New USP Standards for Characterization of Therapeutic Proteins
The U.S. Pharmacopeial Convention (USP) is currently developing a suite of physical and written standards for therapeutic proteins to help manufacturers in the development and analysis of their proteins.
USP’s standards for therapeutic proteins and other biologics are based on input from global scientific experts and on specifications for FDA-approved products. Published in the United States Pharmacopeia—National Formulary (USP–NF), our written standards (monographs and general chapters) provide comprehensive information, validated methods, and approved quality specifications. USP–NF standards are frequently accompanied by associated Reference Standards available for use in method development, validation and testing.
Examples of our most recent protein general chapters and associated Reference Standards include the following:
USP General Chapter <129> Analytical Procedures of Recombinant Therapeutic Monoclonal Antibodies
General Chapter <129> provides analytical procedures for testing common quality attributes of monoclonal antibodies (mAbs) and subtypes (e.g., IgG1 and IgG2). This chapter includes validated procedures and system suitability criteria for purity assessments by chromatographic separation of size variants and capillary sodium dodecyl sulfate (CE–SDS) electrophoresis as well as procedures for analysis of oligosaccharides and sialic acid in mAbs.
- View General Chapter <129> as it appears in USP 39–NF 34, which will be official on May 1, 2016.
- IgG System Suitability Reference Standard (Item #1445550)—This material is an IgG1, 2 mg/vial lyophilized presentation, to be used as a system suitability standard in the size-exclusion chromatography assay (SEC) and the capillary sodium dodecyl sulfate (SDS) electrophoresis (reduced and non-reduced) assays (CE-SDS) described in General Chapter <129>.
USP General Chapter <212> Oligosaccharide Analysis
This chapter includes validated analytical procedures and associated Reference Standards for system suitability assessment that are commonly used to analyze oligosaccharides in recombinant glycosylated biological products. General Chapter <212> is envisioned as a growing collection of procedures for N-glycan analysis that can be used in development or will be referenced in monographs published in USP–NF in the future.
Analytical procedures in <212> include sample preparation and labeling options for the following separation options: normal phase or hydrophilic interaction chromatography (HILIC), high performance anion exchange chromatography (HPAEC), and capillary electrophoresis (CE).
- View Proposed General Chapter <212> as it appeared for public review and comment in Pharmacopeial Forum (PF) 41(5). This proposal is a revision of the official text that first appeared in USP 38–NF 33, 2S. The revision included additional methods and 2 new Reference Standards for multi-sialylated, multi-antennary complex oligosaccharides. If approved, the revised text is scheduled to publish in USP 39–NF 34, 2S.
- These oligosaccharide mixtures are to be used with specifications described in General Chapter <212>:
- Oligosaccharide System Suitability Mixture A Reference Standard (Item #1478210)
- Oligosaccharide System Suitability Mixture B Reference Standard (Item #1478221)
- Oligosaccharide System Suitability Mixture C Reference Standard (Item #1478232)
- Oligosaccharide System Suitability Mixture D Reference Standard (Item #1478243)
USP General Chapter <507> Protein Determination Procedures
Several procedures exist to determine the total protein in drug substances and products. Procedures may differ based on the physical characteristic of the protein, which serves as the basis of the measurement principle (e.g., absorbance of ultraviolet light by aromatic amino acid residues or by dye binding).
General Chapter <507> contains multiple validated methods for the measurement of total protein, providing users with options depending on their sample matrix and measurement purpose. A new USP Reference Standard is included for use as a system suitability standard in the colorimetric procedures or as an all-purpose standard during development or when a suitable specific reference material is unavailable. Because it is impossible to test every potential protein and sample matrix for this general purpose, any selected method must be verified before use as suitable for its intended purpose.
- View Proposed General Chapter <507> as it appeared for public review and comment in PF 41(2). <507> is not currently available but is scheduled to publish in USP 39–NF 34, 1S.
- BSA for Protein Quantitation Reference Standard (Item #1076192)—This Reference Standard is available for use in the methods described in proposed General Chapter <507>.
Interested in learning more about USP’s work developing standards for proteins and biologics? Visit our website and sign up for our quarterly biologics e-newsletter. We welcome your comments and questions—please respond below or email firstname.lastname@example.org.