PDA Journal of Pharmaceutical Science and Technology最新文献

The pharmaceutical industry is constantly evolving, driven by technological innovations aimed at enhancing efficiency, quality, and adaptability in drug manufacturing processes. This presentation highlights the success story of flexible fill and finish platforms over the past decade and introduces groundbreaking advancements shaping the next generation of pharmaceutical manufacturing, such as new container transfer solutions and the next generation of isolated pharma machinery. It also includes regulatory aspects like EU GMP Annex 1 and addresses the requirements relating to novel medicinal products and their individual properties. By exploring these technological advancements, the presentation aims to provide insight into the transformative potential of these innovations in optimizing drug manufacturing processes, ensuring product quality, and meeting the evolving demands of the healthcare landscape.

The R&D Quality (RDQ) Internship at Kite Pharma provided me with a comprehensive introduction to ensuring compliance with health authority regulations and fostering a quality-driven culture within clinical research and development. Key contributions included preparing for regulatory inspections by reconciling clinical trial timelines, conducting gap analyses, and developing mock inspection documentation. I also supported Standard Operating Procedure (SOP) updates to enhance consistency and developed engaging training materials, such as the Quality GCP Training Game, to strengthen employee understanding of Good Clinical Practices (GCP) across departments and functional areas. Additionally, I conducted a training gap analysis to assess current GCP audit report writing skills and support the future creation of team training materials. Overall, this internship reinforced the importance of quality in protecting patients, ensuring product reliability, and managing risks in the development of innovative therapies, and further fueled my interest in the field of Quality.

Regulatory and manufacturing requirements exist to perform product-specific microbial retention testing on sterilizing filters. The implementation of a Quality by Design approach to microbial retention testing supports a paradigm that would obviate the need for product-specific testing for early-stage products that do not have the quantity of material required to easily and efficiently perform such testing. Process and product parameters were varied to determine their effect on microbial retention.

Quality culture is an integral part of a workplace and is one of the foundational traits that lead teams to prioritize compliance and the safety of patients. However, quality culture is merely one of the byproducts of corporate culture. Looking beyond quality culture means examining and implementing the various elements that contribute to a great corporate culture, such as a company's vision, core values, management practices, accountability, and effective communication. Understanding these elements and how they are interconnected within each company can lead to a culture that not only delivers high-quality products or services but also fosters employee satisfaction, engagement, and overall organizational success. As an industry, we need to rethink how we view quality culture.

The 2011 FDA Guidance for Industry, "Process Validation: General Principles and Practices," emphasizes maintaining control of manufacturing processes throughout the product lifecycle through constant reevaluation. For lyophilized drug products, Critical Quality Attributes (CQAs) identified in Stage 1 can be effectively trended and reported annually. However, monitoring Critical Process Parameters (CPPs) such as shelf temperature, chamber pressure, and time presents greater challenges. Methods like comparing actual variation to averages, targets, or proven acceptable ranges (PARs) are defined in Stage 1, validated in Stage 2, and continually assured in Stage 3. Demonstrating a state of control for lyophilization parameters is vital, yet complex. Previously, classical statistical methods were used to evaluate process variability by analyzing data from multiple batches of the same product. These techniques revealed actionable insights into maintaining consistent control. However, in a multiple product facility, utilizing multiple methods to analyze various products can be inexpedient. Expanding on previous research, various batches of lyophilized products were assessed to verify the relative robustness of a specific statistical methodology for the sake of efficiency. This analysis underscores the importance of continual monitoring in lyophilization to ensure product quality and regulatory compliance.

Sterilization of sensitive drug delivery devices such as pre-filled syringes can be significantly enable by implementing Vaporized Hydrogen Peroxide VH2O2 (VHP) Low Temperature Sterilization for the process application. Utilizing VH2O2 has been widely used in biodecontamination of e.g., Pharmaceutical manufacturing spaces, isolators and lyophilizers for over 30 years, and terminal sterilization of sensitive combination products and other medical devices by VH2O2 also increasingly for the past 20 years. The 2022 published ISO 22441 for process validation, adoption by FDA and several other countries and FDA moving VH2O2 sterilization to Established Category A are strengthening its position. The near future EN 17180 for VH2O2 sterilizer equipment will provide specific guidance for implementing to pharmaceutical manufacturing process. Further, the work on VH2O2 specific biological indicator standard ISO 11138-6 and upcoming revision of the AAMI TIR 17 for guidance on material compatibility for sterilization modalities, will provide additional help and guidance. This presentation will provide guidance on all key elements of equipment and process validation of VH2O2 sterilizers and developed processes and recommendation on steps of application implementation, and also puts focus on key requirements of conformance and related materials and documentation, in the light of typical product applications sterilized by VH2O2.

Autoinjectors facilitate self-administration of subcutaneous (SC) medications. Despite their benefits for patients and healthcare systems, experimental research on how they impact drug dispersion and absorption is limited. This study investigates how autoinjector injection parameters influence plume growth, morphology, and diffusion during and post injection. We investigated three commercial autoinjector models of a similar design with varying delivered volumes (0.5 mL, 1 mL, and 2 mL) injected into excised pork belly tissue. Synchrotron radiography provided high-resolution, real-time 2 D visualization of plume dynamics during injection, while the 3 D morphology of the depot postinjection was captured with a synchrotron CT. Our results show that plume growth is nonlinear, with an initial rapid phase slowing over time. The final plume volume exceeds the delivered dose by 25%, reflecting depot spread within the tissue. Regardless of autoinjector model or injection volume, the plume predominantly expands horizontally (parallel to the tissue), with the aspect ratio increasing throughout the injection and reaching a final value of approximately 4. Post-injection diffusion appears to be driven more by tissue properties than by the autoinjector design parameters. These findings provide a foundation for refining autoinjector designs, developing more accurate computational models to predict drug absorption, and optimizing SC delivery systems.

Chlorine dioxide gas (CD) sterilization is an alternative modality to ethylene oxide as well as other sterilization modalities and is of high interest to the EPA and FDA due to both its sustainability as well as effectiveness. The dry method of generating chlorine dioxide gas was developed within Johnson and Johnson and generates a greater than 99% pure form of chlorine dioxide gas. CD gas is an oxidizer which is non-carcinogenic, non-explosive at use concentrations and can perform sterilization at ambient temperature. The presentation will discuss the elements that need to be considered when selecting packaging for a product being sterilized with chlorine dioxide gas. It includes an explanation of what packaging is most suitable for certain product categories as well as packaging suggestions for products with unique restrictions such as absorbable products. The poster will also include expert analysis from material manufacturers on test data on the suitability of chlorine dioxide with their materials. Additionally, residual levels and cytotoxity is analyzed to further indicate compatibility after processing.

Large-volume auto-injectors and wearable devices exceeding 2.25 mL play a crucial role in the transition from hospital-based intravenous (IV) treatments to self-administrated drug delivery via subcutaneous (SC) injection. These devices are especially pivotal in the treatment of oncological, immunologic, and neurodegenerative diseases, where they are often tasked with delivering high-viscosity and delicate biologics to patients in need. Ensuring the highest standards of quality and purity in elastomers, along with flawless functional performances, is imperative to guarantee the reliability of administration and patient safety. A balance of functionality, machinability, and product safety are essential for the entire device system to function. In this presentation, we will delve into the technical hurdles encountered in designing and manufacturing larger coated plungers for pre-filled syringe (PFS) and cartridge containers intended for device integration. We will showcase our journey from conceptualization to commercialization of these coated plungers, as well as evaluating their performance throughout the entire value chain to the patient. Additionally, we will underscore the significance of fostering an open collaboration with the container manufacturer and among the additional stakeholders involved in the development of the final combination product.

This article focuses on describing control measures intended to reduce the risk of glove damages, which can be linked to contamination (particulate or microbiological). Specific risks involving gloves are analyzed, assessed, and minimized by means of appropriate control measures. The aim is to demonstrate that the risk of contamination via isolator gloves cannot be mitigated by a single action, but rather that a combination of several preventative measures is required. Important control measures for the safe handling of gloves at barrier systems include the observation of glove functional use, personnel training, and monitoring control measures. This observation of the glove functional use can represent a higher or lower good manufacturing practice (GMP) risk for the product, depending on the intervention. The handling of the gloves and their use should be documented accordingly and evaluated in a risk assessment. The risk analysis defines measures that are part of the quality risk management for gloves and contribute to the safe production of sterile pharmaceuticals. This raises the question as to the point from which an isolator is at risk of microbiological contamination following damage to a glove, or what size of pinhole in a glove represents a risk. This article works on the assumption that this question can only be answered by means of glove quality risk management.