Evaluation of Metal Ions in Electronic Cigarette Aersol Condensates and Determination of their Effects on Oral Keratinocytes
The goal of year 1 of the proposal is to develop a bioanalytical approach to identify the metal ions and HPHCs present in ECACs that are taken up by normal oral keratinocytes.Our bioanalytical strategy to measure the repertoire of EC hardware-derived metal ions and HPHCs present in ECACs and identify cellular uptake in oral keratinocytes will inform regulatory agencies charged with documenting the toxicological profile of new ECs prior to market authorization. We envision the FDA utilizing data from our assay and developed research tools to make regulatory decisions for both ECs in general and specific ECs (from different manufacturers). University of Maryland, Baltimore faculty contributing to the research are: Drs. Sarah Michel, Maureen Kane, Abraham Schneider, and Richard Dalby.
hERG Channel Pharmacology for CiPA"
The scope of work is to perform applied regulatory research in ion channel pharmacology. The Trudeau lab will collaborate with the FDA as part of the Comprehensive in-vitro Proarrhythmia Assay (CiPA) initiative. Our part of the collaboration will be to measure dose-response curves of 7 different drugs (at 4 different concentrations) that inhibit hERG (KCNH2) potassium channels, expressed in stably transfected HEK293 cells using whole-cell patch-clamp electrophysiology at physiological temperatures. Dr. Matthew Trudeau of the University of Maryland, Baltimore is contributing to this research, along with FDA collaborators David Strauss, Ruth Barratt, Wendy Wu, and Zhihua Li.
Improving FDA Health Communications with Older Women Regarding FDA-Regulated Products
Develop FG guides, materials in conjunction with FDA and M-CERSI content experts
- Guides will be based on the Health Belief Model
- Obtain any devices, communication materials, etc. to be presented during the FGs
- Conduct calls with FDA*Discuss clearances needed, including OMB clearance with FDA
- Recruit for a total of 12 FGs
- 8-10 women per group = 96-120 women, does not account for over recruitment
- Stratify by generation (3 levels) and education
- Strive for SES and demographic diversity, inclusion of caregivers
- Work with community liaisons for recruitment strategies
- Develop any recruitment materials needed
- Identify locations, day/times for FGs
- Develop system for screening participants, collecting demographic information on screener
- Enter screener information in spreadsheet
Dr. C. Daniel Mullins of the University of Maryland, Baltimore is contributing to this project.
Biocompatibility in Additive Manufacturing
Some medical devices not subject to premarket review by FDA are being fabricated by clinicians at the point-of-care using consumer grade 3D printers. However, any medical device in physical contact with a patient should be biocompatible to insure safety. No studies have been published that relate specific 3D manufacturing process parameters to standard industry measures of biocompatibility. Recognizing this, Dr. Lex Schultheis and his research team investigated whether a specific ABS feedstock that was expected to be biocompatible for permanent contact with skin and mucosal membranes would be altered by 3D printing, and thereby change biocompatibility in the final finished medical device.
Transdermal Drug Delivery Systems-Fentanyl: In Vitro Studies
In this project, Dr. Audra Stinchcomb is building on upon the currently FDA-funded project grant NIPTE-U01-MD-2015-001 titled, “Transdermal Drug Delivery Systems-Fentanyl” (program officer representative: Caroline Strasinger). This currently funded project is focused on human in vivo testing. The goal is to understand ways to label drug delivery rates from patches, as current dose labeling is not consistent among patch products. In vivo human studies employ fentanyl patches to determine delivery rates from pharmacokinetic parameters, as well as the residual drug amount left in the patch at the end of the wear time. This research team is creating a database of controlled human studies. In vitro studies are proposed here in order to assess if in vitro studies can mimic ongoing in vivo studies, in terms of delivery rates. In vitro studies would employ the same products that are being evaluated in vivo in humans. This correlation analysis will help develop in vitro tests to predict patch delivery rates.
In vivo Pig-a gene mutation assay
A workgroup of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) is developing an Organisation for Economic Co-operation and Development (OECD) Test Guideline (TG) for the in vivo Pig-a gene mutation assay. The TG will foster regulatory acceptance of the assay for conducting safety assessments. View the database online.
In this project, Dr. Bruce Yu is developing a simple and noninvasive technique to analyze sub-visible particulates in solutions. The method is based on the water proton NMR signal and can be carried out using desktop instruments without even taking the drug solution out of its vial. Sub-visible particulates formed by proteins is a safety concern for biologic products. Current analytics for such particulates are complex and invasive. A simple noninvasive analytical technology has the potential to enable effective regulation and control of sub-visible particulates in biologics.
Impact of Dose on In Vitro Dissolution Predictability
This projects extends on-going work by Dr James Polli to develop an in vitro dissolution test that predicts the absorption and pharmacokinetics of poorly soluble drugs that have been formulated via amorphous solid dispersion technology. In vitro dissolution is an important test of pharmaceutical quality. However, products of low solubility drugs that employ amorphous solid dispersion technology are complex. Results of these formulation and human pharmacokinetic studies aim to yield an in vitro test that others can rely upon.
Improving pre-clinical assessments of safety and efficacy
“Improving pre-clinical assessments of safety and efficacy” focuses on membrane transporters in drug development. Membrane transporters allow nutrients to move throughout the body, and also move drugs throughout the body. However, these doorways can be the basis for drug-to-drug interactions, where a “perpetrator drug” interferes with how a second “victim drug” normally uses a transporter. The University of Maryland is conducting experiments in collaboration with FDA scientists in order to aid FDA to develop decision trees. FDA decision trees will help industry and FDA scientists identify what membrane transporters are most important, in terms of the potential to cause drug-to-drug interactions. FDA decision trees will also provide guidance about how cell culture studies can be used to avoid or require human clinical testing, in order to advise health care professionals and patients about transporter-based drug-to-drug interactions. University of Maryland faculty contributing to the research are Drs. Yan Shu, James Polli, Peter Swaan, and Hongbing Wang.
Ensuring readiness to evaluate innovative and emerging technologies
Ensuring readiness to evaluate innovative and emerging technologies is an important goal for the M-CERSI, focusing on new technologies that will contribute to the scientific underpinning of two device-related product areas: (1) laser-based therapeutic devices; and (2) tissue engineering constructs.
Regarding the first subproject above, there is a lack of reliable, widely-accepted benchtop techniques for characterizing and assessing the sub-surface laser therapeutic dosage. As a result, the potential for understanding the device- and tissue-dependent effects, as well as laser therapy system performance, are diminished. These complicate the regulatory process and increase the burden on manufacturers to provide clinical studies to demonstrate safety and effectiveness. This project will develop and validate novel test methods that will enable rapid and reliable evaluation of laser therapy system performance and advance the innovation and translation of light-based therapeutic techniques.
The second subproject involves the creation of polymeric scaffolds that function within guided tissue regeneration strategies. These need precise control over the formative processing steps and also detailed and standardized characterization of the resulting properties. Here, we are developing methods to evaluate scaffold properties across manufacturers and between product iterations. By undertaking these studies, we anticipate the basis for standardization of scaffold characterization, in general. University of Maryland faculty contributing to the research are Drs. Yu Chen and John Fisher.
Harnessing diverse data through information sciences to improve health outcomes
This project focuses on patient prescriber agreements (PPAs) of prescription opioid analgesic drugs. In recent years, FDA has started to employ strategies to reduce misuse and abuse of opioid pain medications. PPAs are contracts between prescribers and their patients to at least list expectations of each the prescriber and the patient. With pain drugs a serious health issue, and opioids having abuse potential, there are several PPAs for various opioid pain medications. These PPAs often outline terms of treatment, patient responsibilities, education issues, addiction treatments, emergency issues, goals, and prescription limitations. University of Maryland faculty are conducting a review of PPAs currently in use, determining which healthcare professionals are using PPAs and the conditions of use. The researchers are also examining different formats and types of PPAs. University of Maryland faculty contributing to the research are Drs. Frank Palumbo, Francoise Pradel, Gail Rattinger, and Ilene Zuckerman.