Interest in rFC and rCR, which are sustainable BET reagents, has been increasing year by year. Various organizations have been considering and evaluating the equivalence of recombinant reagents and conventional LAL reagents. In May 2025, recombinant reagents were officially listed in the USP as a method to perform the bacterial endotoxin test. As a result of these developments, consideration has begun to switch from LAL reagents to recombinant reagents, resulting in a growing interest in the suitability of recombinant reagents for use in automated analyzers to reduce inter-human variability in quality control using recombinant reagents and operational errors in processing multiple samples. We evaluated the suitability of our rCR reagent, PYROSTAR Neo+, for use in our fully automated, compact endotoxin measurement system, KLANOS. As a result, the measurement results obtained using the automated analyzer were found to have reduced inter-human variability and operational errors in processing multiple samples, compared to manual pipetting. In addition, comparative verification using various pharmaceutical samples showed results equivalent to those obtained using manual pipetting. These results show that, like LAL reagents, recombinant reagents can also be adapted to automated systems and are effective in reducing inter-human variability and operational errors in processing multiple samples.

Microbial identification and strain typing are critical in pharmaceutical microbiology for ensuring product safety, controlling contaminants, and meeting regulatory requirements. Traditional strain typing methods like pulsed-field gel electrophoresis and multi-locus sequence typing have their limitations in scalability and resolution. Increased use of next-generation sequencing (NGS) techniques for microbial identification and characterization, coupled with the availability of bacterial whole genomes, advanced sequence analysis approaches such as single nucleotide polymorphisms (SNPs), core and pan-genome analysis, is opening the door for more modern approaches to microbial strain typing. However, several of these approaches are species-specific and require optimization per species or project. In this study, we analyzed conserved genes from several bacterial species to analyze the possibility of using these genes as a set of universal genes for prokaryotic strain typing. We compared the strain typing results using these universal genes to results from species-specific housekeeping genes and with species with no established strain typing methods. Our data demonstrated that these conserved genes successfully distinguished bacterial strains when compared to the results from established species-specific strain typing schemes, providing a path forward in the development of a rapid, universal strain typing solution using bacterial genomes that is not limited to a single species.

Automated microbial detection systems are becoming increasingly essential in pharmaceutical manufacturing to enhance efficiency, accuracy, and compliance with Good Manufacturing Practice (GMP) standards. The APAS Independence System, developed by Clever Culture Systems, was evaluated at Bristol Myers Squibb (BMS) to assess its suitability for environmental monitoring applications. The APAS system is capable of automated plate counting of both 55 mm and 90 mm plates, following an offline incubation at routine EM parameters. The study compared APAS automated colony counts to traditional manual counts for compendial strains and environmental monitoring samples across multiple weeks of EM sampling. Performance metrics for both plate sizes were analyzed, such as accuracy, precision, false negative and false positive rates, and robustness. The APAS system demonstrated high accuracy (≥70%) and reliability for most tested organisms. Therefore, the system is being implemented for GMP use, with a validation approach that combines vendor validation of the Artificial Intelligence with site specific instrument qualification. This evaluation provides insight into the capabilities and limitations of automated colony detection, informing future digitalization strategies in microbiological quality control.

Biotherapies, and especially cell therapy products, are required to be tested for sterility and mycoplasma. Developing an analytical strategy to test for sterility and mycoplasma can be daunting. There are many variables to consider, including complex matrices with high mammalian cell density and detection of non-viable microbes. Which type of analytical testing can work in an early stage of therapeutic development and then be scaled to meet the challenges later in the production process?Leveraging rapid sterility as well as mycoplasma qPCR-based detection techniques can help provide confidence in the final product by helping to detect potential contamination earlier in the production process.

The regulations are evolving, for example EMA Annex 1, earlier versions did not mention trends, the current draft version mentions it 23 times. WHO, and FDA also talk about trending, root cause analysis, investigation, and using the data for these purposes. PDA technical report 13, the new revision, even states that automation for data management for environmental mentoring is "essential". Trending the data is now a regulatory requirement but what trends should we use, and when? This presentation will include a review of key regulations as they relate to the need to use our data for trending including how often and what events should trigger trending, root cause analysis, and investigations. Also, which trend tools should we use for the different contamination control processes, cut off method, Control charts (Shewhart, etc.), Quantiles, Percentiles, Weibull Distribution, Scatter plot, Regression analysis for slope (upward/downward trends).The last 20 years we have been collecting data and regulations like Annex 11/21 CFR part 11, and more recently the data integrity guidelines, have facilitated that the data is accurate and reliable. Now this regulatory evolution is mandating the use of the data for the betterment of our processes, process control, product quality and patient safety.

This seminar will cover utilizing a contamination control strategy with a risk-based approach to materials transfer into cleanrooms, RABS, isolators, and BSC's. There will be a focus on how to control hard to kill fungal spores such as Aspergillus and Penicillium as well as bacterial spores and viruses. Recent case studies from the past few months in ATMPF facilities and compounding pharmacies will be discussed in relation to materials transfer. Published data will also be mentioned to convey effective methods in control bioburden utilizing VHP, sporicidal chemistries, and disinfectants into the APA. This presentation will be a holistic approach to controlling bioburden from entering cleanrooms, BSC Hoods, RABS, and Isolators. New industry case studies in disinfectant field trials will also be covered and discussed in detail based on recent industry publications.

This session will explore the integration of recombinant Cascade Reagents (rCR) with centripetal microfluidic technology. We will detail our multi-matrix approach for comparing LAL and rCR on different sample types and how we assessed performance metrics such as sensitivity, specificity, and reproducibility across diverse sample types. We also address key technical challenges and practical considerations encountered during this research. Finally, the results of the study will be presented.

Non-sterile drug products represent approximately 30% of annual drug sales. Non-sterile drug products offer therapeutic advantages, manufacturing costs which permit wide patient access, versatility of dosage form and routes of administration which facilitate patient compliance. These advantages have resulted in an increase in the number and nature of non-sterile finished dosage forms. Regulations and standards require the provision of non-sterile drugs to controlled levels of bioburden, the absence of specified microorganisms and the absence of objectionable microorganisms. Thoroughly understanding the microbiological risks and control performance in non-sterile manufacturing is vitally important in the improvement in the quality and compliance of non-sterile manufacturing. Prior publications have reported the magnitude and characteristics for non-sterile product recalls and regulatory compliance shortfalls from 2004 to 2011 and from 2012 to 2019. The purpose of this review is to similarly provide a valuable contemporary update of the microbiologically related quality and compliance issues specifically associated with non-sterile drug products by reviewing drug recalls and Form FDA 483s. This includes evaluation of incidences of microbiological quality and regulatory compliance issues through more detailed abundance analysis. This data and information should assist in the risk assessment and risk management necessary in the manufacture of non-sterile products and beneficial to the pharmaceutical microbiologist.

Developing medicines to serve patients is a complex, highly regulated process in which multiple interdependent factors must be aligned. If one aspect is not thoroughly evaluated, it may adversely affect others and ultimately the final product, leading to delays, additional costs and, in the worst case, market access barriers. This is particularly true for prefilled syringes (PFS) as combination products, where an already challenging market environment is further compounded by intricate regulatory requirements and a highly complex development process.This paper argues that many recurring issues in PFS development are not isolated technical failures, but the consequence of four systemic challenges: diverging regulatory requirements for drugs and devices, division of competencies between drug and device development teams, fragmented supply chains for device components, and non-standardized characterization and evidence generation across stakeholders. Using examples such as break-loose and glide forces, silicone oil, particles, endotoxins, and biocompatibility, the paper illustrates how these challenges manifest as concrete risks along the development pathway, including transitions from vial to syringe and interactions with notified bodies under the MDR. It then outlines system-level strategies to mitigate these risks, including clearer system ownership, integrated risk management and design spaces, earlier and closer collaboration with device experts and suppliers, and more harmonized standards and regulatory expectations. The overall aim is to support a more efficient, predictable and sciencebased pathway to safe, effective and user-appropriate prefilled syringes.

A mold investigation is a focused, science-driven effort to uncover how contamination gets in, spreads, and survives-no assumptions, no shortcuts. It starts with a thorough analysis of mold recoveries across environmental, process, and product-related factors. Isolates are classified by fungal division, with reproductive state, source, and growth behaviour assessed.From there, environmental monitoring data and product failures are examined to complete the full picture. Facility conditions-structural integrity, airflow, material flow, and sanitation-are evaluated to identify weak spots mold might exploit. Operational procedures and personnel practices are scrutinized, revealing possible gaps that can fuel contamination.By combining these elements, the investigation doesn't just react to mold-it anticipates it. This approach lays the groundwork for targeted, effective controls that protect both product integrity and environmental quality in regulated spaces.