Aseptic Processing Research Articles

Microscopic and elemental analysis of jaw bone tissue in injury

Since the jawbone tissue is injured at the stage of metal dental implant introduction, the problem of inflammatory complication development leading to a breakdown in osseointegration remains relevant. Of interest are the immunological mechanisms of inflammatory process development during the emission of metal nanoparticles, as well as the mechanisms of its subsidence after the removal of a metal object. Microscopic and elemental analysis of the bone tissue of the Wistar rat lower jaw after artificial traumatization was carried out. During the experiment, the situation of presence of a metal foreign body in the bone bed was simulated. An insulin needle was injected into the connective tissue of the lower jaw, followed by its removal after seven days. Microscopic analysis of bone tissue was performed using a Tesscan Vega 4 scanning electron microscope. The teeth alveoli cortical layer surface, connection of the jaws with a gap, stratification of the cartilaginous layer were determined at low magnification in direct projection. Using higher magnification in the direct projection there are visible dense-structural crystalline inclusions, foci of necrosis in the area of junctions of the jaws alveolar processes. The elemental composition of bone tissue was obtained by atomic emission spectroscopy by iCAP 6300 Duo. In the test sample, the quantitative ratio of calcium and phosphorus was 1.68, which slightly exceeds the optimal value of 1.67. An upward change in this ratio indicates a decrease in phosphorus level, which can be interpreted as local osteoporosis. In addition, the following elements were found: Bi, Ga, Pb, Ti, Zn in the amount of 0.03-0.06 mass percent. The list of these elements corresponds to the chemical composition of an insulin needle, indicating the penetration of metal particles into bone bed tissues. The emission of nanoparticles and their subsequent association to micro- and submicron sizes, their persistence, as well as biocorrosion in areas of active bone formation can be a trigger for the development of an aseptic inflammatory process. This effect is due to both a direct damaging factor and an indirect effect through specific signal molecules produced in response to tissue damage.

Inactivation of Salmonella enteritidis on the surface of eggs by air activated with gliding arc discharge plasma

Salmonella enteritidis, a Gram-negative foodborne pathogen, causes inflammation of the stomach and intestines. Poultry and poultry products are considered to be the main hosts of S. enteritidis, especially the most common edible eggs, and increase the risk of Salmonella infection. Therefore, developing the inactivation strategy of S. enteritidis on the surface of eggs is the key step during the egg production process. Gas plasma could effectively inactivate bacteria and fungi and is developed as a potential non-thermal sterilization method in the food industry. In this study, the plasma-activated air (PAA) prepared by the air activated with gliding arc discharge contained a variety of reactive species. When the PAA activated at the power of 50 W and 100 W was inducted into the incubation chamber, the numbers of S. enteritidis on egg fragments or the whole eggs were reduced below the detection limit. After PAA treatment, the eggshells exhibited no change in structure demonstrated by scanning electron microscope, the color of eggshells became a little decrease in red, the internal quality of both the raw egg and the cooked egg also exhibited no change, and trace reactive species remained in the albumen. Further, the PAA was also feasible for the batch treatment of stacked eggs. Therefore, this study supplied an effective and safe strategy for aseptic processing in the poultry industry.

Robotics and Aseptic Processing in View of Regulatory Requirements.

Several nanomedicine based medicinal products recently reached the market thanks to the drive of the COVID-19 pandemic. These products are characterized by criticality in scalability and reproducibility of the batches, and the manufacturing processes are now being pushed towards continuous production to face these challenges. Although the pharmaceutical industry, because of its deep regulation, is characterized by slow adoption of new technologies, recently, the European Medicines Agency (EMA) took the lead in pushing for process improvements using technologies already established in other manufacturing sectors. Foremost among these technologies, robotics is a technological driver, and its implementation in the pharma field should cause a big change, probably within the next 5 years. This paper aims at describing the regulation changes mainly in aseptic manufacturing and the use of robotics in the pharmaceutical environment to fulfill GMP (good manufacturing practice). Special attention is therefore paid at first to the regulatory aspect, explaining the reasons behind the current changes, and then to the use of robotics that will characterize the future of manufacturing especially in aseptic environments, moving from a clear overview of robotics to the use of automated systems to design more efficient processes, with reduced risk of contamination. This review should clarify the regulation and technological scenario and provide pharmaceutical technologists with basic knowledge in robotics and automation, as well as engineers with regulatory knowledge to define a common background and language, and enable the cultural shift of the pharmaceutical industry.

Comparison of the Characteristics of Three Acellular Dermal Matrices Subjected to Distinct Processing Methods Using Five Types of Histochemical Staining.

Acellular dermal matrix (ADM) is treated using various devitalization and aseptic processing methods. The processing effects on ADM were evaluated by histochemical tests. From January 2014 to December 2016, 18 patients [average age, 43.0 (range, 30-54) years] who underwent breast reconstruction with an ADM and tissue expander were prospectively enrolled. During the permanent implant replacement, a biopsy of the ADM was performed. We used three different human-derived products, namely, Alloderm®, Allomend®, and Megaderm®. Hematoxylin and eosin, CD68, CD3, CD31, and smooth muscle actin were used to evaluate the collagen structure, inflammation, angiogenesis, and myofibroblast infiltration. Each ADM was semi-quantitatively analyzed. Significant differences in collagen degradation, acute inflammation, and myofibroblast infiltration were observed among the ADMs. Collagen degeneration (p<0.001) and myofibroblast infiltration (smooth muscle actin-positive, p=0.018; CD31-negative, p=0.765) were the most severe in Megaderm®. Acute inflammation, represented by CD68, was most severe in Alloderm® (p=0.024). Both radiation and freeze-drying treatment physically damaged the collagen structure. Collagen degeneration was most severe in Megaderm®, followed by Allomend® and Alloderm®. Since Alloderm® is treated using chemicals, an assessment of the chemical irritation is warranted. The biopsy results were inconclusive. Therefore, to better interpret processing, more large-scale, serial, histochemical studies of each ADM are needed. This journal requires that authors 38 assign a level of evidence to each article. For a full 39 description of these Evidence-Based Medicine ratings, 40 please refer to the Table of Contents or the online 41 Instructions to Authors www.springer.com/00266 .

Diagnostic analysis of toxic damage due to a dose of zoledronic acid

Introduction: Comprehensive analysis is necessary to analyze the widespread use of bisphosphonate drugs in the treatment and prevention of various diseases of connective tissue structures. The relevance of the study depends on the impact they have on the patient’s somatic condition, given the number of early and late complications diagnosed by domestic and foreign clinicians.&#x0D; Materials and methods: The methodology used was developed on Stavropol Regional Clinical Hospital from 2010 to 2022. A randomized and observational study of the state of connective tissue structures was conducted in 186 patients who had a history of taking zoledronic acid and developed bisphosphonate osteonecrosis of the jawbone. At the diagnostic and treatment stages, patients were tested using laboratory methods to monitor amino acids in biological fluids (blood), as well as bone blocks extracted intraoperatively using highly effective gas-liquid chromatography on AAA 500.&#x0D; Results and discussion: Aminograms obtained in the pre-operative period indicate toxic effects of zoledronic acid on neuro, endocrine, and other human systems. The initiation and progression of aseptic inflammatory processes in tissue structures is correlated with the deteriorating general ocular status of patients when amino acids, such as alanine, serine, taurine, phenylalanine, tyrosine, proline, histidine, glycine, and valine, against a background of 90.4±2.1 mmol/L ammonia are reduced critically.&#x0D; Conclusion: Zoledronic acid initiates an aseptic chronic inflammatory process in the jaw bones, accompanied by toxic acidosis, which worsens osteoporotic symptoms.

Micropropagation of Hemp (Cannabis sativa L.)

Hemp (Cannabis sativa L.) is commonly grown for the medicinal secondary metabolites produced by pistillate inflorescences. Micropropagation is a valuable method of propagating hemp plants because of the aseptic process and the production of true-to-type propagules. The hemp cultivar TJ’s CBD was used for a series of experiments to compare media inputs and practices for the clonal micropropagation of hemp. For stage I, shoot tips harvested from stock plants that were grown in a growth chamber produced less endogenous contamination in newly established cultures than shoot tips harvested from the greenhouse. In addition, stage I disinfection treatments with 20%, 40%, and 60% bleach (7.5% sodium hypochlorite) for 10 minutes had no differences in surface contamination rates. All concentrations were able to clean explants equally, and no damage to the explants was observed. For stage II, there were no differences in growth and multiplication rate between shoot tip or nodal explants. In addition, no differences were observed between the gelling agent’s agar, agargellan, and gellan gum at standard rates. When basal nutrient formulations were compared at standard rates and with their respective vitamins, Murashige and Skoog, Linsmaier &amp; Skoog, and Driver &amp; Kuniyuki Walnut media were found to be superior to Lloyd &amp; McCown Woody Plant Medium. Media pH levels of 4.0, 5.0, 5.8, 6.0, and 7.0 were compared, and no differences were observed in final fresh weights, shoot lengths, or quality ratings. The pH levels of 5.8, 6.0, and 7.0 generated a greater number of lateral nodes. Sucrose levels of 0%, 1.5%, 3.0%, 4.5%, and 6.0% (wt/vol) were also compared, with the 1.5% and 3.0% rates showing greater fresh weights, shoot lengths, and quality ratings. Growth room temperatures of 22, 24, 26, and 28 °C were compared, with temperatures of 28 and 26 °C generating greater fresh weights, shoot lengths, numbers of nodes, and quality ratings compared with cooler temperatures. The cytokinins 6-enzylaminopurine (BA), 6-(γ,γ-dimethylallylamino) purine (2iP), and thidiazuron (TDZ) were compared at 1.0, 5.0, and 10.0 μM concentrations. The 5.0-μM TDZ treatment generated greater fresh weights and numbers of lateral nodes; however, it also produced the shortest shoot lengths and lowest quality ratings. The 2iP treatments at 1.0 and 5.0 μM, and the BA treatment at 1.0 μM produced the greatest quality ratings. The 5.0-μM 2iP level was considered the best treatment for stage II multiplication based on high ratings, in addition to the greater final fresh weights, shoot lengths, and numbers of nodes that were produced. For stage III experiments, the auxins indole 3-butyric acid (IBA) and 1-naphthylacetic acid (NAA) were compared at concentrations of 0.25, 0.5, and 2.5 μM. Auxin treatments of 0.25 μM NAA, 0.5 μM NAA, and 2.5 μM IBA generated the greatest final shoot fresh weights, root fresh weights, and numbers of nodes. However, the 2.5-μM IBA treatment resulted in a higher overall rating. For stage IV, ex vitro rooting and acclimation trials compared a dome and an intermittent mist system, as well as treated the unrooted cuttings with an externally applied auxin. Acclimating with a dome produced greater shoot heights, fresh shoot weights, and overall ratings compared with the mist system. The auxin treatment mildly increased fresh root weight, but was not as important to acclimation success as the domed environment. It has been concluded that a micropropagation system that uses lower rates of sucrose, higher growing temperatures, and lower rates of the cytokinins BA and 2iP are optimal for the micropropagation of hemp. In addition, when acclimating hemp plants from tissue culture, an in vitro stage III can be bypassed and plants can be rooted ex vitro during stage IV acclimation with a dome with or without additional auxin treatments.

Managing Risk in Aseptic Processing Environments

Genetic Engineering & Biotechnology NewsVol. 43, No. 2 BioprocessingManaging Risk in Aseptic Processing EnvironmentsSamsung Biologics outlines strategies for protecting drug substances and drug products from potential contaminationJeong Jin-hyeokJeong Jin-hyeokSearch for more papers by this authorPublished Online:10 Feb 2023https://doi.org/10.1089/gen.43.02.12AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 43Issue 2Feb 2023 Information© 2023 by GEN PublishingTo cite this article:Jeong Jin-hyeok.Managing Risk in Aseptic Processing Environments.Genetic Engineering & Biotechnology News.Feb 2023.30-31.http://doi.org/10.1089/gen.43.02.12Published in Volume: 43 Issue 2: February 10, 2023PDF download

A review of conventional and emerging technologies for hydrogels sterilization

Hydrogels are extensively used in the biomedical field, as drug delivery systems, wound dressings, contact lenses or as scaffolds for tissue engineering. Due to their polymeric nature and the presence of high amounts of water in their structure, hydrogels generally present high sensitivity to terminal sterilization. The establishment of an efficient sterilization protocol that does not compromise the functional properties of the hydrogels is one of the challenges faced by researchers when developing a hydrogel for a specific application. Yet, until very recently this aspect was largely ignored in the literature. The present paper reviews the state of literature concerning hydrogels sterilization, compiling the main findings. Conventional terminal sterilization methods (heat sterilization, radiation sterilization, and gas sterilization) as well as emerging sterilization techniques (ozone, supercritical carbon dioxide) are covered. Considerations about aseptic processing are also included. Additionally, and as a framework, hydrogels’ polymeric materials, types of networks, and main biomedical applications are summarily described.

Aseptic process validation of [18F]Sodium Fluoride radiopharmaceutical in-house production

Sodium fluoride ([18F]NaF) is a PET radiopharmaceutical for vizualization of the skeletal system and microcalcification. In the originally designed in-house method, [18F]NaF is recovered in aqueous solution after cyclotron irradiation, sterilized by passage through a 0.22 µm sterile filter and dispensed under aseptic conditions. To ensure the microbiological safety of drugs produced under aseptic conditions, validation of aseptic procedures is always recommended. This is essential for radiopharmaceuticals because most of them are released for administration before any sterility test can be completed due to their radioactive nature. This study reports the validation of the aseptic process applied to the internal production of [18F]NaF carried out in two phases: testing the number of viable microorganisms in radiopharmaceutical product prior to sterilization and process simulation studies (media fill tests). We found that all samples were sterile and the endotoxin concentration was well below the maximum acceptable level reported in the Ph Eur. monograph on [18F]NaF. The results confirmed that the entire production process of [18F]NaF can be carried out under strictly aseptic conditions following the validated procedures preserving the sterility of the final product.

Qualification of Human Liver Microsomes for Antibacterial Activity Screening of Drug Metabolites

Microsomes are commonly used to perform in vitro drug metabolism, predominantly to form phase I drug metabolites. Pooled microsomes from multiple donors can contain microorganisms from underlying microbial diseases. Exposure to microbes can also occur during extraction if aseptic processing is compromised. Although microbial presence does not affect the metabolic activity of microsomes, presence of unwanted microorganisms can cause interference if the downstream application of microsomal drug metabolites is screening for antibacterial activity. In this work, traditional biochemical tests and advanced proteomics-based identification techniques were used to identify two gram-negative bacteria in pooled human liver microsomes. Several decontamination procedures were assessed to eradicate these two bacteria from the microsomes without affecting its metabolic capacity, and organic extraction was found to be the most convenient and efficient approach to decontaminate microsomes and screen drug metabolites for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).

EU GGMP Annex 1 2022 and Pharmaceutical Cleanroom Classification - Consideration of the changes from EU GGMP Annex 1 2008

Classification is an essential part of the qualification activities for pharmaceutical cleanrooms to confirm the effectiveness of the airborne contamination control system. A review of the classification requirements and principles associated with ISO 14644-1:2015 and Annex 1 2008 of the European Union Guide to Good Manufacturing Practice (GGMP) has previously been reported. As this version has now been superseded by the 2022 edition, review of the relevant updates has been completed to assess the impact of the classification process for a cleanroom used for aseptic processing. With some additions and text updates, many of the requirements and expectations for classification can be considered to remain effectively unchanged from the 2008 version. However, there are items of more significant change for consideration and this article summarises those elements that have minimal impact and focuses upon the significant changes and provides recommendations, and options, to ensure continued meaningful classification. Key words: Cleanroom classification, ISO 14644-1, EU GGMP Annex 1 2022

Microbial evaluation of allopathic and herbal non-sterile pharmaceutical liquid dosage forms

Nonsterile pharmaceutical finished products are not manufactured through aseptic processes so are not completely free from microbial contaminations, which can impact their efficacy due to the degradation of active ingredients. The aim of present study was to enumerate, isolate and identify the microbial contaminations in non-sterile liquid finished pharmaceutical dosage forms. A total of 50 nonsterile liquid products were collected from different pharmacies across Lahore city, Pakistan. Pour plate method was used to test the total microbial count as per USP guidelines. The results showed a microbial count of 140 cfu mL-1 in nutraceuticals manufactured liquid dosage form, 60 cfu mL-1 in multinational products, 120 cfu mL-1 in registered herbal products, and 390 cfu mL-1 in non-registered herbal liquid products. Major bacterial contaminants isolated from allopathic (local and multinational) products and herbal (registered and non-registered) products are reported.

Aseptic process validation of [18F]Sodium Fluoride radiopharmaceutical in-house production

Sodium fluoride ([18F]NaF) is a PET radiopharmaceutical for vizualization of the skeletal system and microcalcification. In the originally designed in-house method, [18F]NaF is recovered in aqueous solution after cyclotron irradiation, sterilized by passage through a 0.22 µm sterile filter and dispensed under aseptic conditions. To ensure the microbiological safety of drugs produced under aseptic conditions, validation of aseptic procedures is always recommended. This is essential for radiopharmaceuticals because most of them are released for administration before any sterility test can be completed due to their radioactive nature. This study reports the validation of the aseptic process applied to the internal production of [18F]NaF carried out in two phases: testing the number of viable microorganisms in radiopharmaceutical product prior to sterilization and process simulation studies (media fill tests). We found that all samples were sterile and the endotoxin concentration was well below the maximum acceptable level reported in the Ph Eur. monograph on [18F]NaF. The results confirmed that the entire production process of [18F]NaF can be carried out under strictly aseptic conditions following the validated procedures preserving the sterility of the final product. Keywords: [18F]NaF, radiopharmaceutical, validation, aseptic process

Setup of a Contamination Control Strategy Using the Hazard Analysis Critical Control Point (HACCP) Methodology.

A Contamination Control Strategy (CCS) is a document that focuses on how to prevent contaminations with microorganisms, particles, and pyrogens within sterile and/or aseptic and preferably also in nonsterile manufacturing facilities. This document determines to what extent measures and controls in place are efficient in preventing contamination. In order to efficiently evaluate and control all potential hazards associated with sources of contamination within a CCS, the Hazard Analysis Critical Control Point (HACCP) methodology could be a useful tool to monitor all Critical Control Points (CCPs) related to various sources of contamination. This article describes a way to set up the CCS within a pharmaceutical sterile and aseptic manufacturing facility (GE HealthCare Pharmaceutical Diagnostics) by applying the HACCP methodology. In 2021, a global CCS procedure and a general HACCP template became effective for the GE HealthCare Pharmaceutical Diagnostics sites having sterile and/or aseptic manufacturing processes. This procedure guides the sites through the setup of the CCS by applying the HACCP methodology and helps each site to evaluate whether the CCS is still effective taking all (proactive and retrospective) data following the CCS into account. A summary of setting up a CCS using the HACCP methodology, specifically for the pharmaceutical company GE HealthCare Pharmaceutical Diagnostics Eindhoven site, is provided in this article. Use of the HACCP methodology enables a company to include proactive data within the CCS, making use of all identified sources of contamination, associated hazards, and/or control measures and CCPs. The constructed CCS allows the manufacturer to identify whether all included sources of contamination are under control and, if not, which mitigatory actions need to be performed. All current states are reflected by a traffic light color to reflect the level of residual risk, thereby providing a simple and clear visual representation of the current contamination control and microbial state of the manufacturing site.

Something for Nothing.

This publication reviews the evolution of performance standards for aseptic processing as defined by regulatory, pharmacopieal and industry activities. The increasing rigor of the expectations for sterility testing, environmental monitoring and process simulation have made for improvements in capability for sterile manufacturing. The document explains why contemporary requirements are such that satisfying them requires a shift in operating practice from manned clean rooms to isolation technology.

The release of osteoclast-stimulating factors on supraphysiological loading by osteoprogenitors coincides with expression of genes associated with inflammation and cytoskeletal arrangement

Supraphysiological loading induced by unstable orthopedic implants initiates osteoclast formation, which results in bone degradation. We aimed to investigate which mechanosensitive cells in the peri-implant environment produce osteoclast-stimulating factors and how the production of these factors is stimulated by supraphysiological loading. The release of osteoclast-stimulating factors by different types of isolated bone marrow-derived hematopoietic and mesenchymal stem cells from six osteoarthritic patients was analyzed after one hour of supraphysiological loading (3.0 ± 0.2 Pa, 1 Hz) by adding their conditioned medium to osteoclast precursors. Monocytes produced factors that enhanced osteoclastogenesis by 1.6 ± 0.07-fold and mesenchymal stem cells by 1.4 ± 0.07-fold. Medium from osteoprogenitors and pre-osteoblasts enhanced osteoclastogenesis by 1.3 ± 0.09-fold and 1.4 ± 0.03-fold, respectively, where medium from four patients elicited a response and two did not. Next generation sequencing analysis of osteoprogenitors revealed that genes encoding for inflammation-related pathways and cytoskeletal rearrangements were regulated differently between responders and non-responders. Our data suggest that released osteoclast-stimulating soluble factors by progenitor cells in the bone marrow after supraphysiological loading may be related to cytoskeletal arrangement in an inflammatory environment. This connection could be relevant to better understand the aseptic loosening process of orthopedic implants.

The role of neurohumoral factors in the persistence of aseptic bone inflammation in patients with diabetic neuroosteoarthropathy

BACKGROUND: Diabetic neuroosteoarthropathy (DNOAP, Charcot foot) is a relatively rare complication of diabetes mellitus (DM), which can lead not only to impaired support function of the lower limb in such patients, but also to high amputation. DNOAP is characterized by persistent aseptic inflammation of the bone structures of the foot, which creates significant ­difficulties in planning therapeutic measures. In the medical literature, there are data demonstrating the role of individual ­cytokines and neurohumoral factors in the prolongation of the inflammatory process in diabetes, however, there are currently very few studies that determine reliable markers of aseptic inflammation in DNOAP.AIM: To study the effect of neurohumoral factors and advanced glycation end products on the activity of aseptic inflammation in the bone structures of the foot in patients with type 2 diabetes mellitus (DM2) and diabetic neuroosteoarthropathy.MATERIALS AND METHODS. The study included 88 patients with type 2 diabetes (45 men, 43 women). Group 1 consisted of patients with DM2 and inactive DNOAP (n= 43), group 2 (n= 45) consisted of patients with DM2 and distal diabetic neuropathy without osteoarticular pathology. The diagnosis of diabetic neuropathy was based on the analysis of the clinical picture and indicators of peripheral sensitivity. Diagnosis of DNOAP and determination of its stage was based on clinical data, the results of infrared thermometry and radiology tests of the foot bones. General clinical assessment was used, radiology tests (X-ray, MRI), evaluation of CRP, calprotectin, copeptin, glutathione peroxidase 1 (GP1).RESULTS. According to the results of examination and palpation of the feet, as well as the analysis of the temperature gradient of the skin of the affected and contralateral limb (infrared thermometry), DNOAP was detected and the stage of this complication was determined. The diagnosis of the chronic stage of DNOAP was confirmed by the results of MRI and the clinical picture (no difference in skin temperature on the symmetrical areas of the feet). According to the results of laboratory analysis, a statistically significant difference in copeptin values was revealed — in group 1 — 0.232 µg/ml [0.147; 0.342], in group 2 — 0.115 µg/ml [0.065; 0.203] (p&gt;0.05) and CRP — in group 1 — 7.113 mg/l [2.453; 16.505], in group 2 — 2.187 mg/l [1.131; 5.567] (p&gt;0.05), leukocyte levels in the groups did not differ significantly: group 1 — 7.86 [6.40; 9.00]*10^9, group 2 — 7.00 [6.00; 8.15] (p&gt;0.05). There was a trend towards an increase in the level of calprotectin and glutathione peroxidase-1 in the DNOAP group, however, the differences were not significant. calprotectin — in group 1 — 1.948 [1.229; 2.969], in group 2 — 1.692 [1.16; 2.514] μg/ml and glutathione peroxidase-1 in group 1 — 24.72 [20.1; 31.82], in group 2 — 22.98 [18.94; 31.2] ng/ml.CONCLUSION. In the study, statistically significant differences were obtained in the levels of copeptin and C-reactive protein: in patients with DNOAP, their values were significantly higher, which indicates the persistence of the aseptic inflammatory process in the bone tissue of patients even in the chronic stage of DNOAP. These data may help in deciding whether to use one or another method of unloading the affected joints, which will affect the clinical prognosis. The study of neurohumoral markers of arthropathy in the blood serum of patients with DM2 is carried out for the first time, and therefore it is difficult to compare with the results of other authors. It can be assumed that copeptin and CRP are significant markers of persistent inflammation of the osteoarticular structures of the foot in DNOAP.

Sterilization of Polymeric Implants: Challenges and Opportunities.

Degradable and environmentally responsive polymers have been actively developed for drug delivery and regenerative medicine applications, yet inadequate consideration of their compatibility with terminal sterilization presents notable barriers to clinical translation. This Review discusses industry-established terminal sterilization methods and aseptic processing and contrasts them with innovative approaches aimed at preserving the integrity of polymeric implants. Regulatory guidelines, fiscal considerations, and potential pitfalls are discussed to encourage early integration of sterility regulatory considerations in material designs.

Impact of implementing the aseptic compounding management system, Medcura, on internal error rates within an oncology pharmacy aseptic unit: a mixed methods evaluation

BackgroundAs cancer survivorship improves, pressure on oncology services to provide safe, timely treatments increases. Traditional manual compounding processes are error prone, putting patients at risk. Additionally, errors have a detrimental...

Direct Observation of the Sporicidal Action of Hydrogen Peroxide on Bacillus atrophaeus Spores By Optical Trapping Raman Microscopy

Hydrogen peroxide (H2O2), a strong oxidizer, is frequently used for chemical sterilization in aseptic food processing. Due to their inherent robustness, bacterial spores, i.e. spores of Bacillus atrophaeus, are commonly employed to evaluate the efficacy of the sterilization procedure [1]. Despite its widespread use, however, the details of the sporicidal action of H2O2 are not yet fully understood, with various mechanisms being discussed in the literature [2,3]. Here, we employ optical trapping Raman microscopy to elucidate the sporicidal mechanism of H2O2. Optical trapping Raman microscopy allows us to isolate, investigate, and manipulate individual spores from a sample (Fig. 1A). Combining optical microscopy with the real-time, label-free chemical information obtained from Raman spectroscopy directly reveals the sequence of steps that lead to oxidative spore death after H2O2 exposure (Fig. 1B).We find that spore degradation begins with the fast, cooperative release of dipicolinic acid (DPA), a key spore biomarker and a major component of spore’s core. This indicates a breach of the inner membrane surrounding the core. The onset of DPA release depends on the concentration of H2O2. DPA outflux is accompanied by the formation of oxidation products (mostly carbonyl compounds) and oxidation continues after exchange of DPA with the surrounding medium is complete. The remaining spore shell then slowly disintegrates and continues to shrink on a timescale of hundreds of seconds. Simultaneous observation of spore morphology and size by optical microscopy and particle tracking corroborates this three-step mechanism.The presented assay allows on-line monitoring of spore composition and morphology, which directly reveals the mechanism underlying the sporicidal action of H2O2. In addition, trapped spores can be exposed to different chemical or physical stimuli (temperature, light, chemical composition of the surrounding medium, etc.) to investigate a variety of industrially relevant sterilization conditions. Jildeh, Z. B., Wagner, P. H. & Schöning, M. J. Sterilization of Objects, Products, and Packaging Surfaces and Their Characterization in Different Fields of Industry: The Status in 2020. physica status solidi (a) 218, 2000732 (2021). Setlow, P. & Christie, G. What’s new and notable in bacterial spore killing. World J Microbiol Biotechnol 37, 144 (2021). Setlow, P. Spores of Bacillus subtilis: their resistance to and killing by radiation, heat and chemicals. J Appl Microbiol 101, 514-525 (2006). Figure 1