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  1. FDA STEM Outreach, Education and Engagement

FDA Annual Student Scientific Research Day 2021

FDA Annual Student Scientific Research Day 2021

Each year, FDA gives high school, college, and graduate students from different backgrounds and scientific disciplines the opportunity to train with mentors from across FDA on regulatory science research projects. In 2021, 54% of the students were females and 45% of the students were male.

Students are exposed to the broad expanse of regulatory science activities underway across the Agency as well as the range of scientific disciplines they call on.

Students also learn first-hand about the Agency’s domestic and global impact. The students are able to attend FDA regulatory science trainings that integrates science, law and policy. With this knowledge, the students are able to complete research projects.

After completing their FDA training program, students are encouraged to explore careers in public health and STEM.

This website highlights the importance of FDA student programs and the direct impact that their research projects have on advancing regulatory science at FDA.

The 119 FDA summer student projects address one of the four main FDA Strategic Initiatives highlighted in the 2021 report Advancing Regulatory Science at FDA: Focus Areas of Regulatory Science.

  1. Public Health Emergency Preparedness and Response – 14 projects
  2. Increasing Choice and Competition through Innovation – 35 projects
  3. Unleashing the Power of Data – 50 projects
  4. Empowering Patients and Consumers – 20 projects
Title Synopsis Topic Authors Contact Center
3D Diffusion Model For Evaluating Chondrocyte Activity Post Metal Ion Exposure A 3D diffusion model is established and tested for Matrigel cell toxicity and chondrocyte gene profile expression. Osteoarthritis and rheumatoid arthritis patient-derived chondrocytes will be evaluated post metal ion exposure using qRT-PCR and multiple immunoassays. These assays assess the increase of markers, such as gene and protein expression, related to immune activation and cell viability at variable time points. This 3D diffusion model aims to better represent in vivo metal implant degradation and its impact on surrounding synovial tissue over time. Increasing Choice and Competition through Innovation Chandler Monk, M.S., CDRH (Summer Intern/Ph.D. Student); Nathan Lavey, Ph.D. CDRH (Post Doc ORISE Fellow); Steven Wood, Ph.D., CDRH (Mentor); Enusha Karunasena, Ph.D., CDRH (Mentor); David Kaplan, Ph.D, CDRH (Mentor)   Center for Devices and Radiological Health
A comparison of survival analysis methods with correlated time-to-event data in rare diseases clinical trials Survival analysis methods play a problematic role whose power gets turned down when they meet the rare diseases. What is the solution? Unleashing the Power of Data Wang, Shikun, FDA/CDER (Student); Wang, Yan, FDA/CDER (Mentor); Gurmu, Yared, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
A Horizon Scan of Novel, Unique, and Innovative Science and Technology Approaches for Use as Tools in New Drug Development: A Project with the ISTAND Pilot Program Within the Food and Drug Administration (FDA), paths to drug development tool (DDT) qualification already exist for biomarkers, clinical outcomes assessments (COA), and certain animal models for use in Animal Rule applications. The Innovative Science and Technology Approaches for New Drugs (ISTAND) pilot program seeks to provide a new qualification pathway which supports the development and qualification of innovative technologies that do not fit into the three aforementioned programs. Through this research, we aim to curate a list of areas of innovation that may become relevant to drug development and FDA regulation in the near future. The identification of these areas will allow for more focused and efficient allocation of resources by the ISTAND program, support the development of these novel technologies, and facilitate evaluation of their use in drug development. This will catalyze the drug development and approval processes for medical products entering the market. Ultimately, this will improve access to efficacious treatments for patients. Increasing Choice and Competition through Innovation Lucas Zhou, FDA/CDER (Summer Fellow); Ovya Ganesan, FDA/CDER (Summer Fellow); Margaret VanHeusen, FDA/CDER (Fellow, Peer Mentor); Steve Berman, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
A Probe Based Flow Cytometry Assay for Rapid and Quantitative Detection of BCC The Burkholderia cepacia complex (B. cepacia) is a group of at least 24 closely related species characterized by a high metabolic versatility. This group of Gram-negative, catalase-producing as well as lactose-nonfermenting has been classified as an objectionable microorganism. BCC can survive in organic solvents, antiseptics, and liquids with low nutrient levels. Several BCC outbreaks have been documented in recent decades, leading in the recall of multiple products. An examination of the FDA Enforcement Reports (2012-2019) demonstrates that BCC is the primary source of non-sterile pharmaceutical product recalls. Traditionally, BCC enumeration has been done using culture-based procedures which are laborious, time-consuming and have low sensitivity. Modern molecular techniques specially PCR, qPCR, and ddPCR have shown greater sensitivity and precision for rapid BCC detection.
Our aims here are to establish a more efficient and cost-effective detection of BCC to prevent contamination. As it is inherently difficult to detect and identify BCC due to their specific metabolic requirements and low growth rate with the current phenotypic and genotypic methods available, the goal is to establish a method that will not experience detection limitations. It is specifically important in the pharmaceutical industry to detect and prevent against the transmission of this bacteria and the resulting problems that would prove prominent in the status of public health.
Unleashing the Power of Data Le, David, FDA/NCTR (Student); Daddy Gaoh, Soumana, FDA/NCTR; Williams, Anna, FDA/NCTR; Alusta, Pierre, FDA/NCTR; Buzatu,Dan A., FDA/NCTR; Marasa,Bernard,FDA/CDER; Youngbeom Ahn, FDA/NCTR (Mentor)   National Center for Toxicological Research
A small collection of real-world infant polysomnography signals and data for use in assessing the performance of infant apnea monitors Over the summer, the student was able to examine signals and data collected in a prior study intended to create a set of robust testing requirements for infant apnea monitors. For the study, the FDA created a signal and data acquisition system, which was able to record polysomnographic physiologic waveforms (signals) from infants in a sleep lab. The FDA signals and data were acquired in parallel with the lab s own equipment and in conjunction with already-scheduled polysomnography assessments. Unleashing the Power of Data Lau, Jonathan, FDA/CDRH (Student); Silberberg, Jeffrey, FDA/CDRH (Mentor)   Center for Devices and Radiological Health
A software framework for AI-based radiologic image analysis We are developing a Python software package which provides a framework for the analysis and research of various AI/ML-based clinical tasks using medical imaging datasets. Our package includes methods for preprocessing, visualization, and feature extraction using modern deep learning methods alongside conventional radiomics approaches. We demonstrate the diverse functionality of our package by combining it with classifiers to perform a number of analysis tasks on a chest computed tomography dataset, a chest radiograph dataset, and a digital breast tomosynthesis dataset. Unleashing the Power of Data Briana Malik (Student), Kenny H. Cha, Ravi Samala, Berkman Sahiner, Alexej Gossmann (Mentor) FDA/CDRH   Center for Devices and Radiological Health
A Study of Subgroup Analysis and Precision Medicine in Recent NDA/BLA Submissions Subgroup analysis and precision medicine are approaches to assess treatment effects based on certain patient characteristics, and these are essential topics in the interpretation of clinical trial results. Over the past decades, FDA has developed many informative and pragmatic guidance documents and policies on these topics. To assess the impact of the regulation of subgroup analysis and precision medicine, we provided examples of various elements of precision medicine in recent New Drug Application (NDA) and Biologics License Application (BLA) submissions, such as frequentist and Bayesian subgroup analysis, enrichment designs, biomarker, subgroup identification, and tissue-agnostic trials. The usages of subgroup analysis and precision medicine in recent drug applications were summarized accordingly. Empowering Patients and Consumers Tang, Linli, FDA/CDER (Student); McCabe, Megan, FDA/CDER (Student); Collins, Sylva, FDA/CDER (Mentor); Nie, Lei, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
A survey of new oncology drug pediatric approvals in the USA from 2000 to 2021: focus on the impact of pediatric formulation availability and pediatric dose selection This review aims to determine a need for increasing the availability of age-appropriate formulations for these medications. It also aims to summarize data from clinical trials used to develop safe and effective dosing regimens in different age groups among pediatric populations. Of 185 oncology medications approved by the FDA between January 1998 and June 2021, 32 are indicated for use in pediatric populations, 18 of which are NDAs. About half of these medications (both BLA and NDA) were approved with adequate PK, safety, and efficacy data from clinical trials with pediatric subjects. Currently, only one-third of oncology NDAs approved for use in children have age-appropriate formulations. Unleashing the Power of Data Chen, Meg FDA/CDER (Student); Shen, Guoxiang, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Advanced Statistical Methods and Innovative Designs for Rare Disease Clinical Trials Our poster will include of the following six parts: (1) Abstract (2) Introduction (3) Methodology (4) Simulation Result (5) Conclusion (6) Reference. Increasing Choice and Competition through Innovation Wang, Jialu, FDA/CDER (Student); Chen, Yeh-Fong, Ph.D. & Gwise, Thomas, Ph.D. (Mentor)   Center for Drug Evaluation and Research
Alcohol-Based Hand Sanitizers in COVID-19 Prevention An important part of FDA s public health goal includes ensuring the quality and safety of drug products. Given the current public health emergency of preventing COVID-19 infection the CDER/OTR laboratories were assigned to developing an advanced analytical testing method to ensure of hand sanitizer product quality. Public Health Emergency Preparedness and Response Amal Rahim (Student); Diaa Shakleya (Mentor); Nicolas Abrigo; Patrick Faustino   Center for Drug Evaluation and Research
An Analysis of Pharmaceutical Quality Deficiencies Responsible for Clinical Holds in Investigational New Drug Applications The purpose of this study is to conduct a systematic data search and analysis of pharmaceutical quality related safety issues in quality reviews of Investigational New Drug Applications (INDs) to understand the chemistry, manufacturing and controls (CMC) reasons behind clinical holds in INDs. We have looked at over 1000 Commercial and Research IND applications received at CDER from June 1st, 2016 to June 1st, 2021 and identified and analyzed those placed on clinical holds due to quality related safety issues. The knowledge generated by understanding the results of our study will help inform the development of effective regulatory assessments practices in ONDP, including a Knowledge-aided Assessment and Structured Application (KASA) system for INDs. Unleashing the Power of Data Chatterjee, Rohan, FDA/CDER (Student); Yang, Jack, FDA/CDER (Student); Wu, Larisa, FDA/CDER (Mentor); Wesdyk, Russell, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
An Improved Method for Assessing the Biocidal Activity of Antimicrobial Wound Dressings against Staphylococcus aureus The poster outlines the methods and results for our extended AATCC-100 protocol, as well as our qRT-PCR assay, the latter of which consists of two elements: absolute and relative quantification. We include results acquired to date: our cell viability plate-based assay and our standard curve for absolute quantification of cell concentration in wound-dressing extracts. The discussion includes findings from our plate-based assay and encourages PCR as an addition to the existing evaluation methods. We believe this can improve the methods  accuracy, efficiency, and exhaustiveness. Empowering Patients and Consumers Glover, Thomas, FDA/CDRH (Student); Karunasena, Enusha FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Analysis of Therapeutic Drug Monitoring in Drug Labels Therapeutic drug monitoring (TDM) is a clinical practice that allows for measurement of drug concentration to maximize efficacy and safety. Our analysis identified recent drugs that contain TDM in their labeling and trends related to hepatic impairment, renal impairment, and drug-drug interaction instructions in labeling. TDM studies can be costly and time-consuming but may be worthwhile to optimize therapy for patient care. Increasing Choice and Competition through Innovation Tran, Duy, FDA/CDER (student); Moore, Jason, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Analysis of Viral Clearance Database for Manufacturing of Biotechnology Products Presenting trends in viral clearance unit operations as observed in viral clearance database developed from biotechnology products that have undergone biologics license application process. Unleashing the Power of Data Ajayi, Opeyemi, FDA/CDER (ORISE Fellow); Lute, Scott, FDA/CDER (Mentor); Johnson, Sarah, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Angiotensin converting enzyme 2 fusion protein stability and spike protein variant binding Angiotensin converting enzyme 2 fused to a human IgG1 Fc region (ACE2-Fc) is an experimental fusion protein that has potential therapeutic applicability against COVID-19 onset and progression. In this study, Chinese Hamster Ovary (CHO) cells that stably express a catalytically active or inactive ACE2-Fc fusion protein were generated. Using these cells and laboratory scale protein production technology, the purified ACE2-Fc proteins were obtained to characterize the protein s physicochemical properties and biological activity. Using biolayer interferometry, the binding affinity of the ACE2-Fc fusion proteins to four different variants of the SARS-COV-2 Spike protein were characterized. To determine the stability of ACE2-Fc proteins, the experimental fusion proteins were subjected to different storage conditions and monitored for temperature induced protein instability. To identify excipients that suppress temperature-induced protein instability, the ACE2-Fc fusion proteins were subject to temperature ramping studies in the presence and absence of different excipients to characterize the onset of protein denaturation and aggregation using dynamic light scattering (DLS), static light scattering (SLS) and full spectrum differential scanning fluorimetry (DSF). These findings will support the production of ACE2-Fc fusion proteins and facilitate the development of a preliminary formulation that suppresses temperature-induced protein instability. Public Health Emergency Preparedness and Response Vincent Falkowski, FDA/CDER (Student); Alicia Matthews FDA/CDER (contractor); Xin Bush FDA/CDER (Student); Cyrus Agarabi FDA/CDER (Federal Employee); Talia Faison FDA/CDER (Federal Emplyee), Thomas Biel FDA/CDER (Mentor); Tongzhong Ju FDA/CDER (PI)   Center for Drug Evaluation and Research
Application of the minimal physiologically based pharmacokinetic (mPBPK) model with a zonal liver compartment for the prediction of drug concentrations in human liver The physiologically based pharmacokinetic (PBPK) model is a computational model to predict drug absorption, distribution, metabolism, and excretion. The PBPK models are well accepted by the FDA for new drug applications. The objective of this study is to establish a minimal PBPK model with a zonal liver compartment to predict drug concentrations in liver and to facilitate the prediction of risk for drug induced liver injury (DILI). The model was applied to predict drug concentrations in plasma and liver, and to calculate the drug accumulation factors using clinical data of three drugs (amiodarone, pentamidine and tacrolimus). By applying the zonal liver model, the model can be used to predict drug concentrations at different zones of liver and provide the prediction for potentials to lead to DILI. Unleashing the Power of Data Tai Huynh; (student) Kiara Fairman; Minjun Chen; Annie Lumen; Miao Li (mentor), FDA/NCTR   National Center for Toxicological Research
Arsenic exposure to intestinal epithelial cell increases susceptibility to infection Focus of the present research is to further the current understanding how the Sodium Arsenate exposure may affect bacterial invasion in the intestinal epithelial cells (in vitro model). These in vitro studies are further correlated with the immunoglobulin isotyping in serum and intestinal tissue when animals are exposed to a single dose of Sodium Arsenate via oral or intravenous
Empowering Patients and Consumers Mathur, Aakriti, FDA/NCTR, (Student); Gokulan, Kuppan, FDA/NCTR, (Mentor); Khare, Sangeeta, FDA/NCTR, (Mentor)   National Center for Toxicological Research
Assessing the Use of Non-Invasive Biomarkers in Drug Development for Pre-Cirrhotic Nonalcoholic Steatohepatitis Currently, there is no FDA-approved medication for nonalcoholic steatohepatitis (NASH). One of the key hindrances to drug development for NASH is its long clinical course with the lack of validated non-invasive biomarkers as surrogate endpoints. Histological endpoints detected by liver biopsy are the only FDA-recommended surrogate efficacy endpoints. However, liver biopsy is an invasive procedure associated with potential clinical complications, high cost and long trial duration. The objective of this study is to assess the correlation of non-invasive biomarkers with histological endpoints to better predict and evaluate drug efficacy for pre-cirrhotic NASH. Increasing Choice and Competition through Innovation Tian, Xiaofan, FDA/CDER (Student); Li, Shen (Steven), FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Assessment of additively manufactured lattice strut measurement techniques Lattice Strut thickness is an important lattice parameter used to make critical decisions in the use of these structures in medical devices. The variation of strut measurements by the established methods of stereological characterization raises concern of its applicability in AM lattice structures. This study seeks to investigate the various techniques for measuring strut thickness and to determine the effects of differing measurement locations. Expected results will be levied to continue development of standards for AM lattice strut thickness measurements. Empowering Patients and Consumers Sanni, Oluwatobiloba, FDA/CDRH (Student); Diprima, Matthew FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Assessment of factors impacting material-mediated hemolysis results in the ASTM F756-17 testing standard Blood-contacting medical devices, such as vascular stents, hemodialyzers, and circulatory assist pumps can be vital for patient health, but also have the potential to damage blood elements. The goal of this project is to evaluate and improve testing strategies for assessing material-mediated hemolysis (damage to red blood cells) based on existing procedures detailed in ASTM F756-17 (Standard Practice for the Assessment of Hemolytic Properties of Materials). Positive and negative controls were first identified from the following list of test materials: 4 brands of nitrile gloves, Buna-N (nitrile rubber), latex, dimethyl sulfoxide (DMSO), and high-density polyethylene (HDPE). Variations of the standard protocol were then used to evaluate the effects of blood volume, blood concentration, incubation time, and material pre-washing on hemolysis. Results suggest that water-soluble surfactants on nitrile gloves and increasing DMSO concentrations cause hemolysis, while reducing the testing volume of diluted blood from 8 mL (standard) to 2 mL still provided consistent results. This study will inform the inclusion of new procedures in ASTM F756-17 for future hemolysis testing of medical device materials. Increasing Choice and Competition through Innovation Liu, Cindy, FDA/CDRH (Student); Malinauskas, Richard, FDA/CDRH (Mentor); Lu, Qijin, FDA/CDRH (Supporting Author); Skoog, Shelby, FDA/CDRH (Supporting Author)   Center for Devices and Radiological Health
Assessment of Target Status in Drug Development Programs The extent of assessment of target status in drug development programs vary across different therapeutic classes. The target assessments were more frequently conducted in oncology drug programs than drug programs for genetic or other diseases. Empowering Patients and Consumers Mary Hwang, PharmD Candidate (FDA/CDER/ORISE), Adeniyi Oluseyi, PharmD, Ph.D. (FDA/CDER), Robert Schuck, PharmD, PhD. (FDA/CDER)   Center for Drug Evaluation and Research
Automatic Tool of Response Evaluation in Solid Tumors Generating an in-house automatic tool to apply the guidelines of Response evaluation criteria in solid tumors (RECIST 1.1). A Shiny application will be used to convert the tool to an interactive interface. Increasing Choice and Competition through Innovation Ding, Alec, FDA/CDER (Student); Wang, Yaning, FDA/CDR (Mentor)   Center for Drug Evaluation and Research
Beta Testing of o2S2PARC I beta-test the usability of o2S2PARC (open online Simulations for Stimulating Peripheral Activity to Relieve Conditions), an open-source online simulation platform, in order to ensure the usability for all level of users. The work evaluates all tutorials, manuals, examples, and study templates provided by o2S2PARC. o2S2PARC was recently extended to enable Sim4Life (electromagnetics and electrical neuro stimulation) simulations using anatomically correct models of the human anatomy. My work includes testing and detailed documentation of these novel Sim4Life implementation. The information produced by this investigation will be vital for developers to bring o2S2PARC to the highest standard. Unleashing the Power of Data Ravnitzky, Nathan, FDA/CDRH (Student); Kainz, Wolfgang, FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Bisphenol AF exposure reveals concentration and sex dependent mRNA expression of xenobiotics metabolism genes: higher exposures are correlated with wound healing Banked ileal tissue were assessed to determine developmental exposure to Bisphenol AF in rats. Results from the mRNA expression of xenobiotics metabolism genes reveals concentration and sex dependent mRNA expression of xenobiotics metabolism related genes in the intestinal tissuse. To further investigate if accumulation of BPAF may have any impact on the intestinal epithelial repair, a scratch assay was performed in vitro. Results of scratch assay showed that intestinal epithelial cells introduced to 0.25  g/ml BPAF and 2.5  g/ml BPAF were able to completely heal the scratch in the span of 9 days or less. Healing time decreased as concentrations of BPAF in wells decreased, with some wells introduced to 0.25  g/ml completely almost healing within 5 days. Wells introduced to 25  g/ml did not completely heal by the ninth day but began to significantly close. However, scratched wells introduced to 250  g/ml did not heal and began experiencing cell deaths by as early as the third day. Wells introduced to 1000  g/ml did not heal at all, experiencing cells death as early as the first day after exposure. These preliminary results emphasize the need to assess sex-dependent impact of BPAF pertaining to the healing of intestinal injury. Empowering Patients and Consumers Xiang, Grace, FDA/NCTR (Student); Gokulan, Kuppan, FDA/NCTR (Mentor); Germolec, Dori, NIEHS; Sutherland, Vicki, NIEHS; Khare, Sangeeta, FDA/NCTR (Mentor)   National Center for Toxicological Research
Blood Flow Quantification of Peripheral Nerves using a Multimodal Polarization Sensitive Optical Coherence Tomography Imager To be able to assess and potentially treat acute to chronic effects in humans, better assessment of nerve health during surgical procedures, neuromodulation and animal recovery must be investigated. Our goal is to use optical coherence tomography systems to image and monitor peripheral nerves of animals. Empowering Patients and Consumers Parra, Anthony FDA/CDRH (Student); Saytashev, Ilyas FDA/CDRH; Hammer, Daniel FDA/CDRH (mentor)   Center for Devices and Radiological Health
CDER's Nanoctechnology Database This poster will outline the implementation and design of a nanotechnology database based on a technical profile of drug products containing nanomaterials. In it, we decision translation of an Excel based dataset to a relational database, as well as use cases for the database. The poster will conclude with a summary of progress and future directions. Unleashing the Power of Data Collins, Brendan, FDA/CDER (Student); Wood, Erin FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Change in Pediatric Extrapolation of Efficacy from Adults Pediatric drug development has been a challenge for drug manufacturers due to the relatively small patient population and the need for robust and interpretable studies. Notably, drug manufacturers have difficulty providing enough evidence of efficacy from adequate and well-controlled studies in children. In 1994 the FDA introduced the concept of extrapolation which stated that pediatric efficacy can be supported by efficacy data in adult trials with sufficient safety data. In this study, we examined pediatric extrapolation of efficacy from 2015 to 2020 to evaluate the use of extrapolation in FDA pediatric drug submissions and examine the reasons for its use. Unleashing the Power of Data Henry Nguyen, Gilbert Burckart   Center for Drug Evaluation and Research
Characterization of recombinant Factor C enzyme critical quality attributes Current regulations for biological product manufacturing require testing for sterility, testing for pyrogenic substances, testing to ensure sterile and pyrogen free drug product batch, and in-process microbial tests for manufacturing process monitoring. Compendial methods of bacterial endotoxin testing utilize limulus amebocyte lysate (LAL), which is derived from horseshoe crabs. Recombinant Factor C (rFC) entered the market with promising specificity, reduced variability, and sustainability of the horseshoe crab populations. Unlike traditional LAL kits for endotoxin detection, rFC manufacturing is not regulated by the FDA. To date, there are no studies that assess the rFC protein of the commercial endotoxin testing kits for lot-to-lot variability of key attributes, such as post-translation modifications or overall stability. The impacts of potential differences in critical attributes of endotoxin detection assay performance are unknown. This project aims to compare the rFC protein from commercially available kits for attributes such as thermostability, molecular size, or post-translation modifications. These experiments will allow for a better understanding of the differences between the rFC protein derived from various species, and potential impact to assay Increasing Choice and Competition through Innovation Rachel Carley, FDA/CDER (Student); Xin Bush, Jackie Cullinan, Abigail Workmeister, Opeyemi Ajayi, Patricia Hughes, Scott Lute, Sarah Johnson, Cyrus Agarabi, Talia Faison FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Communication Methods and Workflows to Develop and Implement High Throughput Truthing of Pathologist Annotations as a Reference Standard for Validating Artificial Intelligence in Digital Pathology. We are crowdsourcing pathologists to collect data (images + pathologist annotations) to qualify for the FDA/CDRH medical device development tool program (MDDT). If, successful, the MDDT qualified data along with a statistical software package for data analysis would be available to any algorithm developer to be used to validate algorithm performance in a submission to the FDA/CDRH. This poster will include visual descriptions of how we assist in ongoing data collection and project communication efforts. We will introduce our communication platforms (GitHub, NCI Hub), methods (documentation, updates), and programs (Git, RStudio & R scripts) to improve the project workflow with collaborators and team members. Unleashing the Power of Data Qian, Phoebe, FDA/CDRH (Student); Setty, Kai, FDA/CDRH (Student), Elfer, Katherine, FDA/CDRH (Mentor), Gallas, Brandon, FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Comparison of pharmacokinetic methods across approved biosimilars A biosimilar is a biological product that is highly structurally similar to an FDA-licensed product, with no clinically meaningful difference in terms of product quality, safety and efficacy. To be approved, the proposed biosimilar must demonstrate biosimilarity with the reference product through a comparative pharmacokinetic (PK) profile. Thus, a robust and validated PK method is crucial to support the PK profile analysis. We analyzed and compared the bioanalytical approaches used in 29 FDA-approved biosimilar products across 9 reference products. Preliminary results show diversity of methods, critical reagents, and assay platforms. This study can ultimately help standardize PK method review for future applications of biosimilar drugs in the same class. Unleashing the Power of Data Palen, Trexy, FDA/CDER (Student); Wang, Yow-Ming, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Cone Photoreceptor Function Measured by Phase Sensitive Adaptive Optics   Optical Coherence Tomography Cone photoreceptor response to visual stimuli can act as a functional biomarker for retinal diseases. A new technology using phase-sensitive adaptive optics   optical coherence tomography (PhS-AO-OCT) has proven to be a promising method to quantify photoreceptor function via phase changes in light back-reflected from the retina. For this project, we integrated this approach into our second-generation Fourier domain mode locked laser (FDML) based multimodal AO system for functional imaging of photoreceptors. We designed a stimulus channel to deliver brief flashes of light from a supercontinuum laser to the eye synchronous with our imaging scans. We analyzed cone response using principal component analysis and classified the cones by type. The ability to measure individual cone functionality may lead to new functional biomarkers for early detection of outer retinal diseases such as AMD. Unleashing the Power of Data Zucca, Kelvy, FDA/CDRH (Student); Liu, Zhuolin, FDA/CDRH; Hammer, Daniel X., FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Decreased Retinal Ganglion Cell Density in Multiple Sclerosis Revealed by Adaptive Optics Optical Coherence Tomography Adaptive Optics OCT was used to scan 8 participants' retinas, 7 participants had multiple sclerosis and one healthy volunteer was the control. AO-OCT provides higher resolution OCT images than do clinical OCT scanners. These images were processed and used to count ganglion cell somas in the GCL of the retina and to count nerve fiber bundles in the RNFL of the retina. These were quantified using an AI and then corrected manually for accuracy. The results were compared among MS participants as well as to the healthy volunteer and the expectation is that those with MS will have lower counts of retinal ganglion cells and within participants with MS, those with optic neuritis will have lower counts than those without it. Among the data that has been fully processed and analyzed, people with optic neuritis were found to have lower ganglion cell counts. Further analysis will be discussed in the poster. Empowering Patients and Consumers Kovalick, Katherine, FDA/CDRH (Student); Hammer, Dan X., FDA/CDRH; Liu, Zhuolin, FDA/CDRH (Mentor); Saeedi, Osamah, UMMC; Harrison, Dan, UMMC   Center for Devices and Radiological Health
Design Parameter Effects on Additively Manufactured Ti-6AL-4V Lattice The design of Additive Manufactured (AM) lattice structures constitutes a wide range of variables, such as relative density, strut diameter, heat treatment, and loading modalities of lattice cell structures.  This study will analyze the potential effects these variables have on the mechanical response of AM titanium lattice structures.  Experimental results will also be compared against calculated performance values of the lattice samples using Finite Element Analysis (FEA) in order to better understand the current limitations of simulating the complex architecture of these structures. Unleashing the Power of Data Andrew Cunningham, Matthew Schwerin, Matthew Di Prima, Peter Liacouras, Daniel Porter   Center for Devices and Radiological Health
Determining Technology Trends of Emerging Microfluidic Medical Devices Recent research and development in the emerging area of microfluidics is expected to lead to an influx of novel microfluidic-based device submissions to the FDA. Despite the increasing use of microfluidic technology in medical devices, there are no FDA-recognized standards or regulatory tools specific to microfluidics. This poster describes a datamining project of microfluidic medical device submissions over the past five years. Our datamining and data analysis efforts will allow us to: i) identify commonalities, trends and knowledge gaps among microfluidic medical devices; ii) determine which types of flow-related device performance tests will have the broadest impact for FDA; iii) understand how microfluidic-based medical devices are functionally different than traditional devices that have similar indications for use; and iv) determine the key safety and performance questions related to microfluidic technologies. The results from this datamining and forecasting study will inform OSEL about which flow-related areas to focus on for test method development to support the regulation and assessment of microfluidic medical devices. Unleashing the Power of Data Strachan, Kate, FDA/CDRH (Student); Natu, Rucha, FDA/CDRH; Sena, Grazziela, FDA/CDRH; Guha, Suvajyoti, FDA/CDRH; Herbertson, Luke FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Developing a controlled workflow for clinical studies to collect pathologist annotations We are reviewing the results of a pilot study into pathologist-annotated datasetsto make improvementsto the data-collection processfor a future pivotal study. Data collection in the pilot study showed that participantsincorrectly completed steps.We outline the common mistakesparticipantsmade, their causes,and how these errors are harmful to the integrity of the project. By making changesto the data-collection platforms, we are also able to promote a more efficient workflow. We present these improvementswith an explanation of how they improve data quality and efficiency. Unleashing the Power of Data John Paul Phillips, FDA/CRH/OSEL/DIDSR (Student); Brandon Gallas, FDA/CRH/OSEL/DIDSR (Mentor); Katherine Elfer, FDA/CRH/OSEL/DIDSR (Mentor)   Center for Devices and Radiological Health
Developing a High Content Imaged-Based Method for Evaluating Hepatotoxicity This project aims to develop an image-based assay for evaluating hepatotoxicity in a real time in vitro imaging system using liver hepatocellular carcinoma derived HepG2 cells, ImageXpress Micro 4 High Content Imaging system (IMX4), and MetaXpress software. This assay will be developed in both two-dimensional (2D) and three-dimensional (3D) culture conditions to detect toxicity-induced changes in phenotypic response - such as live cell count, nuclear morphology, and fluorescent intensity of actin and nuclei. The proposed image-based method will contribute to the development of a phenotypic assay for a deeper understanding of cytotoxicity in real time while offering advantages over other biochemical assays. Increasing Choice and Competition through Innovation King, Emily, FDA/NCTR (Student); Arefin, Ayesha, FDA/NCTR (Mentor); Phanavanh, Bounleut, FDA/NCTR (Co-author); Papineau, Katy, FDA/NCTR (Co-author); Shi, Qiang, FDA/NCTR (Co-author); Schnackenberg, Laura, FDA/NCTR (Co-author);   National Center for Toxicological Research
Developing a paradigm to prioritize new pediatric molecular targets using text mining, bioinformatic and computational data resources To support pediatric oncology drug development, the FDA, NCI, and the pediatric cancer community developed a list of molecular targets to guide submissions for pediatric study plans. The aim of this project is to develop a framework for the identification of new molecular targets associated with pediatric cancer as an aid to updating the List by using text mining and several bioinformatic tools and external databases. The integration of these resources will improve the text mining algorithm and prioritized new candidates for addition to the list and can be used by the Agency to further evaluate drug-target interactions and druggability. Unleashing the Power of Data Ridwan Islam, FDA/CDER (Student); Rosane Charlab, Ruby Leong, Alemayehu Akalu, Gregory Reaman, Rebecca Racz, and Paula Hyland, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Developing a Quantitative Interface for Evaluating the Effect of Dosage Modification on Safety and Efficacy The impacts of dose interruptions and modifications on treatment effectiveness and safety mitigation have rarely been systematically evaluated. The R Shiny application displays a variety of tabulation data of dosing records, PK data, responses to drugs, and adverse events and provides a visual output to easily access the data. Furthermore, the application allows the data to be understood easily to evaluate the efficacy of dosage modifications for safety management of the patients and the effectiveness of the treatment throughout the process. Unleashing the Power of Data Jiang, Grace; Yao, Kevin; Xiong, Ye; Liu, Jiang   Center for Drug Evaluation and Research
Developing hybridomas secreting anti-SARS-CoV-2 spike protein monoclonal antibodies from primary and secondary immune responses in immunized mice Despite the success of the current COVID-19 vaccines, there is still a need for therapeutic monoclonal antibodies directed against SARS-CoV-2. The purpose of this study is to develop monoclonal antibodies from the primary and secondary immune responses of mice immunized with Virus Like Particles (VLPs) expressing SARS-CoV-2 spike protein to be used in the SARS-CoV-2 cell fusion studies. These monoclonal antibodies will be assessed for VH and VL gene diversity and will be used in vitro to study their ability to neutralize virus entry. Public Health Emergency Preparedness and Response Rajabi Abhari, Delara, FDA/CDER (Student); Ghosh, Amalendu, FDA/CDER (Mentor); Fitzsimmons, Sean, FDA/CDER (Mentor); Stantchev, Tzanko, FDA/CDER; Shapiro, Marjorie, FDA/CDER (Supervisor)   Center for Drug Evaluation and Research
Development of a Biosimilar 351(k) BLA Clinical Pharmacology Study Database The purpose of this Biosimilar 351(k) Clinical Pharmacology Study Database is consolidate all of the clinical pharmacology studies (PK, PD, CCS, and Safety) from the 54 biosimilar BLAs that have been filed with CDER to date (6/30/21). By doing so, it will become easier to reference past studies and understand the clinical pharmacology study designs of 351(k) BLAs. Such analysis will give OCP the chance to streamline the 351(k) approval process and allow the clinical pharmacology review of biosimilars to progress in a more timely and efficient manner. Unleashing the Power of Data Wong, Mitchell, FDA/CDER (Student); Wang, Yow-Ming, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Development of a Method to Evaluate Third Body Wear of Implant Materials The goal of this study is to develop in vitro test methods for screening materials for susceptibility to third body wear and for quantification of metal ions and particulate debris that are generated during testing. Increasing Choice and Competition through Innovation Lauren Ickes (student) CDRH/OSEL/DBCMS   Center for Devices and Radiological Health
Development of a novel and rapid HPLC-based method for a comparative assessment of biosimilar structural heterogeneity and biological activity Monoclonal antibody (mAb) drug products are the largest product class of US-licensed biosimilars. The glycosylation post-translational modifications (PTMs) on the Fc effector region of mAbs are a well-defined critical quality attribute (CQA). Recently, an affinity chromatography based technology, the TSKgel FcR-IIIA-NPR HPLC affinity column, emerged claiming to provide a faster and straight-forward approach to assessing mAb biosimilar glycosylation and Fc effector mediated activity. We propose to ascertain the feasibility of the TSKgel FcR-IIIA-NPR HPLC affinity column as an rapid assay to identify differences in glycosylation PTMs between proposed biosimilars and their reference products. Increasing Choice and Competition through Innovation Jackie Cullinan FDA/CDER (Student), Rachel CarleyFDA/CDER, Talia Faison FDA/CDER, Sarah Johnson FDA/ CDER, Cyrus Agarabi FDA/CDER, Scott Lute FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Development of a Spectral Flow Cytometry-based assay to analyze drug induced hepatoxicity The purpose of this project is to develop an effective protocol for analyzing primary human hepatocytes by method of spectral flow cytometry. The autofluorescent nature of hepatocytes interferes with the fluorescent antibodies that have similar spectral emission peaks. With the Cytek Aurora Flow Cytometer, we have developed a protocol that will reduce background noise caused by autofluorescence. Using this method, we have identified two different types of cells: apoptotic and necrotic. Additional adjustments in the protocol are needed, however preliminary data shows that we can minimize autofluorescence of primary human hepatocytes. Empowering Patients and Consumers Scherina Chi, Christie Jane Fennell, Taylor Harper, Christina Zhu, Silvia M. Bacot, Tao Wang, Gerald M. Feldman   Center for Drug Evaluation and Research
Distributed Deep Learning on HPC clusters Runtime of deep learning applications with big data is reduced by using high-performance computing techniques. These techniques use singularity---the cutting-edge containerization technology for operating-system-level virtualization well suited for HPC environments. Unleashing the Power of Data Mackey, Tsach, FDA/CDRH (Student); Mikailov, Mike, FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Drug Identifier Standardization for FDA-Approved Drug Labeling Using RxNorm This poster studies the standardization of drug names for FDA approved Drug Labeling using RxNorm, a normalized drug naming system. We investigated the different identifiers of a drug that are used by the FDA. The most prevalent identifiers are Application Number, National Drug Code (NDC), Unique Ingredient Identifier (UNII), and Structured Product Labeling (SPL) Set IDs. We have mapped these various FDA drug identifiers to an external and widely accepted standard, RxNorm s quantified SCDs (Semantic Clinical Drug), in a graphical representation that elucidates the relationship between the different drug identifiers. These standard names, codes, vocabularies, and drug product representations will be available for the benefit of regulatory, clinical, and research applications. Unleashing the Power of Data Isaac Harris; Stephen Harris; Zhichao Liu, Leihong Wu, Taylor Ingle, Junshuang Yang, Weida Tong, and Hong Fang   National Center for Toxicological Research
Effects of Test Sample Diameter and Surface Roughness on the In Vitro Flow Loop Thrombogenicity Assessment of Biomaterials Blood-contacting medical devices are commonly used in patients to treat various diseases, but they may also cause severe complications related to device thrombosis (blood clotting), due to non-physiological blood flow patterns and the exposure of blood to foreign materials. Thus, effective preclinical thrombogenicity evaluations of medical devices are essential to ensure patient safety. In vitro recirculating blood loops are being developed for thrombogenicity testing to overcome some inherent limitations of animal studies; however, there is no standardized or widely accepted test methods, as the key test parameters of different blood loops vary greatly and their impacts on thrombogenicity assessments are not well characterized. In this study, we aim to investigate the effects of test sample diameter and surface roughness on the thrombogenicity assessment of biomaterials using an in vitro dynamic flow loop test system developed in our lab. The information gained from this study is important for understanding the limits of in vitro thrombogenicity test systems and may help to establish test sample size ranges for a specific test loop. Increasing Choice and Competition through Innovation Srinivasan, Keerthana, FDA/CDRH(Student); Patel, Mehulkumar, FDA/CDRH (Mentor); Jamiolkowski, Megan, FDA/CDRH (Mentor); Lu, Qijin, FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Elucidating the Role of Iron and Cis-acting Regulatory Regions on the Expression of Aerobactin, an Iron Acquisition System Detected in Salmonella enterica IncFIB Plasmids. Salmonella enterica is a leading cause of foodborne illness in the United States and around the globe. This bacterium is known to harbor chromosomal and plasmid-encoded host immune evading virulence factors, such as siderophores, which scavenge iron from the host. One siderophore encoded on the IncFIB plasmid of Salmonella enterica strain SE163 is called aerobactin, and it is encoded on the iucABCD-iutA operon. Within the promoter region of this operon, there is a Fur binding region called the Fur box, where the regulatory protein, Fur, can block transcription in the presence of iron. The goal of this project is to mutate the fur box creating a  Fur binding mutant  (fbm) and compare the activity of the mutant to the wildtype using GFP as a reporter gene. Public Health Emergency Preparedness and Response Bushman, Summer, FDA/NCTR (Student); Gudeta, Dereje, FDA/NCTR (Mentor); Khajanchi, BIjay, FDA/NCTR (Mentor); Foley, Steven, FDA/NCTR (Mentor); Henry, Savannah, FDA/NCTR (Student)   National Center for Toxicological Research
Evaluating a reconstructed human barrier culture system as an in vitro model for the human placenta The human placenta is an organ that supports pregnancy. Its primary role is to facilitate and regulate the exchange of substances between the fetus and the mother. Our project has developed an in vitro system composed of two different types of cells to model the human placental barrier; this in vitro system will be used to facilitate the evaluation of embryo-fetal toxicity. Preliminary tests were done on the co-culture system to validate its integrity and functionality. Further characterization of RNA expression and transport function will help us determine the relevance of the co-culture system to the human placenta barrier. Increasing Choice and Competition through Innovation Sophie Li, NCTR (Student); Rebecca Wynne, NCTR; Ying Chen, NCTR; Xiaobo He, NCTR; Xuefei Cao, NCTR; Robert H. Heflich, NCTR; Matthew Bryant, NCTR; Kelly Brant, CDER; Yiying Wang, NCTR (Mentor)   National Center for Toxicological Research
Evaluating Effects on Ventilation of Oxycodone Alone or in Combination with Psychotropic Drugs The impetus for this project was an FDA safety communication in 2016 warning of the dangers of concurrent opioids and benzodiazepines on respiration. A nonclinical in vivo rat study was performed with oxycodone and other sedative-psychotropic drugs  (SPDs) to evaluate effects on respiration; this project further analyzed the data from that study with a focus on paroxetine, quetiapine, ramelteon, and trazodone. Hysteresis plots were created to analyze drugs alone or in combination. Most individual drugs did not exhibit a hysteresis, and linear effect models were considered adequate for describing individual drug effects. The linear regressions from oxycodone and drug alone were used to generate surface plots for comparison with data from the study. Most of the data for paroxetine and ramelteon was above the surfaces generated, indicating a possible synergistic effect on respiration when combined with oxycodone. The opposite was true for quetiapine and ramelteon. Public Health Emergency Preparedness and Response Collins, Brendan, FDA/CDER (Student); Florian, Jeffry FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Evaluating Medical Devices Using Reader Studies The FDA can evaluate the effectiveness of diagnostic imaging tests by utilizing reader studies to evaluate diagnostic decisions. To that end, we are developing a web application that can be used to conduct reader studies in classrooms and online learning environments. The application measures both a participant's sensitivity (the ratio of true positive diagnoses to the total number of diseased cases) and specificity (the ratio of true negative diagnoses to the total number of normal cases), which is a more robust means of analyzing behavioral patterns in diagnostic decisions. Empowering Patients and Consumers Younis, Seif, FDA/CDRH (Student); Samuelson, Frank FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Evaluating Menthol Use and Quit Intentions among past 30-day Youth Cigarette Users, NYTS 2020 Menthol cigarettes have always been the flavor of choice among young smokers, given that it is the only remaining flavor from the 2009 Tobacco Control Act. The poster will include detailed tables regarding menthol use among youth, past-30 day cigarette users, as well as outline quit intentions using the 2020 National Youth Tobacco Survey (NYTS) data. This analysis serves as an update and assists in evaluating menthol use as the FDA ponders a potential ban on the sale of combustible tobacco products containing menthol. Unleashing the Power of Data Shinaba, Muftau, FDA/CTP (Student); Smith, Alexandria, FDA/CTP (Mentor)   Center for Tobacco Products
Evaluating the Adverse Respiratory Effects of Disease-Associated Cytokines in an in vitro Human Airway Tissue Model This study examined potential adverse effects of several disease associated cytokines in an in vitro human air-liquid-interface (ALI) airway tissue model. Findings from this study support the application of the human ALI airway tissue model as a pre-clinical tool for evaluating the safety and efficacy of anti-inflammatory treatments for respiratory diseases. Public Health Emergency Preparedness and Response Joseph Pham (student); Xuefei Cao (collaborator/principal investigator); Rui Xiong (mentor/principal investigator)   National Center for Toxicological Research
Evaluation of a real-time PCR assay for rapid detection of Listeria monocytogenes in artificially contaminated soft cheese and environmental surface samples Listeria monocytogenes is an opportunistic foodborne pathogen that can be associated with a variety of food and environmental sources. Real-time PCR allows rapid and accurate screening of this foodborne pathogen. A real-time PCR method, originally developed to confirm culture identity and later modified to include an internal amplification control and to use on the Applied Biosystems 7500 FAST instrument, was evaluated for rapid screening of L. monocytogenes from cheese and environmental samples. The results show that this detection method following BAM enrichment procedures and real-time PCR provides highly sensitive screening for L. monocytogenes in artificially contaminated soft cheese and environmental samples. Public Health Emergency Preparedness and Response Samira Mitias, Leah Weinstein, Hee Jin Kwon, Jianghong Meng, Thomas Hammack, Karen Jinneman, Yi Chen   Center for Food Safety and Applied Nutrition
Evaluation of Global and Targeted Virulence Factors as Targets for Antivirulence Veterinary Drugs for Avian Pathogenic Escherichia coli to Combat Colibacillosis in Chickens Colibacillosis, caused by avian pathogenic Escherichia coli (APEC), is an infectious disease affecting poultry flocks, causing acute fatal septicemia, subacute pericarditis, airsacculitis, and other sequelae. Given concerns associated with antimicrobial resistance (AMR), alternative therapeutic options   including antivirulence approaches - are needed. However, these novel approaches remain largely unexplored, raising a number of questions that need to be addressed to support both their development and regulation. Using colibacillosis as a model infection, this project explores the kinds of information and data necessary to support CVM s pre-approval evaluations of these alternatives to traditional antimicrobial drug therapies. A total of 129 APEC isolates from chicken sources were selected for analysis. Whole genome sequences and metadata were obtained from NCBI Pathogen Detection Isolate Browser and from the National Antimicrobial Resistance Monitoring System (NARMS). Isolates from asymptomatic carriers (70) and chickens with colibacillosis (59) were analyzed. Negative controls included pathogenic E. coli (ExPEC) from non-chicken sources (34 from swine and 19 human uropathogenic E. coli (UPEC) fom NCBI). With respect to global virulence gene detection, diseased chickens with colibacillosis had the highest levels (42%) of virulence genes detected compared to 39% detection in asymptomatic carriers. Diseased chickens and asymptomatic carriers had a higher % detection of global virulence genes as compared to negative controls [ExPEC from swine (14%) or from UPEC (10%)]. These preliminary data suggest that there is a greater total number of virulence genes being propagated among the E. coli residing in poultry as compared to other species examined. However, the impact of these various genes on disease processes are yet to be determined. In terms of total global AMR genes that could be detected in this sample set, 23% were detected in APEC asymptomatic carrier chickens, 17% were detected from diseased chickens with colibacillosis, 13% were detected from negative control diseased swine with EXPEC, and 20% were detected from negative control human UPEC. Associations between specific AMR genes, virulence genes, and stress genes with plasmid types are being evaluated, in order to identify the kind of information and data needed for development of a pre-approval, regulatory science  roadmap  to evaluate antivirulence drugs across a wide range of diseases impacting animal and human health. Increasing Choice and Competition through Innovation Jessica Paredes, Heather Harbottle, Hershil Kachrani, Maryiln N. Martinez, Steven Foley, and Jeffrey M. Gilbert   Center for Veterinary Medicine
Evaluation of recombinant Factor C assay kits in comparison to compendial Limulus amebocyte lysate (LAL) assays for bacterial endotoxin testing Compendial methods of bacterial endotoxin testing utilize limulus amebocyte lysate (LAL) which is derived from horseshoe crabs. Recombinant protein-based alternatives   recombinant Factor C (rFC) - have entered the market with promising specificity, reduced variability, and sustainability of the horseshoe crab populations. Despite industry adoption, there is limited work in the public sphere showing unbiased side-by-side performance assessment of all commercially available methods to the compendial LAL methods. This study aims to identify potential failure modes of commercially available rFC assays and evaluate the comparability of the compendial LAL assays and rFC assay performance. This internal evaluation of rFC assay technology will provide data to support Agency best practices and guidance to ensure product and patient safety. Increasing Choice and Competition through Innovation Abigail Workmeister, ORISE fellow, FDA/CDER (Student); Xin Bush; Jackie Cullinan; Rachel Carley; Opeyemi Ajayi; Patricia Hughes; Talia Faison; Scott Lute; Cyrus Agarabi; Sarah Johnson, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Evaluation of Reproductive, Developmental, and Genetic Toxicities of Cyclophosphamide and Eugenol Using the promising model, Caenorhabditis elegans, we set forth to study the effects of two commonly used FDA-regulated products, eugenol and cyclophosphamide. Eugenol is an oil derived from clove and is used for fragrances as well as an anesthetic among the fishing industry while cyclophosphamide is an anticancer drug with knowledge of also being a teratogen, mutagen, and carcinogen. In this study, experiments have been conducted to test the chemicals  LC50 (acute toxicity), reproductive (fecundity, brood size, hatchability), developmental (growth rate, body length and lifespan) and genetic (mutation frequencies and types) toxicities using different concentrations of each test compound. Since C. elegans is a model organism that shares many common structural and genetic qualities with mammals and humans, the results from this study can be inferenced on the possible effects of these two compounds on public health. Considering that cyclophosphamide is also a known rodent teratogen, mutagen, and carcinogen, results from this study can be compared to those from rodents to determine whether C. elegans mode can replace or complement the productive, developmental and genetic toxicity studies in rodents. Increasing Choice and Competition through Innovation Bekkala, Amanda, FDA/NCTR (Student); Chen, Tao, FDA/NCTR (Mentor), Yan, Jian, FDA/NCTR (Supervisor), Rodgers, Jenna, FDA/NCTR (PHD STUDENT)   National Center for Toxicological Research
Evaluation of the Prevalence of Dosage Modifications in Pivotal Trials for Recently Approved Oncology Drugs Dosage modifications, including dosage interruptions, reductions, and discontinuations due to intolerable toxicities are frequently required during oncology clinical trials. The impact of dosage modifications on clinical efficacy has not been well characterized. As the first step to address this issue, we conducted a landscape analysis of new molecular entities (NMEs) of oncology small molecule drugs and antibody-drug conjugates (ADCs) approved between 2016 and 2021 to characterize the prevalence of dosage modifications in pivotal trials. The analysis summarizes the different observed rates (%) of dosage modifications for each NME class, and identifies potential deficiencies in the reporting of time to dosage modifications and the differences in the rate of dosage modifications across the lines of treatment as well in collection of PK samples that coincide with the occurrence of these events. The impact of dosage modifications on the clinical outcome was evaluated in only 16% (n=8) of the NME submissions approved in the past 5 years. Further assessment of the impact of dosage reduction and interruptions on clinical efficacy is warranted. Empowering Patients and Consumers Hudson, Rachel, FDA/CDER (Student); Fletcher, Elimika Pfuma, FDA/CDER; Zhao, Hong, FDA/CDER; Bi, Youwei, FDA/CDER; Liu, Jiang, FDA/CDER; Madabushi, Rajanikanth, FDA/CDER; Ayyoub, Amal, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Evaluation of truncated AUC as an alternative metric to assess pharmacokinetic comparability in biologics development Assessment of pharmacokinetic (PK) comparability involves measuring the area under the plasma concentration time curve (AUC) and maximum plasma concentration (Cmax). For biologics products, the current practice has been sampling for an adequate duration (3-5 half-lives) to capture the full PK profile which may translate into long study duration of months for certain products. For small molecule drugs with long half-lives, truncated AUC, i.e., AUC from time 0 to a certain pre-determined time point, is used in assessing the AUC metric in the determination of bioequivalence in generic drug product development arena. Based on the preliminary data analysis of datasets analyzed thus far, utilization of truncated AUC for therapeutic biologics with a long half-life appears to be sensitive and adequate to determine if the two presentations (e.g., AI and PFS) provide comparable systemic bioavailability. However, these results need to be further confirmed by analyzing a large number of datasets and further research in this area is ongoing. Unleashing the Power of Data Sneha Rathi (Lead author), Delaney McGuirt, Ping Ji (Mentor), Renu Singh, Jianmeng Chen, Yow-Ming Wang, Bhawana Saluja, Suresh Doddapaneni, Chandrahas - FDA/CDER Sahajwalla   Center for Drug Evaluation and Research
Examining the Neurodevelopmental Effects of Perinatal Cannabidiol (CBD) Exposure in Sprague-Dawley Rats Cannabidiol (CBD) is a compound found in cannabis that has been used more frequently in recent years in attempt to treat a variety of clinical ailments, including pregnancy-related symptoms. Despite its potential medical uses, there is evidence that using CBD may have adverse effects as well. Due to the role that the endocannabinoid system plays in regulating nervous system development and evidence of negative impacts of cannabis use during pregnancy, the developmental effects of CBD must be further investigated. This poster aims to provide insight into the neurodevelopmental effects that cannabidiol (CBD) can exhibit using neurobehavioral and neurochemical data to better inform Agency decision making. Empowering Patients and Consumers Busch, Nisha, FDA/NCTR (Student); Flanigan, Timothy, FDA/NCTR (Mentor); Shen, Andrew, FDA/NCTR; Gill, W Drew, FDA/NCTR   National Center for Toxicological Research
Exploring Various Sensitivity Methods for the Analysis of Pregnancy and Non-Pregnancy PBPK Models This project focuses on exploring the application of global and local sensitivity analysis to existing non-pregnancy and pregnancy physiologically based pharmacokinetic (PBPK) models of the drug labetalol. It involves changing the parameters input into the PBPK model and analyzing the change in outputs. The existing PBPK models were originally coded in Berkeley Madonna, so as part of this project, they were translated into the R programming language in order to run the global sensitivity analyses. Finally, a parameter sensitivity package will be used to perform the global sensitivity analysis on the models and obtain results. Unleashing the Power of Data Erukulla, Nikith, FDA/NCTR (Student); Fairman, Kiara, FDA/NCTR (Mentor); Lumen, Annie, FDA/NCTR (Mentor); Li, Miao, FDA/NCTR (Mentor)   National Center for Toxicological Research
Failed Pediatric Drug Development Trials Pediatric drug development is a relatively new science. For ethical and practical reasons, pediatric drug development trials should be optimized in such a manner that participation by the pediatric patient is meaningful, and results in important information for the labeling of the drug product for pediatric use. This requires an understanding of the study characteristics of any failed trial so that we can improve pediatric drug development and minimize trials that do not produce meaningful drug use information. Increasing Choice and Competition through Innovation Hwang, Lucia, FDA/CDER (Student); Bhatt-Mehta, Varsha, FDA/CDER (Mentor); Burckart, Gilbert   Center for Drug Evaluation and Research
Histochemical Clues to the Onset and Progression of Plaques in Alzheimer's Pathology We looked at amyloid beta plaque onset and progression in 6-month, 16-month and 20-month AD transgenic rats. We wanted to learn in which regions of the brain and how early plaque accumulation occurs in order to develop future methods of finding plaques earlier in development and even before emergence. Public Health Emergency Preparedness and Response Padala, Sanjana, FDA/NCTR (Student); Setti, Sharay, FDA/NCTR (Postdoc); James Raymick, FDA/NCTR (Lab Technician); Sarkar, Sumit, FDA/NCTR (Mentor)   National Center for Toxicological Research
Horizon Scanning in Plant Biotechnology Plant genetic engineering and genome editing are rapidly advancing, making it possible for a growing number of plant biotechnology developers to bring crops with innovative new traits to the market. It is important for regulatory scientists to conduct horizon scanning to help them prepare for future developments in the use of plant biotechnology in the food supply. This project involves conducting horizon scanning and entering potential pipeline products into an internal pipeline monitoring database. The database will enable analyses to help the agency understand new trends, identify emerging developers, and track global developments. Unleashing the Power of Data Kurapaty, Samantha, FDA/CFSAN (Student); Cournoyer, Patrick FDA/CFSAN (Mentor)   Center for Food Safety and Applied Nutrition
How much information should a prior contain? Investigating informative priors through dynamic borrowing in Bayesian trials Bayesian analyses are particularly useful in the rare disease context as they can increase efficiency of trial design with increased precision of treatment effect estimates and decreased necessary sample size  through informative priors, which effectively borrow information from previous studies. Yet previous and subsequent studies might have divergent results for many reasons such as the previous study results were spurious, there might be treatment drift, or the target population in the subsequent study has somehow changed, resulting in previous studies that are no longer similar enough to be leveraged for the subsequent study. In this context, using an informative prior that fully borrows information from previous studies could introduce substantial bias, resulting ininflated type 1 error rates and erroneous results. In defining informative priors, we need to account for how similar the previous and subsequent study results are to mitigate bias.  Most approaches to borrowing propose discounting the previous study information to avoid the introduction of bias. There are two general approaches to borrowing: 1) static and 2) dynamic. For static borrowing, the degree of discounting is defined a priori, while dynamic borrowing uses the subsequent and previous study data to determine an appropriate degree of borrowing based on the degree of similarity between the data. Especially in the rare disease context where the patient population is extremely limited, research is needed to determine how much discounting should occur to achieve a balance between gathering valuable information and minimizing bias.  This work looks to investigate different dynamic borrowing approaches for prior specification and their impact on operating characteristics for a subsequent study. Unleashing the Power of Data Haine, Lillian, FDA/CDER (Student); Sun, Hengrui FDA/CDER (Mentor); Valappil, Thamban FDA/CDER (Mentor); Mullick, Charu FDA/CDER (Mentor); Price, Dionne FDA/CDER (Mentor)   Center for Drug Evaluation and Research
IG-CNN: Imaging Genomic Data Enabling Convolutional Neural Network for the Enhanced Survival Rate Prediction in Precision Medicine Imagine if we could use the genomics data to draw a painting to enable the well-established convolutional neural network (CNN) for clinical applications, which will be extremely interesting. This poster will walk you through our newly proposed AI-powered IG-CNN model to Image transcriptomic profiles of neuroblastoma (NB) to enable a CNN model for the enhanced and more explainable survival rate prediction to facilitate the precision medicine application. Unleashing the Power of Data Barreiro-Arevalo, Myrine, FDA/NCTR (Student); Liu, Zhichao, FDA/NCTR (Mentor)   National Center for Toxicological Research
Image Quality Evaluation Methods for Augmented Reality Devices Augmented Reality Head Mounted Displays (AR HMDs) are being actively explored by researchers and medical device manufacturers for displaying medical images within the surgical field of view for image-guided interventions. One challenge for AR HMDs in surgical applications is the image quality in bright ambient lighting conditions. To address this regulatory science challenge, we developed testing methodology for the Microsoft HoloLens 2 aimed at characterizing the image contrast and graphical performance under different ambient lighting conditions. Increasing Choice and Competition through Innovation Matthew Johnson, FDA/CDRH (Student); Beams, Ryan, FDA/CDRH (Mentor); Brown, Ellenor, FDA/CDRH; Varshney, Amitabh, UMD-College Park   Center for Devices and Radiological Health
Immune-mediated Liver Injury Caused by Immune Checkpoint Inhibitors Displays a High Immune Tolerance and Rigorous Hepatocyte Regeneration Phenotype Immune Checkpoint Inhibitors (ICI) are a new form of anti-cancer therapy that has revolutionized cancer treatment. Although many patients have seen positive results, others have had to terminate treatment because of Immune-mediated Liver Injury caused by Immune Checkpoint Inhibitors (ILICI). This immune-related adverse event (irAE) currently has very few prognostic biomarkers because the mechanism behind ICI induced hepatotoxicity is not fully understood. Many studies have shown that the immune status of a patient is vital for drug induced hepatotoxicity, yet little is known about the status of immune activation, especially in correlation with liver regeneration in patients with ILICI. In this study, we assessed the association between liver regeneration and immune activation status in using immunohistochemistry (IHC) staining of Ki67, a proliferation marker, and CTLA-4, an immunosuppressive biomarker. We found Ki67 positive hepatocytes present in liver tissue from patients with ILICI and drug induced liver injury (DILI). However, the levels of CTLA-4 positive cells were much higher in patients that developed ILICI. Our results suggest that immune activation can play a critical role in drug-induced liver toxicity and that the correlation between levels of Ki67 and CTLA-4 may provide a new useful tool to predict patient outcomes in response to ILICI. Empowering Patients and Consumers Zhu, Christina, FDA/CDER (Student); Fennell, Christie Jane, FDA/CDER (Fellow); Chi, Scherina, FDA/CDER (Student); Bacot, Silvia M., FDA/CDER (Mentor); Wang, Tao, FDA/CDER (Mentor); Yeh, Matthew M., University of Washington School of Medicine (Mentor); Feldman, Gerald M., FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Immunogenicity of single administration therapeutic biologics for acute indication The propensity of therapeutic biologics to elicit immune responses against the therapeutic biologics and their related proteins may impact therapeutic outcomes including safety and efficacy. Dose and frequency of drug administration can affect the risk of immunogenicity. Here, we evaluated existing immunogenicity data and identified potential factors that may contribute to immunogenicity risk of single administered biologics approved by the FDA Unleashing the Power of Data Park, Bomina, FDA/CDER (Student); Wang, Yow-Ming, FDA/CDER; Maxfield, Kimberly, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Impact of Various Decontamination Methods on Performance of Personal Protective Equipment (PPE) Several decontamination methods were not able to obtain FDA s emergency use authorization (EUA) during the current pandemic. In this poster, we will investigate the impact of decontamination on two PPEs: N95 respirators and gowns with three different methods: microwave generated steam decontamination, autoclave sterilization, and gaseous ozone decontamination. To make sure that these decontamination techniques don t impact PPE performance, filtration efficiency, pressure drop and fit testing will be performed for various models and make of N95 respirators, and AATCC 42 spray impact test, the AATCC 127 hydrostatic head test, and the ASTM F1670/F1671 soils resistance tests performed with gowns. This work will develop our understanding of infrequently evaluated decontamination techniques and their impact on medical personnel s disposable PPE if shortages were to occur in future Public Health Emergency Preparedness and Response Joseph Nelson Dawson, Anne Lucas, Matthew Schwerin, Suvajyoti Guha   Center for Devices and Radiological Health
Implementation of a human in vitro assay to evaluate tissue specificity during irreversible electroporation cardiac ablation Atrial fibrillation (AF) can carry significant cardiac risks for patients. With minimal adverse effects, irreversible electroporation (IRE) ablation is a novel, non-thermal technology that has the potential to treat AF. Using human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs), this study intends to use a human in vitro assay developed at the FDA laboratories to investigate tissue specificity of IRE treatments. Empowering Patients and Consumers Rashid, Sujen, CUNY York College (Student); Casciola, Maura, FDA/CDRH (Mentor), Fester, Tromondae K., FDA/CDRH (co-author), Blinova, Ksenia, FDA/CDRH (commenter)   Center for Devices and Radiological Health
Improved lesion quantification and volume estimation with simulated contrast-enhanced digital breast tomosynthesis using generative adversarial networks. Iodine contrast-enhanced spectral mammography (CEM) combines an iodinated contrast agent, such as one used for a typical CT scan, with mammography imaging. The contrast enhancement improves the ability to see some cancers that may not be visible in standard mammography. Contrast-enhanced mammography has been proposed as a cost-effective and robust alternative to magnetic resonance imaging (MRI) for breast cancer imaging, especially in dense breasts. However, one drawback is poor quantification of contrast agent due to the two-dimensional projection in mammogram images. Digital breast tomosynthesis (DBT) is a pseudo-three-dimensional (3D) imaging modality that uses limited angle tomography. DBT typically exhibits high in-plane resolution, with poor out-of-plane resolution. This out-of-plane blur in DBT distorts the reconstructed lesion and can degrade lesion quantification and volume estimation. Neural networks can be trained to predict a full angle CT reconstruction from a limited angle DBT input image.A network was trained to perform this image restoration using a large number of Monte Carlo simulated lesion volumes-of-interest (VOI) from DBT and breast CT reconstructions. Using the output images of the trained neural networks will hopefully allow for more accurate lesion quantification and volume estimation than is possible with DBT images. Unleashing the Power of Data Toner, Brian, FDA/CDRH/OSEL/DIDSR (student); Makeev, Andrey, FDA/CDRH/OSEL/DIDSR; Kc, Prabhat FDA/CDRH/OSEL/DIDSR; Glick, Stephen FDA/CDRH/OSEL/DIDSR (Mentor)   Center for Devices and Radiological Health
Influence of Aerobactin on Virulence in the Fur-box sequencing of Salmonella enterica Under Iron-rich and Iron-poor Conditions Salmonella enterica (S. enterica) is a Gram-negative member of the Enterobacteriaceae family. S. enterica subsp. enterica (I) is the predominant subspecies containing serovars that have been shown to cause disease in humans. Despite shared genes with a close identity, typhoidal and non-typhoidal Salmonella (NTS) serovars have different disease outcomes and epidemiological patterns. Virulence factors, such as the siderophore, aerobactin, impact the diseases caused by S. enterica serovars. This project aimed to decipher the regulation of aerobactin expression through the fur-box sequence on the iucA promoter and the impact on S. enterica pathogenesis. Understanding the underlying mechanisms in the pathogenicity of different serovars is important to control infection and advance treatment. Public Health Emergency Preparedness and Response Carolyn Henry (student), Steven Foley (mentor),   National Center for Toxicological Research
Influence of lattice orientation on additively manufactured nylon lattice structures The orientation of unit cells in lattice structures is an important consideration when designing additively manufactured medical devices. This research aims to investigate how the AM build orientation of five common unit cell types affects the mechanical response of additively manufactured nylon lattice structures during compression testing. Increasing Choice and Competition through Innovation Noah Zipin, Andrew Cunningham, Kirstie Snodderly, Matthew Schwerin, Daniel Porter   Center for Devices and Radiological Health
Influence of Topology Optimization parameters on the mechanical response of an AM test Topology optimization has been used to reduce the weight of a test structure. Topology optimization parameters and their effects on a structure s performance should be well understood for the structure s intended application. In this project, a pipe-flange structure is optimized using various topology optimization workflow parameters. Finite element analysis and experimental verification are performed to analyze the test structure s mechanical response. Increasing Choice and Competition through Innovation Myung Kyun Sung (Student); Oluwatobiloba Sanni; Yutika Badhe; Sarah Van Bellegham; Matthew Schwerin; Andrew P. Baumann; Daniel Porter (Mentor)   Center for Devices and Radiological Health
Investigating the Effect of Design Parameters on the Corrosion Properties of Additively Manufactured 316 Stainless Steel Additively manufactured (AM) medical devices can result in different metallic microstructures based on the AM build parameters. This research investigated how AM technology, build orientation, and heat treatment affect the corrosion properties of 316 stainless steel. Potentiodynamic polarization testing (ASTM F2129), optical imaging, and profilometry were used to compare AM samples to the conventional wrought control material. Public Health Emergency Preparedness and Response McDermott, Eric, FDA/CDRH (Student); Sivan, Shiril, FDA/CDRH; Di Prima, Matthew, FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Investigating the feasability of classifying breast microcalcifications using GaAs photon-counting spectral mammography The goal of this research was to investigate the use of a Gallium Arsenide (GaAs) photon-counting spectral mammography system to differentiate between Type I and Type II microcalcifications. Type I calcifications are more often associated with benign lesions while Type II calcifications are predominantly associated with malignant lesions. Photon counting spectral mammography and spectral digital breast tomosynthesis (DBT) have great promise for increasing the positive predictive value for tissue biopsy (PPV3). This can potentially improve early breast cancer diagnosis and reduce the number of unnecessary breast biopsies. Increasing Choice and Competition through Innovation Bader, Shahed, FDA/CDRH (Student); Ghammraoui, Bahaa, FDA/CDRH (Mentor); Glick, Stephen, FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Investigation of skin-to-skin transfer risks of topically applied transdermal hormonal drugs Hormonal drugs are widely used by patients for the treatment of hormonal deficiencies and imbalances. Testosterone and estradiol transdermal drug products are the most prescribed medications for transdermal hormonal replacement therapy. A major risk associated with transdermal hormonal replacement therapy is the potential for skin-to-skin drug transfer from a dosed individual to a healthy individual (e.g. partner, children, pets). As such, it is important to understand the correlation between the type of dosage form and the physiochemical properties of the formulation excipients that might be responsible for enhancing the potential risk of drug transfer from the dosed to the healthy individual . From extensive literature review, it was found that testosterone gels and estradiol emulsions were the two dosage forms that posed the greatest risk of skin-to-skin transfer from the dosed individual to healthy individual. However, the effects of physiochemical properties of the formulation excipients on the potential skin to skin drug transfer has not been reported. As such, the current OTR research aims to develop an in vitro permeation method to identify critical formulation variables that may promote skin-to-skin drug permeation of such drug products. Unleashing the Power of Data Samiha Uddin (student), Ahmed Zidan, Muhammad Ashraf, Nahid Kamal* (mentor)   Center for Drug Evaluation and Research
Investigation on the stability of a monoclonal antibody The poster will include the abstract, an introduction, materials and methods, results, conclusions, and references. The abstract will include the abstract of the research. The introduction will include basic information about the study. The materials/method will include materials utilized during the study along with an explained procedure of the study. Pictures will also be included to better illustrate how the study was carried out. Results will include pictures of the SDS page with graphs and analysis of data. Conclusion will include further treatments and possible outcomes from current treatments. References will include the sources used to aid this study. Empowering Patients and Consumers Aser Zidan, FDA/CDER (Student), George Liang, FDA/CDER (Student), Chikkathur Madhavarao FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Laser Diffraction Particle Size Analysis of Mycotoxin Samples Laser diffraction-based measurements offer a more practical and time-efficient alternative for particle size analysis and can be incorporated into routine sample analysis to chracterize homogeneity of prepared samples. Increasing Choice and Competition through Innovation Tan, Steven, FDA/CFSAN (Student); Zhang, Kai, FDA/CFSAN (Mentor); Martinez Lopez, Claudia (Colleague)   Center for Food Safety and Applied Nutrition
Metal Ion Burst Release Characterization and Accelerated Testing Methods on Nitinol Nitinol is often used in medical devices and can release nickel, which can have a range of toxicological effects. ASTM F3306-19, used to quantify metal ion release, has unknown correlation to corrosion that occurs in vivo. An accelerated testing method that can sufficiently characterize the burst release of nickel was investigated. Increasing Choice and Competition through Innovation Zhu, Amanda (student); Nguyen, Alexander (mentor); Sussman, Eric (mentor)   Center for Devices and Radiological Health
Methods for Characterizing Temporal Patterns of Prescription Opioid Utilization The crisis of opioid nonmedical use and overdose in the United States has involved unprecedented levels of opioid analgesic (OA) prescriptions and opioid-related mortality. Several proprietary drug utilization databases are utilized by the U.S. Food and Drug Administration to better understand the scope of prescription OA use and evaluate patterns. Such drug dispensing data include the number of prescriptions dispensed in aggregate over a time frame by geographical locations. In this poster, we describe a two-step approach to: 1) identify geographic areas that had significant change over time in prescription drug dispensing, and 2) characterize clusters of geographic areas that share similar temporal change patterns. Results from a simulation study and analyses of naloxone and buprenorphine prescription dispensing data are discussed to evaluate the utility of the proposed method. Unleashing the Power of Data Yuting Xu, FDA/CDER (Student); Elin Cho, FDA/CDER (Student); Jaejoon Song, FDA/CDER (Mentor); Yueqin Zhao, FDA/CDER (Mentor); Rose Radin, FDA/CDER (Collaborator); Grace Chai, FDA/CDER (Collaborator); Yong Ma, FDA/CDER (Collaborator); Shekhar Mehta, FDA/CDER (Collaborator); Meilan Chen, FDA/CDER (Collaborator); Kyle Lee, FDA/CDER (Collaborator); Corinne Woods, FDA/CDER (Collaborator); Saranrat Wittayanukorn, FDA/CDER (Collaborator).   Center for Drug Evaluation and Research
Missing Field Alert Reports: An Interactive Portal Analyzes their Distribution A natural language processing technique for text mining is applied to 12,000 FDA Establishment Inspection Report (EIRs) from 2012-2020 to create a novel data set of FARs submission failures. Statistical multiplicity tests with non-parametric tests and graphical testing procedure are leveraged to explore the distribution of facilities with FAR submission failures by location, establishment type, count of ANDAs, etc. An interactive portal is developed with R Shiny that could be used by regulators for monitoring facilities with FAR submission failure and potentially to facilitate FDA quality surveillance. Unleashing the Power of Data Born, Joshua, FDA/CDER (Student); Wang, Yow-Ming, FDA/CDER (Mentor); Li, Ye FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Modeling the Risk of Drug-Induced Liver Injury with Adverse Outcome Pathways and Bayesian Networks High throughput in vitro assays have the potential to lead to more efficient, accurate, and less animal-intensive testing. However, how to take advantage of the numerous in vitro tests in actual risk assessment processes is still a significant challenge. In this poster, we present a Bayesian network model based on adverse outcome pathway (AOP) networks for drug-induced liver injury (DILI). The model uses L1000 and Tox21 data for gene expression and nuclear receptor binding. Due to the incorporation of significant expert knowledge in the form of AOP, the Bayesian network model has the advantage of being parsimonious and requires only a small number of assays to predict the risk of toxicity. Unleashing the Power of Data Mahanama, Thilini, FDA/NCTR (Student); Biswas, Arpan, NCTR; Wang, Dong, FDA/NCTR (Mentor)   National Center for Toxicological Research
Modernizing Drug Labeling Presentation Related to Quantitative Clinical Pharmacology Current regulatory practice has gaps in the presentation of quantitative clinical pharmacology information in drug labeling thus leading to inconsistencies that are uninformative. This includes the misrepresentation of ADME parameters such as (terminal/elimination half-life vs effective half-life), inconsistent use of clearance vs. body-size normalized clearance, mis-presentation of population variability vs. parameter precision, inclusion of incomplete PK information of specific population, and inadequacies in the presentation of exposure-response relationships. The objective of the study is to understand how the clinical pharmacology information for a drug is derived and evaluated, and to improve the current quantitative clinical pharmacology labeling practice. The study performs a comprehensive analysis through evaluation of criteria based on clinical pharmacology guidance regarding the labeling for human prescription drugs and biological products. Empowering Patients and Consumers Pernati, Chenchu Vignesh, FDA/CDER (Student); Yao, Kevin, FDA/CDER (Student): Liu, Jiang, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Morphological changes of insulin drug products under real-world stress conditions This study aims to evaluate failure modes of insulin and its analogs under real-world stress conditions which may negatively impact product quality. Stability of the insulin drug products will be evaluated under various stress conditions such as thermal, mechanical and combination stress and analyzed using flow imaging and dynamic light scattering. Particle morphology, size, and concentration data will be obtained to determine the correlation between stress condition and product quality Increasing Choice and Competition through Innovation Amina Tithi, Ashwinkumar Bhirde, Cyrus Agarabi, Kim Minkyung   Center for Drug Evaluation and Research
Natural Language Processing of cGMP Inspectional Observations and Citations for FDA CDER's Risk-Based Site Selection Model FDA 483 observations reflect facilities  compliance performance and potentially contribute to the FDA CDER-ORA site selection model (SSM). We developed a model that understands the corresponding infraction in the 483 based off inspectors  violation descriptions. Unleashing the Power of Data Henderson, Taylor, FDA/CDER (Student); Wan, John, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Optimal Data Parallelization of the BLAST Bioinformatics Application on HPC clusters The widely used bioinformatics application Basic Local Alignment Search Tool (BLAST) was improved by optimally distributing the workload among thousands of computing nodes in the CDRH HPC clusters to gain a speedup of ~200x when comparing a 15 GB query against a 2.5 GB nucleotide sequence database. Unleashing the Power of Data Cheng, Trinity, FDA/CDRH/OSEL/DIDSR (Student); Chin, Pei-Ju, FDA/CBER/OVRR/DVP/LR (Coauthor); Mikailov, Mike, FDA/CDRH/OSEL/DIDSR (Mentor)   Center for Devices and Radiological Health
ORCA Database Methodology: Sacroiliac, Ankle, and Hip Implants Review of premarket notification (510(k)) submissions for orthopedic implants often involves the comparison of design characteristics and mechanical testing results between the newly proposed device and previously cleared  predicate  devices. To streamline the review of future 510(k)s, design information and mechanical testing data from previously reviewed 510(k) submissions and Q-submissions were entered into the Orthopedic Rapid Comparative Analysis (ORCA) database for sacroiliac joint implants, total ankle replacements, and total hip replacements. This allows lead reviewers to effectively and efficiently compare new devices to a substantial collection of previously cleared devices and make confident decisions based on FDA precedent. Unleashing the Power of Data Chow, Megan, FDA/CDRH (Student); Groves, Cecilia, FDA/CDRH (Student); Marine, Marissa, FDA/CDRH (Student); Peluso, Joseph, FDA/CDRH (Student); Peck, Jonathan, FDA/CDRH (Mentor); Kavlock, Katherine, FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Pan T Cells Mediate Cytotoxic CD8 Positive T Cell Resistance in Breast Cancer Cells The research findings from this study reveal a previously unappreciated resistance mechanism of cancer cells to immunotherapy, specifically concerning the development of breast cancer cell resistance to Pan T cells. Unleashing the Power of Data Ju, Anna, FDA/CDER/OBP (Student); Endo, Yukinori FDA/CDER/OBP (Mentor); Takeda Kazuyo FDA/CDER; Winarski Katie FDA/CDER/OBP; Wu, Wen Jin FDA/CDER/OBP (PI)   Center for Drug Evaluation and Research
Particle Size Distribution of Silicon Dioxide Food Additives Several commercially available silicon dioxide food additive samples were analyzed to determine their particle size distribution. The particle size distribution was affected by the method of sample preparation, but nanoparticles were found in all samples. Empowering Patients and Consumers Kalan, Matthew S., FDA/CFSAN/ORS/DAC/SMSB (Student); Croley, Timothy R., FDA/CFSAN/ORS/DAC/SMSB; Khan, Sadia Afrin, FDA/CFSAN/ORS/DAC/SMSB (Mentor)   Center for Food Safety and Applied Nutrition
Path2AI : AI System for Digital Pathology In today's fast paced world, Toxicological Pathology remains to be a bottle neck. In this paper, we propose an alternative AI system based on image processing and machine learning to alleviate part of the process of pathology and create informative whole slide images from raw image data. Unleashing the Power of Data Salman, Hadi, FDA/NCTR (Student); Wu, Leihong, FDA/NCTR (Mentor), Tong, Weida FDA/NCTR (Mentor)   National Center for Toxicological Research
Portfolio of Women-Specific Medical Devices The CDRH Health of Women Program, as part of its research roadmap for sex- and gender-specific medical devices, has developed a Portfolio of Women-Specific Medical Devices. The portfolio includes device names, manufacturers, product codes, instructions for use, cited regulations, and recalls. The portfolio provides information about women-specific medical devices availability, safety, and effectiveness and will support future efforts to identify and address gaps in women-specific medical device research. Increasing Choice and Competition through Innovation Kolarich, Morgan, FDA/CDRH (Student); Cornelison, Terri, FDA/CDRH (Mentor); Hazlett, Antoinette, FDA/CDRH; Krueger, Carol, FDA/CDRH   Center for Devices and Radiological Health
Proposal of a Modified Procedure for AATCC-100-1993 to Account for Viable But Non-Culturable (VBNC) Bacteriaand Evaluate Silver Ion Containing Wound Dressings with Pseudomonas aeruginosa This poster shows the need for a procedure that can effectively track time dependent changes in antimicrobial properties of silver ion containing wound dressings. The proposed method implements additional molecular assays such as qRT-PCR with cell viability assay to better understand changes in bacterial behavior and activity. Empowering Patients and Consumers Sang Hyuk Lee, FDA/CDRH (Student); Thomas Glover, FDA/CDRH (Student); Nathan Lavey, FDA/CDRH; Anne Lucas, FDA/CDRH; Marc Donohue, JHU (Mentor); Enusha Karunasena, FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Protecting the Borders: Evaluation of Rapid Screening Tools for Package Analysis at the International Mail Facilities The development of a method for the rapid screening of food and drug products in violative products for constituents such as opioids, weight-loss drugs, steroids and life style drugs has become increasingly important. Violative products are unapproved products, counterfeit or substandard drugs, and dietary supplements sold for uses including weight loss, sexual enhancement, bodybuilding or pain relief that may contain potentially hazardous ingredients. Direct Analysis in Real Time with thermal desorption mass spectrometry (DART-TD-MS), hand-held mass spectrometry, portable ion mobility spectrometry (IMS), and portable Fourier-transform infrared spectroscopy (FT-IR) were each evaluated as field-deployable screening techniques for rapid package screening. These devices offer the potential for rapid, early detection of unapproved drugs in suspect products entering the United States through international mail facilities and other ports of entry. Increasing Choice and Competition through Innovation Megan Sterling, Sara Kern, Martin M. Kimani, Kirk Gaston   Office of Regulatory Affairs
Ranking Human Arterial Pathways Using Metrics of Curvature and Tortuosity for Simulated Use Bench Testing of Neurovascular Interventional Devices Catheters and guidewires have been used for tracking through tortuous anatomies in a variety of surgical procedures. But there is a concern that the polymer coatings applied to these devices may delaminate and separate during surgery, causing complications. In this study, curvature and tortuosity metrics were quantitatively evaluated to help determine what arterial pathway within a patient-specific anatomy may be a challenging scenario for preclinical testing of future devices with coating materials. The framework established here may be used eventually to evaluate multiple patient-specific anatomies. Increasing Choice and Competition through Innovation Garland, Katherine, FDA/CDRH (Student); Duraiswamy, Nandini, FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Reporting of Demographic Information in Orthopedic Clinical Studies Individual patients and their medical providers may benefit from more data regarding effectiveness and potential adverse events associated with device use in a particular demographic subgroup; yet some demographic subgroups may not be included in clinical studies at rates reflective of the general US population. Total number of study participants as well as demographic information about orthopedic study populations from investigational and control groups was collected from the Summaries of Safety and Effectiveness Data (SSEDs) published for all approved Premarket Approvals (PMAs) and Humanitarian Device Exemptions (HDEs). Descriptive analysis included longitudinal trend analysis compared to data from the US census to see how study demographics compared to the general US population over time. This study will allow FDA staff, patients, and medical providers to have a better understanding of whether clinical studies provided to FDA accurately reflect the general US population, and whether further steps should be taken to encourage participation by any particular demographic subgroup. Unleashing the Power of Data Peluso, Joseph, FDA/CDRH (Student); Chow, Megan, FDA/CDRH (Student); Groves, Cecilia, FDA/CDRH (Student); Marine, Marissa, FDA/CDRH (Student); Kavlock, Katherine, FDA/CDRH (Mentor); Hongying, Jiang, FDA/CDRH (Mentor); Adegboyega-Panox, Elizabeth, FDA/CDRH (Mentor); Peat, Raquel, FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Reporting Sex- and Gender-Specific Information in Medical Device Reports Submitted in 2019 A cross-sectional analysis was performed to determine how often sex and gender information are reported in Medical Device Reports (MDRs) of adverse events submitted to the FDA during a two-week period in December 2019. Unleashing the Power of Data Alexandra Turco (Student), CDRH: Daniel Dill, Antoinette Hazlett, Carol Krueger, Donna Engleman, CAPT Terri Cornelison (Mentor)   Center for Devices and Radiological Health
Safety and Risk Assessment Associated with Nanocrystal Drug (Zileuton) Formulation Nanocrystal drug (ND) formulation is an emerging technology in the field of medicine that helps to improve the solubility and bioavailability of oral drugs. As a result, we expected to observe variation in the reactivity of NDs in the intestinal tissue. To determine the safety and efficacy of NDs, we tested nanocrystal formulated Zileuton (poorly soluble BCS-II drug) in a rat model to evaluate the influence on commensal bacteria and assess its immunotoxicity. Empowering Patients and Consumers Bright, Anshel, FDA/NCTR (Student); Gokulan, Kuppan, FDA/NCTR (Mentor)   National Center for Toxicological Research
Sex- and Gender-Specific Differences in Adverse Events in Medical Devices Reports in CY2019 Adverse events reports were reviewed to determine if there is a sex- or gender-specific difference in reported adverse events for medical devices. Unleashing the Power of Data Alexandra Turco (Student), CDRH: Daniel Dill, Antoinette Hazlett, Carol Krueger, Donna Engleman, CAPT Terri Cornelison (Mentor)   Center for Devices and Radiological Health
Sex- and Gender-Specific Subgroup Analysis in Approved Pre-Market Applications (PMAs) for Calendar Year 2020 Review of PMA applications received in 2020 following the 2014 Guidance  Evaluation of Sex-Specific Data in Medical Device Clinical Studies  to determine the rate of reporting of sex- and gender-specific data in submissions. Unleashing the Power of Data Nayak, Adishree, FDA/CDRH (Student); Cornelison, Terri L., FDA/CDRH (Mentor); Hazlett, Antoinette C., FDA/CDRH (Mentor); Krueger, Carol L., FDA/CDRH (Mentor)   Center for Devices and Radiological Health
Sex- and Gender-Specific Subgroup Analysis in Approved Pre-Market Approval (PMA) Applications for Calendar Year 2019 This poster presents an update to the FDASIA 907 Report regarding sex/gender-specific data analysis and public reporting for approved PMA applications submitted after issuance of the CDRH Guidance on Sex-Specific Data. The review disclosed a decline in the number of PMA applications that included sex-specific data analysis and that made these results publicly available. Unleashing the Power of Data Alexandra Turco (Student), CDRH: Daniel Dill, Antoinette Hazlett, Carol Krueger, Donna Engleman, CAPT Terri Cornelison (Mentor)   Center for Devices and Radiological Health
Skin Pigmentation Impacts on Established and Emerging Optical Diagnostic Devices: A Survey of Mechanisms and Effects To improve public health and facilitate effective regulation of established and emerging optical diagnostic devices there is a need to better understand the extent of device types impacted by epidermal melanin. We provide an overview of the biology and spectral properties of melanin and a summary of research findings on the impact of skin pigmentation on detected optical signals, as well as device performance. For each of these devices we examine the light-tissue interaction mechanisms involved and the manner in which pigmentation impacts clinical results. In addition to common devices like pulse oximeters and wearable PPG devices, we address cerebral oximeters, photoacoustic imagers, hyperspectral imaging systems, bilirubinometers, etc. Finally, we analyze our findings, discuss their scientific and regulatory implications and provide some initial recommendations. Increasing Choice and Competition through Innovation Lin, Isaac, FDA/CDRH (Student); Pfefer, Joshua, FDA/CDRH (Mentor); Vogt, William, FDA/CDRH; Wang, Jianting, FDA/CDRH; Weininger, Sandy, FDA/CDRH; Scully, Chris, FDA/CDRH;   Center for Devices and Radiological Health
Stable Isotopic labeling of 1,2 13C2-Glucose and 1,6 13C2-Glucose for tracing CHO cell and mass spectrometry-based metabolomics This poster will overview isotopic labeling and method development on the Ambr15 bioreactor. Comparison of the metabolite extraction and instrument methods will be used to characterize the impacts on critical quality attributes. This involves the use of UNcle, HPLC-SEC, and LabChip GXII to study protein fragmentation, aggregation, and charge variance. Empowering Patients and Consumers Xin Bush (student, FDA, CDER), Erica Berilla, Sai Rashmika Velugula, David Powers, Nicholas Trunfio, Talia Faison, Roberta King, Cyrus Agarabi (Metntor, CDER, FDA)   Center for Drug Evaluation and Research
Statistical Analyses of Product Acceptance Criteria To ensure drug dosage homogeneity, the FDA requires products to pass USP GC <905> Uniformity of Dosage Units (UDU) acceptance testing. Novel manufacturing methods, such as continuous manufacturing, allow for a large number of samples to be analyzed throughout the manufacturing process. However, the UDU test is not a statistical test and has overly strict acceptance criteria for large sample sizes, limiting the implementation of new processes. To overcome these concerns, several statistical tests, with updated sampling methods and acceptance criteria, have been proposed. The project aims to analyze established and novel sampling plans, with an ultimate goal to develop standardized statistical analyses and acceptance criteria evaluation for large sample size drug quality assessment, which will be used to construct software program(s) and an R Shiny application to facilitate statistical analysis. Establishing standards will benefit multiple offices within CDER by improving efficiency and reproducibility. Unleashing the Power of Data Guglielmo, Kimberly, FDA/CDER (Student); Schuette, Paul, FDA/CDER (Mentor); Stafford, Michelle, FDA/CDER (Mentor); Goldie, Scott, FDA/CDER (Mentor); Viehmann, Alex, FDA/CDER; Li, Ye, FDA/CDER   Center for Drug Evaluation and Research
Sterilization Methods and Their Effects on the Dimensional Stability of Additively Manufactured Medical Devices In this project, we aim to provide an overview of AM technologies, materials, and sterilization methods that are currently in use for 3d printed medical devices. Future trends in sterilization are also discussed. Increasing Choice and Competition through Innovation Capadona, Charisse, FDA/CDRH; David Kaplan and Irada Isayeva (Mentors), Tanmay Jain, and Joyce Kitzmiller   Center for Devices and Radiological Health
Study Population Recommendations in Product-Specific Guidances for In Vivo Bioequivalence Studies of Kinase Inhibitors With Kinase Inhibitors (KIs) developed increasingly for the treatment of various malignancies, a rising interest has been placed into the development of generic version of KI drugs. Product-specific guidance (PSG) is proposed by the Agency to assist the generic pharmaceutical industry for developing drugs and generating evidence needed to support the approval of abbreviated new drug applications (ANDAs). One of the major challenges in developing the PSG for KI drugs is to select appropriate study subjects for bioequivalence (BE) studies. Most PSGs published for KI drugs recommend BE study to be conducted in general population or healthy volunteers. There are a few PSGs recommend patients. Through exploring the rationale of study subject recommendations in BE studies during the PSG development, the purpose of this project is to systemically collect and summarize the rationale for each corresponding BE recommendation for a specific kinase inhibitor drug, subsequently to facilitate the decision making process on selecting appropriate study subjects for bioequivalence studies on KI drugs. Unleashing the Power of Data Cheng, Yijie, FDA/CDER (Student); Yang, Wen Cheng, FDA/CDER (Mentor); Ren, Ping, FDA/CDER; Chan, Theresa, FDA/CDER; Shon, Jihong, FDA/CDER; Gong, Xiajing, FDA/CDER; Boyce, Heather, FDA/CDER; Frost, Mitchell, FDA/CDER; Kim, Myong-Jin, FDA/CDER; Zhang, Yi, FDA/CDER   Center for Drug Evaluation and Research
Survey of FDA-approved presentations of therapeutic biologics The regulatory approval of new presentations for therapeutic biologics may involve pharmacokinetic (PK) comparability assessment which includes area under the concentration-time curve (AUC) and maximum concentration (Cmax) estimation. Current practice for AUC estimation is sampling for an adequate duration (3-5 half-lives) to capture the full PK profile which may translate into long study duration of months for certain products. A comprehensive database of all presentations currently available for 293 FDA-approved therapeutic biologics was created to enable future work aimed at identifying opportunities to simplify the regulatory approval process of biologic presentations. Increasing Choice and Competition through Innovation Delaney McGuirt (Student), Sneha Rathi (Student), Ping Ji, Renu Singh, Jianmeng Chen, Yow-Ming Wang, Bhawana Saluja, Suresh Doddapaneni, Chandrahas Sahajwalla (Mentor)   Center for Drug Evaluation and Research
Temperature and the Susceptibility of Salmonella to Biocides Salmonella are Gram-negative, rod shaped, and facultative anaerobic bacteria that are commonly found in the intestinal tracts of humans and farm animals. Salmonella can also be found in animal feed, soil, polluted water, and fecal matter through contamination, which can result in infectious disease. In the United States, Salmonella is the leading foodborne pathogen, which can cause salmonellosis in humans and Salmonella foodborne outbreaks. To limit the spread and burden of Salmonella in the food processing environment, biocides and other antimicrobial agents are often used. Biocides are chemical agents that do not have a distinct biological target in bacteria and can instead act on one or more sites in the cell, which results in overall damage to the bacteria. This contrasts with antibiotic compounds, which have specific targets in the bacterial cell, such as the cell wall, protein, and nucleic acid synthesis, and cell membrane function. Antibiotics also have a threshold at which they can inhibit or kill bacteria, which biocides do not have. The purpose of this study is to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of seven Salmonella enterica serotypes in biocides at different temperatures. Public Health Emergency Preparedness and Response Aguocha-Sam, Vanessa, FDA/CFSAN (Student); Hoffmann, Maria, FDA/CFSAN (Mentor); Zheng, Jie, FDA/CFSAN; Jayeola, Victor, FDA/CFSAN   Center for Food Safety and Applied Nutrition
The Development of Quantitative System Pharmacology (QSP) Model Platform to Guide Clinical Development of T cell Redirecting Engagers (TCEs) T cell redirecting engagers (TCEs) are a novel class of immunotherapeutics that redirect T cells to tumor surface antigens to trigger target cell (i.e., tumor cell) killings. The development of TCEs still faces considerable challenges partly contributed by the multi-factorial determinants for the activity of TCEs. This QSP model platform developed and presented here may provide useful considerations to assist regulatory decisions and provide guidance for the future drug development of TCEs. The model platform focused on three major aspects: the factors influencing the exposure-response relationship of TCEs, the contribution of soluble targets to the pharmacokinetics and pharmacodynamics (PK/PD) of TCEs, and TCEs PK following intravenous (IV) vs. subcutaneous (SC) administrations. This model platform was able to predict the cytotoxicity and cytokine release of TCEs, demonstrate the TCEs PK/PD changes with the presence of soluble target and provide comparison of TCEs PK following IV vs. SC administrations. Increasing Choice and Competition through Innovation Cheung, Yuen Kiu - FDA/CDER (Student); Jiang, Xiling - FDA/CDER (Mentor); Zhao, Miao - FDA/CDER; Feng, Zhou - FDA/CDER; Okusanya, Olanrewaju - FDA/CDER   Center for Drug Evaluation and Research
The Effect of Lactobacillus plantarum Producing Lysostaphin Impregnated Tampons on Staphylococcus aureus When Grown in a In Vitro Model Simulating the Vaginal Tract Lactobacillus plantarum producing lysostaphin inhibition of toxic shock syndrome toxin-1-producing Staphylococcus aureus when assessed in an in vitro simulated vaginal tract model. Public Health Emergency Preparedness and Response Milligan, Hattie E., FDA/NCTR (Student); Hart, Mark E., FDA/NCTR (Mentor)   National Center for Toxicological Research
The gastric pH-dependent drug interactions with acid-reducing agents for oral oncology drugs current status and future assessment The bioavailability of orally administered weak base drugs that exhibit pH-dependent solubility may be decreased when taken concomitantly with gastric acid reducing agents (ARAs), with potential to decrease the drug s efficacy. The Food and Drug Administration (FDA) recently published a draft guidance for industry Evaluation of Gastric pH-Dependent Drug Interactions With Acid-Reducing Agents: Study Design, Data Analysis, and Clinical Implications. We have designed this study to assess how the guidance recommendations are implemented regarding: 1) when clinical drug-drug interaction (DDI) studies with acid-reducing agents (ARAs) are needed; 2) the design of clinical DDI studies; 3) how to interpret study results; and 4) communicating findings in drug product labeling with focus on oncology drugs. The current study collected into a database available data from FDA approved orally administered oncology new molecular entities (NMEs) which have data on co-administration with ARA treatment. It includes all NME NDAs reviewed for oncology indications and approved from 2008 to present. Next steps include analysis of the data collected in the database to assess the differential effects of identified factors (e.g. solubility pH-dependency, food effect, bioavailability, etc.) on the clinical PK of oncology drugs that are prone to the interaction with ARAs. These assessments will offer insights leading to more comprehensive recommendations on criteria for determination of the need for clinical DDI studies with ARAs; the optimal designs of clinical DDI studies with ARAs; better understanding and interpreting study results; and consistent oncology drug labeling on pH-dependent DDIs. Unleashing the Power of Data Green, Francis (ORISE Fellow); Liu, Yajing; Zhao, Hong   Center for Drug Evaluation and Research
The immunotoxicity of cobalt-chrome (CoCr) particles generated from prosthetic implants in differentiated HL-60 cells Metals, such as cobalt and chromium, are present in prosthetic implants that are used to replace damaged hips, knees, and shoulders. However, there is continued concern about particles and metal ions produced from wear damage of these implants that may impact the success of prosthetic implants in clinical practice. The aim of this study was to develop a model to test the effect of CoCr particles generated from prosthetic hip implants on the phagocytic function of macrophages and to test the chemoattractant capability of these particles to recruit neutrophils in vitro. Results indicate that CoCr particles had an inhibitory effect on the phagocytic function of macrophages and no chemoattractant capacity to neutrophil-like cells differentiated from HL-60 cells. Empowering Patients and Consumers Sidwell, Allie, FDA/NCTR (Student); Trout, Kevin, FDA/NCTR; Canup, Brandon, FDA/NCTR; Fahmi, Tariq, FDA/NCTR (Mentor)   National Center for Toxicological Research
The Operationalization of Food Safety Culture in Retail Food Safety Research: A Systematic Review Food safety is a global concern leading the food industry to seek approaches that prevent outbreaks and improve safety performance. The concept of food safety culture has become a new focus of this sector and has been mentioned as a potential factor to influence employee behavior. However, its conceptualization and assessment remain unclear. This poster describes research and findings on how food safety culture is defined, conceptualized, and operationalized in existing studies of retail food establishments. As food safety culture is widely expressed as a subset of organizational culture, its relationship with the components or theories associated with organizational culture was also investigated. Results showed there is no common definition, conceptualization, or operationalization established for food safety culture, which suggests a need to develop consistent quantitative measures and frameworks for future research. Public Health Emergency Preparedness and Response Kim, Sei Rim (Sally), CFSAN/OFS/RFPS (Student); Liggans, Girvin, CFSAN/OFS/RFPS (Mentor)   Center for Food Safety and Applied Nutrition
Theoretical Comparison and Optimization of CdTe and GaAs Photon-Counting Detectors for Contrast-Enhanced Spectral Mammography There has recently been renewed interest in quantitative iodinated contrast-enhanced breast imaging, sometimes referred to as contrast-enhanced spectral mammography (CESM). Photon counting detectors (PCDs) have a number of benefits for iodinated contrast-enhanced imaging over dual-energy systems (using energy integrating detectors), one of which is the capability of acquiring multi-bin data with one exposure. Most PCDs and prototype systems being developed are using CdTe or CZT sensor material which have non-optimal characteristic X-ray emission with energies in the range used for breast imaging. This causes increased charge sharing and spectral degradation. Recently, a new PCD has been developed using a GaAs sensor. Since GaAs has lower energy characteristic x-rays (lower than CdTe), it is expected that this new PCD detector might be beneficial for spectral x-ray breast imaging. In this work, we have theoretically compared the two detector materials in terms of iodine quantification using the Cramer-Rao lower bound (CRLB) as a figure of merit. Empowering Patients and Consumers Schaeffer, Colin, FDA/CDRH (Student); Glick, Stephen, FDA/CDRH, Ghammraoui, Bahaa, FDA/CDRH   Center for Devices and Radiological Health
Tolerance Interval Method for Quality Assessment We propose an approach to appropriately use the TI method to determine the multiplier of RI that assures certain probability to pass a pre-specified specification under various sample sizes for quality assessment. We will use dose content uniformity (DCU), delivered dose uniformity (DDU), and dissolution test as examples to illustrate how the TI method should be appropriately used for quality assessment. Unleashing the Power of Data Hore, Gaurab, FDA/CDER (Student); Weng, Yu-Ting, FDA/CDER (Mentor   Center for Drug Evaluation and Research
Transcriptomic and Epigenetic Alterations of in vitro Model of Hepatic Steatosis Nonalcoholic fatty liver disease (NAFLD) encompasses a range of liver disorders from liver steatosis or NAFL, characterized by basic fat accumulation, to more significant nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. In the present study two human hepatocyte cell lines, Huh7 and Hep3B, were treated with two prominent free fatty acids (FFA) to model NAFL in vitro. Following treatment, cells were assayed for transcriptional changes including DNA methylation and gene expression. Reduced representation bisulfite sequencing (RRBS) was performed to analyze changes in DNA methylation and RNA-Sequencing was performed to analyze changes in gene expression. The data sets obtained from RRBS and RNA-seq were analyzed to find a subset of gene targets for further analysis. The results of this study demonstrate the usefulness of an in vitro model approach to investigate the molecular pathogenesis of NAFLD, and may assist in future studies of genotoxicity. Unleashing the Power of Data Farnan, Taylor, FDA/NCTR (Student); Tryndyak, Volodymyr, FDA/NCTR (Mentor), Willet, Rose, FDA/NCTR, Pogribny, Igor, FDA/NCTR   National Center for Toxicological Research
Use of genomic biomarkers in clinical trials of neuropsychiatric diseases This study will assess how often biomarkers are used during neuropsychiatric drug development phases along with the association between drug target and disease. Empowering Patients and Consumers Saqib, Anum FDA/CDER (Student); Adeniyi, Oluseye FDA/CDER (Mentor); Schuck, Robert FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Use of knowledge management to track Radioactive Drug Research Committee data The FDA Radioactive Drug Research Committee (RDRC) program permits basic science research not intended for immediate therapeutic, diagnostic, or similar purposes using radioactive drugs in humans without an Investigational New Drug application (IND). The FDA RDRC program approves and oversees local RDRCs at major medical institutions that approve these basic radiation research studies. The local RDRCs submit an annual report to the FDA detailing the studies performed each year. Currently there is no comprehensive database for the RDRC. With the creation of a comprehensive database the FDA RDRC will be able to see larger trends throughout the countrywide RDRC program. The creation of a database requires that 15 years of RDRC annual reports be standardized, condensed and sorted. This was accomplished using Excel macros programed in Visual Basic for Applications, a programming language, in order to automate and streamline the process. The new database provides the FDA with a better understanding of the RDRC research studies and to possibly alert the RDRC program to unnecessary projects which expose participants to radiation with little prospect of providing new research findings. Unleashing the Power of Data Carley, Matthew, FDA/CDER (Student); Krefting, Ira, FDA/CDER (Mentor); Park, Luke, FDA/CDER (Mentor)   Center for Drug Evaluation and Research
Virtual dosimeter for interventional fluoroscopy We have implemented new software tools for the Virtual Dosimeter software package under development at CDRH/OSEL/DIDSR. The Virtual Dosimeter estimates the radiation dose received by operators and patients in interventional fluoroscopy procedures, using real-time tracking of the operator position in the room and the irradiation parameters. The new software coordinates the execution of the four independent modules that compose the Virtual Dosimeter using methods from the Robot Operating System, an open-source library for creating robotic applications. Increasing Choice and Competition through Innovation Lee, Hawon, FDA/CDRH (Student); Badal-Soler, Andreu, FDA/CDRH (Mentor)   Center for Devices and Radiological Health
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