PDA Journal of Pharmaceutical Science and Technology最新文献

This paper is the result of a round-robin activity run by the Technical Committee TC12, Pharma Packaging, of the International Commission on Glass (ICG). The study was motivated by a concern about the risk that the depyrogenation treatment of glass vials, when performed in an abnormal way that deviates from the usual procedure, may have a negative impact on the hydrolytic resistance of the container inner surface after filling with the drug product, for example, by increasing the release of leacheables and/or the propensity to delamination. The study was executed by using 10 mL clear type I borosilicate glass vials representing four different compositions. For the applied depyrogenation process, extreme parameters were chosen with maximum temperature up to 400°C, exposure times up to 72 hours, and different amounts of residual water inside as starting conditions. Those treated samples were tested in seven different laboratories as a round-robin test. A large amount of data was obtained, which clearly indicate that the hydrolytic resistance performance of the Type I borosilicate glass vials is not affected even by such extreme depyrogenation conditions (e.g., 400°C, 72 hours, and not perfectly dried inside). This is an important and useful result, both for glass and pharma companies, based on the 12,000 analytical data collected during the interlaboratory activity.

In silico modeling of subcutaneous injections is a promising tool to derisk and optimize the development of injections systems and improve preliminary understanding of the injectability of drugs. Such modeling can be leveraged early in development, prior to pre-clinical studies, to reduce testing burden and effectively predict aspects such as the time and forces required for full dose delivery into tissue and the tissue-injectate-device interactions. In this work, we address the three main in silico pillars (primary container, injection device, and tissue) that are necessary to simulate a parenteral injection. We showcase how their modeling can be combined and applied to various delivery systems and injection conditions to enable appropriate systems and parameters selection to achieve desired performance. Case studies of viscous drugs in PFS/AI and wearable injection systems with non-rigid component properties are presented to highlight the theoretical treatment of interfaces, the critical inputs required to achieve accurate predictions, the insights gained, and the good agreement between model predictions and experimental results.

We're starting to see a huge shift in the healthcare industry towards sustainability, with stakeholders throughout the sector aiming to drive down emissions and reduce environmental impacts. This graphic focuses on device design, and applies to any sector of the industry. It looks at every phase of a product's lifecycle, and breaks these down into focal points and design opportunities for footprint reduction.The ultimate goal in sustainability is The Circular Economy, the definition of which is the reduction, capture, and reuse of all embodied resources into an indefinite loop, with minimal negative external effects. The graphic illustrates how the journey to circularity can be achieved through considered design at every one of those lifecycle phases. It examines opportunities within raw materials, manufacturing, transport, use, and end-of-life, considering not just technical approaches but business model development and user behaviours as well, aiming to cohesively target a cradle-to-cradle system. Even for products and services where full circularity is not realistic, it identifies multiple opportunities for good design to reduce emissions and perhaps ease the journey to circularity in the future.

Challenges in the manufacturing of high-concentration antibody formulations have seldom been discussed. These are observed mainly from late downstream operations where the antibody gets concentrated to its final strength to final fill finish processing and containerization of the product. The present paper summarizes the challenges typically observed in manufacturing and processing of high-concentration antibody products and provides turnkey solutions to these typical challenges in order to have a consistent and robust manufacturing process for these products. Immunoglobulin G1 (IgG1) has been used as a model protein for studying the challenges and providing solutions to them. The late downstream challenges, like increased viscosity limiting further concentration, can be resolved by use of viscosity modifying agents in the formulation. Replacement of the conventionally used 'A' screen membranes with 'D' screen or using single pass tangential flow filtration can further provide an in targeting higher concentrations for the same protein with lesser shear and aggregation. Using a 0.5 µm/0.2 µm asymmetric or bilayered membrane instead of the conventional 0.2 µm membrane resulted in better flux during filtration of a high-concentration IgG1 formulation. In-process holding time during the filling operation was optimized to be <60 min based on the nozzle drying time for the high-concentration IgG1 formulation. An appropriate control strategy of replacing filling nozzles and performing periodic fill weight checks was proposed for the fill-finish process of a high-concentration IgG1 formulation.

This work focused on understanding the current practice of the intravitreal injections (IVIs) and existing challenges for both patients and healthcare professionals with the ultimate goal of developing a combination device concept for intravitreal injections. Using a systematic approach, an initial user preference study was initiated that incorporated an online survey designed and conducted with retinologists from the EU countries (n = 25), followed by in-person interviews with national and international KOLs (n = 5). Multiple feasibility studies were conducted with focus on the unmet needs of key users such as handling characteristics and accuracy of the injection volume focusing on potential device solutions to address these unmet needs. Finally, laboratory testing and user experience evaluation of device potential concepts were used to find the best fitting device concept for injections of a fixed dose (0.05 ml) into the eye. Both qualitative evaluation and statistical analysis were used to study significant differences between the results of injection with device and standard of care. Compared to the manual IVI procedure, an automated device has the potential to increase safety for patients, decrease procedure times, allow for integrated data storage and documentation, and reduce costs for medical staff and expensive operating rooms.

RFID technology is mainstream in retail where apparel is tracked and inventory is managed with digital reader systems. All items at e.g. Walmart, Nordstrom and H&M are equipped with an RFID tag. Thus, warehouse managers and sales staff have full visibility on the movement and availability of items. The pharma industry is starting to follow this trend.

Prefilled Devices and Combination Drug Products, particularly those with integrated fluid paths or for specific Therapeutic Areas like Ophthalmology, may require final sterilization. Nitrogen Dioxide is a ground breaking novel sterilization technology designed to suit sensitive Prefilled Devices and Combination Drug products. This innovative sterilization process runs at ambient temperature and uses very low sterilant concentration. A SAL ≤10-6 is achieved in a few minutes of exposure, making this new technology highly efficient, without penetrating the drug reservoir. A case study will be shared, illustrating a validated process. This new modality will provide manufacturers with a new gas alternative to consider for their drug product to help ensure product safety for use in patients.

Needle clogging in prefilled syringes can impede drug product injection and negatively impact drug product quality. Computer simulations provide a useful tool to understand clogging mechanisms and elucidate design strategies to minimize or avoid clogging. In this talk, we present multiphysics simulations of clogging in needle syringes prefilled with a monoclonal antibody solution. We use these simulations to evaluate several putative clogging mechanisms, including: (1) fluid ingress into the needle and subsequent solvent evaporation leading to a dried solid plug, and (2) shear-induced jamming driven by rapid plunger compression. We study the impact of solution properties, needle diameter, barrel hub shape, and plunger speed on the onset of clogging. The effect of protein concentration on the solution viscosity is considered. Simulations such as these can offer insight into the critical material, geometric, and operational parameters that increase the probability of clogging, as well as a method to systematically triage drug product formulations based on their clogging probability. Based on these insights, we illustrate how simulations can be leveraged to effectively design prefilled syringes to minimize clogging probabilities for a given drug product formulation.

In February 2023 a restriction proposal to the European Chemicals Agency (ECHA) was submitted by five member countries of the European Union proposing a substantial restriction under the Registration, Evaluation, Authorization and Restriction of Chemical substances (REACH) regulation Annex XV for the use of all PFAS variants, thereby potentialy listing all PFASs as Substances of Very High Concern (SVHC).