Articles in this Issue
James Akers, Ph.D.
Over the last three decades, the sciences of immunology and cell biology have been revolutionized by discovery of complex networks of cell receptors and signals. There is now a rich literature describing interaction between the human immune system and lipopolysaccharides (LPS) which are ubiquitous molecules found embedded in the outer leaflet of the outer membrane of Gram-negative bacteria. At a 30,000 foot level, a unique signaling cascade between Lipid A and LPS Binding Protein (LBP), both soluble and cell surface CD-14, as well as cell surface receptors MD-2 and TLR4, define the basic innate and adaptive human immune response to Gram-negative bacterial endotoxin (Vesy, et al.., 2000). In light of the recent publications regarding potentially “invalid” LAL tests and concerns about patient safety, (PDA, 2019), it is important to reflect on the the human interaction with Gram-negative bacteria as we go through our daily lives and what that means to the establishment of analytical limits for endotoxin testing for parenteral drugs and medical devices.
Karen Zink McCullough
One of the essential but as yet unresolved questions arising from USP’s June 2019 “Workshop on the Future of Endotoxins and Pyrogen Testing: Reference Standards and Procedures” is the issue of an appropriate “fit for purpose” endotoxin analyte to be used in non compendial spike/recovery experiments. The opinions expressed by some follow traditional analytical thinking and require the use of the purest analyte possible, meaning the USP reference endotoxin standard (RSE) or secondary standards (CSE) both of which are extracted, purified and formulated lipopolysaccharide (LPS).
Radhakrishna Tirumalai, Ph.D., Karen Zink McCullough
All parenteral articles and medical devices that contact body tissue or fluids have to be sterile and pyrogen free. A standard method that utilizes increase in body temperature of rabbits to detect acceptable level of pyrogens, USP Chapter <151>, “Pyrogen Test” was first included in USP XII (1942). However, this test has several disadvantages in addition to being an animal based test. It is nonquantitative, very sensitive to animal strain, physiological state of test animal and the stress level of test animal.
Mick Dawson, Brett Hoffmeister
A number of recently published articles and reports contained information that is inaccurate regarding the horseshoe crab population and its use in the biomedical industry. This article is to clarify some of the misleading suggestions made in those publications. It has been suggested that biomedical manufacturers of Limulus Amebocyte lysate (LAL) reagents are a primary contributor to a speculative population decline of the American horseshoe crab, Limulus polyphemus.1,2 There are two components to this assertion: first, the American horseshoe crab population is in danger and second, the manufacturers of LAL are a primary cause of horseshoe crab mortality.
Tim Sandle, PhD
Microbial biofilms - structured consortium of bacteria that are embedded in layers of self-produced polymer matrices, largely composed of polysaccharide, protein and DNA – are well described and known problems for pharmaceutical water systems and medical devices.