PDA Journal of Pharmaceutical Science and Technology

A two-phase flow computational fluid dynamic (CFD) model was developed to study hydrodynamic forces and protein concentration changes of a protein solution in a syringe injector. Proteins were assumed as nano-sized solid spheres commensurate with their molecular weight and suspended in aqueous environment, passing through the rapid constricted sections of the syringe. Interaction between the solid and liquid phase was taken into account and four laminar flow cases were studied under the extensional flow. Profiles of pressure, velocity, and shear stress of the different cases were examined and compared...

During the manufacture of a monoclonal antibody drug product aseptically filled within a vapor phase hydrogen peroxide-sanitized isolator, samples were taken to investigate the hydrogen peroxide uptake behaviors. The results surprisingly yielded no detectable levels of hydrogen peroxide. This finding was later attributed to hydrogen peroxide decomposition after samples were stored frozen at -20oC for two weeks before testing. This case study highlights the criticality of storage conditions for hydrogen peroxide-containing samples and summarizes a comprehensive investigation on hydrogen peroxide stability in aqueous samples and in samples containing monoclonal antibody with a wide protein concentration range (30 - 200 mg/mL)...

The sterility of drug products intended for parenteral administration is a critical quality attribute (CQA) because it serves to ensure patient safety, and is thus a key requirement by health authorities. Whilst sterility testing is a probabilistic test, the assurance of sterility is a holistic concept including adequate design of manufacturing facilities, process performance, and product design. Container closure integrity testing (CCIT) is necessary to confirm the integrity of a container closure system (CCS), until the end of a products's shelf life...

In the production of several anti-cancer drugs, tert-butyl alcohol (TBA) is present as a co-solvent in the aqueous drug solution. In order to ascertain if TBA should be removed beforehand or could be retained to facilitate the freeze drying of the drug solution, it is important to acquire both qualitative and quantitative knowledge of the variations occurring with respect to time in heat and mass transfer during the freeze drying process. In this work, a thermodynamic model employing the UNIFAC (Dortmund) method was developed to determine the values of the currently experimentally unavailable partial vapor pressures of the binary gas mixture of water and TBA in equilibrium with their frozen solid mixtures...

The sensitivity of drugs to one or more elements of the primary packaging is a serious concern for the pharmaceutical industry. Biologics in particular are highly sensitive, leading to a higher risk of incompatibility and stability test failures worst-case scenario. This potential incompatibility - and the consequent formulation instability due to the interactions between the drug and the primary container surface - may have multiple causes: the intrinsic nature of the container surface, leachables coming from the materials used, substances coming from the production process, silicone oil droplets or other particles...

BACKGROUND: In practice it is claimed that the characteristics of a load influence a surface steam sterilization process. [Rev#2 Com#1] 'Limited and mainly qualitative' information on this topic has been found in the literature. AIM: To find if a load influences the duration and the related characteristics of a surface steam sterilization process. METHOD: In a case study 30 days of every load monitoring with an objective, quantifying steam penetration test has been performed...

The European Pharmacopeia (Ph. Eur.) hydrolytic resistance method for glass vials is routinely used to screen pharmaceutical glass vial supply. Due to reliance on this method to reduce the risk of glass vial delamination in pharmaceutical drug products, it is important that the sources of method variability be understood and controlled. Several potential sources of variability in the Ph. Eur. alkalinity method have been studied for 3cc glass vials. Method parameters including vial rinsing, fill volume determination, vial covering, autoclave cycle execution, sample hold times, and titration procedure were evaluated in this study...

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No abstract text is available yet for this article.

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...