Biologics Containment & Delivery
Biopharmaceuticals (e.g., monoclonal antibodies, proteins) require special container/delivery systems in order to help ensure safety and efficacy. Key features of these systems include ability to prevent drug product alteration and suitability for cold storage. This section presents papers addressing these and other topics.
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This study compares plastic container systems for suitability for storing and shipping cell therapy products at low temperatures.<br />
This is a brief comparison of the advantages of COP versus glass.
This study looks at the effect of mild agitation on protein aggregation in prefilled syringes made of either siliconized glass or silicone-free plastic.
This study compares the stability of four proteins in glass vs COP syringes, using turbidity, chromatography, and electrophoresis and assay methods.
To investigate aggregation/adsorption of proteins during storage and/or shipment of samples in Daikyo Crystal silicone oil free vs siliconized glass PFS.
A study was performed to compare the CCI of sterilized glass and CZ vials sealed after cryogenic storage.
This poster investigates CCI properties of glass vs COP at cold temperatures using headspace oxygen and headspace pressure.
To develop assays to determine protein sensitivity to tungstate and the effects of pH and ionic strength on protein aggregation by tungstate polyoxyanions.
The purpose of this study was to develop qualitative and quantitative methods to characterize protein adsorption to containers made of glass or plastic.
Study aimed to investigate the aggregation of proteins in vials made of glass and plastic.
This poster presents results from an investigation comparing protein adsorption/recovery and cell viability using CZ vs glass/polypropylene vials.
This study investigated the suitability of a cyclic olefin polymer (Daikyo Crystal Zenith®) container system as an alternative for the cryogenic storage and shipment of cell therapyproducts at-196°C. The results showed that cryopreservation and recovery of bone-marrow derived hMSCs and umbilical cord isolated CD34+ stem cells in the COP vials is comparable to recovery from screw-cap poly-propylenre cryovial when using well-controlled isolation, cooling, warming and expansion processes.
Presentation demonstrating how using Quality by Design can be applied using a systematic approach and how statistical data can drive product decisions.
<p>This article examines the stability of selected proteins in syringes made of glass and Daikyo Crystal Zenith<sup>®</sup> cyclic olefin polymer (sterilized by either autoclave or electron beam). It was found that stability was comparable, however, polymer syringes provided for better stability under agitated conditions.</p> <p><em>L. Waxman and V. Vilavalam. PDA Journal of Pharmaceutical Science and Technology, 71, 462-477 (2017).</em></p>
Radiolabeled protein molecules are used to demonstrate that there is less adhesion to a vial made of Daikyo Crystal Zenith® cyclic olefin polymer (COP) than to a glass vial, and that COP enables better recovery of protein. <p><em>A. Leece, et al. Applied Radiation and Isotopes, 80, 99-102 (2013)</em></p>
The work described in this article indicates that for limited or expensive peptides, containers comprising cyclic olefin polymer provide for substantially higher recovery and unvarying product yield, as compared to containers comprising glass. <p><em>A. Leece, et al. (Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Harvard Medical School). The Journal of Nuclear Medicine, 53 (supplement 1), 1479 (May 2012)</em></p> <p><em></em></p>
<p>This article discusses the opinions of industry leaders regarding the importance of measuring sub-visible particles (< 10 microns) and understanding if there is a relation between protein aggregation and immunogenicity.</p> <p><em>S. Singh, et al. Journal of Pharmaceutical Sciences, 99 (8) 3302-3321, (August 2010)</em></p> <p>Available for purchase – free to members of American Pharmacists Association (APhA)</p>
This article describes the use of cyclic olefin polymer in closure systems for radiopharmaceuticals - the key benefit being maintaining activity by minimizing loss through adsorption to container surfaces. <p><em>L. Waxman and V. Vilavalam. Drug Development and Delivery (May 2014) </em></p>
This article addresses the chemical modifications to proteins that result from chemical, thermal, and mechanical stress, and how these modifications affect aggregation. <p><em>Q. Luo, et al. Journal of Biological Chemistry, 286 (28), 25134–25144 (July 15, 2011)</em></p> <p> </p>
This article considers how different types of stress (mechanical and thermal) result in the formation of different numbers and types of aggregates. <p><em>M. Joubert, et al. Journal of Biological Chemistry, 286 (28), 25118–25133 (July 15, 2011)</em></p>
This article demonstrates that vials comprising Daikyo Crystal Zenith<sup><sup>®</sup></sup> cyclic olefin polymer are well-suited to cryogenic storage/transport of cell therapy products. <p><em>E. Woods, et al. Regen. Med., 5 (4), 659-667 (2010)</em></p>
<p>Employing gold nanoparticle staining, this article demonstrates that level of adsorption of protein molecules to a cyclic olefin polymer is substantially less than to type 1 glass.</p> <p><em>by Gold Nanoparticles. B. Eu, et al. Journal of Pharmaceutical Sciences, 100 (5), 1663-1670 (May 2011) </em></p>
<p>This review focuses on understanding how protein aggregates potentially interact with the immune system to enhance immune responses. Necessarily implied by this is the critical need for packaging and delivery systems that minimize the possibility of forming protein aggregates.</p> <p><em>A. Rosenberg. The AAPS Journal, 8 (3), E501-E507 (2006)</em></p>
<em>S.S. Quadry, et al. International Journal of Pharmaceutics, 252 (1-2), 207-212 (2003)</em>
<p>This article describes research demonstrating that subvisible particles comprising silicone oil can act as adjuvants to promote immune response against protein molecules. </p> <p><em>C.F. Chisholm, et al. Journal of Pharmaceutical Sciences, 104 (11), 3681-3190 (November 2015)</em></p>
<p>This article discusses the five major mechanisms by which protein molecules can aggregate to form particles. These mechanisms are not exclusive; more than one may operate for a given protein molecule.</p> <p><em>J. Philo and T. Arakawa. Current Pharmaceutical Biotechnology, 10, 348-351 (2009)</em></p>
This article considers the ill effects that particles can have on protein drug product efficacy, including inducement of immune response. <p><em>J. Carpenter et al. Journal of Pharmaceutical Sciences, 98 (4) 1201-1205 (April 2009)</em></p> <p>Available for purchase – free to members of American Pharmacists Association (APhA)</p>
<p>This article considers the effects on protein aggregation resultant from agitation-related exposure to silicone-oil/water interfaces and oil/water interfaces.</p> <p><em>A. Gerhardt, et al. Journal of Pharmaceutical Sciences, 103 (6), 1601–1612 (June 2014)</em></p> <p>Available for purchase – free to members of American Pharmacists Association (APhA)</p>
<p>This article reviews potential pathways for protein aggregation, and analytical methods to detect, characterize, and quantify said aggregates. It is also emphasized that no single method can be employed for the entire range and types of aggregates.</p> <p><em>H.C. Mahler, et al. Journal of Pharmaceutical Sciences, 98 (9), 2909-2934 (September 2009)</em></p>
This article discusses how interactions with surfaces and leachables can result in aggregate formation, as well as strategies to mitigate this issue. <p><em>J. Bee, et al. Journal of Pharmaceutical Sciences, 100 (10), 4148-4170 (October 2011)</em></p> <p>Available for purchase – free to members of American Pharmacists Association (APhA)</p>
<p>This article discusses the methods to perform, and evaluate results of, stress testing of proteins. Typical methods include elevated temperatures, freeze/thaw cycles, mechanical stress and exposure to radiation.</p> <p><em>A. Hawe et al. Journal of Pharmaceutical Sciences, 101 (3), 895-913 (March 2012)</em></p> <p> </p>
<p>This article considers the effect of agitation on protein aggregation. Stirring and shaking result in different types of aggregates and in different quantity. Stirring was determined to generate the greater level of stress.</p> <p><em>S. Kiese, et al., Journal of Pharmaceutical Sciences, 97 (10), 4347-4366 (October 2008)</em></p> Available for purchase – free to members of American Pharmacists Association (APhA)<br /> <div> </div>
<p>This article examines the effects on aggregation of proteins resulting from silicone oil exposure, in conjunction with agitation, temperature, pH or ionic strength.</p> <p><em>R. Thirumangalathu, et al. Journal of Pharmaceutical Sciences, 98 (9) 3267-3181 (September 2009)</em></p>
<p>It is well established that silicone oil induces formation of protein aggregates. The mechanism proposed in this report is that the oil either has a direct effect on protein surface intermolecular interactions, or indirectly by effecting the solvent.</p> <p><em>L.S. Jones, et al. Journal of Pharmaceutical Sciences, 94 (4), 918-927 (2005)</em></p>
As the parenteral drug industry evolves towards demanding more from the quality and performance of primary packaging materials, unresolved technical challenges which slow innovation are coming into focus. In particular, the drive to eliminate silicone oil from prefilled syringes and cartridges has highlighted the challenges associated with managing the sliding friction of two sealing surfaces. Here we discuss the evolving industry trends in the packaging and delivery of therapeutic proteins and how innovations in packaging materials and technologies are enabling fully silicone-oil-free syringe systems.<br /> <br /> <em>S. Dounce. Pharmaceutical Commerce (www.pharmaceuticalcommerce.com). 24-25 (November/December 2017)</em>
<p>This excellent article by Amgen scientists overviews the structures and functions of different drug products, namely: small molecules, therapeutic proteins, monoclonal antibodies, fusion proteins, bispecific T-cell engager antibody constructs, bispecific antibodies, peptides, peptibodies, oncolytic immunotherapy viruses, antibody drug conjugates, car-T cells, RNA interference, and listeria-based immunotherapy.</p> <p> </p>
For biologic drug products in prefilled syringes, this article considers sources of protein aggregation (e.g., interaction with silicone oil) and methods for mitigation (e.g., use of polymer-based components) <p><em>A. Siew. BioPharm International, 29 (11), 50-52 (2016)</em></p> <p> </p>
Daikyo Crystal Zenith® is a registered trademark of Daikyo Seiko, Ltd.
Daikyo Crystal Zenith® technology is a registered trademark of Daikyo Seiko, Ltd.