PDA Journal of Pharmaceutical Science and Technology最新文献

As biopharmaceutical manufacturing evolves toward digitalization, the need for structured, interoperable, and regulatory-compliant data is intensifying. Digital Reference Materials (dRMs), the machine-readable counterparts of physical reference standards, have emerged as critical tools for enhancing data integrity, enabling automated quality control (QC), and supporting regulatory transparency. This article explores the definition, structure, and implementation of dRMs within the pharmaceutical landscape. It examines regulatory initiatives such as the FDAâs eCTD 4.0 and KASA, pharmacopeial digitization efforts, and pioneering commercial applications like Merck/MilliporeSigma's ChemisTwin™. Technical foundations, such as XML, JSON, and AnIML formats, are discussed alongside their integration into laboratory systems such as LIMS, ELNs, and CDS platforms. Special attention is given to the challenges of implementing dRMs in chromatography, where method-specific variability complicates standardization. Ultimately, dRMs are positioned as enablers of intelligent manufacturing, supporting AI-driven analytics, digital twins, and harmonized global quality systems. This work underscores the strategic imperative for stakeholders to invest in digital infrastructure, standards, and collaboration to fully realize the potential of digital reference materials in modern pharmaceutical development.

Alternative and rapid microbiological methods (ARMM) used in biopharmaceutical manufacturing have potential advantages over current compendial methods in that they can enable faster product release and improved process monitoring and quality assurance. There is value in community-wide discussion on ARMMs to help understand the challenges of ARMM adoption in biopharmaceutical manufacturing. The National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) attempted to understand the successes and challenges around ARMM adoption through surveys, interviews, and a facilitated Active Listening Meeting between industry and FDA representatives. Through these interactions, it was observed that many organizations have successfully implemented ARMMs in approved manufacturing processes, suggesting an absence of significant regulatory obstacles to implementation. Further, five key elements impacting technology adoption were identified: technology readiness, vendor support, organizational adoption readiness, business case/economics, and regulatory interaction. The Active Listening Meeting format proved valuable for fostering honest and informal conversations between both sponsors and regulators.

Drug product leachables are substances that are leached from the drug products manufacturing system components during manufacturing operations, drug product packaging systems during storage over shelf-life, and delivery systems during administration. Medical device leachables are substances that are released from medical devices during their clinical use. Thus, packaged drug products and medical devices are profiled for leachables (and/or extractables as probable leachables) to establish that the levels of leachables are sufficiently small that they present a negligible risk of adversely affecting patient health. This profiling is accomplished by screening the drug product or extracts of the medical device for released organic substances via nontargeted analysis (NTA) employing chromatographic methods coupled with mass spectrometric detection.The topics of how many possible organic extractables and leachables (E&L) there are and what are the most commonly reported organic E&Ls has been widely discussed in the E&L community of practice.One means of charting this universe of organic extractables and leachables is to review and collate those substances that have been encountered over the course of performing E&L studies. To this end, Nelson Labs Europe, a major contract research organization performing E&L testing for decades, has collated the results of several thousand E&L studies performed over the past several years, representing modern best practices in E&L assessment. These collated results, considering only those compounds reported with confirmed identities, are summarized and discussed herein. Although the use of compounds with only confirmed identities limits the number of considered compounds somewhat, so doing ensures that potentially false identifications and not published and do not result in a biased analysis of the collected information.

Viral clearance by virus-retentive filters is a crucial step in many biomanufacturing process streams, including production of monoclonal antibodies and cell culture media. Studies with model viruses or bacteriophage are needed to determine whether a specific filter should be categorized as a small or large virus retentive filter. In this study, viral retention and flowrates were compared between Meissner's 50 kDa and 500 kDa SepraPor® Hollow Fiber (HF) Ultrafiltration (UF) membranes used for Tangential Flow Filtration (TFF). These filters were challenged with ∼10 million plaque forming units (PFU) of the small bacteriophage ΦX174 suspended in deionized (DI) water. It was determined that the 50 kDa SepraPor® HF UF membranes gave log-reduction values (LRVs) ≥ 5 with flowrates ranging from 15.9 to 46.7 mL/min at 15 psi constant pressure. The 500 kDa SepraPor® HF UF membranes gave LRVs ≤ 0.74 with flowrates ranging from 8.8 to 286 mL/min. These results show that Meissner's 500 kDa SepraPor® filter membrane does not retain ΦX174 in water and does not function as a small virus retentive filter, while the 50 kDa SepraPor® filter membrane gives robust clearance of ΦX174 and can be categorized as a small virus retentive filter.

This study investigates trends in FDA warning letter issuance between 2019 and 2023, focusing on the agency's efficiency and evolving priorities during this period. By analyzing both quantitative and qualitative data, the research highlights an increase of 43% in warning letters issued per 100 inspections. Using a novel approach combining regex filtering and web scraping, this presentation examines recurring keywords, department-specific citations, and legal references. The analysis aims to help attendees understand how structured data from regulatory agencies can be harnessed to improve compliance and inspection readiness.

Detecting migrant compounds from pharmaceutical packaging and medical devices is crucial for patient safety. Lyophilization, often used to enhance detection limits by removing water and concentrating analytes, may cause analyte losses. This study evaluated the impact of lyophilization on the recovery of antioxidants and UV stabilizers across different matrices. Solutions of six potential leachables-4-hydroxybenzophenone, Uvinul 3030 (UV stabilizers), Irganox 245, Irganox MD 1024, BHT, and Irganox 1010 (antioxidants)-were prepared in acetonitrile/water, saline, and a biological-like matrix. Recovery after lyophilization and reconstitution was quantified using HPLC-DAD, with T-tests (n = 6) comparing analyte retentions. Results showed that high-vapor-pressure antioxidants (e.g., BHT) suffered significant losses, while complex matrices improved retention. Biological-like media provided the highest retention (p < 0.01), exceeding saline and acetonitrile/water. Saline solutions resulted in more significant losses than biological-like media. These findings highlight that lyophilization may be unsuitable for salt-based solutions due to volatile analyte losses. The study illustrates the importance of considering analyte properties and matrix composition when optimizing sample preparation for detecting leachables in pharmaceutical and biological systems.

Continued Process Verification (CPV) is the third stage of the FDA Process Validation guideline and is a critical component of modern pharmaceutical manufacturing, ensuring that processes remain in a state of control throughout the product lifecycle. However, CPV has historically been overlooked, with many companies unaware of the need for CPV program implementation as a regulatory requirement. This poster uses a case study to describe the key steps for successful CPV program implementation using a phased-approach for both legacy, approved products, as well as products entering process validation.

Artificial intelligence (AI) continues to evolve and propel businesses forward; however, the Life Science industry's adoption of these technologies is delayed in comparison with other industries. AI technologies have the ability to greatly reduce cost and time to market of products, especially when applied to and integrated with the process validation lifecycle. Due to the nature of the highly regulated industry, these technologies also introduce a number of challenges to the industry, particularly when it comes to validating these solutions. This presentation aims to demonstrate how developing AI solutions integrates with the process validation lifecycle, while demystifying some of the nuances around various AI solutions and terminology. It also works to lay out comparisons between AI, multivariate statistics, and traditional Continued Process Validation (CPV) methods; highlighting the benefits of each and use cases where each solution may be preferred.

Ensuring the integrity of parenteral drug packaging is critical for maintaining product sterility and patient safety. This poster presents case study data on two applications of non-destructive, deterministic Container Closure Integrity Testing (CCIT) technologies: Vacuum Decay for IV bags and MicroCurrent (HVLDmc) for pre-filled syringes. The first study evaluates the effectiveness of Vacuum Decay Technology in detecting micro defects in 200 mL and 300 mL IV bags. A statistical footprint was established using thirty negative controls, followed by testing IV bags with defects ranging from 5 μm to 20 μm. Results confirm reliable detection of 20 μm leaks in both sizes, with a demonstrated sensitivity down to 10 μm at six standard deviations (LOD6SD) in 300 mL bags. The study further validates the robustness of Vacuum Decay by showing consistent leak detection across various defect locations and sample orientations. The second study assesses the repeatability of the HVLDmc technology in detecting defects in pre-filled syringes over four weeks. Weekly testing confirmed consistent identification of negative controls, while all positive controls were detected in the first two weeks. In weeks three and four, two positive samples were not detected, possibly due to defect variability or clogging effects. These findings highlight the robustness of HVLDmc while emphasizing the need to understand defect characteristics and influencing factors. Key Takeaways: Gain a deeper Understanding the role of two technologies in parenteral packaging integrity testing. Effectiveness of Vacuum Decay for IV Bags • Vacuum Decay Technology reliably detects leaks as small as 10 μm in 300 mL IV bags with a statistical confidence level (LOD6SD). • Leak detection is consistent across various defect locations (bag body and ports) and sample orientations within the test chamber. • Demonstrates non-destructive and deterministic testing for IV bag integrity. Repeatability of HVLD MicroCurrent for Pre-Filled Syringes • HVLDmc provides a reliable method for leak detection in pre-filled syringes over a multi-week study. Practical Implications for Parenteral Drug Manufacturers • The importance of repeatability studies in CCIT to ensure robustness and reliability. • Considerations for sample preparation and defect consistency when implementing these technologies. • Reinforces compliance with regulatory expectations for deterministic, non-destructive integrity testing.