Biologic Standards in Development at USP

Currently, USP is working vigorously to develop new chapters on mono-and oligossacharide analysis, residual DNA analysis, protein determination analysis, vaccines, excipient performance characteristics, and more. In addition, monographs and general chapters that are integral to biological product development are continually being developed and revised. Please note, a new general chapter will not necessarily apply to any particular article, unless and until it is called out for application in a monograph or General Notices.  Information on proposed USP–NF standards and those currently in development can be accessed for free through Pharmacopeial Forum (PF). Learn more about the development and revisions process and how you can get involved.

  • COMING SOON: New Proposed General Chapter <129> Analytical Procedures for Recombinant Therapeutic Monoclonal Antibodies [scheduled for publication in PF 39 (3) (May–Jun 2013)]
  • PF 39 (2) (Nov–Dec 2012) Comment deadline: May 31, 2013 (View PF Online)
    • Cosyntropin
      Because there is no existing USP monograph for this drug substance, a new monograph based on validated methods of analyses is proposed. The chromatographic procedure in the Assay and the test for Organic Impurities is based on analyses performed with the Macherey Nagel Nucleosil 120-5 brand of L1 column. The typical retention time for cosyntropin is 19–20 min. The chromatographic procedure in the Amino Acid Analysis Identification test is based on analyses performed with the Waters Nova-Pak AccQTag Ultra brand of L1 column.

       

    • <345> Assay for Citric Acid/Citrate and Phosphate (USP 37–NF 32 1S)
    • <671> Containers-Performance Testing (USP 37–NF 32 1S)
    • <787> Subvisible Particulate Matter in Therapeutic Protein Injections [NEW]
      (USP 37–NF 32 1S)

      On the basis of comments received, this new general chapter that first appeared in PF38(3) [May–June 2012] was canceled and a new, revised version is now being proposed.

      Particulate Matter in Injections <788> was designed to control subvisible particles for small-molecule drug products that are delivered intravenously. The chapter outlines
      two procedures, a light-obscuration (LO) method and a microscopic analysis method, of which the former is preferred. The two procedures quantify particles in drug products, helping ensure patient safety by preventing the acceptance of products that contain particles that may cause capillary occlusion.

      Since general chapter <788> became official, the number of protein therapeutics has increased markedly. Therapeutic protein manufacturers tend to use the LO method despite several technical issues in using it for testing therapeutic proteins. Sample handling of protein therapeutics is critical in obtaining reproducible subvisible particle measurements. These drug products often are delivered as viscous, highly concentrated formulations that can trap air bubbles if they are not handled properly when tested. These air bubbles result in artificially high subvisible particle measurements. Proteins also can aggregate, or the protein particles may break or agglomerate, thus resulting in artificially altered subvisible particle measurements. In addition, the sonication procedure described in <788> for degassing is not appropriate for biological samples, and degassing by letting the sample stand for 2 min is not always effective. The large sample volumes required by the procedures in <788> also are an issue because protein therapeutics typically are manufactured in small quantities, are delivered in small volumes, are expensive, and early in development often are not available in the quantities required for analysis by the procedures described in <788>. USP proposes this new general chapter to address these issues.

    • <852> Atomic Absorption Spectroscopy [NEW] (USP 37–NF 32 1S)
    • <854> Mid-Infrared Spectroscopy [NEW] (USP 37–NF 32 1S)
    • <857> Ultraviolet-Visible Spectroscopy [NEW] (USP 37–NF 32 1S)
    • <1044> Cryopreservation of Cells [NEW] (USP 37–NF 32 1S)

      This chapter presents best practices for cryopreservation, maintenance, and use of a wide range of cells, cell therapy products, and cell banks derived from a variety of sources including human, animal, and microbial cell cultures or banks (the chapter also contains an Appendix with additional guidance documents that are useful for particular cell types and applications). Cryopreserved cells provide a ready source of viable cells that can be used, either directly or indirectly, for therapeutic purposes. In some cases the cells themselves, after cryopreservation and thaw, constitute the patient therapy, and in other cases the cells are propagated or otherwise manipulated ex vivo in order to generate the product (e.g., a culture-expanded cellular therapy, a therapeutic protein, or a monoclonal antibody). In all cases, proper cryopreservation is essential for retention of required cellular properties and, ultimately, for application toward the advancement of patient therapies.

    • <1229.4> Sterilizing Filtration of Liquids [NEW] (USP 37–NF 32 1S)
    • <1229.10> Radiation Sterilization [NEW] (USP 37–NF 32 1S)
    • <1852> Atomic Absorption Spectroscopy-Theory and Practice [NEW]
      (USP 37–NF 32 1S)
    • <1854> Mid-Infrared Spectroscopy-Theory and Practice [NEW] (USP 37–NF 32 1S) Heparin Lock Flush Solution
    • <1056> Biotechnology-Derived Articles-Polyacrylamide Gel Electrophoresis (Stage 4 Harmonization)

      The European Pharmacopoeia is the coordinating pharmacopeia for the international harmonization of the compendial standards for this general chapter as part of the process of international harmonization of monographs and general analytical methods of the European, Japanese, and United States pharmacopeias. The following chapter, which represents the OFFICIAL INQUIRY STAGE 4 document, is based in part on comments from the Japanese Pharmacopoeia and the U.S. Pharmacopeia in response to the PROPOSAL STAGE 3 draft prepared by the European Pharmacopoeia.

  • PF 39 (1) (May–Jun 2012) Comment deadline: Jan 31, 2012
    (View PF Online)
    • General Notices and Requirements (USP 37–NF 32)
    • <853> Fluorescence Spectroscopy [NEW] (USP 37–NF 32)
    • <1853> Fluorescence Spectroscopy-Theory and Practice [NEW] (USP 37–NF 32)
    • Stimuli to the Revision Process:Elemental Impurities in Pharmaceutical Waters
    • Stimuli to the Revision Process: Public Documentary Standards and Reference Materials
  • PF 38 (6) (Nov–Dec 2012) Comment deadline: Jan 31, 2013 (View PF Online)
    • Adenine
    • Adenosine
    • Bovine Acellular Dermal Matrix
    • Heparin Lock Flush Solution
    • Heparin Sodium [Comment Period Extended to March 31, 2013]
    • Heparin Sodium Injection
    • Scaffold Bovine Dermis
    • Dextrose (Stage 4 Harmonization)
    • <1> Injections and Implanted Drug Products (Parenterals)—Product Quality Tests
    • <7> Labeling
    • <571> Vitamin A Assay
    • <581> Vitamin D Assay
    • <645> Water Conductivity
    • <659> Packaging and Storage Requirements
    • <697> Container Content for Injections [NEW]
    • <790> Visible Particulates in Injections [NEW]
    • <1121> Nomenclature
    • <1197> Good Distribution Practices for Bulk Pharmaceutical Excipients
    • <1911> Rheometry [NEW]