PDA Journal of Pharmaceutical Science and Technology最新文献

The digital transformation of pharmaceutical manufacturing brings about several opportunities and challenges in ensuring data integrity, one of the foundational elements of GxP compliance. As automated systems, advanced analytics, and interoperable digital tools become intrinsic parts of the operation, so too does the risk of vulnerabilities in data. This presentation covers the overall framework for mitigating these risks using a risk-based approach to data governance and integrity management.Key topics will include building resilient data governance frameworks, leveraging automation for proactive monitoring, and ensuring data traceability throughout the product lifecycle. Practical case studies will demonstrate how risk-based strategies enhance compliance, drive operational efficiency, and align with regulatory expectations such as FDA, EMA, and global GxP standards.This session bridges the gap between compliance and digital innovation, equipping attendees with actionable strategies to protect data integrity while optimizing manufacturing processes. Whether you are involved in quality assurance, regulatory affairs, or manufacturing science, this presentation will empower you to confidently navigate the complexities of the digital age.

As the use of imaging devices and artificial intelligence (AI) gain traction in culture plate reading, the question of performance on detection of mixtures of organisms often arises. This is typically borne through traditional thoughts of validating alternative quantitative methods for micro-organisms to ensure methods do not demonstrate any interference or bias towards organism recovery or detection. This approach, however, may not be applicable to newer technologies. In the case of the APAS Independence, an AI-based culture plate reading system, testing of bacterial mixtures is not necessary. The system is designed to detect both bacterial and mold colonies, with each colony being classified as a result of pixel level detection in an independent and uninfluenced manner. The pixel result is entirely based on the way the algorithm is developed, which remains agnostic to any species identification within bacterial or mold groups themselves and only requires differentiation between these groups at a high level. This poster will provide insights into imaging and AI-analysis tools to demonstrate how mixtures of organisms are detected, highlighting the independent nature of colony assignment. If the segregation of mold and bacterial colonies is important, additional specificity testing may be considered.

Navigating the complexities of compliance in the biopharmaceutical landscape-particularly for cell and gene therapies-requires innovative and effective solutions. In response to these challenges, Syner-G | Sequoia have developed a Quality Risk Management (QRM) Playbook aimed at standardizing and enhancing the adoption of quality and risk management practices across global operations. This Playbook ensures operational excellence through streamlined processes, advanced technologies, and an engaged workforce. One of the key benefits of implementing this Playbook is a transformative shift in organizational culture towards a proactive QRM approach, fostering a collective sense of quality and ownership among teams, particularly in multi-site environments. This cultural evolution not only reduces the risks associated with drug development but also redefines compliance activities by highlighting their critical role in ensuring patient safety. By embracing a practical and effective methodology to quality risk management, organizations can reshape compliance from a perceived obstacle into a strategic advantage, leading to better outcomes for the business and improved patient care. This poster will discuss how the QRM Playbook empowers teams to refine their compliance strategies and advance their drug development initiatives.

The primary purpose of this study was to determine the inactivation kinetics of Geobacillus stearothermophilus biological indicators (BIs) exposed to nitrogen dioxide (NO₂) gas in the presence of humidity. BIs inoculated with 6 log₁₀ G. stearothermophilus spores were used as a test substrate. Three BI lots manufactured from each of three different BI spore crops were evaluated. Test cycles were run at room temperature with approximately 80% relative humidity. Direct enumeration methods were used to quantify the resistance of spores with surviving populations greater than approximately 50 colony forming units (CFU). Fraction negative methods were used to estimate the surviving spore populations in the quantal region_. The methods were combined in order to show spore inactivation from 6 log₁₀ to approximately -2 log₁₀ The D value and coefficient of determination (r²) were calculated. Over 100 direct enumeration and fraction negative cycles were completed at a fixed NO₂ concentration varying only exposure time. Process parameters were maintained over all cycles. Empirical data confirmed a log-linear relationship over an 8 log₁₀ population range with r² values greater than 0.8, allowing for extrapolation of the curve to achieve a sterility assurance level (SAL) of 10^-6 Study outcomes were comparable for all manufactured BI lots. NO₂ sterilization follows first-order log-linear microbial inactivation kinetics, which is consistent with a mechanism of action based on a single active species. This is the first study to report on the microbial inactivation kinetics of NO₂ sterilization.

Active and passive air monitoring is crucial for gaining knowledge about the microbial status of clean room environments for aseptic processing. Most agencies require active air monitoring of defined volumes in short time periods. However, active air monitoring methods may disrupt the unidirectional airflow of filtered air and are therefore difficult to use for continuous air monitoring. Hence, settle plates are additionally placed at areas of high risk during the whole filling process, including setup. Although EU GMP Annex 1 9.30 defines a maximum duration of 4 hours for settle plates with a diameter of 90 mm, and USP <1116> defines a maximum of 4-5 hours, there are no recommendations for settle plates with a diameter of 150 mm. Agencies expect validation studies, including recovery rates, as a basis to determine the exposure time. This study provides data that show that settle plates with a diameter of 150 mm can be placed under unidirectional airflow for up to 8 hours in a clean room with moderate humidity. No negative effect on the suitability of the media was observed. Moreover, it is shown that settle plates with a diameter of 150 mm can be exposed to unidirectional airflow for up to 6 hours in a clean room with very low humidity as used for aseptic filling of lyophilized products. Increased exposure times of settle plates for up to 6 to 8 hours significantly reduce the exchange frequency of settle plates, which ultimately lowers the risk of microbial contamination during filling due to less interventions.

Pre-use post-sterilization integrity testing is implemented in sterile filtration applications by drug manufacturers using a risk-based approach with consideration of the stipulation in Eudralex Volume 4, Annex 1, Manufacture of Sterile Medicinal Products, which states that "The integrity of the sterilizing filter should be verified before use". Within the bacterial retention test design, performed as part of the process-specific sterile filter validation, it is important to simulate the filtration process under evaluation as closely as possible. Worst-case conditions experienced by the process filter during routine use that may impact the process filters' ability to produce a sterile effluent should be accounted for in the study. As performing pre-use post-sterilization integrity tests introduces additional mechanical stress on the process filter and a new potential route for the introduction of bioburden into the process fluid flow path related to the filter wetting procedure, a risk-based bacterial retention test design incorporating a pre-use post-sterilization integrity test simulation phase should be considered after a thorough evaluation of the process-specific conditions. The risk assessment should include evaluation of process pre-use post-sterilization integrity test conditions, including but not limited to the integrity test method and specifications, the wetting fluid type, the maximum allowable number of pre-use post-sterilization integrity test repetitions, as well as the permitted bioburden level of the pre-use post-sterilization integrity test wetting fluid. The outcome of the assessment provides a basis for the process-specific bacterial retention test design. In the following, we present our perspective on the topic as well as detailed insight into various aspects of pre-use post-sterilization integrity test simulation test design for consideration. Finally, we present all three PUPSIT-BCT approaches described (non-bactericidal, partially bactericidal, and bactericidal). Executed studies yielded acceptable results. Target parameters agreed upon were met.

The shortage of skilled workers in the pharmaceutical and biotech sectors has become a significant barrier to industry growth and the success of new companies in local areas. Without a reliable talent pool trained in essential industry standards, companies struggle to meet regulatory requirements, operate efficiently, and scale their operations. This challenge highlights the pressing need for a collaborative approach between educational institutions, economic development organizations, and industry leaders to develop a steady supply of skilled professionals. A key solution to this issue has been the implementation of GMP (Good Manufacturing Practices) Bootcamp programs, where industry leaders and colleges partner to offer hands-on training in foundational GMP concepts. These programs are designed to benefit new graduates, career changers, and others seeking stable, well-paying jobs by equipping them with skills that are immediately relevant to the pharmaceutical and biotech sectors. For companies, hiring workers already trained in GMP standards shortens onboarding times and reduces training costs, while local economic development groups benefit from a talent pipeline that attracts industry investment and fosters job growth. This collaboration not only addresses the skilled labor gap but also supports regional economic development by creating attractive, sustainable career opportunities in these growing sectors.

In 2024 we completed a case study outlining the development of a bespoke User Requirement Specification (URS) for a full Electronic Quality Management System (EQMS) in the Irish Blood Transfusion Service (IBTS) as part of our 2021-2025 Strategy. This abstract outlines the next stage in the project where we evaluated a number of tender responses to the URS and chose a vendor based on a number of criteria using a coring methodology. We also discuss the planning of the next project stages to prepare for pre installation testing, phase planning and outlining validation requirements. Methods 1. How to review the tender response? We created scoring for Functional, Non Functional and Costings responses 2. How did we evaluate the responses and score the responses? 3. Completed summary comments and final ranking which were reviewed and discussed by the project steering committee Results 1. Award contract and develop SLA 2. Project planning for the next stages 3. Preparation of data for moving databases.

As markets for recombinant biologicals constantly grow, the risks related to the biohazardous materials used are not yet always understood and assessed systematically. Thus, there is a strong need to systematically assess technical solutions in the good manufacturing practice (GMP) area and best practices for all steps in biotechnological production using biohazardous materials up to biological safety level 2 (BSL2). Especially viral vectors, as virus-based vaccines are coming to market as novel therapies, asking for different safety requirements. As single-use solutions (SUSs) are widely used in clinical and production scale in upstream and downstream processing until final fill operations, new practices must be developed with a different approach to enable production under BSL2. Production of biologics that are produced in the BSL2 area regime using SUSs must be reviewed under different aspects in terms of safety for the product and staff equally and probable contamination of the environment. SUSs for this new purpose must be differently handled with care from goods entry until final discard of products post usage. The production starting at fabrication of the SUS items itself might require modifications. The design of SUS items for the BSL2 purpose must be tested already in a different way in production to fulfill the higher safety level regimes to protect the product and operators. In this paper, we give examples for consideration of how to unpack and store such SUS consumables and which conditions in the facility are favorable in combination with proper staff training. Examples of suitable components and existing SUS equipments for the upstream and downstream processing of such products, to give operators, suite and plant managers, A + E with planners, and people in regulatory departments the needed information to enable the safe and regulatory aligned production of such biologic therapies.

Proposal DescriptionGene therapies hold tremendous potential, yet manual operations, product loss, and high costs impede patient access to vital treatments. The fill/finish processes are pivotal in optimizing drug product availability. Precision is paramount in formulating, filling, and packaging the therapies to preserve their efficacy and integrity. These challenges are leveraging advanced technologies like the adaptable Optima FillCell. This flexible and modular system streamlines operations, reducing reliance on manual labor and mitigating the risk of errors and contamination. Real-time monitoring and data analysis provide crucial insights, empowering manufacturers to optimize production parameters and minimize wastage, ultimately increasing the number of viable drug vials. By enhancing efficiency and maximizing overall yield.