Articles in this Issue

• Current USP Perspectives on Low Endotoxin Recovery (LER)

  Karen Zink McCullough
  The topic of LER, or “Low Endotoxin Recovery” has dominated endotoxin discussions since 2013. What is LER? The term was coined to describe an LAL assay interference (inhibition) that was observed in an undiluted monoclonal antibody formulation containing a chelating buffer and polysorbate (Chen and Vinther, 2013). LER has raised questions regarding patient safety and the validity of the compendial Bacterial Endotoxins Test in detecting low levels of endotoxin contamination in biological products. Since the initial report of LER, the United States Pharmacopeia, General Chapters- Microbiology Expert Committee (EC),

• Removal of Endotoxin from Protein in Pharmaceutical Processes

  Tim Sandle, PhD
  Bacterial endotoxin is the lipopolysaccharide component of the cell wall of Gram-negative bacteria, together with other cellular material that combines to form an endotoxin complex. Endotoxin is pyrogenic and it presents a risk to patients who are administered intravenous and intramuscular preparations.1 Thus bacterial endotoxins pose a risk to many pharmaceutical processes and, where not controlled, to the finished products. There are different methods for endotoxin removal.

• Naturally Occurring Endotoxin: A New Reference Material Proposed By the US Pharmacopeia

  Radhakrishna Tirumalai, Ph.D.
  In response to stakeholder requests, USP (US Pharmacopeial Convention; www.usp.org) is proposing a new reference standard, Naturally Occurring Endotoxin (NOE), to be prepared from cell wall extracts of a well characterized Gram negative bacterium. The proposed reference standard (RS) was developed by analyzing and observing the properties of currently available endotoxin reference materials (purified lipopolysaccharide, or LPS), such as, USP Endotoxin RS as analytes in depyrogenation and hold-time studies. This proposed NOE standard is intended to be used in hold-time studies, depyrogenation studies, and other studies that require, or would benefit from, the use of a “naturally occurring” endotoxin.

• (1→3)-ß-D-Glucan: Pharmaceutical Contaminant and Biological Response Modifier

  Malcolm A. Finkelman, PhD
  The establishment of consistent safety and efficacy of parenteral pharmaceutical products is a key goal in GMP operations. Within the spectrum of activities that support GMP operations, the control of bioactive contaminants is a critical concern. Practically, and perhaps principally, this has meant sterility and within-specification endotoxin burdens. Over the last seven decades, tests for bacterial endotoxin burdens have developed from exclusively animal-based bio-assays to LAL (Limulus Amebocyte Lysate), or LAL-derivative, biochemical assays and mammalian cell-based assays.

• Rapid Bacterial Endotoxin Testing (BET)

  Veronika Wills
  One of the most frequently asked questions by the end user of endotoxin testing systems is “How can I make my endotoxin test as time effi cient as possible while still running a fully compliant test?” This article off ers a number of ways in which you can perform a BET compliant test with your current methodologies, while minimizing the time to successfully complete the assay.