Good Manufacturing Practice Research Articles

Aflatoksin: Aspek kesehatan, metode reduksi dan deteksinya

Food contaminant aflatoxin is a mycotoxin produced by Aspergillus flavus and A. parasiticus. This article aims to discover the pathophysiological, immunological, pharmacological, toxicity, and reduction and detection methods of aflatoxin. Kinds of literature were obtained from Research Gate, Pubmed, and Science Direct with the primary keyword “aflatoxin”. Pathophysiologically, aflatoxin-contaminated food has been proven to cause necrosis in liver cells, developing into liver cancer. Immunologically, aflatoxin decreases monocyte and dendritic cell phagocytosis, neutrophil cell ATP production, and pro-inflammatory cytokine synthesis. Aflatoxin toxicity is at the LD50 of 12-16 mg/kg b.w, causing death. Pharmacologically, 120-201 µg/kg b.w causes aflatoxicosis, in vivo studies indicated that NovaSil, Sulfarophan, and Monanthotaxis caffra leaf extract may reduce its toxicity. Aflatoxins are highly thermostable; hence, once food has been contaminated, they cannot be destroyed by normal cooking process. The control and reduction should be conducted in post-harvest handling, common physical means practiced are heating, drying, and smoking. Chemically using ozone, 0.5 sodium bisulfate, 1% sodium hydroxide, 5% acetic acid, and prochloraz. Biologically using Flavobacterium aurantiacum B-184, Bacillus velezensis DY3108, and, a consortium of Geobacillus and Tepidimicrobium bacteria. Aflatoxin can be detected using TLC, HPLC, MS, ELISA, and UHPLC-ESI MS/MS. The prevention of aflatoxin occurrence is done through good post-harvest handling, good manufacturing practices, and applying regulations accordingly to ensure food products and feed are at acceptable levels of aflatoxin.

Analysis of the application of good manufacturing practices (GMP) and sanitation standard operating procedures (SSOP) for products "Emping Singkong Super Telur Bu Siti" in Bantul, Yogyakarta

Analysis of the application of good manufacturing practices (GMP) and sanitation standard operating procedures (SSOP) for products "Emping Singkong Super Telur Bu Siti" in Bantul, Yogyakarta

Evaluation of Hygienic Practices and Microbiological Quality of Street Vended Fruit Salads in Morogoro, Tanzania

Street vended foods have gained popularity due to economic benefits. However, they have been recognized as a potential hazard to public health as a result of poor hygienic practices. The study was conducted to assess the hygienic practices and microbiological quality of street vended fruit salads vended in Morogoro Municipal, Tanzania. A total of 30 respondents were involved in the study to assess of quality of fruit salad vended by town street vendors (TSV), University cafeterias (UCV), and town restaurants vendors (TRV). The findings revealed that most vendors (86.3%) were unaware of food safety, 73.3% were unaware of food safety standards and laws, and every seller evaluated was unaware of food safety initiatives such as Good Manufacturing Practices (GMP) and Good Hygienic Practices (GHP) and had never implemented any of them. All vendors saw the doctor only when they were ill. Nevertheless, none of vendor had a quality registration certificate or had undergone training in food safety and hygiene. Most of the salad preparation settings (46.7%) did not adhere to the fundamental requirements of a food preparation facility, and the vending facilities were in disrepair. Piles of dirty were observed in the food salad preparation and vending premises and 80% of the vendors used uncovered waste bins that were observed to encourage pests such as flies and cockroaches in the premises. The total aerobic count (TAC) ranged from 3.92±0.31 to 4.29±0.21 log CFU/g. All fruit salad samples were contaminated with coliforms and the level of coliform count exceeded 1.4×104 MPN/g in fruit salad samples indicating poor hygiene and fecal contamination. Possible sources of contamination were found to be water quality, cross-contamination, food handling and preparation equipment, and environmental factors such as dust, pests, and air quality. According to the study's findings, the majority of fruit salad sellers in the study area did not adhere to hygienic practices, and the made fruit salads were of poor microbiological quality, putting consumers at risk for food safety.

Influence of cell specific parameters in a dielectric spectroscopy conversion model used to monitor viable cell density in bioreactors.

In the biopharmaceutical industry, the use of mammalian cells to produce therapeutic proteins is becoming increasingly widespread. Monitoring of these cultures via different analysis techniques is essential to ensure a good quality product while respecting good manufacturing practice (GMP) regulations. PAT (Process Analytical Technologies) tools provide real-time measurements of the physiological state of the culture and enable process automation. Dielectric spectroscopy is a PAT that can be used to monitor the viable cell concentration of living cells (VCC) after processing raw permittivity data. Several modeling approaches exist and estimate biomass with different accuracy. The accuracy of the Cole-Cole and Maxwell Wagner's equations are studied here in the determination of the VCC and cell radius in Chinese hamster ovary (CHO) culture. A sensitivity analysis performed on the parameters entering the equations highlighted the importance of the cell specific parameters such as internal conductivity (σi ) and membrane capacitance (Cm ) in the accuracy of the estimation of VCC and cell radius. The most accurate optimization method found to improve the accuracy involves in-process adjustments of Cm and σi in the model equations with samplings from the bioreactor. This combination of offline and in situ data improved the estimation precision of the viable cell concentration by 69% compared to a purely mechanistic model without offline adjustments. This article is protected by copyright. All rights reserved.

Microbiological Skip Test: Fundamentals and Evaluation of Water Activity in Pharmaceutical Ingredients

Quality control is essential for Good Manufacturing Practices in the pharmaceutical industry. The time and costs associated with microbiological quality control are well known. It is proposed the reduction of traditional microbiological methods of counting the total number of microorganisms and research of specific pathogens using the water activity (Aw) method, a practice known as the skip test. The raw material selected as a prototype for this study met the criteria for the feasibility of reductions in analyses having synthetic origins, solid physical state, low or high pH in aqueous solution, and Aw results below 0.75 at a temperature of 25°C, and absence of nonconformity records. The risk management process was implemented using risk analysis with the mode, effect, criticality, failure analysis tool, and opening change control with the replacement of microbiological standard by Aw in 20 sequential batches after complete analysis of the first batch received in the year. It was possible to certify the microbiological quality of the selected pharmaceutical ingredients using the AW results, thereby confirming the feasibility of the skip test.

Preclinical development and characterization of a human plasma-derived high-purity factor X concentrate for therapeutic use.

Hereditary factor X deficiency is a rare bleeding disorder, with limited treatment options. This paper describes the approach to pre-clinical development and characterization of a high-purity plasma-derived factor X concentrate, to achieve orphan drug marketing authorization for the treatment of hereditary factor X deficiency. A chromatographic process was developed, to purify factor X from human plasma for fractionation. The product was characterized using in vitro, in vivo and ex vivo tests for potency, purity, thrombogenicity, immunogenicity, toxicity and stability. The production process complied with good pharmaceutical manufacturing practice. It achieved 6000-fold purification and 100-fold concentration of the factor X protein compared to human plasma. The factor X protein was 94%-96% pure. Other residual plasma proteins were well below levels in plasma, minimizing potential interference in hemostasis after therapeutic administration. Effective virus-reduction during manufacture, and the absence of thrombogenicity, toxicity and immunogenic potential were confirmed, addressing the main safety concerns historically associated with plasma-derived therapeutics. The freeze-dried product remained stable between +2°C and +30°C for at least three years. After reconstitution with water for injections, the factor X activity was maintained for at least 48h at +18°C to +22°C. Targeted pre-clinical development of the first highly-purified concentrate to treat hereditary factor X deficiency is described. Following international guidelines for nonclinical safety testing, particular strategies were adopted for unmodified products derived from human blood plasma. This approach may also be relevant to the development of other ultra-orphan medicinal products.

Universal ddPCR-based assay for the determination of lentivirus infectious titer and lenti-modified cell vector copy number

The translation of cell-based therapies from research to clinical setting requires robust analytical methods that successfully adhere to current good manufacturing practices and regulatory guidelines. Lentiviral vectors are commonly used for gene delivery to generate genetically modified therapeutic cell products. For some cell therapy products, standardized characterization assays for potency and safety have gained momentum. Translational applications benefit from assays that can be deployed broadly, such as for lentiviral vectors with various transgenes of interest. Development of a universal method to determine lentivirus infectious titer and vector copy number (VCN) of lenti-modified cells was performed using droplet digital PCR (ddPCR). Established methods relied on a ubiquitous lenti-specific target and a housekeeping gene that demonstrated comparability among flow cytometry-based methods. A linearized plasmid control was used to determine assay linearity/range, sensitivity, accuracy, and limits of quantification. Implementing this assay, infectious titer was assessed for various production runs that demonstrated comparability to the flow cytometry titer. The ddPCR assay described here also indicates suitability in the determination of VCN for genetically modified CAR-T cell products. Overall, the development of these universal assays supports the implementation of standardized characterization methods for quality control.

Progress in the generation of spinal cord organoids over the past decade and future perspectives.

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo. As emerging bioengineering methods have led to the optimization of cell culture protocols, spinal cord organoids technology has made remarkable advancements in the past decade. Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes. Moreover, fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment. These qualities make spinal cord organoids valuable tools for disease modeling, drug screening, and tissue regeneration. By utilizing this emergent technology, researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases. However, at present, spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine. Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

Microbiological Quality of Selected Non-Sterile Pharmaceutical Products Retailed in Anyigba, Kogi State, Nigeria

This study was designed to check for the microbiological quality of non-sterile products retailed in Anyigba. The use of contaminated non-sterile pharmaceutical products can cause hazards in a majority of ways like economic loss to the industrialists, alter the therapeutic effect of the drug and affect the health of a patient. A total of 10 samples were collected; the isolated organisms were characterized and identified by using morphological, cultural and biochemical tests. The organisms isolated were Staphylococcus aureus, E.coli and Pseudomonas spp, Aspergillus spp, Mucorspp, Saccharomyces spp and Rhizopus spp. The percentage of the isolate includes S. aureus 37 (45.7%), E.coli 16 (19.7%) Pseudomonas spp 28 (34.5%) to safeguard the product from contamination, it is important to ensure that good manufacturing practices such as raw material testing, equipment sanitization and automation, microbial testing of water, training of personnel, post marking surveillance, monitoring of environment among others were employed. The focus should also be on surveillance and effective monitoring of the distribution and marketing of pharmaceutical products. Local regulatory agencies such as the Standard Organization of Nigeria (SON), and the National Agency for Food,drug administration and Control (NAFDAC) should always ensure that all pharmaceuticals released into the market for sales and consumption should conform to specifications and are fit for their intended use.

The Growth Potential of Bacillus cereus in Ready-to-Reheat Vegetable Soups

Bacillus cereus (hereafter, B. cereus) poisoning often arises from the consumption of Ready-To-Reheat vegetable soups in which an intensive growth of the vegetative cells of B. cereus take place. The market for these soups is increasing significantly worldwide. For the producer it is important to determine if soups can promote the growth of B. cereus, by calculating its growth potential. We can achieve this goal by carrying out an efficient challenge test. In our study we have designed and performed a challenge test in three batches of an emmer (Triticum monococcum) and vegetable soup that undergo a second pasteurization treatment after packaging. We found out that under refrigeration conditions B. cereus is unable to multiply in the soup, instead, under conditions of thermal abuse, B. cereus can grow during 90 days of shelf life with a growth potential of 0.82 logarithms. It is essential to keep the entire production phase under control using effective GMP (Good Manufacturing Practices) and GHP (Good Hygiene Practices) measures, to ensure that the freshly produced soups contain low loads of the spores of B. cereus. In this way, the vegetative cells born from the germination of the spores cannot reach the infectious dose necessary to induce the food poisoning.

Comparability exercise of critical quality attributes of clinical-grade human mesenchymal stromal cells from the Wharton’s jelly: single-use stirred tank bioreactors versus planar culture systems

Background aimsThe increasing demand of clinical-grade mesenchymal stromal cells (MSCs) for use in advanced therapy medicinal products (ATMPs) require a re-evaluation of manufacturing strategies, ensuring scalability from two-dimensional (2D) surfaces to volumetric (3D) productivities. Herein we describe the design and validation of a Good Manufacturing Practice–compliant 3D culture methodology using microcarriers and 3-L single-use stirred tank bioreactors (STRs) for the expansion of Wharton's jelly (WJ)-derived MSCs in accordance to current regulatory and quality requirements. MethodsMSC,WJ were successfully expanded in 3D and final product characterization was in conformity with Critical Quality Attributes and product specifications previously established for 2D expansion conditions. ResultsAfter 6 days of culture, cell yields in the final product from the 3D cultures (mean 9.48 × 108 ± 1.07 × 107 cells) were slightly lower but comparable with those obtained from 2D surfaces (mean 9.73 × 108 ± 2.36 × 108 cells) after 8 days. In all analyzed batches, viability was >90%. Immunophenotype of MSC,WJ was highly positive for CD90 and CD73 markers and lacked of expression of CD31, CD45 and HLA-DR. Compared with 2D expansions, CD105 was detected at lower levels in 3D cultures due to the harvesting procedure from microcarriers involving trypsin at high concentration, and this had no impact on multipotency. Cells presented normal karyotype and strong immunomodulatory potential in vitro. Sterility, Mycoplasma, endotoxin and adventitious virus were negative in both batches produced. ConclusionsIn summary, we demonstrated the establishment of a feasible and reproducible 3D bioprocess using single-use STR for clinical-grade MSC,WJ production and provide evidence supporting comparability of 3D versus 2D production strategies. This comparability exercise evaluates the direct implementation of using single-use STR for the scale-up production of MSC,WJ and, by extension, other cell types intended for allogeneic therapies.

Quality Assurance: Role in the Pharmaceutical Industry

Quality management system is an integral part of quality assurance. The main purpose of quality standards is to provide consumer satisfaction. Quality management of pharmaceutical products was started with production premises based on the principle of good manufacturing practices (GMP) and Food and Drug Administration (FDA) regulating bodies. Quality policy controls all critical points starting from raw material, in-process check, equipment, production, packaging material, and packing of finished goods till dispatch. The goal of quality assurance is to ensure that pharmaceutical manufacturing is done with safety, identity, quality and compliance with marketing values. It describes various documentation, records, procedures, and implementation of written procedures (SOPs) to maintain uniformity for the proper functioning of the system. The main aim of quality assurance is to prevent defects rather than detection of mistakes. According to ISO, quality management focuses on providing confidence that quality management will be improved. The process of quality assurance is to identify and analyze the information and judge the quality. The principle of quality assurance is on customer focus, leadership, process approach, continual improvement, and mutual benefit between customer and company. Quality assurance is the heart and soul of quality control. It is the sum of quality control and good manufacturing practices and another related quality system. Under the quality system products designed and controlled operations are specified in written form. There is a procedure of self-inspection for the effective evaluation of pharmaceutical quality products. There is regular evaluation and analysis of deviations and incidents, out-of-specification/trends, and change control during the manufacturing of drugs. Quality assurance staff is present everywhere to monitor each activity of the organization. So, it is considered as backbone of pharma companies without this they will be unable to manufacture products

Xeno-free generation of new Yazd human embryonic stem cell lines (Yazd4-7) as a prior stage toward good manufacturing practice of clinical-grade raw materials from discarded embryos: A lab resources report.

Xeno-free generation of human embryonic stem cells (hESCs) is important to prevent potential animal contaminations in culture for advanced cell-based therapeutic applications. Xeno-free production of hESCs is the first step for manufacturing clinical-grade hESC lines. To produce new hESC lines in xeno-free condition. This lab resources report was conducted at Stem Cell Biology Research Center, Yazd, Iran from 2019-2022. 4 new hESC lines from 11 (10 fresh and 1 frozen) donated surplus discarded human embryos were established. In this study, we report the xeno-free derivation of new Yazd hESC lines (Yazd4-7), without using immunosurgery, by culturing intact zona-free blastocysts obtained from discarded embryos onto the YhFF#8 cells as a feeder layer in a microdrop culture system. The pluripotency gene expression profile of the cell lines was assessed by reverse transcription polymerase chain reaction and the expression of specific surface markers was detected using immunofluorescent staining. In vitro differentiation was induced using embryoid body formation and gene expression profile of 3 germ layers and germ cells. Reverse transcriptase polymerase chain reaction was investigated to prove their pluripotent capacity. In sum, we have been able to generate 4 new hESC lines (Yazd4-7) from 11 discarded embryos in xeno-free culture conditions using a micro drop culture system and YhFF#8 as a human source feeder layer. The outcome of this work can be the foundation for the future allogeneic cell-based therapeutic application using clinical grade good manufacturing practice-derived hESC derivatives.

Analysis of Heavy metal, Aflatoxin, Pesticide Residue and Microbial Contamination of Siddha Herbal Formulation Muppirandai Chooranam

Aim: The aim of the study was to evaluate the presence of Heavy metal, Aflatoxin, Pesiticide residue and Microbial contamination of Siddha herbal formulation Muppirandai Chooranam (MRC).
 Place of study: Heavy metal analysis, Aflatoxin assay, Pesiticide residue, Microbial contamination analysis were conducted at Noble Research Solutions, Kolathur, Chennai -99.
 Methodology: The Siddha formulation Muppirandai Chooranam was prepared as per Good Manufacturing Practices(GMP) guidelines and the Heavy metal analysis, Aflatoxin assay, Pesiticide residue, Microbial contamination analysis were conducted at Noble Research Solutions, Kolathur, Chennai -99. 
 Results: The results of Heavy metal analysis of Muppirandai Chooranam (MRC) shown the presence of Lead at 3.54 PPM and Arsenic, Cadmium, Mercury at Below Detection Limit (BDL). Aflatoxin assay of MRC shown the absence of Aflatoxin B1, Aflatoxin B2, Aflatoxin G1, Aflatoxin G2. Pesticide residue analysis showed that there were no traces of Pesticide residues such as Organo chlorine, Organo phosphorus, Organo carbamates and Pyrethroids. In Microbial contamination analysis, Test for Specific Pathogen shown the absence of Organisms E-coli, Salmonella, Staphylococcus Aureus, Pseudomonas Aeruginosa and No Bacterial and fungal growth or colonies were observed in the Sterility test of MRC as per the methods of AYUSH specifications.
 Conclusion: From the results, it is concluded that the study medicine MRC has Heavy metal content below the permissible limit as per PLIM guidelines of AYUSH, and the sample were free from Aflatoxins, Pesiticides, Microbes, and Specific Pathogens which ensures that the study medicine Muppirandai Chooranam was safe therapeutically.

Good Manufacturing Practice (GMP) in Tofu MSMEs in North Aceh

This study examined tofu MSMEs in Lhokseumawe City and the North Aceh District. Observations indicate discrepancies between tofu production and the GMP requirements for Good Manufacturing Practices. The amount that the tofu sector has adopted appropriate food production procedures by the Regulation of the Ministry of Sector of the Republic of Indonesia Number 75/M-IND/PER/7/2010 is determined using a GMP approach. This research is anticipated to improve the product safety of the tofu industry and provide recommendations for improvement. In this study, data collection techniques included candid interviews related to the GMP aspect questionnaire consisting of 11 inspection aspects, direct field observation of 21 MSMEs by marking the location conditions, production equipment, and materials used, and following the processing process, followed by a search for deviations from GMP aspects and comparison with the literature review, documentation of the necessary data related to GMP assessment, and a search for relevant literature. According to the evaluation, 12 MSMEs with a value range of 41% to 60% fell into the category of not meeting the requirements. The second criterion is extremely inadequate, ranging from 21% to 40% for five MSMEs. Additionally, the criteria for sufficient completion with a range of values between 61% and 80% for up to 4 MSMEs led to an evaluation of 11 GMP aspects in 21 MSMEs. Know on the location aspect with a percentage of 71% in the sufficient category, building aspects with a percentage of 11% in the critical category, aspects of sanitation with a percentage of 40% in the category of very less fulfilling, aspects of machinery and equipment with a percentage of 80% in the category of sufficiently fulfilling, aspects of materials with a percentage of 100% in the category of fulfilling, and aspects of supervision with a percentage of 40% in the category of fulfilling.

Microbial Quality Evaluation of Seafood Samples from the Vishakhapatnam Coast, Andhra Pradesh, India

Consumption of seafood has increased, resulting in the production and productivity of aquaculture in the past few years. Since, seafood is crucial in human nutrition, providing essential nutrients and proteins. However, their perishable nature and vulnerability to microbial contamination make them prone to spoilage and foodborne illnesses. Therefore, the microbiological analysis of fish samples is paramount to ensure their quality and safety for consumption. In this study, microbiology of fish samples, encompassing various aspects such as microbial load assessment, and pathogen detection. Isolation and identification of pathogenic bacteria viz., Total plate count, Escherichia coli, Total coliforms, Vibrio spp, Staphylococcus aureus, and Salmonella spp. These pathogens pose severe health risks to consumers and highlight the necessity of effective monitoring and control measures throughout the seafood supply chain. Proper handling, storage, and processing practices minimise microbial contamination and preserve fish quality. Implementing Hazard Analysis Critical Control Point (HACCP) plans and Good Manufacturing Practices (GMP) helps ensure the safety of fish products and prevent outbreaks of foodborne illnesses.

Quality of medicines in Sri Lanka: a retrospective review of safety alerts

BackgroundMany medicine quality problems are detected after they arrive at health facilities. Thus, critically defective medicines that may pose health risks to patients need to be withheld or recalled.AimsTo investigate the withheld and recalled medicines in relation to the types of defects, their total numbers, therapeutic categories, pharmaceutical dosage forms, and country of manufacturer during the study period.MethodsA retrospective review was performed on withheld and recalled medicines published on the publicly available National Medicines Regulatory Authority (NMRA) official website in Sri Lanka between June 2018 and August 2021. Details on substandard medicines (SM) were extracted and documented. Each record of SM was individually reviewed to determine the type of defect, subsequent action taken by NMRA, therapeutic category, pharmaceutical dosage form, and country of manufacturer.ResultsA total of 163 defects were identified in 143 defective medicines, among which the most common types of defects were contamination (n = 59, 36.2%), stability defects (n = 41, 25.2%), packaging and labelling defects (n = 27, 16.6%) and active pharmaceutical ingredient defects (n = 26, 15.9%). Out of 143 total defective medicines identified, anti-infectives accounted for 41.9%, while parenteral preparations (44.0%) were found to be frequently defective. Nearly 70% of the recalled and withheld medicines were of Indian origin, and some manufacturers were identified to be repeatedly involved.ConclusionsThis study revealed that contamination was the most frequent cause of defective medicines, while parenteral preparations and anti-infectives were the most susceptible pharmaceutical dosage form and therapeutic category found to be substandard, respectively. In addition, the findings show that some manufacturers were accountable for repetitive withholdings and recalls, which reflects the ignorance of quality control measures and weak regulatory inspections as a violation of Good Manufacturing Practice (GMP).

Truncated vitronectin with E-cadherin enables the xeno-free derivation of human embryonic stem cells

Human embryonic stem cells (hESCs) have unique abilities that enable their use in cell therapy, disease modeling, and drug development. Their derivation is usually performed using a feeder layer, which is undefined and can potentially cause a contamination by xeno components, therefore there is a tendency to replace feeders with xeno-free defined substrates in recent years. Three hESC lines were successfully derived on the vitronectin with a truncated N-terminus (VTN-N) in combination with E-cadherin in xeno-free conditions for the first time, and their undifferentiated state, hESC morphology, and standard karyotypes together with their potential to differentiate into three germ layers were confirmed. These results support the conclusion that the VTN-N/E-cadherin is a suitable substrate for the xeno-free derivation of hESCs and can be used for the derivation of hESCs according to good manufacturing practices.

Application of visible near-infrared spectroscopy combined with colorimetric sensor array for the aroma quality evaluation in tencha drying process

The drying process is a critical stage in developing the aroma quality of tencha. In our research, visible near infrared (Vis-NIR) and colorimetric sensor array (Vis-NIR-CSA) were used for evaluating the aroma quality of tencha drying process. Vis-NIR recorded the spectral signal of CSA after the reaction in samples. Subsequently, the aroma quality was predicted by a combination of different data fusion strategies and classification and regression tree (CART) in tencha drying process. The high-level fusion strategy showed the best performance, with calibration and prediction set accuracy of 94.68% and 93.48%, respectively. The results indicated that Vis-NIR-CSA combined with high-level data fusion could be applied satisfactorily in the aroma quality evaluation of tencha. Moreover, pentanal was identified to be highly correlated with aroma quality during tencha drying process, which verified the sensor identification results. This study contributed to controlling good manufacturing practices and designing optimal tencha processing systems.

Radionuclide Cisternography with [64Cu]Cu-DOTA.

Radionuclide cisternography (RNC) is a method for conducting imaging of the cerebrospinal system and can be used to identify cerebrospinal fluid leaks. So far, RNC has commonly employed radiopharmaceutical agents suitable only for single-photon emission tomography techniques, which are thus lacking in terms of image resolution and can potentially lead to false-negative results. Therefore, [64Cu]Cu-DOTA was investigated as an alternative radiopharmaceutical for RNC, employing positron emission tomography (PET) instead of single-photon emission tomography. A formulation of [64Cu]Cu-DOTA was produced according to the guidelines for good manufacturing practice. The product met the requirements of agents suitable for intrathecal application. [64Cu]Cu-DOTA was administered to a patient and compared to the approved scintigraphic RNC agent, [111In]In-DTPA. While no cerebrospinal fluid leak was detected with [111In]In-DTPA, [64Cu]Cu-DOTA RNC exhibited a posterolateral leak between the vertebral bodies C1 and C2. Thus, in this patient, PET RNC with [64Cu]Cu-DOTA was superior to RNC with [111In]In-DTPA. Since radiopharmaceuticals have a very good safety profile regarding the occurrence of adverse events, PET RNC with [64Cu]Cu-DOTA may become an attractive alternative to scintigraphic methods, and also to computed tomography or magnetic resonance imaging, which often require contrast agents, causing adverse events to occur much more frequently.