Drug Administration Center Research Articles

FDA and industry collaboration: Identifying opportunities to further reduce reliance on nonhuman primates for nonclinical safety evaluations

The nonhuman primate (NHP) has always been a limited resource for pharmaceutical research with ongoing efforts to conserve. This is due to their inherent biological properties, the growth in biotherapeutics and other modalities, and their use in small molecule drug development. The SARS-CoV-2 pandemic has significantly impacted the availability of NHPs due to the immediate need for NHPs to develop COVID-19 vaccines and treatments and the China NHP export ban; thus, accelerating the need to further replace, reduce and refine (3Rs) NHP use. The impact of the NHP shortage on drug development led DruSafe, BioSafe, and the United States (U.S.) Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) to discuss this issue at their 2021 annual meeting. This meeting identified areas to further the 3Rs in NHP use within the current nonclinical safety evaluation regulatory framework and highlighted the need to continue advancing alternative methods towards the aspirational goal to replace use of NHPs in the long term. Alignment across global health authorities is necessary for implementation of approaches that fall outside existing guidelines. This article captures the proceedings from this meeting highlighting current best practices and areas for 3Rs in NHP use.

Nicotine Gummies, Tablets Popular Among Adolescents

Back to table of contents Previous article Next article Clinical & ResearchFull AccessNicotine Gummies, Tablets Popular Among AdolescentsNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:24 Nov 2022https://doi.org/10.1176/appi.pn.2022.12.11.14AbstractA recent survey conducted at Southern California high schools found that over 3% of 9th and 10th graders have tried nontherapeutic nicotine gum, gummies, tablets, or lozenges.iStock/brazzoA recent survey of high schoolers in Southern California has found that nontherapeutic oral nicotine products such as tablets or gummies are popular among adolescents, ranking only second in use to e-cigarettes. The survey findings were published in Pediatrics.“Nontherapeutic nicotine gums, lozenges, tablets, and gummies have a number of features that could potentially attract youth,” said Alyssa F. Harlow, Ph.D., a postdoctoral scholar at the Keck School of Medicine at the University of Southern California (USC) who led the survey. “These products resemble candy and are highly discreet, making them easy to hide.” The act of popping a piece of gum or candy in the mouth might also feel less risky to an adolescent than inhaling nicotine, the researchers noted in the Pediatrics paper.The decision to add questions about nicotine products to an ongoing behavioral health survey of adolescents across seven school districts in Southern California arose after the researchers noticed increased marketing of these products on social media and other platforms. The survey included questions about nicotine pouches (which are placed in between the lip and gums like snus, but are filled with cellulose, nicotine salt, and flavorings rather than shredded tobacco), as well as nicotine gums, lozenges, tablets, and gummies.The youth were also asked about their use of combustible cigarettes, e-cigarettes, snus, cigars, little cigars or cigarillos, and hookahs or waterpipes.The researchers analyzed the responses of 3,516 9th and 10th graders who completed the survey between September 30 and December 14, 2021.Overall, e-cigarette use was the most prevalent among the respondents, with 9.6% of students reporting ever vaping and 5.5% vaping in the past six months. The use of oral nicotine products (not including nicotine pouches) was second most prevalent among the youth, with 3.1% of students reporting ever use and 1.4% reporting past six-month use.The reported use of all other products (including nicotine pouches) was lower than 1%. In the paper, Harlow and colleagues suggested pouches might seem less appealing to use or possibly more difficult to access than other nicotine or tobacco products. But as pouches are also heavily marketed and come in fruit flavors, continued monitoring of these products is also warranted, they wrote.“Since there have been no prior estimates of the use of these oral products, we had no exact idea of what to expect,” Harlow said. Still, she said her team was a little surprised to see that adolescents were using oral nicotine products more than other tobacco-based products.The researchers also found that the use of any oral nicotine product (including nicotine pouches) was more likely among Hispanic teens; females; and teens identifying as transgender, nonbinary, or a sexual minority.Shortly after the publication of the study, the Food and Drug Administration (FDA) issued its first warning letter to a company for illegally marketing flavored nicotine gummies without FDA authorization. In a statement, FDA Commissioner Robert M. Califf, M.D., acknowledged that these oral products “are a public health crisis just waiting to happen to our nation’s youth.” The company has since discontinued its line of flavored nicotine gummies.Harlow hopes her group’s findings serve as a call to action for groups involved in health surveillance. “National surveys documenting trends in the use of these oral products are a must,” she said. Such data could help researchers to better understand when youth start using these products, which groups are most vulnerable, and if use of oral products leads to other illicit substance use.Harlow and colleagues noted that in their analysis, over 77% of the adolescents who reported using oral nicotine products also reported a history of using other nicotine products, but the survey did not identify which products were initiated first.Richard Miech, Ph.D., M.P.H., a research professor at the University of Michigan Institute for Social Research, told Psychiatric News that beginning in 2023 many more high school students will be asked about use of nicotine products as part of the Monitoring the Future survey. Miech is the principal investigator for this national survey, which is funded by the National Institute on Drug Abuse.Miech thinks the use of these products has the potential to skyrocket, so his team is planning on watching the usage trends closely.This study was supported by awards from the National Cancer Institute; National Institute on Drug Abuse; National Heart, Lung and Blood Institute; and Food and Drug Administration Center for Tobacco Products. ■Resources“Adolescent Use of Flavored Non-Tobacco Oral Nicotine Products”The warning letter from the FDA ISSUES NewArchived

Clinicians' Perceptions of an Artificial Intelligence-Based Blood Utilization Calculator: Qualitative Exploratory Study.

According to the US Food and Drug Administration Center for Biologics Evaluation and Research, health care systems have been experiencing blood transfusion overuse. To minimize the overuse of blood product transfusions, a proprietary artificial intelligence (AI)-based blood utilization calculator (BUC) was developed and integrated into a US hospital's electronic health record. Despite the promising performance of the BUC, this technology remains underused in the clinical setting. This study aims to explore how clinicians perceived this AI-based decision support system and, consequently, understand the factors hindering BUC use. We interviewed 10 clinicians (BUC users) until the data saturation point was reached. The interviews were conducted over a web-based platform and were recorded. The audiovisual recordings were then anonymously transcribed verbatim. We used an inductive-deductive thematic analysis to analyze the transcripts, which involved applying predetermined themes to the data (deductive) and consecutively identifying new themes as they emerged in the data (inductive). We identified the following two themes: (1) workload and usability and (2) clinical decision-making. Clinicians acknowledged the ease of use and usefulness of the BUC for the general inpatient population. The clinicians also found the BUC to be useful in making decisions related to blood transfusion. However, some clinicians found the technology to be confusing due to inconsistent automation across different blood work processes. This study highlights that analytical efficacy alone does not ensure technology use or acceptance. The overall system's design, user perception, and users' knowledge of the technology are equally important and necessary (limitations, functionality, purpose, and scope). Therefore, the effective integration of AI-based decision support systems, such as the BUC, mandates multidisciplinary engagement, ensuring the adequate initial and recurrent training of AI users while maintaining high analytical efficacy and validity. As a final takeaway, the design of AI systems that are made to perform specific tasks must be self-explanatory, so that the users can easily understand how and when to use the technology. Using any technology on a population for whom it was not initially designed will hinder user perception and the technology's use.

Lung mitochondrial DNA copy number, inflammatory biomarkers, gene transcription and gene methylation in vapers and smokers.

SummaryBackgroundMitochondrial DNA copy number (mtCN) maintains cellular function and homeostasis, and is linked to nuclear DNA methylation and gene expression. Increased mtCN in the blood is associated with smoking and respiratory disease, but has received little attention for target organ effects for smoking or electronic cigarette (EC) use.MethodsBronchoscopy biospecimens from healthy EC users, smokers (SM), and never-smokers (NS) were assessed for associations of mtCN with mtDNA point mutations, immune responses, nuclear DNA methylation and gene expression using linear regression. Ingenuity pathway analysis was used for enriched pathways. GEO and TCGA respiratory disease datasets were used to explore the involvement of mtCN-associated signatures.FindingsmtCN was higher in SM than NS, but EC was not statistically different from either. Overall there was a negative association of mtCN with a point mutation in the D-loop but no difference within groups. Positive associations of mtCN with IL-2 and IL-4 were found in EC only. mtCN was significantly associated with 71,487 CpGs and 321 transcripts. 263 CpGs were correlated with nearby transcripts for genes enriched in the immune system. EC-specific mtCN-associated-CpGs and genes were differentially expressed in respiratory diseases compared to controls, including genes involved in cellular movement, inflammation, metabolism, and airway hyperresponsiveness.InterpretationSmoking may elicit a lung toxic effect through mtCN. While the impact of EC is less clear, EC-specific associations of mtCN with nuclear biomarkers suggest exposure may not be harmless. Further research is needed to understand the role of smoking and EC-related mtCN on lung disease risks.FundingThe National Cancer Institute, the National Heart, Lung, and Blood Institute, the Food and Drug Administration Center for Tobacco Products, the National Center For Advancing Translational Sciences, and Pelotonia Intramural Research Funds.

The importance of harmful and potentially harmful constituents in the implementation of the 2009 US Family Smoking Prevention and Tobacco Control Act.

Implementing the 2009 US Tobacco Control Act established a new infrastructure for tobacco and nicotine science. At its heart is the Food and Drug Administration (FDA) Center for Tobacco Products (CTP). A key challenge facing FDA CTP is determining whether nicotine products are "appropriate to the protection of the public health," and this is the central component of the Premarket Tobacco Application (PMTA) and Modified Risk Tobacco Application (MRTP) processes. CTP has granted such marketing orders for only a few products but has been consistent in its reasoning: the applicant demonstrated that the product(s) has low levels of Harmful and Potentially Harmful Constituents (HPHCs). By doing so, FDA has equated low levels of HPHCs with public health benefit. Other factors will be increasingly important, but the regulatory history indicates that no product will be granted a marketing order unless it has low levels of HPHCs. This science-driven regulatory approach has been possible due to the rapid evolution of the knowledge base and expansion of scientific human resources, including establishment of a robust CTP Office of Science to evaluate the extensive dossiers that manufacturers must submit. Companies therefore established internal regulatory science programs, and contract research organizations developed capabilities needed to support regulatory dossiers. This article focuses on the chemistry and toxicology part of the regulatory science process and also presents the industry side of the regulatory process by examining the experience of one company-Swedish Match-that was granted the first PMTA and MRTP marketing authorizations.

A Versatile and Scalable Platform That Streamlines Data Collection for Patient-Centered Studies: Usability and Feasibility Study.

BackgroundThe Food and Drug Administration Center for Biologics Evaluation and Research (CBER) established the Biologics Effectiveness and Safety (BEST) Initiative with several objectives, including the expansion and enhancement of CBER’s access to fit-for-purpose data sources, analytics, tools, and infrastructures to improve the understanding of patient experiences with conditions related to CBER-regulated products. Owing to existing challenges in data collection, especially for rare disease research, CBER recognized the need for a comprehensive platform where study coordinators can engage with study participants and design and deploy studies while patients or caregivers could enroll, consent, and securely participate as well.ObjectiveThis study aimed to increase awareness and describe the design, development, and novelty of the Survey of Health and Patient Experience (SHAPE) platform, its functionality and application, quality improvement efforts, open-source availability, and plans for enhancement.MethodsSHAPE is hosted in a Google Cloud environment and comprises 3 parts: the administrator application, participant app, and application programming interface. The administrator can build a study comprising a set of questionnaires and self-report entries through the app. Once the study is deployed, the participant can access the app, consent to the study, and complete its components. To build SHAPE to be scalable and flexible, we leveraged the open-source software development kit, Ionic Framework. This enabled the building and deploying of apps across platforms, including iOS, Android, and progressive web applications, from a single codebase by using standardized web technologies. SHAPE has been integrated with a leading Health Level 7 (HL7®) Fast Healthcare Interoperability Resources (FHIR®) application programming interface platform, 1upHealth, which allows participants to consent to 1-time data pull of their electronic health records. We used an agile-based process that engaged multiple stakeholders in SHAPE’s design and development.ResultsSHAPE allows study coordinators to plan, develop, and deploy questionnaires to obtain important end points directly from patients or caregivers. Electronic health record integration enables access to patient health records, which can validate and enhance the accuracy of data-capture methods. The administrator can then download the study data into HL7® FHIR®–formatted JSON files. In this paper, we illustrate how study coordinators can use SHAPE to design patient-centered studies. We demonstrate its broad applicability through a hypothetical type 1 diabetes cohort study and an ongoing pilot study on metachromatic leukodystrophy to implement best practices for designing a regulatory-grade natural history study for rare diseases.ConclusionsSHAPE is an intuitive and comprehensive data-collection tool for a variety of clinical studies. Further customization of this versatile and scalable platform allows for multiple use cases. SHAPE can capture patient perspectives and clinical data, thereby providing regulators, clinicians, researchers, and patient advocacy organizations with data to inform drug development and improve patient outcomes.

Detection of allergic transfusion-related adverse events from electronic medical records.

Transfusion-related adverse events can be unrecognized and unreported. As part of the US Food and Drug Administration's Center for Biologics Evaluation and Research Biologics Effectiveness and Safety initiative, we explored whether machine learning methods, such as natural language processing (NLP), can identify and report transfusion allergic reactions (ARs) from electronic health records (EHRs). In a 4-year period, all 146 reported transfusion ARs were pulled from a database of 86,764 transfusions in an academic health system, along with a random sample of 605 transfusions without reported ARs. Structured and unstructured EHR data were retrieved, including demographics, new symptoms, medications, and lab results. In unstructured data, evidence from clinicians' notes, test results, and prescriptions fields identified transfusion ARs, which were used to extract NLP features. Clinician reviews of selected validation cases assessed and confirmed model performance. Clinician reviews of selected validation cases yielded a sensitivity of 67.9% and a specificity of 97.5% at a threshold of 0.9, with a positive predictive value (PPV) of 84%, estimated to 4.5% when extrapolated to match transfusion AR incidence in the full transfusion dataset. A higher threshold achieved sensitivity of 43% with specificity/PPV of 100% in our validation set. Essential features predicting ARs were recognized transfusion reactions, administration of antihistamines or glucocorticoids, and skin symptoms (e.g., hives and itching). Removal of NLP features decreased model performance. NLP algorithms can identify transfusion reactions from the EHR with a reasonable level of precision for subsequent clinician review and confirmation.

Efficacy and safety of intravenous acetaminophen (2g/day) for reducing opioid consumption in Chinese adults after elective orthopedic surgery: A multicenter randomized controlled trial.

Background: Acetaminophen is an important component of a multimodal analgesia strategy to reduce opioid consumption and pain intensity after an orthopedic surgery. The opioid-sparing efficacy of intravenous acetaminophen has been established at a daily dose of 4 g. However, it is still unclear for the daily dose of 2 g of acetaminophen, which is recommended by the China Food and Drug Administration Center for Drug Evaluation, in terms of its efficacy and safety. Objectives: This study aimed to evaluate the efficacy and safety of intravenous acetaminophen at a daily dose of 2 g for reducing opioid consumption and pain intensity after orthopedic surgery. Methods: In this multicenter, randomized, double-blind, placebo-controlled phase III trial, 235 patients who underwent orthopedic surgery were randomly assigned to receive intravenous acetaminophen 500 mg every 6 h or placebo. Postoperative morphine consumption, pain intensity at rest and during movement, and adverse events were analysed. Results: For the mean (standard deviation) morphine consumption within 24 h after surgery, intravenous acetaminophen was superior to placebo both in the modified intention-to-treat analysis [8.7 (7.7) mg vs. 11.2 (9.2) mg] in the acetaminophen group and the placebo group, respectively. Difference in means: 2.5 mg; 95% confidence interval, 0.25 to 4.61; p = 0.030), and in the per-protocol analysis (8.3 (7.0) mg and 11.7 (9.9) mg in the acetaminophen group and the placebo group, respectively. Difference in means: 3.4 mg; 95% confidence interval: 1.05 to 5.77; p = 0.005). The two groups did not differ significantly in terms of pain intensity and adverse events. Conclusion: Our results suggest that intravenous acetaminophen at a daily dose of 2 g can reduce morphine consumption by Chinese adults within the first 24 h after orthopedic surgery, but the extent of reduction is not clinically relevant. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT02811991].

PCR39 Patient and Caregiver Diversity in FDA Patient Engagement Activities and CBER-Regulated Therapeutics: A Review of the Literature

This review of literature is aim one of a multipronged pilot project to understand what is known about current research and efforts related to increasing diverse patient engagement in drug development and factors that contribute to variances in knowledge of- and participation in- patient engagement activities relevant to U.S. Food and Drug Administration (FDA) Center for Biologics Evaluation and Research (CBER) regulated products for food allergies. A two-fold approach was used to conduct this review: (1) a scoping systematic literature, and (2) a review of grey literature. Research abstracts were screened and reviewed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for articles published between years 2012-2021. All abstracts were screened by two trained researchers and reviewed by a third using predefined inclusion criteria. Grey literature was information identified from food allergy organization websites and screened for inclusion by two trained researchers following prespecified criteria. A Microsoft excel® tracking tool was built to organize extracted data. Finally, a framework developed by the National Health Council (NHC) was adapted and used to synthesize the extracted data for both approaches. Seven out of 1,370 research abstracts were included for full text data analysis. In most (86%), patients and caregivers were solely study participants, compared to one study (14%) in which they were actively involved in informing the research process. Sixteen organization websites were identified for screening—seven of which were included for analysis. 71.4% (5/7 organizations) reported engagement opportunities for patients/caregivers but did not explicitly share how diverse populations were encouraged to engage. The importance of diverse patient engagement in food allergy therapeutic development has been stressed by both patient organizations and in research. However, further exploration is needed in how to meaningfully engage diverse groups of patients and caregivers impacted by food allergies to help inform regulatory decision-making

Moo-re Gene-edited Animals Get Regulatory Clearance: U.S. FDA Approves Genetically Engineered Cattle for Human Consumption

Moo-re Gene-edited Animals Get Regulatory Clearance: U.S. FDA Approves Genetically Engineered Cattle for Human Consumption

Development and validation of a liquid chromatographic method for the determination of nitrofuran residues in fish samples

A sensitive, accurate and efficient liquid chromatographic method has been developed for determination of nitrofuran residues in a honey sample; It was found that the detection minimum for all four nitrofuran group substances is 0.03 μg / ml, the specific wavelength is 376 nm, the specificity coefficient of variation for both on one working day and one working week is <2%, accuracy for solutions of three different concentrations is <2 %, The accuracy of the method for all four test substances is <2%, indicating the relevance of the method specificity to the criteria set for the analytical methods; The caliber graph for nitrofuran group is linear in the range 0.03 μg / ml - 1 μg / ml - 1 - 5 μg / ml and is acceptable as long as the correlation coefficient in all cases is> 0.999 (> 0.99); Sample preparation is satisfactory as the obtained sampling coefficient is> 0.6. Thus, as a result of validation of the liquid chromatographic method developed for the quantitative determination of nitrofuran residues in the honey sample, the method was fully complied with the requirements of the Government of Georgia according to the following validation characteristics: detection minimum, specificity, accuracy, correctness and linearity. (#499, Guidance for Industry Bioanalytical Method Validation U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM) May 2001).

Trophoblast Organoids: A New Tool for Studying Placental Development.

Trophoblast Organoids: A New Tool for Studying Placental Development.

Proposed Cardiac End Points for Clinical Trials in Immunoglobulin Light Chain Amyloidosis: Report From the Amyloidosis Forum Cardiac Working Group.

Immunoglobulin light chain amyloidosis is a rare, multisystemic, phenotypically heterogenous disease affecting cardiovascular, renal, neurological, and gastrointestinal systems to varying degrees. Its underlying cause is a plasma cell dyscrasia characterized by misfolding of monoclonal immunoglobulin light chains which leads to aggregation and deposition of insoluble amyloid fibrils in target organs. Prognosis is primarily dependent on extent of cardiac involvement and depth of hematologic response to treatment. To facilitate development of new therapies, a public-private partnership was formed between the nonprofit Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research. In 2020, the Amyloidosis Forum launched an initiative to identify novel/composite end points and analytic strategies to expedite clinical trials for development of new therapies for the primary hematologic disorder and organ system manifestations. Specialized working groups identified organ-specific end points; additional working groups reviewed health-related quality of life measures and statistical approaches to data analysis. Each working group comprised amyloidosis experts, patient representatives, statisticians, and representatives from the Food and Drug Administration, the UK Medicines and Healthcare Products Regulatory Agency, and pharmaceutical companies. This review summarizes the proceedings and recommendations of the Cardiac Working Group. Using a modified Delphi method, the group identified, reviewed, and prioritized cardiac end points relevant to immunoglobulin light chain amyloidosis in the context of an antiplasma cell therapy. Prioritized cardiovascular end points included overall survival, hospitalization, N-terminal pro-B-type natriuretic peptide level, 6-minute walk test, Kansas City Cardiac Questionnaire, and cardiac deterioration progression-free survival. These recommended components will be further explored through evaluation of clinical trial datasets and formal guidance from regulatory authorities.

This Free Life Campaign: Increasing Intention to Quit Among LGBTQ+ Young Adult Nondaily Smokers in Minneapolis.

PURPOSELGBTQ+ young adults smoke at disproportionately higher rates than their non-LGBTQ+ counterparts, but prevention efforts are limited. Furthermore, prior to This Free Life (TFL), no known campaigns target LGBTQ+ nondaily smokers. In this study Blue Cross and Blue Shield of Minnesota evaluated a local partnership extension of the Food and Drug Administration (FDA) Center for Tobacco Products’ TFL campaign.METHODSThe intervention featured a variety of LGBTQ+-tailored events, social/digital media, and out-of-home media placed in locations with a high density of LGBTQ+ young adults. Cross-sectional surveys (n = 1215) were collected from LGBTQ+ young adult (18-26) nondaily smokers at 4 time points between 2016 and 2019. The national TFL campaign was tracked in a separate evaluation conducted by the FDA.RESULTS43.0% of nondaily LGBTQ+ smokers reported awareness of the campaign (n = 522), and 63.4% of those also engaged with TFL (n = 330). Engagement was highest for gay, lesbian and transgender participants, and for Asian and Black/African American participants. Each additional instance of campaign engagement increased participants’ odds of intending to quit smoking by 20% (AOR = 1.20; 95% CI = 1.05, 1.36). The relationship between campaign engagement and intention to quit was fully mediated by the campaign’s impact on attitudes against smoking and perceived normative trends, but not by perceived behavioral control.CONCLUSIONThe local extension of TFL increased intentions to quit for LGBTQ+ nondaily smokers. Future research should further explore the relationship between perceived behavioral control and intentions to quit for nondaily smokers.

The Food and Drug Administration Biologics Effectiveness and Safety Initiative Facilitates Detection of Vaccine Administrations From Unstructured Data in Medical Records Through Natural Language Processing.

Introduction: The Food and Drug Administration Center for Biologics Evaluation and Research conducts post-market surveillance of biologic products to ensure their safety and effectiveness. Studies have found that common vaccine exposures may be missing from structured data elements of electronic health records (EHRs), instead being captured in clinical notes. This impacts monitoring of adverse events following immunizations (AEFIs). For example, COVID-19 vaccines have been regularly administered outside of traditional medical settings. We developed a natural language processing (NLP) algorithm to mine unstructured clinical notes for vaccinations not captured in structured EHR data.Methods: A random sample of 1,000 influenza vaccine administrations, representing 995 unique patients, was extracted from a large U.S. EHR database. NLP techniques were used to detect administrations from the clinical notes in the training dataset [80% (N = 797) of patients]. The algorithm was applied to the validation dataset [20% (N = 198) of patients] to assess performance. Full medical charts for 28 randomly selected administration events in the validation dataset were reviewed by clinicians. The NLP algorithm was then applied across the entire dataset (N = 995) to quantify the number of additional events identified.Results: A total of 3,199 administrations were identified in the structured data and clinical notes combined. Of these, 2,740 (85.7%) were identified in the structured data, while the NLP algorithm identified 1,183 (37.0%) administrations in clinical notes; 459 were not also captured in the structured data. This represents a 16.8% increase in the identification of vaccine administrations compared to using structured data alone. The validation of 28 vaccine administrations confirmed 27 (96.4%) as “definite” vaccine administrations; 18 (64.3%) had evidence of a vaccination event in the structured data, while 10 (35.7%) were found solely in the unstructured notes.Discussion: We demonstrated the utility of an NLP algorithm to identify vaccine administrations not captured in structured EHR data. NLP techniques have the potential to improve detection of vaccine administrations not otherwise reported without increasing the analysis burden on physicians or practitioners. Future applications could include refining estimates of vaccine coverage and detecting other exposures, population characteristics, and outcomes not reliably captured in structured EHR data.

Racial and Ethnic Differences in Drug Disposition and Response: Review of New Molecular Entities Approved Between 2014 and 2019.

Race and ethnicity can contribute to differences in drug exposure and/or response. Here, we report that about 10% of the new molecular entities (NMEs) approved between 2014 and 2019 by the US Food and Drug Administration's Center for Drug Evaluation and Research showed differences in exposure and/or response based on race/ethnicity or pharmacogenetic factors known to vary in frequency across global populations. Fewer NMEs (10%) reported differences in the labeling in 2014 to 2019 when compared to about 21% of NMEs approved between 2008 and 2013 that had differences in pharmacokinetics, safety, response, and/or pharmacogenetics. Understanding the underlying mechanisms that lead to such differences and adequate enrollment of racial and ethnic subgroups is essential to obtain sufficient information on exposure and response. Though drug development is global, when heterogeneous populations are not adequately enrolled, the risk-benefit assessments can remain incomplete for certain subgroups. Consequently, this can result in regional differences in drug approval, population-specific prescribing recommendations, or need for additional postmarketing studies to address concerns related to exposure, response, or lack of representation that lead to gaps in information.

Regulatory considerations for emergency use authorizations of medical products U/s 564 of the federal food drug and cosmetic act, usa

The United States (US) remains the greatest medical device (MD) market on earth $156 billion (40 percent of the overall MD market in 2017). By 2023, it is depended upon to create to $208 billion. As per USFDA, the MD are orchestrated into three classifications. The U.S. Food and Drug Administration's and Center for Devices and Radiological Health (CDRH) supervises MD advertised in the United States. The United States Federal Food, Drug, and Cosmetic Act (abbreviated as FFDCA, FDCA, or FD&C) is a group of laws passed by Congress in 1938 offering power to the U.S. Food and Drug organization (FDA) to administer the safety of food, drugs, cosmetic products and MD’s. An Emergency Use Authorization (EUA) under Section 564 of the FD&C Act considers the unique utilization of medications and other clinical products during particular kinds of crises. This review articles focused the process of EUA of medical products u/s 564 of the Federal Food Drug and Cosmetic Act, USA.

Immunocompromised patients in the USA and UK should receive third dose of COVID-19 vaccine.

A third dose of COVID-19 vaccine should be offered to severely immunocompromised people to improve immunogenicity, the UK's Joint Committee on Vaccination and Immunisation (JCVI) advised on Sept 1, 2021. The decision followed similar announcements by the US Food and Drug Administration (FDA) and US Centers for Disease Control and Prevention (CDC) in August.

Development and validation of liquid chromatographic method for the determination nitrofuran residues in honey

Sensitive, accurate and efficient Liquid Chromatographic Method is developed for the quantitative determination of Nitrofuran residues in fish samples. It was found that the coefficient of variation for all four test substances of the Nitrofuran group is from 0.03 ìg / ml less than 2%, respectively the detection minimum was considered to be 0.03ìg / ml; 376 nm wavelength is specific for Nitrofurans; For the quantification of nitrofuran residues in a fish sample validation of the developed Liquid Chromatographic Method revealed complete compliance of the method (Guidance for Industry Bioanalytical Method Validation U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM) May 2001) with the following validation characteristics of the requirements: detection minimum, specificity, accuracy, correctness and linearity.

PNS46 Development of Consumer-Reported Outcome Measure (CROM) Standards for the Tobacco Industry with Respect to Psychometric CROM Using a Consortium-Based Approach: Methodology and Scope

In November 2018, CORESTA approved the formation of a new Task Force (TF) to establish best practices and guidelines for the integration of consumer-reported outcome measures (CROM) in tobacco regulatory research. The primary objective of the CROM TF is to provide guidance on how to identify, develop, and validate CROM, and to provide access to CROM for evaluating tobacco and nicotine-containing products for pre-market and post-market purposes. Here, we describe the research completed by one of the TF working groups, WG02, with the purpose of developing CROM standards for tobacco regulatory research with respect to psychometric CROM (i.e., CROM intended to measure underlying psychological attributes – e.g., reinforcing effects). WG02 comprises 11 researchers from the CROM TF, representing 7 different tobacco companies and with experience in psychometrics, patient-reported outcomes (PRO), survey methodology, and product use behavior. WG02 members collaboratively drafted an operational definition of psychometric CROM and devised an approach for developing the standards. Consistent with approaches taken by other outcomes research organizations WG02 adopted a consensus-based approach for drafting the standards, which includes (1) review of literature and (2) an iterative peer-review process leveraging various sources, such as conference presentation and review by subject matter experts from tobacco, PRO, and related fields. Through literature review and WG02 member input, the scope was defined and initial content for the 5 components of the standards was drafted. These components include: (1) appropriate content, (2) development process and validation, (3) adaptation/modification of existing CROM, (4) application/implementation and interpretation of CROM, and (5) linguistic/cultural translation. This research represents the development of draft standards for Psychometric CROM for tobacco regulatory research, with the intention to complement 2020 draft guidance issued by the Food and Drug Administration Center for Tobacco Products. The initial draft content is being disseminated for peer-review.