In-Process Testing

• Concentration

  Determination of the number of molecules per unit volume, expressed in milligrams 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

• 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 Protein

    • 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

      
      

      Other Resources

      Presentation: USP Standards Host Cell Protein Analysis by MS

  • 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)

• 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

      Poster: Standards for Cation Exchange Chromatography

      Presentation: Reference Standards, Analysis of Charge Variants

  • 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

      Presentation: Reference Standards, Analysis of Charge Variants

      Poster: Standards for Cation Exchange Chromatography

      Tech Note: Charge Variant Analysis of USP mAb Standards

  • 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

• 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)

      <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

• 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

• 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