PDA Journal of Pharmaceutical Science and Technology最新文献

Regulatory intelligence (RI) is an emerging and increasingly fundamental function within regulatory affairs, particularly in the biotechnology sector. Defined by its focus on the systematic collection, analysis, and dissemination of regulatory information, RI supports informed decision-making and strategic planning in a complex and rapidly evolving regulatory landscape. Despite its growing significance, regulatory intelligence remains underrepresented in academic literature. This paper seeks to provide a foundational understanding of the discipline by examining the evolving regulatory landscape, the processes involved in regulatory intelligence, and future considerations for its advancement. Data sources include peer-reviewed publications, regulatory authority documents, web-based articles, and industry blog posts. An integrated literature review identified three core components of regulatory intelligence: (1) information collection, (2) information analysis, and (3) information dissemination. The effectiveness of these components is closely linked to the maturity and integration of systems employed by biotechnology organizations. As regulatory frameworks become more dynamic and digital technologies advance, the role of RI will become increasingly central to proactive compliance, innovation strategy, and global market access.

Current guidance on the microbiological qualification testing of preservative-free multidose ophthalmic systems is limited and lacking in detail with respect to methodology. This study describes the testing performed to assess the potential for biofilm formation on the tip of a preservative-free multidose device and the microbiological quality of the delivered dose following a mixed culture microbial immersion challenge, simulating a severe, repeated microbial exposure event. Biofilm was assayed quantitatively through viable microbial recovery, semi-quantitatively by staining the biomass in conjunction with ImageJ analysis, and qualitatively by microscopy. The study demonstrated the utility of the immersion challenge as a relevant means of modeling biofilm growth on the preservative-free multidose device nozzle as well as the capability to reliably assess biofilm through a variety of measurements. The study further demonstrated the efficacy of the liner cap as a means of maintaining the microbiological quality of the delivered dose and significantly mitigating biofilm formation following a series of severe microbial immersion challenges.

Analytical testing and an appropriate sampling method are instrumental in confirming that equipment surfaces have been adequately cleaned during cleaning validation or verification activities. The sampling method is critical to generating accurate results. Regulatory Health Authorities (RHAs) expect manufacturers to employ rinse, surface swab, or a combination of the two, with one favoring swab sampling methods. Surface swab sampling is performed manually by directly holding the swab (hand swabbing) or attaching the swab to the end of an extension pole (remote swabbing). Remote swabbing is an alternative for cases in which the equipment surfaces to be sampled are not readily accessible and would otherwise require confined space entry. This study evaluated the performance of a prototype automated swabbing device constructed from configurable microcontrollers, microelectronics, and electromechanical components against representative manual sampling methodologies. The automated swabbing device was designed and built to automate the swabbing work process for surfaces exhibiting various accessibility issues and challenges. Automated swab sampling of pharmaceutical manufacturing equipment offers several advantages over hand swabbing or remote swabbing, including decreased variability, the necessity for swab qualification of operators, increased accuracy versus remote swabbing, and decreased risk to personnel. To determine if automated swabbing can replace the current state of the art in manual swabbing, Hyde Engineering + Consulting performed a comparative analysis of manual swabbing methods, hand and remote, and an automated swabbing method using a prototype device developed by Swabbot Solutions. This case study evaluated the three swabbing methods using multiple replicates, concentrations, representative soils, and controls to gauge the relative recovery performance of the accuracy and variability of each method. The study showed that the automated swabbing device achieved recovery levels comparable to those of the hand swabbing method but with lower variability. The remote swabbing method exhibited higher variability and lower recovery levels statistically dissimilar to both the hand and automated swabbing methods. Based on these performance results, we concluded that an automated swabbing method is an acceptable alternative to hand swabbing and outperforms the remote swabbing method.

Many on-body delivery systems (OBDSs) for subcutaneous (SC) delivery require a change in primary container closure system (CCS). This necessitates compatibility and stability testing with original packaging materials and distribution and assembly, which are often laborious and time-consuming. Exploring new primary CCSs rather than using an original CCS can introduce risks, prolong timelines, and increase costs. In this study, 21 US-based combination product experts completed a double-blinded online survey between 6 October and 20 November 2023. The survey included 15 screening questions and 23 survey questions, including questions about compatibility issues between new CCSs and drug and stability testing for new CCSs. The largest proportion of participants (28.6%) reported that 5%-10% of the products that they had worked directly on had experienced compatibility issues between a new CCS and a drug, with a weighted mean of 11.9%. The most common compatibility issues were particulate challenges in 55.6%, sterility in 27.8%, and leachables in 16.7%. Most respondents (76.2%) rated the timeline showing that using an original CCS can save 12-24 months as somewhat (38.1%) or very (38.1%) representative. Most participants (57.1%) estimated that the range of direct costs, including development costs, drug product, engineering runs, line changes, and other costs, when using an OBDS with a new CCS is $10-15 million, 38.1% estimated <$10 million, and 4.8% estimated $21-25 million. Most participants (80.9%) reported that challenges in the primary CCS qualification/validation process delay entry of combination products into clinical trials or delay their commercial launch. The weighted mean of the delay was 9.7 months. Using an original CCS during combination product development would therefore be of significant economic benefit to the development of combination products in terms of time, cost, and risk.

Mycoplasma testing is a mandatory assay for all cell-derived products as part of the microbial control strategy. The compendial methods include an indicator cell culture method and a culture assay. Because the culture assay takes 28 days, the time-to-result (TTR) is one of the longest in the microbiology laboratory. Besides this, the compendial Mycoplasma methods are highly complex, subjective, and need strict segregation of labs to avoid cross-contamination with Mycoplasma. The pharmaceutical industry is seeking faster solutions, like nucleic acid testing (NAT)-based methods. There are alternative and rapid NAT methods on the market enabling a reduction of the TTR to approximately 1 day (1). Although some of these NAT methods offer partial automated solutions (e.g., nucleic acid extraction), many of them still require strict separation of test areas to avoid false-positive results and provide only limited hands-on-time reduction and simplification. In contrast, the BioFire® Filmarray® technology is a NAT method that is easy to use thanks to a closed process-a so called "lab in a pouch"-and provides the result within only 2 hours, including sample preparation. Besides the risk reduction of human errors due to the limited manual work involved, the automation can also lead to improved data integrity compared to the compendial method. This paper describes the roadmap of implementation of the BioFire^® Filmarray^® technology. The approach from feasibility studies to validation and regulatory submission for a monoclonal antibody (mAb)-based product is provided. As a first, J&J received regulatory approval from several agencies (including the US FDA and the EMA) to apply this technology for a biopharmaceutical product and has started global roll-out to additional products and testing sites. Understanding the risk concomitant with introducing new methods is essential to develop an appropriate validation, implementation, and filing strategy. The process applied at J&J for the first product will be shared in this publication.

Driven by more patient-centric at-home treatments, the pharmaceutical industry is shifting toward subcutaneous drug formulations, particularly for biologics. This aids in simplifying patient self-administration, improving adherence, and reducing healthcare costs. Hence, there is an increasing need for optimized drug containment systems, as these will frequently be used by non-professionals in home settings. This study evaluates the break-loose and gliding forces (BLGFs) as well as the inorganic and organic leachable profiles of cartriQ^® 3 mL ready-to-use (RTU) cartridges to ensure safe and effective drug delivery. The cartridges, made from FIOLAX^® clear Type I borosilicate glass, underwent hot forming into tubular cartridges, ensuring a hydrolytic resistance of not more than 80% of the ISO 4802-1 limit, followed by washing, siliconization, and steam sterilization. Testing was conducted after accelerated aging over up to 24 weeks at 40°C using ultrapure water, histidine buffer, and phosphate buffer as model solutions. Key performance metrics, including BLGF, siliconization performance, and levels of inorganic leachables, for example, boron, sodium, silicon, and select organic leachables, were assessed following ISO 21881 and ICH Q3D guidelines.

Sterile drug products' endotoxin specifications are set in accordance with a compendial method that considers a patient population's body weight and the threshold pyrogenic dose for the particular route of administration (e.g., parenterally, subcutaneously, intrathecally). These specifications are designed to prevent pyrexia (fever) from occurring. For intravenously derived products, the threshold pyrogenic dose is 5 EU per kg body weight. All clinical studies supporting the pyrogenic dose have only incorporated adult (>18 years) recipients of intravenous standard endotoxin. These studies have not considered the potential for children to respond differently to administered endotoxins. Here, an evaluation is reported using patient fever data from the FDA Adverse Events Reporting System (FAERS) to assess potential child patient age (<1 to 18 years) and body weight implications to parenteral product endotoxin specifications. Data indicate that the response to endotoxin by children is not uniform across the body weight range of individual age groups (<1, 1-2, 3-4 years, etc.). Furthermore, that children <3-4 years of age appear more prone to pyrexia. Notwithstanding the inherent limitations and caveats in this study, the sum aggregate of information suggests the necessary adoption of worst case (5^th percentile of population body masses) for children aged <3-4 years.

Mollicutes class (e.g. mycoplasma species) are notorious bacterial contaminants in eukaryotic cell cultures, known for being particularly difficult to detect and eliminate. Their presence can negatively impact the health of cultured cells, decrease bioreactor yields, interfere with in vitro tests and, in some cases, cause disease. Accordingly, mycoplasma testing represents a common bottleneck in the manufacturing process for which compendial mycoplasma tests may not be suitable due to their lengthy turnaround times. This is even more true, in the case of short shelf-life products, that requires short turnaround time for manufacturing. To address the need for more rapid test methods, pharmacopoeias have provided guidance on the use of mycoplasma Nucleic Acid Amplification Techniques (NATs) as an alternative to compendial methods for lot release testing and in-process testing. In this article, we summarize the discussion of a group of pharmaceutical experts who met to propose recommendations and a path forward for the method validation and method suitability testing of a new mycoplasma nucleic acid-based test, the BIOFIRE® Mycoplasma Test. In contrast to conventional NATs, which require a significant amount of hands-on time from highly skilled operators, BIOFIRE® Mycoplasma test provides a closed and fully automated "lab in a pouch" NAT system. This innovative solution offers minimal hands-on time, minimal user training and skill, and delivers the results in about one hour. This paper offers a summary of the different working sessions held outlining key recommendations for validating the BIOFIRE® Mycoplasma test for release of commercial drug products.