Monoclonal Antibody Standards

USP’s public quality standards and products are critical tools for manufacturers and regulators to help ensure the quality of monoclonal antibodies (mAbs). USP Documentary Standards, Reference Standards, and Analytical Reference Materials (ARMs) are available for analytical testing from the earliest stages of mAb product development through fill & finish. They provide a means to reliably measure quality attributes and characterize components of biologics, facilitate the advancement of leading-edge analytical technologies that define quality for the industry, and reduce the variability that is inherently challenging in biological products.

USP mAb Manufacturing and Testing Infographic

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NEW! Host Cell Proteins (HCPs)

Demonstrating clearance of HCPs is required for mAbs. USP now supports HCP analysis by mass spectrometry with our new Recombinant CHO PLBL2 protein. This well characterized material can be used as a standard or control in a PLBL2 ELISA or mass spectrometry-based workflows to monitor the clearance of this HCP from your therapeutic product. HCP by MS is supported by <1132.1> Residual Host Cell Protein Measurement in Biopharmaceuticals by Mass Spectrometry*, in PF 49(3).

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New resource - Find what you need to access the quality and safety of mAbs

mAb-related USP-NF Standards and Analytical Reference Materials

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mAb-related USP Products

mAb Educational Resources

Standards for Excipients used in mAb manufacturing

Injectables-related USP-NF Documentary Standards

Support for the development of new mAb Standards

Below is a current list of mAb-related USP official standards published in the United States Pharmacopeia-National Formulary (USP-NF), with related USP Reference Standards or ARMs. Included in the table below are some of the monographs and general chapters currently under development or in revision (labeled with an *).

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  1. Application Note: Aggregation Analysis Using SE-HPLC and SE-UHPLC Methods in USP General Chapter <129> Analytical Procedures for Recombinant Therapeutic Monoclonal Antibodies
  2. USP Unpacks The Evolving HCP Identification And Quantitation Story Behind <1132.1>
  3. Impurity testing: PLBL2 Host cell protein reference material
  4. Here’s How USP mAb Standards Support Fast-Evolving Platform Approaches
  5. Knowledge sharing enables manufacturers to make the right decisions when implementing continuous manufacturing for biologics
  6. Peptides and recombinant protein therapeutics can elicit product-specific anti-drug antibodies (ADAs) that can impact their safety and efficacy
  1. Monoclonal Antibody-related USP Reference Standards
  2. Monoclonal IgG System Suitability
  3. BSA for protein quantitation
  4. Endotoxin (USP General Chapter <85> Bacterial Endotoxins Test)
  5. Impurities
    1. Reference materials for host cell proteins (HCPs)
    2. Reference standards for residual host cell genomic DNA
    3. Excipients
  6. Raw starting materials
    1. Hemoglobin Protease Substrate
    2. Pepsin for Assay
    3. Lactase
    4. Methotrexate
    5. Amino acids
    6. Insulin
  1. Product literature
    1. USP Monoclonal Antibody Reference Standards (EnglishSpanishChinesePortuguese)
    2. Development of New USP Reference Standards: Characterization of Three Monoclonal Antibodies Using High Resolution Mass Spectrometry
    3. Charge Variant Analysis of USP Monoclonal Antibody Reference Standard
    4. Standards for Cation Exchange Chromatography
  2. User guides and mAb education
    1. mAb Analytical Guide
    2. mAb Analytical Guide Flyer
    3. What are Monoclonal Antibodies [mAb]? | John F. Kokai-Kun, PhD
    4. Infographic: Ensuring quality in monoclonal antibody therapeutics with USP Standards
    5. The Role of Public Standards in the Development of Biosimilars
    6. New USP Standards for Characterization of Therapeutic Proteins | Quality Matters | U.S. Pharmacopeia Blog
    7. Multi-Attribute Method (MAM)
      1. USP’s MAM Knowledge Hub
        1. Biologics Open Forum on MAM
        2. Best Practices for Mass Spectrometry-Based Multi-Attribute Method (MAM) for Therapeutic Proteins USP General Chapter 1060
  3. mAb Attribute Information
    1. Overview of USP General Chapter <129> Analytical Procedures of Recombinant Therapeutic Monoclonal Antibodies
      1. Characterization of Maurice CE-SDS PLUS for USP <129> Suitability
    2. Glycosylation
      1. USP Reference Standard Monoclonal Antibodies: Tools to Verify Glycan Structure
      2. More Comprehensive Standards for Monitoring Glycosylation
      3. Measurement of macro- and micro-heterogeneity of glycosylation in biopharmaceuticals: a pharmacopeia perspective
      4. Characterization of USP mAbs as a Tool for Verification of Macro- and Micro-Heterogeneity of Glycosylation in mAbs and Other Biotherapeutics
    3. Aggregation
      1. Application Note: Aggregation Analysis Using SE-HPLC and SE-UHPLC Methods in USP General Chapter <129> Analytical Procedures for Recombinant Therapeutic Monoclonal Antibodies 
    4. Higher order structure (HOS)
      1. Higher Order Structure of Proteins in Biopharmaceutical Development
      2. Higher-Order Structure (HOS) Characterization of USP Monoclonal Antibody Reference Standards
    5. Biopharmaceutical continuous manufacturing
      1. Roundtable Discussion on Continuous Manufacturing in Biologics
      2. What's The Environmental Impact Of Biopharma Continuous Manufacturing? Part I
      3. What's The Environmental Impact Of Biopharma Continuous Manufacturing? Part II
    6. Impurity testing
      1. Residual DNA
        1. USP Reference Standards for Residual DNA Testing of Recombinant Biotherapeutics
        2. Residual DNA Testing Flyer
      2. Host cell proteins (HCPs)
        1. USP Unpacks The Evolving HCP Identification And Quantitation Story Behind...
        2. Best Practices for Residual Host Cell Protein Measurement in Biopharmaceuticals by Mass Spectrometry: USP Chapter <1132.1
  4. Online courses
  5. FDA Regulatory information
USP offers the following reference standards for excipients used in the mAb manufacturing process or present in mAb formulations. Pharmaceutical excipients are substances other than the active pharmaceutical ingredient (API) that have been appropriately evaluated for safety and are intentionally included in a drug delivery system.

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All currently available monoclonal antibody therapies are administered either subcutaneously or by intravenous infusion. Provided below are the USP Documentary Standards related to Injectables published in the United States Pharmacopeia-National Formulary (USP–NF).

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Collaboration between USP and industry plays a vital role in improving global public health by developing and ensuring the availability of quality standards worldwide. USP often receives donated candidate reference materials from manufacturers and subjects those materials to rigorous analysis and review to determine if they are suitable for development of a Reference Standard. In addition, USP continues to develop supporting materials for mAb-associated methods, such as impurity testing (ex. host cell proteins) and the mass spectrometry-based multi-attribute method (MAM).
  • In addition, USP continues to develop supporting materials for mAb-associated methods, such as impurity testing (ex. host cell proteins) and the mass spectrometry-based multi-attribute method (MAM).
  • Learn how you can donate material or methods by visiting our biologics standards engagement page or by contacting us at uspbiologics@usp.org.