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PDA Journal of Pharmaceutical Science and Technology

Joseph Nashaat Tanyous Boctor
1. Abstract: Cross contamination is a major concern in pharmaceutical industry, especially with long term dosing and accumulative possible effects. The risk is dependent on many factors that can be divided into three main groups: - 1.1. Individual related - starting from the genomic makeup, age, gender, environment, even their diet and psychological state, which in return, alters the individual response to contamination and to any pharmaceutical API. 1.2. Formulation related: - like it`s clean-ability, solubility of the API, batch size, maximum daily dose or inactive materials and most importantly the PDE (permitted daily exposure) of the API/s, which covers the toxicological profile of this API, including its genotoxic, reproductive toxicity, sensitizing potential or any adverse effects that would result from long or short term cross contamination...
October 25, 2018: PDA Journal of Pharmaceutical Science and Technology
Jakob Buecheler, Joerg Luemkemann, Henning Gieseler, Silke Mohl, Alexander Streubel
The capping of vials plays a critical role in drug product manufacturing process due to its complex interplay of several adjustable process steps. Seal quality, integrity and assurance of containment is essential for parenteral pharmaceuticals as the vial's content may be contaminated, or in case of highly potent drugs (e.g. antibody drug conjugates) may bear a risk of contamination. The residual seal force (RSF) method can enable further insight in capping equipment settings independently of the container closure system (CCS) and their resulting seal quality...
October 25, 2018: PDA Journal of Pharmaceutical Science and Technology
Richard O Montes, Richard K Burdick, David J LeBlond
Tolerance intervals are used to statistically derive acceptance limits that drugs must conform to upon manufacture (release) and throughout shelf-life. The single measurement per lot in release data and repeated measurements per lot longitudinally for stability data have to be considered in the calculation. Methods for the one-way random effects model by Hoffman and Kringle (2005) [HK] for two-sided intervals and Hoffman (2010) [H] for one-sided limits are extended to a random intercepts, fixed slope model in this paper...
October 25, 2018: PDA Journal of Pharmaceutical Science and Technology
Jeffrey Weber, James Hauschild, Pieta IJzerman-Boon, Ren-Yo Forng, Jeff Horsch, Lisa Yan, Aditya Prasad, Robert 'Bo' Henry, Marja Claassen, Philip Villari, Shebeer Shereefa, Jane Wyatt, Jay S Bolden, Jean-Thierry Pycke, Dawood Dassu
This white paper provides recommendations for quality oversight, manufacturing operations, and industry perspective of regulatory expectations to enable aseptic facilities to move toward real-time and continuous microbiological environmental monitoring and thereby reducing interventions and the future replacement of Grade A settle plates and non-remote active air sampling. The replacement of traditional monitoring with bio-fluorescent particle counting systems provides an improvement in process understanding, product safety, and reduces operator manipulations assuring product quality and real-time process verification...
October 25, 2018: PDA Journal of Pharmaceutical Science and Technology
Søren Dahl, Jonas Olsen Hede, Philip Loldrup Fosbøl, Signe Willestofte Berg
The regulatory expectations introduced by USFDA in 1999, ICH Q5C and revised draft Annex-1-Eudralex volume 4 for consultation, the recent update of USP general chapters 1207.1 and 1207.2, regarding Container Closure Integrity testing (CCIT), has created a need for further development of testing methods, although there are no universally accepted testing method to test and evaluate the CCI of a Biopharmaceutical drug product. Each testing method and principle has merits and demerits. This paper will present a simple approach to be used in method validation of a CCIT method based on headspace oxygen analysis for freeze dried biopharmaceutical drug products in vials, as well as a method for testing and verifying positive control vials...
October 25, 2018: PDA Journal of Pharmaceutical Science and Technology
David R Machak, Gary L Smay
Lyophilization is a commonly used and often preferred method for the preparation of certain drug products. In this process, the liquid pharmaceutical product is packaged in glass vials, frozen and then dried via sublimation at low pressures. One of the problems that can be encountered during lyophilization is the occasional failure of the glass vial, a condition that will be referred to in this paper as "lyo-breakage". Lyo-breakage, while relatively rare, can be a serious problem as it results in lost product, additional costs to remediate any spillage, and inspection time to ensure that all of the broken vials are discarded...
October 25, 2018: PDA Journal of Pharmaceutical Science and Technology
Dennis Jenke
Pharmaceutical drug products are packaged in containers so that they can be manufactured, distributed and stored. During these events in a drug product's lifecycle, the drug product and it's packaging could interact, resulting in substances leaching from the plastic and accumulating in the drug product. As the leached substances could adversely impact a key quality attribute of the drug product, drug products must be tested to establish what leachables are present and in what quantities they are present. Because a drug product's lifetime can be long, it is common practice to accelerate leaching by using temperatures higher than the conditions of clinical use...
October 25, 2018: PDA Journal of Pharmaceutical Science and Technology
Paul W Barone, Stephen Avgerinos, Rob Ballard, Audrey Brussel, Phil Clark, Chris Dowd, Lionel Gerentes, Ian Hart, Flora J Keumurian, Johanna Kindermann, Nguyen Ly, Sheldon Mink, Stefan Minning, Jürgen Mülberg, Marie Murphy, Kerstin Nöske, Sandra Parriott, Bonnie Shum, Stacy L Springs
Appropriate segregation within manufacturing facilities is required by regulators and utilized by manufacturers to ensure that the final product has not been contaminated with 1) adventitious viruses, 2) another pre-/ post-viral clearance fraction of the same product, or 3) with another product processed in the same facility. However, there is not consensus on what constitutes appropriate facility segregation to minimize these risks. In part, this is due to the fact that a wide variety of manufacturing facilities and operational practices exist, including single and multi-product manufacturing, using traditional segregation strategies with separate rooms for specific operations that may use stainless steel or disposable equipment to more modern ballroom style operation that use mostly disposable equipment (i...
October 25, 2018: PDA Journal of Pharmaceutical Science and Technology
Denise Bohrer, Patricia Mattiazzi, Carine Viana, Paulo Nascimento, Leandro Carvalho, Marlei Veiga
Flexible medical devices are primarily made of plasticized polyvinyl chloride (PVC). Lately, PVC is being replaced with ethyl vinyl acetate (EVA) and polypropylene (PP) to avoid undesired migration of the PVC plasticizers. Nevertheless, other additives are necessary to generate useful polymeric materials. Metallic species present in such additives can also leach out into the infusion solutions. The migration of Ba, Cd, Sn, Pb, and Zn from devices made from PVC, EVA, and PP was evaluated. Bags and infusion sets were decomposed, and their metallic contents were analyzed...
September 19, 2018: PDA Journal of Pharmaceutical Science and Technology
Jennifer Johns, Paolo Golfetto, Tia Bush, Gianmaurizio Fantozzi, John Shabushnig, Anthony Perry, Fran DeGrazio, Dorothee Streich, Jahanvi Miller, Herve Soukiassian, Amy Stanton, Rick Watson
The reduction of visible particles in injectable products is an important element in the consistent delivery of high-quality parenteral products. An important part of this effort is the control of particles that may emanate from the primary packaging materials. The Parenteral Drug Association (PDA), with the support of the Pharmaceutical Manufacturers Forum (PMF) has undertaken the task of developing test methods to assess the cleanliness of primary packaging components used in the manufacture of sterile injectable products...
September 19, 2018: PDA Journal of Pharmaceutical Science and Technology
Xia Cathy Zhao, Le Ho, Daniel L Bantz, Doug Hostetler, Liang Fang
This case study is the first to address the risk, at the device-to-vial interface, of a spike pushing a stopper into a vial. It was performed after healthcare workers at cancer care hospitals complained about the risk of possible exposure to hazardous injectable drugs during the transfer if the spike pushed the stopper into the vial. This case study took a three-step approach to understand the device-to-vial interface, and the factors that determine stopper push-in force threshold and spike puncture force, respectively...
September 19, 2018: PDA Journal of Pharmaceutical Science and Technology
Dennis Jenke
The safety aspects of elemental impurities in finished drug products is a topic of considerable importance in the pharmaceutical community and guidelines such as ICH Q3D and USP <232> and <233> have been published to provide directions on how to assess finished drug products with respect to such impurities. Although a drug product's packaging system has been identified as a potential source of elemental impurities, comparable guidelines have not been established for assessing packaging systems, and their materials and components of construction, with respect to their potential to contribute leached elements to packaged drug products...
September 19, 2018: PDA Journal of Pharmaceutical Science and Technology
Philippe Lam, Thomas W Patapoff
"Elegant" lyophilized pharmaceutical product cakes are expected to appear as uniform foamy plugs with little shrinkage and minimal cracking. While studying internal cake structures, we have on occasion observed some cakes that were split horizontally, roughly in halves, with foamy top and lamellar bottom regions. After many years and numerous experiments, we can finally propose a mechanism for the formation of these cakes with unusual internal structures. This phenomenon involves a complex interplay of momentum, heat, mass transfer and phase equilibria...
August 29, 2018: PDA Journal of Pharmaceutical Science and Technology
Liang Fang, Cathy Zhao
Polymer films were widely used as barriers for blocking certain organic molecules (such as leachables and extrables) in both food and parenteral pharmaceutical packaging applications. However, a good understanding of the barrier properties of those polymer films is still lacking for combination drug product manufacturers to make practical risk-based assessment regarding the effectiveness of the barrier films against potential leachables. The present work addressed this issue by a combined theoretical/experimental approach: a new mathematical model based on Hansen Solubility Parameters, the size, and the shape of organic molecules was developed to quantitatively estimate the Steady State Permeation Rate (SSPR) of organic migrants through a model ETFE fluoropolymer film, by considering contributions from both solubility and diffusivity...
August 29, 2018: PDA Journal of Pharmaceutical Science and Technology
John D Ayres
Visible particulate matter in injectables presents one important question for consideration: ″What are the potential implications to the patient?″; The risks of visible particulate matter to patient safety have been comprehensively reviewed elsewhere. However, the methods utilized to assess and characterize the risk have been explained with various degrees of specificity and supporting rationale. To date, the assessment process lacks the necessary consensus to permit a more standardized and consistent approach to evaluate the potential patient risks...
August 29, 2018: PDA Journal of Pharmaceutical Science and Technology
Richard Levy
No abstract text is available yet for this article.
September 2018: PDA Journal of Pharmaceutical Science and Technology
Junfen Ma, Thomas R Kreil
The discussion on facility risk mitigation was included for the first time at the 2017 Viral Clearance Symposium. A few topics were discussed in this session, including sanitization/cleaning against viruses, viral segregation, as well as the definition of a "functionally closed" system.Virus inactivation by disinfectants is critical for the biotechnology industry. The efficacy can differ, depending on whether applied to surfaces, in solutions, or in gas phases, as well as the respective disinfectants (i...
September 2018: PDA Journal of Pharmaceutical Science and Technology
Johannes Blümel, Junfen Ma
In many downstream processes, chromatographic purification steps contribute significantly to the overall virus reduction capacity. The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guideline Q5A(R1) outlines that "Over time and after repeated use, the ability of chromatography columns and other devices used in the purification scheme to clear virus may vary. Some estimate of the stability of the viral clearance after several uses may provide support for repeated use of such columns...
September 2018: PDA Journal of Pharmaceutical Science and Technology
Astrid Schwantes, Rachel Specht, Qi Chen
Appropriate performance of virus validation studies and testing of unprocessed bulk harvests for retrovirus particle count are procedures in the demonstration of an acceptable level of viral safety for cell-derived biotechnology products. Product-specific validation studies on virus reduction with two model viruses [usually murine leukemia virus (MuLV) and a parvovirus] performed in duplicate runs are standard for clinical trial applications. For the retroviral safety margin, a 6 log reduction is normally expected...
September 2018: PDA Journal of Pharmaceutical Science and Technology
Thomas R Kreil, David Roush
The manufacturing processes of biological medicinal products are expected to be capable of removing and/or inactivating viruses, to primarily provide for adequate safety margins to patients and to thus satisfy the corresponding regulatory expectations. To achieve this goal, process segments specifically dedicated to the task of virus removal or inactivation are designed into manufacturing flows. The state of the art now includes virus removal by nanofiltration, and the more traditional low pH or (solvent-) detergent treatments are used widely, often to provide for two complementary and mechanically different means of virus clearance...
September 2018: PDA Journal of Pharmaceutical Science and Technology
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