Search Results (147)

Background and Objectives: Bone regeneration (BR) is a cornerstone technique in reconstructive dental surgery, traditionally using either barrier membranes, titanium meshes, or perforated non-resorbable membranes to facilitate bone regeneration. Recent advancements in 3D technology, including CAD/CAM and additive manufacturing, have enabled the development of customized scaffolds tailored to patient needs, potentially overcoming the limitations of conventional methods. Materials and Methods: A scoping review was conducted according to the PRISMA guidelines. Electronic searches were performed in MEDLINE (PubMed), the Cochrane Library, Scopus, and Web of Science up to January 2025 to identify studies on digital technologies applied to bone augmentation. Eligible studies encompassed randomized controlled trials, cohort studies, case series, and case reports, all published in English. Data regarding digital workflows, software, materials, printing techniques, and sterilization methods were extracted from 23 studies published between 2015 and 2024. Results: The review highlights a diverse range of digital workflows, beginning with CBCT-based DICOM to STL conversion using software such as Mimics and Btk-3D^®. Customized titanium meshes and other meshes like Poly Ether-Ether Ketone (PEEK) meshes were produced via techniques including direct metal laser sintering (DMLS), selective laser melting (SLM), and five-axis milling. Although titanium remained the predominant material, studies reported variations in mesh design, thickness, and sterilization protocols. The findings underscore that digital customization enhances surgical precision and efficiency in BR, with several studies demonstrating improved bone gain and reduced operative time compared to conventional approaches. Conclusions: This scoping review confirms that 3D techniques represent a promising advancement in BR. Customized digital workflows provide superior accuracy and support for BR procedures, yet variability in protocols and limited high-quality trials underscore the need for further clinical research to standardize techniques and validate long-term outcomes. Full article

Starting Active Materials for Synthesis (SAMS) represents a critical stage in drug manufacturing, directly influencing the microbiological quality and safety of the final product. The introduction of SAMS marks the point where Good Manufacturing Practices (GMP) begin to apply, which are essential for ensuring sterility and preventing microbial contamination during the synthesis process. However, defining the exact point in the process that qualifies as the SAMS is subject to uncertainties, as earlier stages are not always governed by stringent GMP standards. The regulatory differences between various countries further contribute to this issue. This study explores the implications of SAMS selection and use in relation to sterility and infection control, analyzing the guidelines of major Regulatory Authorities and comparing their approaches to GMP. Regulations from several international regulatory agencies were examined, with a particular focus on microbiological control measures and infection protection in the SAMS manufacturing process. The analysis focused on the microbiological control requirements and safety measures applicable to the stages preceding the introduction of SAMS into the production of the final Active Pharmaceutical Ingredients (APIs). Documents published between 2015 and 2025 were included based on predefined criteria regarding relevance, accessibility, and regulatory authority. The analysis revealed significant discrepancies between regulations regarding the definition and management of SAMS. In particular, the regulations in Mexico and India have notable gaps, failing to provide clear guidelines on SAMS sterility and protection against infectious contamination. Conversely, China has introduced risk-based approaches and early-stage microbiological controls, especially for sterile products, aligning with international standards. The European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), the Pharmaceutical Inspection Co-operation Scheme (PIC/S), and the World Health Organization (WHO) have well-established systems for microbiological quality control of SAMS, including rigorous measures for the validation of suppliers and risk management to ensure that SAMS does not compromise the microbiological safety of the final product. The regulations in Brazil and Canada introduce additional measures to protect the microbiological quality of SAMS, with specifications for contamination control and certification of critical stages. The lack of a harmonized language for the definition of SAMS, coupled with a fragmented regulatory framework, presents a challenge for infection protection in pharmaceutical manufacturing. Key issues include the absence of specific regulations for stages prior to the introduction of SAMS and the lack of standards for inspections related to these stages. A desirable solution would be the mandatory extension of GMPs to the stages before SAMS introduction, with centralized control to ensure sterility and protection against infection throughout the entire manufacturing process. Full article

Medicinal products available on the market should be characterised by therapeutic efficacy, high quality, and safety for patients. They must either be sterile or comply with the appropriate pharmacopoeial microbiological purity requirements. Pharmacopoeial monographs related to microbiological tests of drug quality were also referenced. Despite stringent regulations governing pharmaceutical production, irregularities in the microbiological quality of drugs still occur. These are monitored by relevant agencies, which may order the recall of defective product batches from the market. However, in recent years, numerous cases of microbiological contamination in drugs and drug-related infections have been reported. Both isolated incidents and larger outbreaks or epidemics linked to contaminated medicines have been documented. Various microorganisms, including Gram-negative and Gram-positive bacteria, anaerobes, and yeast-like and mould fungi, have been identified in medicinal products or in patients affected by contaminated drugs. Ensuring the appropriate purity or sterility of pharmaceutical raw materials; maintaining cleanliness in the manufacturing environment, facilities, and equipment; and adhering to hygiene protocols and Good Manufacturing Practice regulations are essential for the production of safe and high-quality medicinal products. The aim of this study is to collect and compile information on the microbiological quality of drugs available on the market, with particular attention to identified irregularities, objectionable microorganisms isolated from medicinal products, and drug-related infections. Full article

Objective: Current good manufacturing practice (cGMP) guidance for positron emission tomography (PET) drugs has been established in Europe and the United States. In Japan, the Pharmaceuticals and Medical Devices Agency (PMDA) approved the use of radiosynthesizers as medical devices for the in-house manufacturing of PET drugs in hospitals and clinics, regardless of the cGMP environment. Without adequate facilities, equipment, and personnel required by cGMP regulations, the quality assurance (QA) and clinical effectiveness of PET drugs largely depend on the radiosynthesizers themselves. To bridge the gap between radiochemistry standardization and site qualification, the Japanese Society of Nuclear Medicine (JSNM) has issued guidance for the in-house manufacturing of small-scale PET drugs under academic GMP (a-GMP) environments. The goals of cGMP and a-GMP are different: cGMP focuses on process optimization, certification, and commercialization, while a-GMP facilitates the small-scale, in-house production of PET drugs for clinical trials and patient-specific standard of care. Among PET isotopes, N-13 has a short half-life (10 min) and must be synthesized on site. [¹³N]Ammonia ([¹³N]NH₃) is used for myocardial perfusion imaging under the Japan Health Insurance System (JHIS) and was thus selected as a working example for the manufacturing of PET drugs in an a-GMP environment. Methods: A [¹³N]NH₃-radiosynthesizer was installed in a hot cell within an a-GMP-compliant radiopharmacy unit. To comply with a-GMP regulations, the air flow was adjusted through HEPA filters. All cabinets and cells were disinfected to ensure sterility once a month. Standard operating procedures (SOPs) were applied, including analytical methods. Batch records, QA data, and radiation exposure to staff in the synthesis of [¹³N]NH₃ were measured and documented. Results: 2.52 GBq of [¹³N]NH₃ end-of-synthesis (EOS) was obtained in an average of 13.5 min in 15 production runs. The radiochemical purity was more than 99%. Exposure doses were 11 µSv for one production run and 22 µSv for two production runs. The pre-irradiation background dose rate was 0.12 µSv/h. After irradiation, the exposed dosage in the front of the hot cell was 0.15 µSv/h. The leakage dosage measured at the bench was 0.16 µSv/h. The exposure and leakage dosages in the manufacturing of [¹³N]NH₃ were similar to the background level as measured by radiation monitoring systems in an a-GMP environments. All QAs, environmental data, bacteria assays, and particulates met a-GMP compliance standards. Conclusions: In-house a-GMP environments require dedicated radiosynthesizers, documentation for batch records, validation schedules, radiation protection monitoring, air and particulate systems, and accountable personnel. In this study, the in-house manufacturing of [¹³N]NH₃ under a-GMP conditions was successfully demonstrated. These findings support the international harmonization of small-scale PET drug manufacturing in hospitals and clinics for future multi-center clinical trials and the development of a standard of care. Full article

The use of 3D printing in the fabrication of immediate prosthetic restorations requires the possibility of sterilization. This study aimed to evaluate the effects of different sterilization methods on the parameters of 3D-printing materials for dental prosthesis plates compared to conventional acrylic material. Forty-four samples were prepared for each tested material: Denture 3D+ (NextDent, The Netherlands), Denturetec (Saremco, Switzerland), Optiprint Laviva (Dentona, Germany), and Rapid Simplified (Vertex Dental, Netherlands). The impact strength of the samples was tested in a HIT 5.5P instrument (Zwick Roell, Germany) after three sterilization methods (pressurized steam, ethylene oxide, and radiation) and without sterilization as a control group. Significantly higher energy and impact strength were recorded for the conventional acrylic material. For Nextdent material, the recommended method of sterilization in terms of impaction is autoclave or ethylene oxide sterilization, Saremco—ethylene oxide sterilization, and Denton—ethylene oxide or radiation sterilization. Conventional acrylic material has a higher impact strength than 3D-printed material, which may encourage the selection of this material for restorations requiring higher fracture strength. The possibility of sterilizing the Nextdent 3D-printed material in the autoclave without worsening its durability makes it a recommended choice for digital clinical practice. Full article

The discontinuation of commercially available saline and hypertonic saline wound dressings for the veterinary market has restricted options available to veterinary practitioners treating contaminated and infected wounds. Clinicians may manufacture their own homemade solutions in clinics or field settings to treat equine or livestock species; however, information is limited on whether autoclave sterilization is necessary or sufficient to eliminate bacterial growth in isotonic and concentrated salt solutions and how long they may subsequently be stored prior to use. The purpose of this study was to assess sterility of saline (0.9%) and hypertonic saline (20%) solutions manufactured three ways (1—autoclaved glass bottle that was autoclaved again following solution preparation; 2—autoclaved glass bottle, not autoclaved again following preparation; 3—non-autoclaved plastic bottle, not autoclaved following preparation). Solutions were stored two different ways (1—solution in sealed bottle or 2—soaked gauze in vacuum-sealed plastic packets). Products were assessed for bacterial growth at four time points (baseline, one week, one month, six months). At each time point, samples of each solution were plated on Luria–Bertani (LB) agar plates and assessed for bacterial growth at 24 h. Vacuum-sealed soaked gauze was placed in antibiotic-free growth media for 24 h, and then media were plated on LB agar plates and assessed for bacterial growth at 24 h. If bacterial growth was detected, qualitative culture with sensitivity was performed to identify bacterial isolates. No bacterial growth was detected in stored solutions for any preparation method, concentration or time point assessed. Bacterial growth was detected from 0.9% saline-soaked gauze at 1 week, 1 month and 6 months in all container types for at least one time point. Bacterial culture revealed Ralstonia, Bacillus, Sphingomonas and Staphylococcus species. Environmental controls (water, containers, salt, biosafety cabinet and benchtop) were submitted for culture to identify the source of contamination, yielding light mixed growth from tap water and no growth from any other locations. These findings provide clinicians with practical information to guide preparation and storage of homemade saline-based products for wound care. Full article

Triiodide resin has an antimicrobial effect on bacteria in water. In the traditional TR manufacturing method, potassium iodide (KI) and crystalline I₂ are reacted to form triiodide ion (I₃⁻). However, I₂ is difficult to use and store because it is vaporizable and poorly soluble in water. This study was conducted to develop a method of producing triiodide resin (TR) without using crystalline I₂. A chemical radical reaction between a commercially available peracetic acid (PAA) solution and a potassium iodide (KI) solution was used to produce I₂ and I₃⁻ ions, which combined with a strong basic anion exchange resin to produce TR. The disinfection of pathogenic microorganisms (e.g., Escherichia coli, Salmonella spp.) present in anaerobically digested livestock wastewater is essential prior to its discharge into public water systems or marine environments, in order to safeguard environmental integrity and public health. Anaerobically treated contaminated livestock wastewater was sterilized through three rounds of treatment with a TR column and prepared by the oxidation of a 100 mM KI solution. Full article

Clostridioides difficile is an anaerobic bacterium that causes disease in both animals and humans. Despite the known significance of this agent, there are no commercial vaccines available for humans, and only one immunogen is marketed for swine. However, no studies have evaluated this vaccine. Background/Objectives: Therefore, the aim of this study was to assess the potency of the first commercial vaccine for C. difficile infection in piglets and to compare the humoral response in rabbits and sows. Methods: Pregnant sows were divided into two groups: a vaccinated group (n = 12), receiving two doses before farrowing, according to the manufacturer’s recommendation, and an unvaccinated control group (n = 6). Blood samples were taken from sows and also from piglets up to two days after birth. In addition, two groups of New Zealand rabbits (Oryctolagus cuniculus) received either a half-dose (G1) or a full-dose (G2) of the vaccine, with a control group receiving sterile saline (0.85%). Rabbits were vaccinated twice, 21 days apart, with blood samples collected before each dose and 14 days after the final dose. A serum neutralization assay in Vero cells was performed to evaluate the titers of neutralizing antibodies. Results: The vaccine demonstrated immunogenicity by stimulating the production of neutralizing antibodies in both rabbits and sows. Additionally, these antibodies were passively transferred to piglets through colostrum, reaching levels comparable to those found in sows. Furthermore, vaccinated rabbits developed antibody titers that do not significantly differ from those obtained in sows and piglets. Conclusions: The tested vaccine can induce a humoral immune response against C. difficile A/B toxins in sows and these antibodies are passively transferred to neonatal piglets through colostrum. Also, the vaccination of rabbits might be a useful alternative for evaluating the potency of vaccines against C. difficile. Full article

Sterilized processed cheese is a dairy product with prolonged shelf life compared to regular processed cheese. The extension of durability is made possible by the thermosterilization of processed cheese, while regular processed cheese is submitted to pasteurization process during manufacturing. Sterilized processed cheese can be classified as long-life foods and their shelf life may reach up to 24 months, if stored at ambient temperature (approx. 25 ± 1 °C). This fact is an advantage over regular processed cheese, which has a shelf life of only around 6 months. Sterilized processed cheese finds application in everyday life when refrigeration facilities are not available; i.e., it is intended for regular retail. However, their most important use is for storage in state material reserves and, moreover, for catering for members of the armed forces and/or members of the integrated rescue system. This review aimed to gather general information on sterilized processed cheeses, their characterization, usage and production. Furthermore, the review discusses the principles of sterilization and factors affecting the course of sterilization focusing on the setting the sterilization limits and sterilization parameters in order to maximize end-product quality. Moreover, last part of the review is devoted to the effect of sterilization and long-term storage on the qualitative parameters of sterilized processed cheese. Full article

Interest in Current Good Manufacturing Practices (cGMP)-grade extracellular vesicles (EVs) is expanding. Some obstacles in this new but rapidly growing field include a lack of standardization and scalability. This review focuses on automated biomanufacturing of EVs in conditioned media collected from cultured mesenchymal stromal cells (MSCs). Different automated cell culture systems are discussed, including factors affecting EV quantity and quality, isolating EVs manufactured in an automated system, and validations needed. The ultimate goal when manufacturing cGMP-grade EVs is to identify a specific application and characterize the EV population in detail. This is achieved by validating every step of the process, choosing appropriate release criteria, and assuring batch-to-batch consistency. Due to the lack of standards in the field, it is critical to ensure that the cGMP-grade EVs meet FDA standards pertaining to identity, reproducibility, sterility, safety, purity, and potency. A closed-system automated bioreactor can be a valuable tool to generate cGMP-EVs in a scalable, economical, and reproducible manner. Full article

The continuous advancement of medical technologies and the increasing demand for high-performance medical devices have driven the search for innovative solutions in biomaterials engineering. However, ensuring the sterility of polymeric biomaterials while maintaining their mechanical integrity remains a significant challenge. This research examines how steam sterilization impacts the mechanical properties of four polymeric biomaterials frequently utilized in medical applications: MED610, PEEK, PET-G HT100, and RGD720. Samples were produced using additive manufacturing (AM), specifically Material Jetting (MJT) and Material Extrusion (MEX) processes, and exposed to steam sterilization at 121 °C and 134 °C. A comprehensive verification process was conducted to ensure the effectiveness of sterilization, including pre-sterilization cleaning, disinfection procedures, and the use of process indicators such as the Bowie–Dick test. Mechanical evaluation included bending tests and Rockwell hardness measurements to assess changes in structural integrity and mechanical strength after sterilization. The results revealed that, while some materials exhibited significant alterations in mechanical properties, others demonstrated high resistance to thermal and humidity exposure during sterilization. These findings provide critical insights into the selection and optimization of polymeric biomaterials for sterilizable medical applications, ensuring their durability and safety in clinical use. Full article

The consumption of canned fish as an affordable and shelf-stable food product having high nutritional value is steadily growing in many parts of the world. An important and often overlooked factor that influences the quality of canned fish is the freshness of raw materials used in the production process. It has been shown previously that the freshness status of fish can be assessed using fast proteins and metabolite liquid chromatography (FPMLC) detecting the relative content of post-mortem adenosine triphosphate (ATP) metabolites. The aim of this study is to evaluate the applicability of FPMLC to evaluate the quality of canned fish. Eighteen samples of various canned fish from different manufacturers were acquired from local supermarkets. FPMLC chromatograms of the samples were processed with the compact optoelectronic chromatographic sensor using PD-10 gel columns as a separation medium. The sensor has a photometric detector based on a deep UV LED emitting at 255–265 nm. All chromatograms showed two combined peaks: the first one was related to proteins and the second one was formed by adenosine ATP metabolites. The delay time between the peaks (the Time index) varied in a range from 138 s to 193 s. It was suggested that the higher the Time index, the fewer fresh raw fish materials were used for production. For additional verification of the FPMLC technique, four samples chosen as the most representative were analyzed by high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR) spectroscopy. The Time index was in good correlation with the well-established nucleotide-based K and K_I indices (quality factors) estimated from the HPLC chromatograms and NMR spectra, which confirms the fact that FPMLC can be used to assess the freshness of raw materials in thermally processed fish products. The correct interpretation of the Time index and other nucleotide-based indicators applied to canned food requires taking into account the effects of nutritional nucleotide thermal degradation that occur during high-temperature sterilization. Full article

Single-use bioreactors (SUBs) are revolutionizing biotechnology and biopharmaceutical manufacturing by offering cost-efficient, flexible, and scalable alternatives to traditional reusable systems. These bioreactors, made from disposable and pre-sterilized materials, streamline cell cultivation for biological production while minimizing the need for complex cleaning and sterilization. A critical aspect of SUB performance lies in optimizing hydrodynamic parameters flow field, power consumption, mixing time, and energy efficiency, which directly influence process outcomes. This study investigates the hydrodynamic performance of an SUB system through stereo Particle Image Velocimetry (PIV) to analyze flow fields, Planar Laser-Induced Fluorescence (PLIF) for mixing time, and Electro Resistance Tomography (ERT) for further insights into mixing dynamics. The results, evaluated at varying impeller speeds and fill heights, provide a comprehensive understanding of flow behavior, mixing efficiency, and power requirements. This work highlights the importance of hydrodynamic characterization in optimizing SUB design and operation, contributing to more sustainable and efficient biopharmaceutical production. Full article

This paper investigates the symmetrical layout effect in ultrasonic cleaning via acoustic solid coupling simulation, with emphasis on how the symmetrical arrangement of transducers influences sound pressure distribution. Two specific transducer layout methods are examined: uniform arrangement at the bottom and symmetrical arrangement along the sides. The findings indicate that when the tank length is an integer multiple of one-quarter of the acoustic wavelength, the symmetrical side arrangement markedly enhances the sound pressure level within the tank and optimizes the propagation and reflection of acoustic waves. In megasonic cleaning, focusing is achieved through a 7 × 7 transducer array by precisely controlling the phase, and the symmetrical arrangement ensures uniform sound pressure distribution. By integrating 1 MHz megasonic sources from both focused and unfocused configurations, the overall sound pressure distribution and peak sound pressure at the focal point are calculated using multi-physics field coupling simulations. A comparative analysis of the sound fields generated by focused and unfocused sources reveals that the focused source can produce significantly higher sound pressure in specific regions. Leveraging the enhanced cleaning capability of the focused acoustic wave in targeted areas while maintaining broad coverage with the unfocused acoustic wave significantly improves the overall cleaning efficiency. Ultrasonic cleaning finds extensive applications in industries such as electronic component manufacturing, medical device sterilization, and automotive parts cleaning. Its efficiency and environmental friendliness make it highly significant for both daily life and industrial production. Full article

Doce de leite is a caramel-like confection, mainly produced in several Latin American countries, with increasing popularity worldwide. This overview outlines nine distinct industrial technologies for the production of doce de leite: (1) total batch manufacturing process; (2) batch manufacturing system with fractionated mix addition; (3) manufacturing with pre-concentration in a vacuum evaporator and finishing in an open pan; (4) manufacturing with pre-concentration in a vacuum evaporator, finishing in an open pan, and lactose micro-crystallization; (5) continuous flow manufacturing with total concentration in a vacuum evaporator and a viscosity control holding tank (hot well); (6) manufacturing with total concentration in a vacuum evaporator and sterilization in an autoclave system; (7) manufacturing with sucrose pre-caramelization and a total batch system; (8) manufacturing in colloidal mill without an evaporation process; and (9) manufacturing based of doce de leite bars with a sucrose crystallization stage. We conducted a literature review to gather data on the discussed processes and their principal characteristics, which may be pertinent to doce de leite manufacturers. The choice of a specific process will depend on the desired doce de leite characteristics, the type of doce de leite to be produced, and the manufacturing company’s requirements. When properly integrated, these technologies contribute to efficient and profitable production, yielding high-quality products with appropriate chemical, microbiological, and sensory characteristics at an industrial scale. Full article