PDA Journal of Pharmaceutical Science and Technology最新文献

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.

The BIOSECURE Act, along with the recent election, stands to influence the reshoring of biomanufacturing activities in the United States, significantly impacting the growth of international technology transfers. However, these technology transfers are complex, requiring careful coordination across regulatory, quality, operations, and technical disciplines. When executed between international sites, these transfers become even more intricate due to varying regulatory requirements, compliance landscapes, and operational constraints. The resultant stress placed on people, processes, and technology results in an increased likelihood of misalignment, knowledge gaps, and inefficiencies that can negatively impact project timelines, budget, and ultimate product quality. In this poster, we will discuss a refined International Technology Transfer Playbook that we have developed to successfully approach technology transfer planning and execution. Included are strategies for comprehensive scope planning, successful knowledge and process transfer, risk management, validation, operational infrastructure, and training/proficiency requirements, which lay the groundwork for successful project delivery. Through practical examples, we will illustrate how this framework leads to successful outcomes for both companies and patients. Through deliberate planning and coordination, companies can accelerate commercialization timelines while maintaining product quality and compliance, extending their reach in global markets.

Lyophilization, the process of dehydrating a material at low temperature and reduced pressure, is used to extend the shelf life of biologic drug products. Because the object is extended shelf life, long-term performance testing of any lyophilization containment system is essential. That testing must include not only measurement of container closure integrity (CCI), but measurement of system ability to maintain drug product water content. Both parameters depend upon stopper composition. This presentation discusses a strategy for two-year evaluation of four types of lyophilization stoppers (two bromobutyl elastomers, two chlorobutyl elastomers) in both 13 mm and 20 mm sizes, paired with borosilicate glass vials and aluminum seals. Lyophilization was performed in a commercial chamber using a solution blend of 20 mg/ml mannitol and 40 mg/ml sucrose - nitrogen backfill was to 11.6 psi. Evaluation comprised: - CCI (unsealed) - ability to maintain vacuum (24 hrs) - CCI (sealed) - ability to maintain vacuum - water vapor pressure in headspace - water content of cake - water content of stopper. The strategy proved effective in demonstrating that while all systems maintained acceptable CCI and water levels, composition of stopper does influence water level of drug product.

A comparative study of Polysorbate adsorption to membrane filters for Fill & Finish applications, considering a potentially upcoming restriction of the use of PFAS based membranes, such as PVDF.

With increased demand on sealed packed, pre-sterilized ready-to-use (RTU) components like Syringes & Vials, the ebeam technology is used as Annex 1 compliant transfer technology with surface sterilization for transfer of the RTU to higher grade A environment like Isolator.