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Drug Discovery Today Jun 2024To introduce products in the US market, pharmaceutical companies must first obtain FDA clearance. Manufacturers might recall a product if it poses a risk of damage or... (Review)
Review
To introduce products in the US market, pharmaceutical companies must first obtain FDA clearance. Manufacturers might recall a product if it poses a risk of damage or violates FDA regulations. This study investigates the types, causes and consequences of recalls, as well as FDA participation and suitable recall strategies. We relied on the FDA website to gather recall data sets from 2012 to 2023, collecting information on the date of issuance, company and type of violation. The most frequent causes for recalls were sterility issues and inadequate compliance with current good manufacturing practices (cGMP). An examination of sterility recalls revealed two primary causes: a lack of assurance in sterility (accounting for 48% of recalls) and instances of non-sterility (making up 45% of recalls). A thorough examination of cGMP recalls revealed five primary types of violations: process control issues, inadequate storage practices, manufacturing problems, the presence of nitroso-amine impurities and concerns regarding stability. The findings demonstrate that sterility and cGMP compliance are FDA priorities. Pharmaceutical companies must, therefore, enhance quality compliance and create effective quality management systems that oversee the manufacturing process, quality control, personnel training and documentation to avoid these recalls. Companies should establish an internal compliance checklist and be prepared for the rectification process.
Topics: United States; United States Food and Drug Administration; Drug Industry; Drug Recalls; Humans; Retrospective Studies
PubMed: 38670257
DOI: 10.1016/j.drudis.2024.103993 -
Proceedings. IEEE International... Dec 2023Tandem mass spectrometry (MS/MS) stands as the predominant high-throughput technique for comprehensively analyzing protein content within biological samples. This...
Tandem mass spectrometry (MS/MS) stands as the predominant high-throughput technique for comprehensively analyzing protein content within biological samples. This methodology is a cornerstone driving the advancement of proteomics. In recent years, substantial strides have been made in Data-Independent Acquisition (DIA) strategies, facilitating impartial and non-targeted fragmentation of precursor ions. The DIA-generated MS/MS spectra present a formidable obstacle due to their inherent high multiplexing nature. Each spectrum encapsulates fragmented product ions originating from multiple precursor peptides. This intricacy poses a particularly acute challenge in de novo peptide/protein sequencing, where current methods are ill-equipped to address the multiplexing conundrum. In this paper, we introduce Casanovo-DIA, a deep-learning model based on transformer architecture. It deciphers peptide sequences from DIA mass spectrometry data. Our results show significant improvements over existing STOA methods, including DeepNovo-DIA and PepNet. Casanovo-DIA enhances precision by 15.14% to 34.8%, recall by 11.62% to 31.94% at the amino acid level, and boosts precision by 59% to 81.36% at the peptide level. Integrating DIA data and our Casanovo-DIA model holds considerable promise to uncover novel peptides and more comprehensive profiling of biological samples. Casanovo-DIA is freely available under the GNU GPL license at https://github.com/Biocomputing-Research-Group/Casanovo-DIA.
PubMed: 38665266
DOI: 10.1109/bibe60311.2023.00013 -
Current Research in Food Science 2024The traceability of geographic origin is essential for guaranteeing the quality, safety, and protection of oyster brands. However, the current outcomes of traceability...
The traceability of geographic origin is essential for guaranteeing the quality, safety, and protection of oyster brands. However, the current outcomes of traceability lack credibility as they do not adequately explain the model's predictions. Consequently, we conducted a study to evaluate the efficacy of utilizing explainable machine learning combined with mineral elements analysis. The study findings revealed that 18 elements have the ability to determine regional orientation. Simultaneously, individuals should pay closer attention to the potential risks associated with oyster consumption due to the regional differences in essential and toxic elements they contain. Light gradient boosting machine (LightGBM) model exhibited indistinguishable performance, achieving flawless accuracy, precision, recall, F1 score and AUC, with values of 96.77%, 96.43%, 98.53%, 97.32% and 0.998, respectively. The SHapley Additive exPlanations (SHAP) method was used to evaluate the output of the LightGBM model, revealing differences in feature interactions among oysters from different provinces. Specifically, the features Na, Zn, V, Mg, and K were found to have a significant impact on the predictive process of the model. Consistent with existing research, the use of explainable machine learning techniques can provide insights into the complex connections between important product attributes and relevant geographical information.
PubMed: 38659973
DOI: 10.1016/j.crfs.2024.100738 -
ArXiv Apr 2024Tandem mass spectrometry (MS/MS) stands as the predominant high-throughput technique for comprehensively analyzing protein content within biological samples. This...
Tandem mass spectrometry (MS/MS) stands as the predominant high-throughput technique for comprehensively analyzing protein content within biological samples. This methodology is a cornerstone driving the advancement of proteomics. In recent years, substantial strides have been made in Data-Independent Acquisition (DIA) strategies, facilitating impartial and non-targeted fragmentation of precursor ions. The DIA-generated MS/MS spectra present a formidable obstacle due to their inherent high multiplexing nature. Each spectrum encapsulates fragmented product ions originating from multiple precursor peptides. This intricacy poses a particularly acute challenge in de novo peptide/protein sequencing, where current methods are ill-equipped to address the multiplexing conundrum. In this paper, we introduce DiaTrans, a deep-learning model based on transformer architecture. It deciphers peptide sequences from DIA mass spectrometry data. Our results show significant improvements over existing STOA methods, including DeepNovo-DIA and PepNet. DiaTrans enhances precision by 15.14% to 34.8%, recall by 11.62% to 31.94% at the amino acid level, and boosts precision by 59% to 81.36% at the peptide level. Integrating DIA data and our DiaTrans model holds considerable promise to uncover novel peptides and more comprehensive profiling of biological samples. DiaTrans is freely available under the GNU GPL license at https://github.com/Biocomputing-Research-Group/DiaTrans.
PubMed: 38659639
DOI: No ID Found -
BMJ (Clinical Research Ed.) Apr 2024
Topics: Humans; Antitussive Agents; Drug Recalls; Cough; Africa
PubMed: 38649184
DOI: 10.1136/bmj.q923 -
PLoS Neglected Tropical Diseases Apr 2024Filariasis, a neglected tropical disease caused by roundworms, is a significant public health concern in many tropical countries. Microscopic examination of blood...
Filariasis, a neglected tropical disease caused by roundworms, is a significant public health concern in many tropical countries. Microscopic examination of blood samples can detect and differentiate parasite species, but it is time consuming and requires expert microscopists, a resource that is not always available. In this context, artificial intelligence (AI) can assist in the diagnosis of this disease by automatically detecting and differentiating microfilariae. In line with the target product profile for lymphatic filariasis as defined by the World Health Organization, we developed an edge AI system running on a smartphone whose camera is aligned with the ocular of an optical microscope that detects and differentiates filarias species in real time without the internet connection. Our object detection algorithm that uses the Single-Shot Detection (SSD) MobileNet V2 detection model was developed with 115 cases, 85 cases with 1903 fields of view and 3342 labels for model training, and 30 cases with 484 fields of view and 873 labels for model validation before clinical validation, is able to detect microfilariae at 10x magnification and distinguishes four species of them at 40x magnification: Loa loa, Mansonella perstans, Wuchereria bancrofti, and Brugia malayi. We validated our augmented microscopy system in the clinical environment by replicating the diagnostic workflow encompassed examinations at 10x and 40x with the assistance of the AI models analyzing 18 samples with the AI running on a middle range smartphone. It achieved an overall precision of 94.14%, recall of 91.90% and F1 score of 93.01% for the screening algorithm and 95.46%, 97.81% and 96.62% for the species differentiation algorithm respectively. This innovative solution has the potential to support filariasis diagnosis and monitoring, particularly in resource-limited settings where access to expert technicians and laboratory equipment is scarce.
Topics: Artificial Intelligence; Microscopy; Humans; Animals; Filariasis; Microfilariae; Algorithms; Smartphone; Elephantiasis, Filarial
PubMed: 38630833
DOI: 10.1371/journal.pntd.0012117 -
The Lancet. Infectious Diseases Apr 2024There is no vaccine against the major global pathogen Chlamydia trachomatis; its different serovars cause trachoma in the eye or chlamydia in the genital tract. We did a...
An investigation of trachoma vaccine regimens by the chlamydia vaccine CTH522 administered with cationic liposomes in healthy adults (CHLM-02): a phase 1, double-blind trial.
BACKGROUND
There is no vaccine against the major global pathogen Chlamydia trachomatis; its different serovars cause trachoma in the eye or chlamydia in the genital tract. We did a clinical trial administering CTH522, a recombinant version of the C trachomatis major outer membrane molecule, in different dose concentrations with and without adjuvant, to establish its safety and immunogenicity when administered intramuscularly, intradermally, and topically into the eye, in prime-boost regimens.
METHODS
CHLM-02 was a phase 1, double-blind, randomised, placebo-controlled trial at the National Institute for Health Research Imperial Clinical Research Facility, London, UK. Participants were healthy men and non-pregnant women aged 18-45 years, without pre-existing C trachomatis genital infection. Participants were assigned into six groups by the electronic database in a pre-prepared randomisation list (A-F). Participants were randomly assigned (1:1:1:1:1) to each of the groups A-E (12 participants each) and 6 were randomly assigned to group F. Investigators were masked to treatment allocation. Groups A-E received investigational medicinal product and group F received placebo only. Two liposomal adjuvants were compared, CAF01 and CAF09b. The groups were intramuscular 85 μg CTH522-CAF01, or placebo on day 0 and two boosters or placebo at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (A); intramuscular 85 μg CTH522-CAF01, two boosters at day 28 and 112 with additional topical ocular administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (B); intramuscular 85 μg CTH522-CAF01, two boosters at day 28 and 112 with additional intradermal administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (C); intramuscular 15 μg CTH522-CAF01, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (D); intramuscular 85 μg CTH522-CAF09b, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (E); intramuscular placebo (F). The primary outcome was safety; the secondary outcome (humoral immunogenicity) was the percentage of trial participants achieving anti-CTH522 IgG seroconversion, defined as four-fold and ten-fold increase over baseline concentrations. Analyses were done as intention to treat and as per protocol. The trial is registered with ClinicalTrials.gov, NCT03926728, and is complete.
FINDINGS
Between Feb 17, 2020 and Feb 22, 2022, of 154 participants screened, 65 were randomly assigned, and 60 completed the trial (34 [52%] of 65 women, 46 [71%] of 65 White, mean age 26·8 years). No serious adverse events occurred but one participant in group A2 discontinued dosing after having self-limiting adverse events after both placebo and investigational medicinal product doses. Study procedures were otherwise well tolerated; the majority of adverse events were mild to moderate, with only seven (1%) of 865 reported as grade 3 (severe). There was 100% four-fold seroconversion rate by day 42 in the active groups (A-E) and no seroconversion in the placebo group. Serum IgG anti-CTH522 titres were higher after 85 μg CTH522-CAF01 than 15 μg, although not significantly (intention-to-treat median IgG titre ratio groups A-C:D=5·6; p=0·062), with no difference after three injections of 85 μg CTH522-CAF01 compared with CTH522-CAF09b (group E). Intradermal CTH522 (group C) induced high titres of serum IgG anti-CTH522 neutralising antibodies against serovars B (trachoma) and D (urogenital). Topical ocular CTH522 (group B) at day 28 and 112 induced higher total ocular IgA compared with baseline (p<0·001). Participants in all active vaccine groups, particularly groups B and E, developed cell mediated immune responses against CTH522.
INTERPRETATION
CTH522, adjuvanted with CAF01 or CAF09b, is safe and immunogenic, with 85 μg CTH522-CAF01 inducing robust serum IgG binding titres. Intradermal vaccination conferred systemic IgG neutralisation breadth, and topical ocular administration increased ocular IgA formation. These findings indicate CTH522 vaccine regimens against ocular trachoma and urogenital chlamydia for testing in phase 2, clinical trials.
FUNDING
The EU Horizon Program TRACVAC.
PubMed: 38615673
DOI: 10.1016/S1473-3099(24)00147-6 -
Frontiers in Nutrition 2024Dairy products and fermented foods have a reported association with maintained cognitive function. Camembert cheese, a dairy product fermented by the white mold , has...
Milk-based culture of and its component oleamide affect cognitive function in healthy elderly Japanese individuals: a multi-arm randomized, double-blind, placebo-controlled study.
Dairy products and fermented foods have a reported association with maintained cognitive function. Camembert cheese, a dairy product fermented by the white mold , has also been shown to enhance cognitive function . Oleamide, derived from the fermentation of the white mold, is a candidate for an active component, and expected to improve both cognitive function and sleep conditions. Thus, this study investigated whether the milk-based culture of white mold (MCW), and oleamide, could improve cognitive function and sleep state clinically. A multi-arm randomized, double-blind, placebo-controlled trial was conducted in Tokyo, Japan. 60 healthy Japanese individuals aged 50-75 who were aware of their cognitive decline were randomly and equally divided into three groups of 20 participants using computer-generated random numbers. Participants took either MCW (equivalent to 60 μg/day of oleamide), 60 μg/day of oleamide, or placebo capsules for 12 weeks. Serum BDNF, cognitive function by Cognitrax as primary and MCI Screen as secondary outcome, and sleep status using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) were assessed before and after intervention. The participants, outcome assessors and analysts, and research assistants were blinded to the group assignment. Of the 60 participants, 58 completed the study and were analyzed. No adverse events related to test foods were observed. The placebo group showed a negative rate of change in serum BDNF (-10.5% ± 19.7%), whereas the MCW and oleamide groups showed positive changes (2.0% ± 27.1% and 1.3% ± 13.5%, respectively). Cognitrax scores increased after 12 weeks in all groups. Conversely, the MPI score of the MCI Screen demonstrated a significant improvement in the MCW and oleamide groups compared to the placebo group ( = 0.013 and < 0.001, respectively). The subscales, immediate free recall and delayed free recall, also significantly increased in them compared to the placebo group. Although PSQI-J revealed no significant differences among groups, the MCW and oleamide groups showed significant improvement after intervention in overall score, subjective sleep quality, and sleep latency. Our results suggest that MCW and its component, oleamide, are safe and contribute to maintaining cognitive functions, particularly short-term and working memory, and improving sleep state. : https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054792, identifier UMIN-CTR UMIN000048084.
PubMed: 38600994
DOI: 10.3389/fnut.2024.1357920 -
F1000Research 2023Enteric coating films in acidic labile tablets protect the drug molecule from the acidic environment of the stomach. However, variations in the excipients used in the...
Enteric coating films in acidic labile tablets protect the drug molecule from the acidic environment of the stomach. However, variations in the excipients used in the coating formulation may affect their ability to provide adequate protection. This study is the first to investigate the potential effects of coating materials on the protective functionality of enteric coating films for pantoprazole (PNZ) generic tablets after their recall from the market. A comparative analysis was conducted between generic and branded PNZ products, using pure drug powder for identification. The release of the drug was evaluated in different pH media. The study also utilized various analytical and thermal techniques, including differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), and confocal Raman microscopy. The assessment results revealed significant variations in the release profile for the generic product in acidic media at 120 min. DSC and TGA thermal profile analyses showed slight variation between the two products. XRD analysis exhibited a noticeable difference in peak intensity for the generic sample, while SEM revealed smaller particle sizes in the generic product. The obtained spectra profile for the generic product displayed significant variation in peaks and band intensity, possibly due to impurities. These findings suggest that the excipients used in the enteric coating film of the generic product may have affected its protective functionality, leading to premature drug release in acidic media. Additionally, the presence of polysorbate 80 (P-80) in the brand product might improve the properties of the enteric coating film due to its multi-functionality. : In conclusion, the excipients used in the brand product demonstrated superior functionality in effectively protecting the drug molecule from acidic media through the enteric coating film, as compared to the generic version.
Topics: Pantoprazole; Drug Liberation; Excipients; Solubility; Tablets; Stomach
PubMed: 38596002
DOI: 10.12688/f1000research.140607.1 -
Therapeutic Innovation & Regulatory... Jul 2024This study aims to explore the characteristics of drug recall announcements issued over six years by the SFDA in Saudi Arabia. Additionally, to examine the patterns of...
PURPOSE
This study aims to explore the characteristics of drug recall announcements issued over six years by the SFDA in Saudi Arabia. Additionally, to examine the patterns of voluntary drug recall requests by pharmaceutical companies (both innovator and generic) in response to product defects.
METHODS
A retrospective data analysis was conducted on drug recall announcements issued by the SFDA between 2017 and December 2022. The study included recalls of registered and unregistered drugs posted on the SFDA Drugs Circulars and Withdrawal webpage. Descriptive analysis was performed on relevant variables: recall year, therapeutic class, recall type, pharmaceutical company type, recall reasons and voluntary or involuntary product defect reports.
RESULTS
During the study period, a total of 371 products were recalled, with the majority being involuntary recalls (82.4%). About two-thirds of the recalls (66.0%) were related to registered products. The most common reasons for recalls were non-compliance with the manufacturer's specifications (33.2%), contamination (23.7%), and violations (20.5%). A total of 109 pharmaceutical companies were associated with the recalled products, with (85.3%) being generic pharmaceutical companies. The majority of innovator pharmaceutical companies (68.8%) requested voluntary drug recalls of defective products. Innovator pharmaceutical companies requested voluntary recalls more often than generic pharmaceutical companies.
CONCLUSION
The study findings highlight the most frequent causes of drug recalls and the patterns of voluntary recall requests by pharmaceutical companies. Non-compliance with manufacturer's specifications was the most common reason for recalls. Significantly, more innovative pharmaceutical companies request voluntary recalls for product defects compared to generic pharmaceutical companies.
Topics: Saudi Arabia; Drug Recalls; Retrospective Studies; Humans; Drug Industry; Product Recalls and Withdrawals
PubMed: 38546962
DOI: 10.1007/s43441-024-00635-4