PDA Journal of Pharmaceutical Science and Technology最新文献

FDA recommends monitoring differential pressure across filter membranes during sterile filtration process validation. However, few resources are available to help pharmaceutical manufacturers anticipate expected differential pressures during sterilizing filtration of different solutions. To address this gap, Meissner evaluated differential pressures across different filtration membranes using various test solutions at increasing pump speeds. Specifically, we investigated differential pressures across sterilizing-grade PVDF, PES, and PTFE membrane discs, either in series or with downstream 0.4 μm PES analysis discs commonly used in bacterial retention testing. The test solutions employed for this study include saline, grapeseed oil, FBS, and DMEM cell culture media with 10% FBS. These solutions were chosen based on their differing physicochemical properties and their relevance to the pharmaceutical industry. This work will serve as a reference for pharmaceutical manufacturers and help them anticipate differential pressures across sterilizing filter membranes at different pump speeds based on the physicochemical properties of their drug products.

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. 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 to 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, 72hours and not perfect 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.

The pursuit of harnessing data for knowledge creation has been an enduring quest, with the advent of machine learning (ML) and artificial intelligence (AI) marking significant milestones in this journey. ML, a subset of AI, emerged as the practice of employing mathematical models to enable computers to learn and improve autonomously based on their experiences. In the pharmaceutical and biopharmaceutical sectors, a significant portion of manufacturing data remains untapped or insufficient for practical use. Recognizing the potential advantages of leveraging the available data for process design and optimization, manufacturers face the daunting challenge of data utilization. Diverse proprietary data formats and parallel data generation systems compound the complexity. The transition to Pharma 4.0 necessitates a paradigm shift in data capture, storage, and accessibility for manufacturing and process operations. This paper highlights the pivotal role of AI in converting process data into actionable knowledge to support critical functions throughout the whole product life cycle. Furthermore, it underscores the importance of maintaining compliance with data integrity guidelines, as mandated by regulatory bodies globally. Embracing AI-driven transformations is a crucial step toward shaping the future of the pharmaceutical industry, ensuring its competitiveness and resilience in an evolving landscape.

Visible particle is an important issue in the biopharmaceutical industry, and it may occur across all the stages in the life cycle of biologics. Upon the occurrence of visible particles, it is often necessary to conduct chemical identification and root cause analysis to safeguard the safety and efficacy of the biotherapeutic products. In this article, we present a number of typical particles and relevant root cause analysis in the categories of extrinsic, intrinsic, and inherent particles that are commonly encountered in the biopharma industry. In particular, the optical images of particles obtained both in situ and after isolation are provided, along with spectral and elemental information. The particle identification was carried out with multiple microscopic and microspectroscopic techniques, including stereo optical microscopy, Fourier-transform infrared microscopy, confocal Raman microscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Both commercial and in-house spectral databases were used for comparison and identification. In addition to particle identification, we placed significant efforts on the root cause analysis of the addressed particles with the intention to provide a relatively whole picture of the particle-related issues and practical references to particle mitigation for our peers in the biopharmaceutical industry.

A prefilled syringe (PFS) should be able to be adequately and consistently extruded during injection for optimal safe drug delivery and accurate dosing. To facilitate appropriate break-loose and gliding forces (BLGFs) required during injection, certain primary packaging materials (PPMs) such as the syringe barrel and plunger are usually coated with silicone oil, which acts as a lubricant. Due to its direct contact with drug, silicone oil can increase the number of particles in the syringe, which could lead to adverse interactions. Compliance with regulatory-defined silicone oil quantities in certain drug products, such as ophthalmics, presents a trade-off with the necessity for desirable low and consistent BLGF. In addition to its siliconization, the dimensional accuracy of the PPM has an important role in controlling the BLGF. The dimensions of the PPM are individualized depending on the product and its design and have certain tolerances that must be met during manufacturing. Most studies on ophthalmics focused on the adverse interactions between silicone oil and the drug. To the authors' knowledge, there have been no public studies so far that have investigated the impact of the dimensional variability of the PPM on the BLGF in ophthalmic PFSs. In this study, we applied advanced optical shaft and tactile measuring technologies to investigate this impact. The syringes investigated were first sampled during aseptic production and tested for the BLGF. Subsequently, defined dimensions of the PPM were measured individually. The results showed that the dimensional variability of the PPM can have a negative impact on the BLGF, despite their conformity to specifications, which indicates that the currently available market quality of PPMs is improvable for critical drug products such as ophthalmics. This study could serve as an approach to define product-specific requirements for primary packaging combinations and thus appropriate specifications based on data during the development stage of drug products.

The Coalition for Epidemic Preparedness Innovations (CEPI) has developed a robust CMC (Chemistry, Manufacturing, and Controls) Framework to enhance the likelihood of successful vaccine development. This Framework serves as a comprehensive guide, aiding developers in building effective strategies to overcome the challenges posed by the different phases of vaccine development, including the ones often referred to as the "valleys of death". The Framework lists stage-appropriate deliverables, categorized and refined, spanning five key areas: manufacturing process, formulation and stability, analytics, supply chain, and compliance. By emphasizing the critical aspects of CMC development, CEPI's objective is to expedite the progression of vaccine candidates from research to deployment, reducing delays, mitigating risks, and optimizing the overall development process, all while upholding uncompromising quality standards, ultimately increasing the probability of success.

Vial and syringe filling by peristaltic pump has been widely implemented by contract manufacturing organizations and biopharmaceutical companies. Fill volume is commonly considered as critical quality attribute related in aseptic filling process and the variation needs to be well controlled to guarantee the safety, efficacy and consistency of drug products. However, the criteria for justifying the filling variation and underlying mechanisms that affect the variability are not fully revealed quantitatively in the literatures. This study selected filling accuracy, filling process capability and filling precision as three criteria for evaluating the filling process performance with four statistical indexes: Relative Error Mean, Critical Control Limit (Cpk ≥ 1.33), Relative Standard Deviation and Relative Moving Range Mean. The impact of liquid properties, pump tubing sizes and pump settings on above indexes were investigated using a bench-top system with a peristatic pump and a high-precision balance. The results showed that the viscosity, target fill volume, pump tubing size, pump speed, acceleration/deceleration rate and suck-back had statistical significance on the fill volume variability. Definitive Screening Design was further applied to clarify and visualize the priorities and interaction impact of above factors on fill volume variability. Stepwise approach for fill volume variability optimization and control based on predictive models was established and verified for drug product solution with viscosity between 1-23 cp and target fill volume between 0.2-2.0 mL.

The mechanics of microneedle insertion have thus far been studied in a limited manner. Previous work has focused on buckling and failure of microneedle devices, while providing little insight into skin deformation, puncture, and the final positioning of needle tips under full microneedle arrays. The current study aims to develop a numerical approach capable of evaluating deformation and puncture conditions for full microneedle array designs. The analysis included a series of finite element submodels used to calibrate the microneedle-epidermal interface for failure properties using traction-separation laws. The single needle model is validated using experimental data and imaging, including results from a customized nanoindentation procedure to measure loads and displacements during microneedle insertion. Upon validation, full microneedle arrays are implemented in a 3 D finite element model and a design framework is developed, allowing evaluation of different design variables (i.e. needle shape, material, spacing) with respect to outputs relevant to successful microneedle performance. Results from the model include skin deformation, force to puncture, penetration depth, and the punctured state at each microneedle tip. In addition to microneedle parameters, patient parameters such as subcutaneous tissue thickness are included to evaluate the sensitivity of different microneedle designs to expected patient and anatomical region variability.

Activation against a hard surface according to ISO 11608-1 is not always representative of device use on a soft injection site. A softer injection site - which is an anthropometric property found in obese patients - presents a distinct viscoelastic property which can lead to greater autoinjector activation forces that are not captured in standardized activation testing methodology. Soft tissue simulation and physical testing were developed at SHL to advance the development of autoinjectors, allowing for rigorous testing and challenging these in scenarios involving even the softest injection sites.