Glycosylation

       

• Potency & Biological Activity

  Tests for biologic activity, dependent on target binding and cellular interactions

   

  • Cell Based

    • Documentary Standards (USP-NF)

      <111> Design and Analysis of Biological Assays

      <1030> Biological Assay Chapters - Overview and Glossary

      <1032> Design and Development of Biological Assays

      <1033> Biological Assay Validation

      <1034> Analysis of Biological Assays

  • Binding Assay

    • Documentary Standards (USP-NF)

      <1103> Immunological Tests Methods—Enzyme-Linked Immunosorbent Assay (ELISA)

  • Fc Function

    • Documentary Standards (USP-NF)

      <1105> Immunological Test Methods—Surface Plasmon Resonance

      <1108> Assays to evaluate fragment crystallizatable (FC)-mediated effector function

• Process Related Impurities

  Tests for substances like host cell proteins that are produced during the manufacturing process

   

  • Residual DNA

    • Reference Standards

      1130710: CHO Genomic DNA

       

      Documentary Standards (USP-NF)

      <509> Residual DNA Testing

      <1130> Nucleic Acid-Based Techniques-Approaches for Detecting Trace Nucleic Acids (residual DNA testing)

       

      Other Resources

      Poster: Reference Standards for Residual DNA Testing

  • Host Cell Proteins

    • Documentary Standards (USP-NF)

      <1102> Immunological Test Methods—General Considerations

      <1103> Immunological Test Methods—Enzyme-Linked Immunosorbent Assay (ELISA)

      <1132> Residual Host Cell Protein Measurement in Biopharmaceuticals

       

      Analytical Reference Materials

      1582716: PLBL2 (Phospholipase B-like 2) Host Cell Protein

       

      Stable Isotope Labeled (SIL) Peptides

      1130730: CHO HCP Clusterin Heavy Peptide 1 NEW!

      1130741: CHO HCP Clusterin Heavy Peptide 2 NEW!

      1130752: CHO HCP Clusterin Heavy Peptide 3 NEW!

      1130763: CHO HCP Lipoprotein Lipase Peptide 1 NEW!

      1130774: CHO HCP Lipoprotein Lipase Peptide 2 NEW!

      1130785: CHO HCP Lipoprotein Lipase Peptide 3 NEW!

       

      USP Educational Content

      Best Practices for Residual Host Cell Protein Measurement in Biopharmaceuticals by Mass Spectrometry: USP Chapter 1132.1

      Application Note: Using Stable-Isotope–Labeled Peptide Analytical Reference Materials for Quantifying Host Cell Proteins in Protein Therapeutics NEW!

       

      Other Resources

      Presentation: USP Standards Host Cell Protein Analysis by MS

      USP Host Cell Protein page

  • Residual Proteins

    (e.g. Protein A)

    • Documentary Standards (USP-NF)

      <1102> Immunological Test Methods—General Considerations

      <1103> Immunological Test Methods—Enzyme-Linked Immunosorbent Assay (ELISA)

• Stability

  Tests for the consistency of physical and biological properties over time and at various storage conditions

   

  • Documentary Standards (USP-NF)

    <1049> Quality Of Biotechnological Products: Stability Testing Of Biotechnological/Biological Product

     

    USP Educational Content

    USP general chapter 1049.1 design of stability studies for biotechnology product development and lifecycle management

• Safety

  Tests for possible contamination with microorganisms

   

  • Endotoxin

    • Reference Standards

      1235503: Endotoxin

       

      Documentary Standards (USP-NF)

      <85> Bacterial Endotoxins Test

      <1085> Guidelines On Endotoxin Test

  • Bioburden

    • Documentary Standards (USP-NF)

      <1229.3> Monitoring of Bioburden

      <61> Microbiological Examination Of Nonsterile Products: Microbial Enumeration Tests

      <62> Microbiological Examination Of Nonsterile Products: Tests For Specified Microorganisms

       

      USP Educational Content

      Essentials of Testing and Control of Microbial Quality of Nonsterile Drug Substances and Products

  • Sterility

    • Documentary Standards (USP-NF)

      <71> Sterility Tests

      <1071> Rapid Microbial Tests for Release of Sterile Short-Life Products: A Risk-Based Approach

       

      USP Educational Content

      Microbiology and Sterility Assurance

  • Mycoplasma

    • Documentary Standards (USP-NF)

      <63> Mycoplasma Tests

• Excipients

  Common materials used in mAb formulations.

   

  • Commonly used excipients in mAb formulations

     

    Reference Standards

    1673715: Trehalose

    1617000: Sorbitol

    1623637: Sucrose

    1308505: L-Histidine

    1372005: L-Lysine Hydrochloride

    1547969: Polysorbate 80

    1547925: Polysorbate 20

    Documentary Standards (USP-NF)

    Trehalose

    Sorbitol

    Sucrose

    Histidine

    Lysine Hydrochloride

    Polysorbate 80

    Polysorbate 20

    USP Educational Content

    USP Excipients Workshop: Excipient Composition and the Formulation of Biotechnology Drugs

    New Understanding Relating to Existing Excipients and Formulation Approaches

• Concentration

  Determination of the number of molecules per unit volume, expressed in milligram per milliliter

   

  • Reference Standards

    1076192: BSA for Protein Quantitation

    1445539: USP mAb 001, monoclonal IgG1

    1445547: USP mAb 002, monoclonal IgG1

    1445595: USP mAb 003, monoclonal IgG1

    Documentary Standards (USP-NF)

    <507> Protein Determination Procedures

    <857> Ultraviolet-visible Spectroscopy

    <1057> Biotechnology-derived Articles —Total Protein Assay