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Environmental monitoring (EM) is the cornerstone for the assurance of sterility during aseptic manufacturing. In this study, the EM quality aspects in the radiopharmaceutical cleanrooms of the University Medical Center Groningen (UMCG), The Netherlands, were evaluated. Hereto, data obtained from EM over the period 2010–2022 were analyzed. The data were sorted according to the Good Manufacturing Practice (GMP) classification of the respective premises with their corresponding limits, and frequencies of excursions were determined per location. The frequency of conducted measurements gradually increased between the start and end of the assessed period. There was a trend of increased action limit excursions observed between 2010–2022. We found that EM in grade A areas appeared to be significantly less compliant with GMP specifications than the combined data from all sampled premises at the facility (p < 0.00001; two-sided Fisher's exact test). A trend was found for reduced action limit excursions for passive air sampling and particle counting, suggesting improved GMP compliance over time for this specific type of EM. The contamination recovery rate (CRR) found for cleanroom conditions, around 10%, was considered sufficient. From this comprehensive data analysis, we learn that, in order to be fully compliant with the requirements set in the recent revision of EU (European Union)-GMP Annex 1 'Manufacture of sterile medicinal products' (in force as of 25 August 2023), strategies to further improve product protection are justified. For example, improved cleaning and disinfection procedures, more efficient working methods as well as optimization of the conditions under which aseptic manufacturing is performed are to be considered. [ABSTRACT FROM AUTHOR]

The present study addresses advanced monitoring techniques for particles and airborne molecular contaminants (AMCs) in cleanroom environments, which are crucial for ensuring the integrity of semiconductor manufacturing processes. We focus on quantifying particle levels and a representative AMC, hydrogen chloride (HCl), having known detrimental effects on equipment longevity, product yield, and human health. We have developed a compact laser sensor based on open-path cavity ring-down spectroscopy (CRDS) using a 1742 nm near-infrared diode laser source. The sensor enables the high-sensitivity detection of HCl through absorption by the 2-0 vibrational band with an Allan deviation of 0.15 parts per billion (ppb) over 15 min. For quantifying particle number concentrations, we examine various detection methods based on statistical analyses of Mie scattering-induced ring-down time fluctuations. We find that the ring-down distributions' 3rd and 4th standard moments allow particle detection at densities as low as ~105 m−3 (diameter > 1 μm). These findings provide a basis for the future development of compact cleanroom monitoring instrumentation for wafer-level monitoring for both AMC and particles, including mobile platforms. [ABSTRACT FROM AUTHOR]

Environmental monitoring (EM) is the cornerstone for the assurance of sterility during aseptic manufacturing. In this study, the EM quality aspects in the radiopharmaceutical cleanrooms of the University Medical Center Groningen (UMCG), The Netherlands, were evaluated. Hereto, data obtained from EM over the period 2010–2022 were analyzed. The data were sorted according to the Good Manufacturing Practice (GMP) classification of the respective premises with their corresponding limits, and frequencies of excursions were determined per location. The frequency of conducted measurements gradually increased between the start and end of the assessed period. There was a trend of increased action limit excursions observed between 2010–2022. We found that EM in grade A areas appeared to be significantly less compliant with GMP specifications than the combined data from all sampled premises at the facility (p < 0.00001; two-sided Fisher’s exact test). A trend was found for reduced action limit excursions for passive air sampling and particle counting, suggesting improved GMP compliance over time for this specific type of EM. The contamination recovery rate (CRR) found for cleanroom conditions, around 10%, was considered sufficient. From this comprehensive data analysis, we learn that, in order to be fully compliant with the requirements set in the recent revision of EU (European Union)-GMP Annex 1 ‘Manufacture of sterile medicinal products’ (in force as of 25 August 2023), strategies to further improve product protection are justified. For example, improved cleaning and disinfection procedures, more efficient working methods as well as optimization of the conditions under which aseptic manufacturing is performed are to be considered.

The establishment of a compliant radiopharmacy facility within a university setting is crucial for supporting fundamental and preclinical studies, as well as for the production of high-quality radiopharmaceuticals for clinical testing in human protocols as part of Investigational New Drug (IND) applications that are reviewed and approved by the U.S. Food and Drug Administration (FDA). This manuscript details the design and construction of a 550 ft2 facility, which included a radiopharmacy and a radiochemistry laboratory, to support radiopharmaceutical development research and facilitate translational research projects. The facility was designed to meet FDA guidelines for the production of aseptic radiopharmaceuticals in accordance with current good manufacturing practice (cGMP). A modular hard-panel cleanroom was constructed to meet manufacturing classifications set by the International Organization of Standardization (ISO), complete with a gowning room and an anteroom. Two lead-shielded hot cells and two dual-mini hot cells, connected via underground trenches containing shielded conduits, were installed to optimize radioactive material transfer while minimizing personnel radiation exposure. Concrete blocks and lead bricks provided sufficient and cost-effective radiation shielding for the trenches. Air quality was controlled using pre-filters and high-efficiency particulate air (HEPA) filters to meet cleanroom ISO7 (Class 10,000) standards. A laminar-flow biosafety cabinet was installed in the cleanroom for preparation of sterile dose vials. Noteworthy was a laminar-flow insert in the hot cell that provided a shielded laminar-flow sterile environment meeting ISO5 (class 100) standards. The design included the constant control and monitoring of differential air pressures across the cleanroom, anteroom, gowning room, and controlled research space, as well as maintenance of temperature and humidity. The facility was equipped with state-of-the-art equipment for quality control and release testing of radiopharmaceuticals. Administrative controls and standard operating procedures (SOPs) were established to ensure compliance with manufacturing standards and regulatory requirements. Overall, the design and construction of this radiopharmacy facility exemplified a commitment to advancing fundamental, translational, and clinical applications of radiopharmaceutical research within an academic environment. [ABSTRACT FROM AUTHOR]

As part of a publicly funded cooperation project, novel high-performance lubricants (oils, greases, assembly pastes) based on ionic liquids and with the addition of specific micro- or nanoparticles are to be developed, which are adapted in their formulation for use in applications where their negligible vapor pressure plays an important role. These lubricants are urgently needed for applications in cleanrooms and high vacuum (e.g., pharmaceuticals, aerospace, chip manufacturing), especially when the frequently used perfluoropolyethers (PFPE) are no longer available due to a potential restriction of per- and polyfluoroalkyl substances (PFAS) due to European chemical legislation. Until now, there has been a lack of suitable laboratory testing technology to develop such innovative lubricants for extreme niche applications economically. There is a large gap in the tribological test chain between model testing, for example in the so-called spiral orbit tribometer (SOT) or ball-on-disk test in a high-frequency, linear-oscillation test machine (SRV-Tribometer from German "Schwing-Reib-Verschleiß-Tribometer"), and overall component testing at major space agencies (ESA—European Space Agency, NASA—National Aeronautics and Space Administration) or their service providers like the European Space Tribology Laboratory (ESTL) in Manchester. A further aim of the project was therefore to develop an application-orientated and economical testing methodology and testing technology for the scientifically precise evaluation and verifiability of the effect of ionic liquids on tribological systems in cleanrooms and under high vacuum conditions. The newly developed test rig is the focus of this publication. It forms the basis for all further investigations. [ABSTRACT FROM AUTHOR]

Cleanrooms are critical in the semiconductor industry, particularly for optical fabrication, where even minor contamination can compromise product quality. Effective airflow and uniform airflow distribution help to prevent contaminant accumulation, mitigate temperature variations, and avoid cross-contamination, which is crucial for achieving high-quality results and compliance with industry standards. This study introduces a novel approach to optimizing Fan Filter Unit (FFU) configurations to enhance thermal performance and contaminant removal in cleanroom settings. Integrating field measurements with advanced Computational Fluid Dynamics (CFD) simulations to comprehensively evaluate four distinct FFU designs, from dispersed to centralized configurations, focused on their impact on airflow dynamics, temperature uniformity, and particle concentration. The study identifies a significant advancement in FFU configuration by demonstrating that centralized arrangements (Designs 2 and 4) substantially improve cleanroom performance. Design 4 emerged as the most effective, showcasing a marked improvement in airflow circulation, a 12 % reduction in temperature variation, and a 15 % decrease in particle concentration compared to conventional designs. This achievement underscores the novel contribution of this study in optimizing FFU configurations to enhance both thermal performance and contaminant control. These findings not only advance the theoretical understanding of FFU design but also provide practical insights for improving cleanroom environments. The study offers a significant step forward in developing efficient cleanroom designs, contributing valuable guidelines for achieving good environmental control in sensitive manufacturing processes.

Cleanrooms are controlled environments where the number of airborne particles is reduced to a level defined by an International Organization for Standardization (ISO) standard. These facilities have applications in different fields, such as the electronic, pharmaceutical, and healthcare sectors, and are also necessary for the assembly, testing and handling of space hardware. Cleanrooms are expensive to build and maintain and require the permanent designation of infrastructures and dedicated spaces within a building. Once built, clean rooms cannot be used for any other purpose, as contamination is a significant risk. The restricted access to these facilities limits the process of designing, testing, and calibrating instruments developed by academic institutions, small companies, and space startups. Here we present a Commercial Off-The-Shelf (COTS) procedure for building and maintaining a highly controlled ISO class 5 cleanroom, according to ISO14644 standards. We provide a detailed explanation of how to design, develop and operate a portable, modular, and cost-effective ISO class 5 cleanroom that can be used for the usual workflow of development, integration, test procedures and planetary protection associated with the design of instrumentation for planetary exploration.

Abstract Developing a cleanroom and clean chambers (CCs) for Hayabusa2 returned samples has been discussed with the committee for Hayabusa2 sample curation facility since 2015. One major difference from the specifications of the CCs used for Itokawa samples is that a part of samples was decided to be handled and preserved in vacuum to avoid terrestrial nitrogen contamination with organics or unknown materials that might easily react with the samples. Thus, the CCs for Hayabusa2 samples were divided into two CCs for vacuum processes and three CCs for purified nitrogen conditions. The cleanroom was built in summer 2017, while the CCs were installed in the summer of 2018. After the installation of the CCs, instruments for initial descriptions, sample containers, handling tools for powder and particle samples, and jigs to assist handling samples were developed in parallel with functional checks and repeated rehearsals between the fall of 2018 and the fall of 2020. The curatorial works on Hayabusa2-retuned samples were conducted as previously planned. Simultaneously, contaminations and influences of inorganics, organics, microbial, and magnetic constructs have been assessed to evaluate their potential effects on the analysis of the returned samples. Additionally, the tools used to touch samples directly have been demagnetized to avoid sample magnetization during their handling and the tool magnetization was measured before and after their usages. The series of developments and experiences from the curatorial works of Hayabusa2-returned samples represent valuable implications for future sample return missions. Graphical Abstract

Developing a cleanroom and clean chambers (CCs) for Hayabusa2 returned samples has been discussed with the committee for Hayabusa2 sample curation facility since 2015. One major difference from the specifications of the CCs used for Itokawa samples is that a part of samples was decided to be handled and preserved in vacuum to avoid terrestrial nitrogen contamination with organics or unknown materials that might easily react with the samples. Thus, the CCs for Hayabusa2 samples were divided into two CCs for vacuum processes and three CCs for purified nitrogen conditions. The cleanroom was built in summer 2017, while the CCs were installed in the summer of 2018. After the installation of the CCs, instruments for initial descriptions, sample containers, handling tools for powder and particle samples, and jigs to assist handling samples were developed in parallel with functional checks and repeated rehearsals between the fall of 2018 and the fall of 2020. The curatorial works on Hayabusa2-retuned samples were conducted as previously planned. Simultaneously, contaminations and influences of inorganics, organics, microbial, and magnetic constructs have been assessed to evaluate their potential effects on the analysis of the returned samples. Additionally, the tools used to touch samples directly have been demagnetized to avoid sample magnetization during their handling and the tool magnetization was measured before and after their usages. The series of developments and experiences from the curatorial works of Hayabusa2-returned samples represent valuable implications for future sample return missions. [ABSTRACT FROM AUTHOR]

Abstract For places where non-sterile drug production occurs, regulatory bodies recommend monitoring of the environmental bioburden. This procedure provides information regarding possible microbiological risks to which the products may be exposed, so that subsequent action measures may be implemented. The aim of the present work was to quantify and characterize the microorganisms present in Grade D (ISO 8) cleanrooms of a Brazilian pharmaceutical industry, identifying any possible seasonal climatic influences on these environments. Sampling was performed by surface and air monitoring, over 12 months during the year 2019, in rooms that were in operation. For both sampling methods, no statistically significant differences in bacteria and fungi counts were found between months or seasonal periods. Microorganisms that presented higher incidence included Staphylococcus epidermidis (15%) and Micrococcus spp. (13%), common to the human microbiota, and the fungi Cladosporium sp. (23%) and Penicillium sp. (21%), typical of the external environment. The results showed that microbial contamination in the Grade D cleanrooms was within the permissible maximum levels and remained similar throughout the year. Microbiological quality control in the clean areas of the pharmaceutical industry investigated was considered effective, with regular maintenance being necessary to keep bioburden levels controlled.

Abstract Treatments for skin injuries have recently advanced tremendously. Such treatments include allogeneic and xenogeneic transplants and skin substitutes such as tissue-engineered skin, cultured cells, and stem cells. The aim of this paper is to discuss the general overview of the quality assurance and quality control implemented in the manufacturing of cell and tissue product, with emphasis on our experience in the manufacturing of MyDerm®, an autologous bilayered human skin substitute. Manufacturing MyDerm® requires multiple high-risk open manipulation steps, such as tissue processing, cell culture expansion, and skin construct formation. To ensure the safety and efficacy of this product, the good manufacturing practice (GMP) facility should establish a well-designed quality assurance and quality control (QA/QC) programme. Standard operating procedures (SOP) should be implemented to ensure that the manufacturing process is consistent and performed in a controlled manner. All starting materials, including tissue samples, culture media, reagents, and consumables must be verified and tested to confirm their safety, potency, and sterility. The final products should also undergo a QC testing series to guarantee product safety, efficacy, and overall quality. The aseptic techniques of cleanroom operators and the environmental conditions of the facility are also important, as they directly influence the manufacturing of good-quality products. Hence, personnel training and environmental monitoring are necessary to maintain GMP compliance. Furthermore, risk management implementation is another important aspect of QA/QC, as it is used to identify and determine the risk level and to perform risk assessments when necessary. Moreover, procedures for non-conformance reporting should be established to identify, investigate, and correct deviations that occur during manufacturing. This paper provides insight and an overview of the QA/QC aspect during MyDerm® manufacturing in a GMP-compliant facility in the Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia.

As part of a publicly funded cooperation project, novel high-performance lubricants (oils, greases, assembly pastes) based on ionic liquids and with the addition of specific micro- or nanoparticles are to be developed, which are adapted in their formulation for use in applications where their negligible vapor pressure plays an important role. These lubricants are urgently needed for applications in cleanrooms and high vacuum (e.g., pharmaceuticals, aerospace, chip manufacturing), especially when the frequently used perfluoropolyethers (PFPE) are no longer available due to a potential restriction of per- and polyfluoroalkyl substances (PFAS) due to European chemical legislation. Until now, there has been a lack of suitable laboratory testing technology to develop such innovative lubricants for extreme niche applications economically. There is a large gap in the tribological test chain between model testing, for example in the so-called spiral orbit tribometer (SOT) or ball-on-disk test in a high-frequency, linear-oscillation test machine (SRV-Tribometer from German “Schwing-Reib-Verschleiß-Tribometer”), and overall component testing at major space agencies (ESA—European Space Agency, NASA—National Aeronautics and Space Administration) or their service providers like the European Space Tribology Laboratory (ESTL) in Manchester. A further aim of the project was therefore to develop an application-orientated and economical testing methodology and testing technology for the scientifically precise evaluation and verifiability of the effect of ionic liquids on tribological systems in cleanrooms and under high vacuum conditions. The newly developed test rig is the focus of this publication. It forms the basis for all further investigations.

The establishment of a compliant radiopharmacy facility within a university setting is crucial for supporting fundamental and preclinical studies, as well as for the production of high-quality radiopharmaceuticals for clinical testing in human protocols as part of Investigational New Drug (IND) applications that are reviewed and approved by the U.S. Food and Drug Administration (FDA). This manuscript details the design and construction of a 550 ft2 facility, which included a radiopharmacy and a radiochemistry laboratory, to support radiopharmaceutical development research and facilitate translational research projects. The facility was designed to meet FDA guidelines for the production of aseptic radiopharmaceuticals in accordance with current good manufacturing practice (cGMP). A modular hard-panel cleanroom was constructed to meet manufacturing classifications set by the International Organization of Standardization (ISO), complete with a gowning room and an anteroom. Two lead-shielded hot cells and two dual-mini hot cells, connected via underground trenches containing shielded conduits, were installed to optimize radioactive material transfer while minimizing personnel radiation exposure. Concrete blocks and lead bricks provided sufficient and cost-effective radiation shielding for the trenches. Air quality was controlled using pre-filters and high-efficiency particulate air (HEPA) filters to meet cleanroom ISO7 (Class 10,000) standards. A laminar-flow biosafety cabinet was installed in the cleanroom for preparation of sterile dose vials. Noteworthy was a laminar-flow insert in the hot cell that provided a shielded laminar-flow sterile environment meeting ISO5 (class 100) standards. The design included the constant control and monitoring of differential air pressures across the cleanroom, anteroom, gowning room, and controlled research space, as well as maintenance of temperature and humidity. The facility was equipped with state-of-the-art equipment for quality control and release testing of radiopharmaceuticals. Administrative controls and standard operating procedures (SOPs) were established to ensure compliance with manufacturing standards and regulatory requirements. Overall, the design and construction of this radiopharmacy facility exemplified a commitment to advancing fundamental, translational, and clinical applications of radiopharmaceutical research within an academic environment.

Treatments for skin injuries have recently advanced tremendously. Such treatments include allogeneic and xenogeneic transplants and skin substitutes such as tissue-engineered skin, cultured cells, and stem cells. The aim of this paper is to discuss the general overview of the quality assurance and quality control implemented in the manufacturing of cell and tissue product, with emphasis on our experience in the manufacturing of MyDerm®, an autologous bilayered human skin substitute. Manufacturing MyDerm® requires multiple high-risk open manipulation steps, such as tissue processing, cell culture expansion, and skin construct formation. To ensure the safety and efficacy of this product, the good manufacturing practice (GMP) facility should establish a well-designed quality assurance and quality control (QA/QC) programme. Standard operating procedures (SOP) should be implemented to ensure that the manufacturing process is consistent and performed in a controlled manner. All starting materials, including tissue samples, culture media, reagents, and consumables must be verified and tested to confirm their safety, potency, and sterility. The final products should also undergo a QC testing series to guarantee product safety, efficacy, and overall quality. The aseptic techniques of cleanroom operators and the environmental conditions of the facility are also important, as they directly influence the manufacturing of good-quality products. Hence, personnel training and environmental monitoring are necessary to maintain GMP compliance. Furthermore, risk management implementation is another important aspect of QA/QC, as it is used to identify and determine the risk level and to perform risk assessments when necessary. Moreover, procedures for non-conformance reporting should be established to identify, investigate, and correct deviations that occur during manufacturing. This paper provides insight and an overview of the QA/QC aspect during MyDerm® manufacturing in a GMP-compliant facility in the Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia. [ABSTRACT FROM AUTHOR]

This paper presents the results of experimental measurements of the number of aerosol particles in cleanroom air of a biotechnology laboratory for DNA analysis. The aerosol content in the air can harm the accuracy of any analysis performed. The experimental measurements demonstrate compliance with the ISO cleanroom requirements for class 7. The indoor environment of the investigated biotechnology laboratory cleanroom can be classified as ISO cleanroom class 8. The particle count values depend on the month in which the measurement is made. The location of the measurement site, on the other hand, does not have too much influence. Our results showed that the values of particle number in the laboratory ranged from 325,965 to 2,740,877 pc/m3 for particles of 0.5 μm and more. From these measurements, it can be concluded that the biotechnology laboratory premises were not very suitable locations to perform for the intended DNA tests since microbiological contamination had the capacity to distort the results of these tests. As such, the authors propose several strategies to improve the current situation. These strategies are based on changing the laboratory work organization and cleaning methodology. In addition, the monitoring of particles with a size of 5 µm or more is recommended. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to comprehensively assess the challenges faced by a newly established clean room in the oncology center of Omid Hospital, Isfahan, Iran, one of the first of its kind in the country. The research also sought to identify the underlying causes of these challenges and propose potential solutions to address them. Methods: A 6-month cross-sectional study was conducted from December 2021 to May 2022. International guidelines such as British Columbia Cancer Agencies' guideline of hazardous drugs, the National Institute for Occupational Safety and Health guideline for working with hazardous drugs, and United States pharmacopeia related to cleanroom performance were studied, translated, and summarized into a checklist. The staff performance in Omid Hospital's clean room was compared to the data collection form, and all medication errors were documented and analyzed. The study also explained the underlying causes of these challenges and proposed potential solutions. Findings: Among 1005 chemotherapy regimens, 836 errors were detected, stemming from issues such as engineering and construction challenges, lack of human resources and essential equipment, and budgetary constraints. Conclusion: Despite the involvement of a trained oncology clinical pharmacist, Omid Hospital's cleanroom faces significant challenges within the medical and hospital system, leading to non-standard challenges. The study recommends multidisciplinary approaches in the hospital to mitigate these challenges and improve cleanroom performance.

Given the growth of cleanroom manufacturing for high-tech products and the high costs of operating within a cleanroom environment, an accompanying efficient manufacturing system is important. While abundant examples of efficient assembly manufacturing systems exist today, implementation of these into a sensitive cleanroom manufacturing environment has proven to be difficult. Against this background, this paper presents a transferable methodology to support the design of cleanroom assembly workstations which brings together aspects like cleanliness, ergonomics, modularity/flexibility and flow in an integrated manner. A set of guidelines was developed and embedded into a systematic procedure. The methodology was implemented and validated in a case at a high-tech precision manufacturing company, with high-mix-low-volume characteristics. The case study underlines the feasibility of the approach and the multicriterial improvement of workstation design towards the current state of the art. It also lead to a transferable cleanroom workstation design. [ABSTRACT FROM AUTHOR]

Silicon chip demand increased in recent years while the linewidth of the integrated circuits (ICs) has decreased. Improvement of the wafer process yield has become a key factor in chip manufacturing. The yield of the wafer process is closely related to the quality of the mask in the lithography process. The environmental conditions of the mask stocker room need to be carefully monitored and controlled to maintain the mask quality. The moist air invasion from the stocker room when the mask box exchange door is open can significantly increase the internal ambient humidity. This humidity leads to mask defects. Therefore, the moist air invasion from the stocker room should be minimized. In this study, an innovative flow isolation device (FID) is designed and manufactured. This device is used to block the flow of air through the mask exchange door. Smoke flow visualization and particle image velocimetry (PIV) were performed to evaluate the FID performance. The experimental results show that when the pressure of the stocker room is 0.3 Pa and the face velocity of FID is 2.0 m/s, the isolation efficiency is around 83.03%. The newly designed FID can significantly reduce the volume of CDA used during manufacturing. This can significantly reduce waste and energy cost.

Cleanrooms are controlled environments where the number of airborne particles is reduced to a level defined by an International Organization for Standardization (ISO) standard. These facilities have applications in different fields, such as the electronic, pharmaceutical, and healthcare sectors, and are also necessary for the assembly, testing and handling of space hardware. Cleanrooms are expensive to build and maintain and require the permanent designation of infrastructures and dedicated spaces within a building. Once built, clean rooms cannot be used for any other purpose, as contamination is a significant risk. The restricted access to these facilities limits the process of designing, testing, and calibrating instruments developed by academic institutions, small companies, and space startups. Here we present a Commercial Off-The-Shelf (COTS) procedure for building and maintaining a highly controlled ISO class 5 cleanroom, according to ISO14644 standards. We provide a detailed explanation of how to design, develop and operate a portable, modular, and cost-effective ISO class 5 cleanroom that can be used for the usual workflow of development, integration, test procedures and planetary protection associated with the design of instrumentation for planetary exploration., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thasshwin Mathanlal reports financial support was provided by 10.13039/100011690UK Space Agency. Javier Martin-Torres reports financial support was provided by 10.13039/100011690UK Space Agency. Maria-Paz Zorzano reports financial support was provided by 10.13039/501100004837Spanish Ministry of Science and Innovation., (© 2024 The Authors.)

This paper presents the results of experimental measurements of the number of aerosol particles in cleanroom air of a biotechnology laboratory for DNA analysis. The aerosol content in the air can harm the accuracy of any analysis performed. The experimental measurements demonstrate compliance with the ISO cleanroom requirements for class 7. The indoor environment of the investigated biotechnology laboratory cleanroom can be classified as ISO cleanroom class 8. The particle count values depend on the month in which the measurement is made. The location of the measurement site, on the other hand, does not have too much influence. Our results showed that the values of particle number in the laboratory ranged from 325,965 to 2,740,877 pc/m3 for particles of 0.5 μm and more. From these measurements, it can be concluded that the biotechnology laboratory premises were not very suitable locations to perform for the intended DNA tests since microbiological contamination had the capacity to distort the results of these tests. As such, the authors propose several strategies to improve the current situation. These strategies are based on changing the laboratory work organization and cleaning methodology. In addition, the monitoring of particles with a size of 5 µm or more is recommended.

Air–water heat transfer is a crucial method for achieving stable air supply in cleanrooms. This paper models the heat transfer process in the specific scenarios, enabling estimation of the heat exchangers' outlet temperature response based on variations in the inlet temperature. Additionally, considering practical requirements, we derive the outlet performance in scenarios involving multiple heat exchangers in series. An experimental setup was established to evaluate the time-domain and frequency-domain responses of the heat exchanger outlet airflow under different flow rates and numbers of heat exchangers. The spectral distribution fits of the outlet air consistently exceeded 82%. Furthermore, precise estimation error at the m ° C level was achieved, with the average error ratio of the outlet air approaching 10%. The experimental results validated the model's accuracy and provided guidance for achieving high-precision air supply, particularly in maintaining a temperature-stable output airflow through constant-temperature water and air–water heat exchange processes. • Developing the air–water cross-flow heat transfer process model. • Deriving the output performance under series heat exchangers. • Achieving accurate heat exchanger outlet temperature estimates. • Reference for realizing high-precision supply air temperature in cleanrooms. [ABSTRACT FROM AUTHOR]

Ensuring biological cleanliness while assembling and launching spacecraft is critical for robotic exploration of the solar system. To date, when preventing forward contamination of other celestial bodies, NASA Planetary Protection policies have focused on endospore-forming bacteria while fungi were neglected. In this study, for the first time the mycobiome of two spacecraft assembly facilities at Jet Propulsion Laboratory (JPL) and Kennedy Space Center (KSC) was assessed using both cultivation and sequencing techniques. To facilitate enumeration of viable fungal populations and downstream molecular analyses, collected samples were first treated with chloramphenicol for 24 h and then with propidium monoazide (PMA). Among cultivable fungi, 28 distinct species were observed, 16 at JPL and 16 at KSC facilities, while 13 isolates were potentially novel species. Only four isolated species Aureobasidium melanogenum , Penicillium fuscoglaucum , Penicillium decumbens , and Zalaria obscura were present in both cleanroom facilities, which suggests that mycobiomes differ significantly between distant locations. To better visualize the biogeography of all isolated strains the network analysis was undertaken and confirmed higher abundance of Malassezia globosa and Cyberlindnera jadinii. When amplicon sequencing was performed, JPL-SAF and KSC-PHSF showed differing mycobiomes. Metagenomic fungal reads were dominated by Ascomycota (91%) and Basidiomycota (7.15%). Similar to amplicon sequencing, the number of fungal reads changed following antibiotic treatment in both cleanrooms; however, the opposite trends were observed. Alas, treatment with the antibiotic did not allow for definitive ascribing changes observed in fungal populations between treated and untreated samples in both cleanrooms. Rather, these substantial differences in fungal abundance might be attributed to several factors, including the geographical location, climate and the in-house cleaning procedures used to maintain the cleanrooms. This study is a first step in characterizing cultivable and viable fungal populations in cleanrooms to assess fungal potential as biocontaminants during interplanetary explorations. The outcomes of this and future studies could be implemented in other cleanrooms that require to reduce microbial burden, like intensive care units, operating rooms, or cleanrooms in the semiconducting and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

The high-energy requirements of cleanrooms are the main motivation for optimizing their operational conditions. The ventilation system consumes the most energy in order to ensure the precise air conditioning of the room (filtration, temperature, and humidity adjustment). The main function of the ventilation system is to keep particle concentration to a minimum. This work deals with the optimization of an experimental operating room via the optimization of air supply through the distribution element (laminar airflow ceiling) in the range of 0.15–0.25 m·s−1. The laminar airflow between the distribution element and the patient is influenced by the operating light and different airflow velocities. These factors affect changes in particle concentration. Ansys Fluent software was used to investigate the nature of the flow, velocity profiles, and particle trajectories. The results of our numerical simulation demonstrate that a suitable flow rate setting increases the efficiency of particle reduction in the operating table area by up to 54%, which can, in turn, reduce operating costs. The simulated air velocity profile was subsequently verified using the particle image velocimetry (PIV) method. The typical size of particles monitored for in cleanrooms is 0.5 μm according to ISO EN 7. Therefore, the results of this study should be helpful in correctly designing distribution elements for clean rooms. [ABSTRACT FROM AUTHOR]

High particulate matter (PM) concentrations in the cleanroom semiconductor factory have become a significant concern as they can damage electronic devices during the manufacturing process. PM can be predicted before becoming more concentrated based on its historical data to support factory management in regulating the air quality in the cleanroom. In this paper, a Multi-Dense Layer BiLSTM model is proposed to predict PM2.5 concentrations in the indoor environment of the cleanroom. To obtain reliability, validity, and interoperability data, the datasets containing temperature, humidity, PM0.3, PM0.5, PM1, PM2.5, PM5, and PM10 were retrieved in a standardized manner via oneM2M-defined representational state transfer application programmable interfaces by employing software platforms compliant with the Internet of Things (IoT) standard. Based on the proposed model, an algorithm was built providing short-term PM2.5 concentration predictions (one hour ahead, two hours ahead, and three hours ahead). The proposed model outperformed the RNN, LSTM, CNN-LSTM, and Single-Dense Layer BiLSTM models in terms of MSE, MAE, and MAPE values. The model created in this study could predict high PM2.5 concentration levels more accurately, thus providing vital support for operation and maintenance for the semiconductor industry. [ABSTRACT FROM AUTHOR]

Ensuring biological cleanliness while assembling and launching spacecraft is critical for robotic exploration of the solar system. To date, when preventing forward contamination of other celestial bodies, NASA Planetary Protection policies have focused on endospore-forming bacteria while fungi were neglected. In this study, for the first time the mycobiome of two spacecraft assembly facilities at Jet Propulsion Laboratory (JPL) and Kennedy Space Center (KSC) was assessed using both cultivation and sequencing techniques. To facilitate enumeration of viable fungal populations and downstream molecular analyses, collected samples were first treated with chloramphenicol for 24 h and then with propidium monoazide (PMA). Among cultivable fungi, 28 distinct species were observed, 16 at JPL and 16 at KSC facilities, while 13 isolates were potentially novel species. Only four isolated species Aureobasidium melanogenum, Penicillium fuscoglaucum, Penicillium decumbens, and Zalaria obscura were present in both cleanroom facilities, which suggests that mycobiomes differ significantly between distant locations. To better visualize the biogeography of all isolated strains the network analysis was undertaken and confirmed higher abundance of Malassezia globosa and Cyberlindnera jadinii. When amplicon sequencing was performed, JPL-SAF and KSC-PHSF showed differing mycobiomes. Metagenomic fungal reads were dominated by Ascomycota (91%) and Basidiomycota (7.15%). Similar to amplicon sequencing, the number of fungal reads changed following antibiotic treatment in both cleanrooms; however, the opposite trends were observed. Alas, treatment with the antibiotic did not allow for definitive ascribing changes observed in fungal populations between treated and untreated samples in both cleanrooms. Rather, these substantial differences in fungal abundance might be attributed to several factors, including the geographical location, climate and the in-house cleaning procedures used to maintain the cleanrooms. This study is a first step in characterizing cultivable and viable fungal populations in cleanrooms to assess fungal potential as biocontaminants during interplanetary explorations. The outcomes of this and future studies could be implemented in other cleanrooms that require to reduce microbial burden, like intensive care units, operating rooms, or cleanrooms in the semiconducting and pharmaceutical industries.

Strict planetary protection practices are implemented during spacecraft assembly to prevent inadvertent transfer of earth microorganisms to other planetary bodies. Therefore, spacecraft are assembled in cleanrooms, which undergo strict cleaning and decontamination procedures to reduce total microbial bioburden. We wanted to evaluate if these practices selectively favor survival and growth of hardy microorganisms, such as pathogens. Three geographically distinct cleanrooms were sampled during the assembly of three NASA spacecraft: The Lockheed Martin Aeronautics' Multiple Testing Facility during DAWN, the Kennedy Space Center's Payload Hazardous Servicing Facility (KSC-PHSF) during Phoenix, and the Jet Propulsion Laboratory's Spacecraft Assembly Facility during Mars Science Laboratory. Sample sets were collected from the KSC-PHSF cleanroom at three time points: before arrival of the Phoenix spacecraft, during the assembly and testing of the Phoenix spacecraft, and after removal of the spacecraft from the KSC-PHSF facility. All samples were subjected to metagenomic shotgun sequencing on an Illumina HiSeq 2500 platform. Strict decontamination procedures had a greater impact on microbial communities than sampling location Samples collected during spacecraft assembly were dominated by Acinetobacter spp. We found pathogens and potential virulence factors, which determine pathogenicity in all the samples tested during this study. Though the relative abundance of pathogens was lowest during the Phoenix assembly, potential virulence factors were higher during assembly compared to before and after assembly, indicating a survival advantage. Decreased phylogenetic and pathogenic diversity indicates that decontamination and preventative measures were effective against the majority of microorganisms and well implemented, however, pathogen abundance still increased over time. Four potential pathogens, Acinetobacter baumannii, Acinetobacter lwoffii, Escherichia coli and Legionella pneumophila, and their corresponding virulence factors were present in all cleanroom samples. This is the first functional metagenomics study describing presence of pathogens and their corresponding virulence factors in cleanroom environments. The results of this study should be considered for microbial monitoring of enclosed environments such as schools, homes, hospitals and more isolated habitation such the International Space Station and future manned missions to Mars.

BackgroundRecent studies posit a reciprocal dependency between the microbiomes associated with humans and indoor environments. However, none of these metagenome surveys has considered the viability of constituent microorganisms when inferring impact on human health.ResultsReported here are the results of a viability-linked metagenomics assay, which (1) unveil a remarkably complex community profile for bacteria, fungi, and viruses and (2) bolster the detection of underrepresented taxa by eliminating biases resulting from extraneous DNA. This approach enabled, for the first time ever, the elucidation of viral genomes from a cleanroom environment. Upon comparing the viable biomes and distribution of phylotypes within a cleanroom and adjoining (uncontrolled) gowning enclosure, the rigorous cleaning and stringent control countermeasures of the former were observed to select for a greater presence of anaerobes and spore-forming microflora. Sequence abundance and correlation analyses suggest that the viable indoor microbiome is influenced by both the human microbiome and the surrounding ecosystem(s).ConclusionsThe findings of this investigation constitute the literature's first ever account of the indoor metagenome derived from DNA originating solely from the potential viable microbial population. Results presented in this study should prove valuable to the conceptualization and experimental design of future studies on indoor microbiomes aimed at inferring impact on human health.

As the field of cell and gene therapy (CGT) continues to grow, so too must the infrastructure and regulatory guidance supporting the manufacture of these potentially life-saving products-especially early-phase products manufactured at an increasing number of academic or hospital-based facilities providing decentralized (or point of care) manufacturing. An important component of current good manufacturing practices, including those regulating cell and gene therapies, is the establishment of an effective environmental monitoring (EM) program. While several guidelines for establishing an EM program are available, these guidelines do not specifically address the unique aspects of manufacturing CGT products and they do not provide real-world evidence demonstrating the effectiveness of the program. Here, we describe the establishment and evolution of an EM program in a cell therapy manufacturing facility at an academic hospital. With 10 years of EM data, we analyze the effectiveness for identifying trends in environmental conditions and highlight important findings, with the aim of providing practical evidence and guidance for the development of future early-phase EM programs., Competing Interests: Declaration of Competing Interest PJH is an advisor or on the advisory board of Cellevolve, Cellenkos, March Biosciences, Autolomous and Microfluidx., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

The genome of Paenibacillus phoenicis, a spore-forming bacterium isolated from the spacecraft assembly facility of the Phoenix mission, was generated via hybrid assembly by merging short and long reads. Examining this genome may shed light on strategies to minimize the risk of contaminating extraterrestrial environments with Earth-based microorganisms., Competing Interests: The authors declare no conflict of interest.

The article presents methods for constructing and implementing an automated electronic system for collecting and analyzing information about various physical parameters of the environment under conditions of long-term continuous measurements. The system is based on microprocessor devices using wireless technologies with the implementation of the EKF SLAM algorithm for localizing places with an uneven distribution of environmental parameters to minimize pollution of cleanrooms. Also, it can then transmit signals through the operator's computer to the control elements of the room. Thus, the minimization of environmental factors for physical diseases and high-precision equipment is carried out, thereby extending its service life. [ABSTRACT FROM AUTHOR]

• The heat pipe heat recovery technology has the highest EER when used in different climate regions. • A two-stage heat pipe heat recovery device is proposed. • The device has significantly improved the heat recovery efficiency, shortened the investment recovery period. To investigate the efficient waste heat recovery (WHR) technology suitable for cleanrooms, the energy-saving effectiveness of three WHR technologies of heat pipe, liquid circulation, and solution absorption was compared and the comparison was conducted across four different climate regions: severe cold, cold, hot summer cold winter, and hot summer warm winter. The findings reveal that the energy efficiency ratio (EER) of the heat pipe WHR surpasses that of the other two technologies. Specifically, the EER values for the heat pipe WHR in the four climate regions are 21.0, 15.4, 14.1, and 7.3, respectively. Furthermore, a two-stage heat pipe WHR technology is proposed to enhance the heat recovery efficiency of the heat pipe WHR technology, and experimental research has been conducted. The results show that the average heat recovery efficiency reaches 61.64 % when the wind speed is 2 m/s and the new exhaust air temperature difference is 6–11 °C. Compared to the single-stage HPHE, the use of two-stage heat pipe WHR technology in the four climates regions resulted in 6.9 %, 12.8 %, 21.5 %, and 13.6 % higher net heat recovery, 7.1 %, 13.5 %, 16.6 %, and 40.2 % higher energy-efficiency ratios, and 8.2 %, 13.5 %, 12.2 %, and 37.3 % shorter static payback periods, respectively. The heat recovery solution shows a good application prospect in cleanroom WHR. [ABSTRACT FROM AUTHOR]

Aim of a low radon cleanroom technology is to minimize at the same time radon, radon decay products concentration and aerosol concentration and to minimize deposition of radon decay products on the surfaces. The technology placed in a deep underground laboratory such as LSM Modane with suppressed muon flux and shielded against external gamma radiation and neutrons provides “Zero dose” space for basic research in radiobiology (validity of the LNT hypothesis for very low doses) and for the fabrication of nanoelectronic circuits to avoid undesirable “single event effects.” Two prototypes of a low radon cleanroom were built with the aim to achieve radon concentration lower than 100 mBq·m3 in an interior space where only radon-free air is delivered into the cleanroom technology from a radon trapping facility. The first prototype, built in the laboratory of SÚRO Prague, is equipped with a standard filter-ventilation system on the top of the cleanroom with improved leakproofness. In an experiment, radon concentration of some 50 mBq·m−3 was achieved with the filter-ventilation system switched out. However, it was not possible to seal the system of pipes and fans against negative-pressure air leakage into the cleanroom during a high volume ventilation with the rate of 3,500 m3·h−1. From that reason more sophisticated second prototype of the cleanroom designed in the LSM Modane uses the filter-ventilation system which is completely covered in a further improved leakproof sealed metal box placed on the top of the cleanroom. Preliminary experiments carried out in the SÚRO cleanroom with a high radon activity injection and intensive filter-ventilation (corresponding to room filtration rate every 13 s) showed extremely low radon decay products equilibrium factor of 0.002, the majority of activity being in the form of an “unattached fraction” (nanoparticles) of 218Po and a surface deposition rate of some 0.05 mBq·m−2·s−1 per Bq·m−3. Radon exhalation from persons may affect the radon concentration in a low radon interior space. Balance and time course of the radon exhalation from the human body is therefore discussed for persons that are about to enter the cleanroom.

High particulate matter (PM) concentrations in the cleanroom semiconductor factory have become a significant concern as they can damage electronic devices during the manufacturing process. PM can be predicted before becoming more concentrated based on its historical data to support factory management in regulating the air quality in the cleanroom. In this paper, a Multi-Dense Layer BiLSTM model is proposed to predict PM2.5 concentrations in the indoor environment of the cleanroom. To obtain reliability, validity, and interoperability data, the datasets containing temperature, humidity, PM0.3, PM0.5, PM1, PM2.5, PM5, and PM10 were retrieved in a standardized manner via oneM2M-defined representational state transfer application programmable interfaces by employing software platforms compliant with the Internet of Things (IoT) standard. Based on the proposed model, an algorithm was built providing short-term PM2.5 concentration predictions (one hour ahead, two hours ahead, and three hours ahead). The proposed model outperformed the RNN, LSTM, CNN-LSTM, and Single-Dense Layer BiLSTM models in terms of MSE, MAE, and MAPE values. The model created in this study could predict high PM2.5 concentration levels more accurately, thus providing vital support for operation and maintenance for the semiconductor industry.

The biotech cleanroom industry presents a biological basis for living organisms or their components (bacteria or enzymes) to produce helpful medicine. However, biotech industries such as vaccine production need a clean critical environment and contamination control that is always a vital concern for the manufacturing process. This study investigates a biotech cleanroom through a comprehensive field measurement and numerical simulation. The field measurement test results conformed to the design specification to satisfactorily meet with the cleanroom standard of PIC/S and EU GMP. Furthermore, the field measurement data were used as a basic validation and boundary condition for numerical simulation. The numerical simulation results revealed that the concentration distribution in case 1 as a baseline case showed satisfactory results, with a removal efficiency of 75.2% and ventilation efficiency of 80%. However, there was still a high concentration accumulated in certain areas. The improvement strategy was analyzed through non-unidirectional flow ventilation with different face velocities and by adding one return air grille for case 2 and two return air grilles for case 3. The results revealed that case 2 presented the best results in this study, with a removal efficiency of 86.7% and ventilation efficiency of 82% when supplying air velocity at 0.2 m/s. In addition, increasing the supply air velocity to 0.3 m/s could enhance removal ventilation by around 19% and ventilation efficiency by around 5%.

The high-energy requirements of cleanrooms are the main motivation for optimizing their operational conditions. The ventilation system consumes the most energy in order to ensure the precise air conditioning of the room (filtration, temperature, and humidity adjustment). The main function of the ventilation system is to keep particle concentration to a minimum. This work deals with the optimization of an experimental operating room via the optimization of air supply through the distribution element (laminar airflow ceiling) in the range of 0.15–0.25 m·s−1. The laminar airflow between the distribution element and the patient is influenced by the operating light and different airflow velocities. These factors affect changes in particle concentration. Ansys Fluent software was used to investigate the nature of the flow, velocity profiles, and particle trajectories. The results of our numerical simulation demonstrate that a suitable flow rate setting increases the efficiency of particle reduction in the operating table area by up to 54%, which can, in turn, reduce operating costs. The simulated air velocity profile was subsequently verified using the particle image velocimetry (PIV) method. The typical size of particles monitored for in cleanrooms is 0.5 μm according to ISO EN 7. Therefore, the results of this study should be helpful in correctly designing distribution elements for clean rooms.

A Gram-positive, coccoid, motile, aerobic bacterium, designated strain B12T was isolated from a Jet Propulsion Laboratory spacecraft assembly cleanroom, Pasadena, CA, United States. Strain B12T was resistant to chloramphenicol (100 μg/mL), and is a relatively slow grower (3–5 days optimal). Strain B12T was found to grow optimally at 28 to 32°C, pH 7 to 8, and 0.5% NaCl. Fatty acid methyl ester analysis showed that the major fatty acid of the strain B12T was anteiso C15:0 (66.3%), which is also produced by other Kineococcus species. However, arachidonic acid (C20:4 ω6,9,12,16c) was present in strain B12T and Kineococcus glutinatus YIM 75677T but absent in all other Kineococcus species. 16S rRNA analysis revealed that strain B12T was 97.9% similar to Kineococcus radiotolerans and falls within the Kineococcus clade. Low 16S rRNA gene sequence similarities (

A Gram-positive, coccoid, motile, aerobic bacterium, designated strain B12T was isolated from a Jet Propulsion Laboratory spacecraft assembly cleanroom, Pasadena, CA, United States. Strain B12T was resistant to chloramphenicol (100 μg/mL), and is a relatively slow grower (3–5 days optimal). Strain B12T was found to grow optimally at 28 to 32°C, pH 7 to 8, and 0.5% NaCl. Fatty acid methyl ester analysis showed that the major fatty acid of the strain B12T was anteiso C15:0 (66.3%), which is also produced by other Kineococcus species. However, arachidonic acid (C20:4 ω6,9,12,16c) was present in strain B12T and Kineococcus glutinatus YIM 75677T but absent in all other Kineococcus species. 16S rRNA analysis revealed that strain B12T was 97.9% similar to Kineococcus radiotolerans and falls within the Kineococcus clade. Low 16S rRNA gene sequence similarities (<94%) with other genera in the family Kineosporiaceae , including Angustibacter (93%), Kineosporia (94% to 95%), Pseudokineococcus (93%), Quadrisphaera (93%), and Thalassiella (94%) demonstrated that the strain B12T does not belong to these genera. Phylogenetic analysis of the gyrB gene show that all known Kineococcus species exhibited <86% sequence similarity with B12T. Multi-locus sequence and whole genome sequence analyses confirmed that B12T clades with other Kineococcus species. Average nucleotide identity of strain B12T were 75–78% with other Kineococcus species, while values ranged from 72–75% with species from other genera within family Kineosporiaceae. Average amino-acid identities were 66–72% with other Kineococcus species, while they ranged from 50–58% with species from other genera. The dDDH comparison of strain B12T genome with members of genera Kineococcus showed 20–22% similarity, again demonstrating that B12T is distantly related to other members of the genus. Furthermore, analysis of whole proteome deduced from WGS places strain B12T in order Kineosporiales , confirming that strain B12T is a novel member of family Kineosporiaceae. Based on these analyses and other genome characteristics, strain B12T is assigned to a novel species within the genus Kineococcus , and the name Kineococcus rubinsiae sp. nov., is proposed. The type strain is B12T (=FJII-L1-CM-PAB2T; NRRL B-65556T, DSM 110506T). [ABSTRACT FROM AUTHOR]

Numerous research reports have demonstrated that the supply air volumes of cleanrooms areusuallyover-designed to satisfy air cleanliness classes, which may lead to enormous energy waste. In this study, five well-recognised international mathematical models for calculating cleanroom particle concentration were analysed, which are all based on uniform particle distribution in the cleanroom, indoor particle conservation, and mass airflow balance, and an improved and more general model has been established for calculating the minimum air change rates according to the expected air cleanliness class. Following the introduction of non-dimensional concentration correction factors, based on the least-squares method, the average relative error between the model-predicted and measured particle concentration is approximately 13.5%. Based on the improved model with correction factor, the test results demonstrate that the particle concentration depends mainly on the air change rate, particle emission rate and return airflow patterns, among others. When the air change rate per hour and ratio of particle concentrations between the return airflow and room average were varied from 40 h−1 to 120 h−1 and 0.7–1.3, respectively, the concentration consequently decreased by approximately 65% and 46%. The particle deposition caused by gravity can be neglected for small particles. [ABSTRACT FROM AUTHOR]

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Abstract Background The built environment of the International Space Station (ISS) is a highly specialized space in terms of both physical characteristics and habitation requirements. It is unique with respect to conditions of microgravity, exposure to space radiation, and increased carbon dioxide concentrations. Additionally, astronauts inhabit a large proportion of this environment. The microbial composition of ISS particulates has been reported; however, its functional genomics, which are pertinent due to potential impact of its constituents on human health and operational mission success, are not yet characterized. Methods This study examined the whole metagenome of ISS microbes at both species- and gene-level resolution. Air filter and dust samples from the ISS were analyzed and compared to samples collected in a terrestrial cleanroom environment. Furthermore, metagenome mining was carried out to characterize dominant, virulent, and novel microorganisms. The whole genome sequences of select cultivable strains isolated from these samples were extracted from the metagenome and compared. Results Species-level composition in the ISS was found to be largely dominated by Corynebacterium ihumii GD7, with overall microbial diversity being lower in the ISS relative to the cleanroom samples. When examining detection of microbial genes relevant to human health such as antimicrobial resistance and virulence genes, it was found that a larger number of relevant gene categories were observed in the ISS relative to the cleanroom. Strain-level cross-sample comparisons were made for Corynebacterium, Bacillus, and Aspergillus showing possible distinctions in the dominant strain between samples. Conclusion Species-level analyses demonstrated distinct differences between the ISS and cleanroom samples, indicating that the cleanroom population is not necessarily reflective of space habitation environments. The overall population of viable microorganisms and the functional diversity inherent to this unique closed environment are of critical interest with respect to future space habitation. Observations and studies such as these will be important to evaluating the conditions required for long-term health of human occupants in such environments.

Abstract: Background and aims: Nowadays, cleanrooms have become impartible parts of an industry with sensitive products. Sources of contamination in cleanrooms are impaired performance and quality sensitive products in the cleanrooms .The aim of this study was to evaluate the efficiency of HEPA filter and check the concentration and number of airborne particles in cleanrooms for pharmaceutical industry. Methods: This study an experimental study that was conducted at 2015 in the pharmaceutical industry. The method of this study investigated the HEPA filter leakage test and number concentration of particles in the cleanroom according to the ISO 14644 – 3 standards .17 HEPA filters were studied for cleanroom with cleanliness class B, C and D. The leakage filters using aerosol photometer, aerosol generator and Positive injection pump and the Particle Counter was used to measure the concentration of particles. Results: In HEPA filter leakage test, 17 filters have been tested and only 3) 18 %( filters indicate leakage and had an efficiency lower than standard limits. Other filters had a no leakage and show acceptable results (99.99%). The results show that with increasing velocity, permeability and pressure drop in the range of particle size increased and decreased quality factor. In addition, the measurement results show that the concentration of particles in the cleanroom the average density of particles pollution in the cleanliness class B, C and D of the ISO-14644 standard limits was lower. Conclusion: the study showed that the airborne particles concentration are lower than the permissible limits which determined by ISO 14644 standards. Interestingly in this study, the impact of high air quality cleanroom was a good performance HEPA filters.

Introduction: Nowadays, many modern industries require an environment with no contamination by particles and bacteria. An enclosed clean room environment is a place where parameters such as airborne particles, temperature, humidity, air pressure and air flow pattern is controlled. The aim of this study was to evaluate functional parameters of a clean room in a selected pharmaceutical industry. Material and Method: This study was an experimental study conducted in 2015 in a pharmaceutical industry. The air flow rate and flow rate with airflow capture hood was used and multi sensor devices for measuring temperature, humidity and pressure of multi-sensor device. HEPA filter leakage test and counting concentration of particles in the cleanroom was done according to the ISO 14644 – 3(2005) standards using aerosol photometer and aerosol generator. In this study, 6 clean room relating to the 3 cleanliness classes B, C and D (in accordance with standard EU GMP) were evaluated. Meanwhile, both the 2 and 3-dimensional flow model using Computational Fluid Dynamics Software was simulated in this study. Result: Measuring the parameters flow rate and air velocity, temperature (average temperature 20 ° C), relative humidity (below 50%), pressure (pressure less than 15 psi) for every three classes of cleanliness are all acceptable and less than the proposed standard. Furthermore, the results of modelling showed that the pattern of air flow in the room is correct paths in circulation. In the case of leakage test filters, the filter 29 filters tested 5 was leaking and ultimately determine the HEPA filters remove particles that average efficiency is 99.99%. Conclusion: This study showed that the high volume and good quality of air entering the clean room affect the optimal efficiency and air flow rate, pressure drop and air penetration of the HEPA filters Also, the results of study show that the concentration of airborne particles in clean room is depend on the air flow rate and speed and adopting a good air flow pattern will affect the particle concentration.

Objective: This study aimed to comprehensively assess the challenges faced by a newly established clean room in the oncology center of Omid Hospital, Isfahan, Iran, one of the first of its kind in the country. The research also sought to identify the underlying causes of these challenges and propose potential solutions to address them., Methods: A 6-month cross-sectional study was conducted from December 2021 to May 2022. International guidelines such as British Columbia Cancer Agencies' guideline of hazardous drugs, the National Institute for Occupational Safety and Health guideline for working with hazardous drugs, and United States pharmacopeia related to cleanroom performance were studied, translated, and summarized into a checklist. The staff performance in Omid Hospital's clean room was compared to the data collection form, and all medication errors were documented and analyzed. The study also explained the underlying causes of these challenges and proposed potential solutions., Findings: Among 1005 chemotherapy regimens, 836 errors were detected, stemming from issues such as engineering and construction challenges, lack of human resources and essential equipment, and budgetary constraints., Conclusion: Despite the involvement of a trained oncology clinical pharmacist, Omid Hospital's cleanroom faces significant challenges within the medical and hospital system, leading to non-standard challenges. The study recommends multidisciplinary approaches in the hospital to mitigate these challenges and improve cleanroom performance., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Research in Pharmacy Practice.)

Knowing the normal cleanroom microbiota is the basis for ensuring microbiological quality; assess changes and the introduction of new sampling methods. During our study, we prepared a catalogue of cleanroom microorganisms located in four different cleanrooms in University Clinical Centre Ljubljana Pharmacy. Catalogue is prepared as a basis for assessing the suitability of the new rapid microbiological method and subsequent correlation of the results of both methods. The results of our study showed that 78% of isolated bacteria are Gram-positive. However, in more than 70% isolated bacteria were the part of the normal human microbiota, 10–15% of the microorganisms originated from the air, mainly spore-forming bacteria of the genus Bacillus and fungi, and 5–10% of the Gram-negative microorganisms that originated from the water and represent the potential endotoxins (pyrogens). [ABSTRACT FROM AUTHOR]

This study presents the conception of a simulator for training and evaluating workers that are going to enter and operate in a cleanroom. First, this article explains the pedagogical engineering process developed in order to conceive this pedagogical tool. Second, it describes the scientific protocol designed to test the efficiency of the simulator. A comparative study has been done in order to verify the influence of training via the simulator on the performance in real life. The preliminary results seem to confirm a better efficiency of the simulator compared to a traditional training program.

Since the 1970s, the Planetary Protection Group at the Jet Propulsion Laboratory (JPL) has maintained an archive of spacecraft-associated bacterial isolates. Identification of these isolates was routinely performed by sequencing the 16S rRNA gene. Although this technique is an industry standard, it is time consuming and has poor resolving power for some closely related taxa. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry is widely used in clinical diagnostics and is a promising method to substitute standard 16S rRNA sequencing. However, manufacturer-provided databases lack the bacterial diversity found in spacecraft-assembly cleanrooms. This study reports the development of the first custom database of MALDI-TOF MS profiles of bacterial isolates obtained from spacecraft and associated cleanroom environments. With the use of this in-house database, 454 bacterial isolates were successfully identified in concurrence with their 16S rRNA sequence-based classifications. Additionally, MALDI-TOF MS resolved strain-level variations, identified potential novel species and distinguished between members of taxonomic groups, which is not possible using conventional 16S rRNA sequencing. MALDI-TOF MS has proved to be an accurate, high-throughput approach for real-time identification of bacterial isolates during the spacecraft assembly process.

Since the 1970s, the Planetary Protection Group at the Jet Propulsion Laboratory (JPL) has maintained an archive of spacecraft-associated bacterial isolates. Identification of these isolates was routinely performed by sequencing the 16S rRNA gene. Although this technique is an industry standard, it is time consuming and has poor resolving power for some closely related taxa. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry is widely used in clinical diagnostics and is a promising method to substitute standard 16S rRNA sequencing. However, manufacturer-provided databases lack the bacterial diversity found in spacecraft-assembly cleanrooms. This study reports the development of the first custom database of MALDI-TOF MS profiles of bacterial isolates obtained from spacecraft and associated cleanroom environments. With the use of this in-house database, 454 bacterial isolates were successfully identified in concurrence with their 16S rRNA sequence-based classifications. Additionally, MALDI-TOF MS resolved strain-level variations, identified potential novel species and distinguished between members of taxonomic groups, which is not possible using conventional 16S rRNA sequencing. MALDI-TOF MS has proved to be an accurate, high-throughput approach for real-time identification of bacterial isolates during the spacecraft assembly process. [ABSTRACT FROM AUTHOR]