32 results match your criteria method depyrogenation

Nanopharmaceuticals for Eye Administration: Sterilization, Depyrogenation and Clinical Applications.

Biology (Basel) 2020 Oct 14;9(10). Epub 2020 Oct 14.

Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.

As an immune-privileged target organ, the eyes have important superficial and internal barriers, protecting them from physical and chemical damage from exogenous and/or endogenous origins that would cause injury to visual acuity or even vision loss. These anatomic, physiological and histologic barriers are thus a challenge for drug access and entry into the eye. Novel therapeutic concepts are highly desirable for eye treatment. Read More

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October 2020

Vapor-Phase Hydrogen Peroxide Uptake by Silicone Tubing and Primary Packaging Components during Protein Drug Product Aseptic Filling: Impact of Pretreatment and Sterilization Process.

PDA J Pharm Sci Technol 2019 Sep-Oct;73(5):443-458. Epub 2019 Apr 19.

Pharmaceutical Processing and Technology Development, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080

In the vapor-phase hydrogen peroxide (VPHP)-sanitized environment, VPHP uptake by product-contacting components could eventually lead to undesired oxidation of biological drug products. Silicone tubing and primary packaging materials are prominent examples of such product-contacting surfaces that are typically processed/sterilized prior to use. This study investigated the VPHP-uptake tendency of these components and how their respective processing/sterilization methods affect the uptake behaviors. Read More

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Impact of Vial Washing and Depyrogenation on Surface Properties and Delamination Risk of Glass Vials.

Pharm Res 2018 May 23;35(7):146. Epub 2018 May 23.

Late Stage Pharmaceutical and Processing Development, Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070, Basel, Switzerland.

Purpose: The proper understanding of glass delamination is important to glass manufacturers, pharmaceutical companies, and health authorities to mitigate the occurrence of glass flakes from the vial when in contact with specific drug product solutions. The surface of glass vials is altered during glass cane- and vial forming processes and is exposed to different stress conditions during drug product processing before coming in contact with the drug product solution. In this study, the impact of vial washing and depyrogenation including an evaluation of various residual water volumes on surface properties of glass vials was investigated for a defined set of vials. Read More

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Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: Challenges, considerations and strategy.

J Control Release 2015 Dec 5;220(Pt B):571-83. Epub 2015 Sep 5.

Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, NCI at Frederick, Frederick, MD 21702, United States. Electronic address:

Assorted challenges in physicochemical characterization, sterilization, depyrogenation, and in the assessment of pharmacology, safety, and efficacy profiles accompany pre-clinical development of nanotechnology-formulated drugs. Some of these challenges are not unique to nanotechnology and are common in the development of other pharmaceutical products. However, nanoparticle-formulated drugs are biochemically sophisticated, which causes their translation into the clinic to be particularly complex. Read More

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December 2015

Depyrogenation options for the compounding cleanroom.

Int J Pharm Compd 2014 Nov-Dec;18(6):446-54

Compounding pharmacies, especially those awarded 503B status under the U.S. Federal Food, Drug, and Cosmetic Act that resulted from the Drug Quality and Security Act, must meet increasingly strict standards for the preparation of sterile formulations. Read More

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LPS from bovine serum albumin drives TNF-α release during ex-vivo placenta perfusion experiments, contaminates the perfusion system but can be effectively removed by oxidative cleaning.

Placenta 2014 Dec 18;35(12):1095-8. Epub 2014 Oct 18.

Department of Pediatrics, McMaster University Medical Centre, Hamilton, Ontario, Canada. Electronic address:

Introduction: The dual ex-vivo perfusion of human placental tissue is useful to study inflammatory pathways. We found significant TNF-α release in negative controls similar in concentration to lipopolysaccharide (LPS) stimulated placentas. The aim of the current study was to (i) identify sources driving TNF-α release and (ii) develop an approach to control for it. Read More

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December 2014

Challenges facing sterilization and depyrogenation of nanoparticles: effects on structural stability and biomedical applications.

Nanomedicine 2014 Oct 4;10(7):1391-9. Epub 2014 Apr 4.

Toxicology and Biochemistry Section, National Institute for Occupational Health, National Health Laboratory Services, Johannesburg, South Africa; Department of Molecular Medicine and Haematology, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.

This review outlines and compares techniques that are currently available for the sterilization of nanoparticles and addresses the topic of endotoxin contamination. Several techniques are available for the removal of microbial contamination from nanoparticles developed for use in nanomedicine applications. These techniques include filtration, autoclaving and irradiation, as well as formaldehyde, ethylene oxide and gas plasma treatments. Read More

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October 2014

An efficient depyrogenation method for recombinant bacterial outer membrane lipoproteins.

Protein Expr Purif 2014 Jun 12;98:10-7. Epub 2014 Mar 12.

Centro de Investigação Interdisciplinar em Sanidade Animal (CIISA), Faculdade de Medicina Veterinária, Universidade de Lisboa, Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal; Instituto de Investigação Científica Tropical, CVZ, Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal. Electronic address:

Bacterial outer membrane lipoproteins are anchored in the outer membrane lipid layer in close association with lipopolysaccharides (LPS) and with other hydrophobic membrane proteins, making their purification technically challenging. We have previously shown that a thorough delipidation of outer membrane preparations from the Escherichia coli expression host is an important step to eliminate contaminant proteins when purifying recombinant antigens expressed in fusion with the Pseudomonas aeruginosa OprI lipoprotein. Here we report the cloning and expression of three antigens in fusion with OprI (ovalbumin, eGFP and BbPDI) and our efforts to deal with the variable LPS contamination levels observed in different batches of purified lipoproteins. Read More

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Endotoxin inactivation via steam-heat treatment in dilute simethicone emulsions used in biopharmaceutical processes.

Biotechnol Prog 2014 Sep-Oct;30(5):1145-60. Epub 2014 Apr 2.

Amgen Inc., 40 Technology Way, West Greenwich, RI, 02817.

Simethicone emulsion is used to regulate foaming in cell culture operations in biopharmaceutical processes. It is also a potential source of endotoxin contamination. The inactivation of endotoxins in dilute simethicone emulsions was assessed as a function of time at different steam temperatures using a Limulus amebocyte lysate kinetic chromogenic technique. Read More

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Investigating factors leading to fogging of glass vials in lyophilized drug products.

Eur J Pharm Biopharm 2013 Oct 19;85(2):314-26. Epub 2013 Jun 19.

Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Vial "Fogging" is a phenomenon observed after lyophilization due to drug product creeping upwards along the inner vial surface. After the freeze-drying process, a haze of dried powder is visible inside the drug product vial, making it barely acceptable for commercial distribution from a cosmetic point of view. Development studies were performed to identify the root cause for fogging during manufacturing of a lyophilized monoclonal antibody drug product. Read More

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October 2013

Determining the delamination propensity of pharmaceutical glass vials using a direct stress method.

PDA J Pharm Sci Technol 2013 Jan-Feb;67(1):35-42

Department of Process and Product Development, Amgen Inc., Thousand Oaks, CA.

Unlabelled: An accelerated lamellae formation (ALF) methodology has been developed to determine the delamination propensity and susceptibility of pharmaceutical glass vials. The ALF process consists of a vial wash and depyrogenation mimic procedure followed by stressing glass vials with 20 mM glycine pH 10.0 solution at 50 °C for 24 h and analyzing the resulting solutions by visual inspection for glass lamellae. Read More

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[Depyrogenation test regarding inox and glass containers in the preparation of parenteral nutrition mixtures].

Ann Pharm Fr 2012 Sep 7;70(5):271-80. Epub 2012 Sep 7.

Service pharmaceutique, fabrication et contrôles des médicaments, plateforme FRIPHARM, pavillon X, groupement hospitalier Édouard-Herriot, place d'Arsonval, 69437 Lyon cedex 03, France.

Introduction: The preparation of parenteral nutrition mixture (PNM) in an open chamber requires the use of intermediate containers sterile and non-pyrogenic. A sterilization of containers by moist heat in large autoclaves is the suitable method. However, sterilization by moist heat is not a depyrogenation method. Read More

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September 2012

Surface contamination of dental implants assessed by gene expression analysis in a whole-blood in vitro assay: a preliminary study.

J Clin Periodontol 2012 Oct 2;39(10):987-94. Epub 2012 Aug 2.

Department of Prosthodontics, Propaedeutics and Dental Materials, Christian-Albrechts University, Kiel, Germany.

Aim: We aimed at evaluating pyrogen contamination of dental implants made of titanium and zirconia by using gene expression analysis in a whole-blood in vitro assay.

Material And Methods: Titanium and zirconia implants (five each) were incubated in human whole blood. Samples were assayed for gene expression levels of toll-like receptor 4 (TLR4), TLR9, interleukin (IL)-1β, nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-kB), tumour necrosis factor (TNF)-α, and Fas-associated protein with death domain (FADD) as indicators of surface contamination resulting in lipopolysaccharides (LPS)-stimulated TLR- or TNF-mediated immune responses. Read More

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October 2012

Formation of high-capacity protein-adsorbing membranes through simple adsorption of poly(acrylic acid)-containing films at low pH.

Langmuir 2012 May 16;28(17):6885-92. Epub 2012 Apr 16.

Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States.

Layer-by-layer polyelectrolyte adsorption is a simple, convenient method for introducing ion-exchange sites in porous membranes. This study demonstrates that adsorption of poly(acrylic acid) (PAA)-containing films at pH 3 rather than pH 5 increases the protein-binding capacity of such polyelectrolyte-modified membranes 3-6-fold. The low adsorption pH generates a high density of -COOH groups that function as either ion-exchange sites or points for covalent immobilization of metal-ion complexes that selectively bind tagged proteins. Read More

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[Depyrogenation in key manufacturing processes of Reduning injection].

Zhongguo Zhong Yao Za Zhi 2011 Mar;36(6):663-5

Jiangsu Kanion Pharmaceutical Company Limited, Lianyungang 222001, China.

Objective: To investigate the effect of removing bacterial endotoxin in the key processes of Reduning injection.

Method: The content of bacterial endotoxins was detected by kenitic-turbidimetry and the removal efficacy was studied before and after using 0.8% of activated carbon and ultrafiltration with molecular weight cut-off of 10 x 10(3). Read More

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Removing Endotoxin from Metallic Biomaterials with Compressed Carbon Dioxide-Based Mixtures.

J Supercrit Fluids 2011 Jan;55(3):1052-1058

Department of Engineering Sciences and Materials, University of Puerto Rico, Mayagüez PR 00681 USA.

Bacterial endotoxins have strong affinity for metallic biomaterials because of surface energy effects. Conventional depyrogenation methods may not eradicate endotoxins and may compromise biological properties and functionality of metallic instruments and implants. We evaluated the solubilization and removal of E. Read More

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January 2011

Inactivation of Escherichia coli endotoxin by soft hydrothermal processing.

Appl Environ Microbiol 2009 Aug 5;75(15):5058-63. Epub 2009 Jun 5.

Institute for Animal Experimentation, Tohoku University, Sendai, Japan.

Bacterial endotoxins, also known as lipopolysaccharides, are a fever-producing by-product of gram-negative bacteria commonly known as pyrogens. It is essential to remove endotoxins from parenteral preparations since they have multiple injurious biological activities. Because of their strong heat resistance (e. Read More

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Efficiency in endotoxin removal by a reprocessing protocol for electrophysiology catheters based on hydrogen peroxide plasma sterilization.

Int J Hyg Environ Health 2006 Nov 21;209(6):557-65. Epub 2006 Jun 21.

Department of Materials Engineering and Industrial Technologies, University of Trento,Via Mesiano 77, 38050 Trento, Italy.

Electrophysiology and ablation cardiac catheters, which come in contact with blood during clinical use, are required to be non-pyrogenic (<20 endotoxin units (EU)/device). This study aimed to quantify the residual endotoxin load in reprocessed devices as a mandatory step to guarantee safe reuse. We monitored the pyrogenic status of the device (n=61) in three fundamental steps of the reprocessing protocol: after clinical use, after decontamination-cleaning treatments and after complete reprocessing, including sterilization by hydrogen peroxide gas plasma. Read More

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November 2006

GRP94/gp96 elicits ERK activation in murine macrophages. A role for endotoxin contamination in NF-kappa B activation and nitric oxide production.

J Biol Chem 2003 Aug 12;278(34):31853-60. Epub 2003 Jun 12.

Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Vaccination of mice with GRP94/gp96, the endoplasmic reticulum Hsp90, elicits a variety of immune responses sufficient for tumor rejection and the suppression of metastatic tumor progression. Macrophages are a prominent GRP94/gp96 target, with GRP94/gp96 reported to activate macrophage NF-kappa B signaling and nitric oxide production, as well as the MAP kinase p38, JNK, and ERK signaling cascades. However, recent studies report that heat shock protein elicited macrophage activation is due, in large part, to contaminating endotoxin. Read More

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Sterilization and depyrogenation principles and methods.

M J Akers Phd

Int J Pharm Compd 1999 Jul-Aug;3(4):263-9

Eli Lilly and Company, Indianapolis, IN 46285.

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Strategies for the depyrogenation of contaminated immunoglobulin G solutions by histidine-immobilized hollow fiber membrane.

J Chromatogr B Biomed Sci Appl 1997 Mar;691(1):33-41

Université de Technologie de Compiègne, Centre de recherches de Royallieu, Compiègne, France.

The depyrogenation of different IgG solutions using the histidine-linked hollow fiber membrane developed in our laboratory is presented here. Three strategies for endotoxin (ET) removal were investigated according to the immobilized histidine's ability to bind different immunoglobulins: (1) ET removal from 1 mg/ml non histidine-binding mouse monoclonal IgG1 (MabCD4) solution was achieved in the presence of acetate buffer (pH 5.0) without any protein loss. Read More

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The use of heated citric acid for dialyzer reprocessing.

J Am Soc Nephrol 1995 Dec;6(6):1578-85

Division of Nephrology and Hypertension, Beth Israel Medical Center, New York, NY 10003, USA.

Dialyzer reprocessing with heated water (100 to 105 degrees C) for 20 h can be used safely in lieu of chemical methods for disinfection. All infective agents including spores are destroyed and depyrogenation may occur. However, these temperatures may result in structural damage to the dialyzer, limiting reuse. Read More

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December 1995

Validation of dry heat inactivation of bacterial endotoxins.

PDA J Pharm Sci Technol 1994 Jul-Aug;48(4):197-204

Sandoz Pharma Limited, Basle, Switzerland.

Bacterial endotoxins (ETs) are lipopolysaccharides from the cell wall of Gram negative bacteria. ETs get into the environment as a result of autolytic desintegration of the bacterial cells. There exist a number of depyrogenation methods, either serving to remove or to inactivate ET. Read More

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January 1995

Depyrogenation of pharmaceutical solutions using submicron and ultrafilters.

S Brown A C Fuller

J Parenter Sci Technol 1993 Nov-Dec;47(6):285-7

Sterling Winthrop Pharmaceuticals Research Division, Alnwick Research Centre, Northumberland, UK.

The effect of varying the pH and ionic strength on endotoxin removal (depyrogenation) from Water for Injections (WFI) was investigated. Studies using submicron filters showed that endotoxin aggregation and filter retention increased with increasing molarity and decreasing pH. Using a Sartorius 0. Read More

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Destruction of typical endotoxins by dry heat as determined using LAL assay and pyrogen assay.

T Nakata

J Parenter Sci Technol 1993 Sep-Oct;47(5):258-64

Ibaraki Plant, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.

The kinetics of destruction by dry heat of two typical endotoxins, Escherichia coli 055:B5 (E. coli endotoxin) and Salmonella abortus equi (S. abortus equi endotoxin), were determined using the Limulus Amebocyte Lysate (LAL) and pyrogen assays. Read More

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January 1994

Depyrogenation by endotoxin removal with positively charged depth filter cartridge.

K C Hou R Zaniewski

J Parenter Sci Technol 1990 Jul-Aug;44(4):204-9

Cuno, Inc., Meriden, Connecticut.

Bacterial endotoxin, a major quality of parenteral pharmaceuticals, is negatively charged lipopolysaccharide (LPS). A depth filter chemically modified to carry positively charged functional groups is applied to remove endotoxin from aqueous solutions and buffers through charge interaction. The environmental conditions, such as pH and electrolytes, known to affect the efficiency of endotoxin removal by the filter were studied. Read More

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November 1990

A simplified process for large-scale isolation of IgG from goat serum.

Bioseparation 1990 ;1(1):59-67

Whatman Specialty Products Division, Media Technology Operations (Europe), Maidstone, Kent, UK.

Immunoglobin G (IgG) is routinely used in many immunoassay systems. Whilst various laboratory-scale procedures exist for the isolation of IgG from host serum few are appropriate for scale-up. We have previously reported the improvement of an existing process for isolation of IgG from goat serum at laboratory scale (Schwartz et al. Read More

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Preparation and use of endotoxin indicators for depyrogenation process studies. LAL Users Group.


J Parenter Sci Technol 1989 May-Jun;43(3):109-12

Biological Indicators (B.I.'s) have traditionally been employed in the validation and routine monitoring of sterilization processes used for the manufacture and control of pharmaceuticals and medical devices. Read More

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