UHSP Pharmaceutical and Administrative Sciences Chair Receives $1.2 Million FDA Contract for Generic Drug Research

Dr. Giovanni Pauletti, Gustavus and Henry Pfeiffer Chair of Pharmaceutical and Administrative Sciences, professor of pharmaceutics and associate dean of graduate studies at the University of Health Sciences and Pharmacy in St. Louis (UHSP), has received a $1.2 million contract from the U.S. Food and Drug Administration (FDA). The funding will support Pauletti’s work to develop a computational tool with the potential to accelerate the development of generic forms of medications which are delivered through the oral cavity.

Over the past five years, Pauletti has been conducting research to examine how in vitro systems could be used in conjunction with pharmacokinetic modeling in drug development. Utilizing this three-year FDA contract, Pauletti will further extend his research by developing an in silico computer modeling and simulation platform with the capability to predict drug concentrations in human subjects for generic formulations after administration to the oral cavity without the use of clinical trials.

“Through in vivo studies, generic drug developers measure the blood levels of medications at various times in real people to ensure that the generic product is bioequivalent to the already approved innovator product,” Pauletti explained. “These studies take a significant amount of time and are very expensive, so what we’re hoping to do is evaluate bioequivalence though other types of studies with a combination of computer simulations informed by results from in vitro experiments. This approach will utilize mathematical equations that we would validate, and these equations will provide us with data similar to what in vivo studies would offer. If we’re successful, this may be a way to get certain drugs, including those that can be delivered through the oral cavity, on the market as generics without in vivo studies, which means more rapid access to generic products for patients.”

Pauletti’s contract comes from the FDA’s Office of Generic Drugs, which works to ensure—through its scientific and regulatory process—that the U.S. population has access to safe, effective and high-quality generic drugs. In recent years, the organization has been particularly focused on improving physiologically based pharmacokinetic models of drug absorption via complex routes of delivery, including administration via the oral cavity, nose, eye and lungs.

Most drug development outside of the United States focuses on generics, since this requires fewer resources, Pauletti pointed out. Rather than performing

extensive clinical trials to determine the safety of existing drugs, generics researchers can rely on information gathered from other countries and scientists. This enables development of a generic version for the local market faster and cheaper. Depending on where the generic development is taking place, it may be the only opportunity that patients have to gain access to certain effective medications. In contrast, many companies based in the United States invest more resources for new drug development over generics. While patients benefit from the discovery of novel therapeutics, new drug development is a costly endeavor that many countries cannot afford.

“Oral cavity drug delivery continues to gain interest as an alternative to the conventional oral route of administration because of the enhanced drug absorption qualities it offers and its benefits for pediatric patients and those who are unable to swallow tablets,” Pauletti said. “This also includes fast dissolving pain medications that can carry a significant risk of abuse. Our tool is designed to allow for the optimization of drug formulations for rapid onset or limited absorption out of the oral cavity, depending on a patient’s needs. This is important as the FDA works to achieve its goal of making safe and effective generic medications more readily available to the public.”

Pauletti’s research is being aided by GastroPlus®’s physiologically based pharmacokinetic modeling platform from the software company Simulations Plus Inc. GastroPlus® is a mechanistically based simulation software package that simulates intravenous, oral, oral cavity, ocular, inhalation, dermal, subcutaneous, and intramuscular absorption, biopharmaceutics, pharmacokinetics and pharmacodynamics in humans and animals. Currently, Simulations Plus Inc. is the only company with a computational model for absorption of drugs in the oral cavity.

Using this novel simulation tool that is informed by results from in vitro experiments, Pauletti said researchers involved in generic development will be able to assess what needs to be fine-tuned in the drug formulation to create drug profiles that are most similar to the approved reference listed drug. “Our tool offers a standardized process for measuring generic drug formulations and can help inform decisions on whether the formulations meet the criteria and level of similarity the FDA wants for generic drugs,” he said. “We are excited to initiate this FDA-funded project in collaboration with our colleagues at Simulations Plus. The value of this partnership between academia and industry lies in its potential to accelerate translation of innovative discoveries into tangible patient benefits.”

“This project is a combination of pharmaceutical sciences and engineering, but at the end of the day, it’s all designed to benefit the patient,” Pauletti explained. “We’re not making new molecules, we’re just learning how to deal with existing molecules in a more effective way, and this tool helps accelerate the process.” Pauletti’s research efforts are now underway and will continue until September 2023. His team is currently working to develop the system to compare computational predictions with real lab-generated data and information from clinical trials. This will assure the researchers that their predictions about a drug are appropriate for humans. At press time, his team was initiating the early

laboratory experiments that will take six to nine months. The researchers are also developing technology to help transfer data into their computational predictions.

“What we hope to do is facilitate the interaction between the agencies and researchers,” Pauletti noted. “The idea is to provide researchers that developed generics with a tool that could help them to really assess some of their new formulations for generics, ahead of clinical trials. We have started to develop a consortium of different companies that are focusing on the development of generics to best understand what their needs are and how we can help. The final product that is developed under this contract will be really meaningful for both FDA as well as the end users in the companies that develop generics.”

Pauletti’s team includes student pharmacists in addition to seasoned researchers. While the COVID-19 pandemic has added complications to the process and restricted who can enter the laboratory, Pauletti noted that student pharmacists have been helping on the computational side of his research. This gives students hands-on experience with pharmacokinetics and the use of computer and simulation tools. “That helps them to gain insight into the contemporary pharmaceutical research component, and also provides them with opportunities to explore some of their future career paths, which for pharmacy is quite diverse,” he said. “We teach them pretty much the clinical routes, but the tools that they learn are certainly applicable also for industrial or research and development career paths.”

In addition to his role at UHSP, Pauletti is also a member of the International Pharmaceutical Federation (FIP). Pauletti has served in numerous roles at FIP since his years as a student in Switzerland. He is currently serving his second fouryear term as the scientific secretary, a member of the cabinet who advises the president of FIP on all scientific affairs relevant to pharmacy and pharmaceutical sciences. P

Reprinted with permission from the University of Health Sciences and Pharmacy in St. Louis. Additional reporting by Emily Jacobs, a freelance writer based in Toledo, Ohio.

By Joseph A. Cantlupe

In the heart of Appalachia, better, more accessible healthcare is needed for populations beset by higher poverty and disease rates than in other parts of the country. The leaders of East Tennessee State University (ETSU) Bill Gatton College of Pharmacy say they embrace this evolving challenge and want to pursue a commitment in the place they call home. “We’re right in the thick of Appalachia, and we focus on the rural and undeserved and improve lives of people in this region,” said Dr. Debbie C. Byrd, dean of the college of pharmacy, which is located in the South Central Appalachian region.

“One of the things that is unique is that we are attracting students from this geographic region and students are committed to this community and want to go back to the community to study and serve,” said Dr. Ralph Lugo, founding chair of the Department of Pharmacy Practice. “At ETSU, there has been a long history with the medical school of a rural primary care track that trains healthcare providers in this region.”

Rural Americans, who make up at least 15 to 20 percent of the U.S. population, face inequities that result in worse healthcare outcomes than that of urban and suburban residents. The rural health disparities, reflected in Appalachia, “are rooted in economic, social, racial, ethnic, geographic and health workforce factors,” according to the university. The healthcare challenges include lack of access to care, with fewer local doctors, and more remote locations.

With these deficits in mind, pharmacy schools believe that they can help bridge those healthcare gaps, and universities such as ETSU are taking steps to broaden their academic reach to bring in student pharmacists to focus on the specific needs of the communities. Other pharmacy schools are also bolstering their educational programs, including those in bigger communities that border rural areas. The result has been a keen interest among students, more of whom are drawn to the rural healthcare offerings that are constantly expanding.

While Chicago may be one of the biggest cities in America, its suburbs flow quickly into rural parts of Illinois. The University of Illinois Chicago (UIC) College of Pharmacy has embraced rural pharmacy education at its campus 90 miles away in Rockford with rural pharmacy education program (RPHARM), part of the University’s National Center for Rural Health. Student pharmacists complete a concentration in rural pharmacy services, said Dr. Kevin O. Rynn, clinical professor and vice dean at the College of Pharmacy. Twenty percent of the student body is enrolled and about 60 percent of graduates with the rural pharmacy concentration practice in a rural community. In many cases, “they may be the only healthcare provider in the community, so they have to be a healthcare leader and step up to the challenge,” he said.

In Des Moines, Drake University’s College of Pharmacy & Health Sciences offers a Rural Health Initiative Program, an interprofessional certificate program designed to enable students to understand the value of and nuances faced by healthcare practitioners in rural settings, said Dr. Renae Chesnut, dean and professor. The pharmacy program also continues to have students complete experiential rotations in rural settings. “The pandemic has changed a lot of things,” Chesnut said, “but our students are still going to rural settings for their experiential education, practicing in pharmacies and hospitals that are open to serve their communities.”

These programs are becoming more popular and are attracting more students, with a focus on interprofessional teams drawn from other health profession schools, specifically eyeing the gap in care that the pharmacists can fill in rural communities. Over the past two years, ETSU’s College of Pharmacy has expanded its rural curricula under a rural health initiative strategic plan that specifically targets improved coordination among the academic community, hospitals and healthcare providers in the area. The idea, according to the school’s educators, is to nurture

An ETSU student pharmacist administers the COVID-19 vaccine at Johnson City Medical Center, Ballad Health, in Tennessee.

progressive, team-oriented pharmacists while improving healthcare in rural and underserved communities.

One of the school’s top initiatives is a partnership with Remote Area Medical (RAM) that allows student pharmacists to work with other healthcare professionals to provide care for patients. This care includes documenting medical histories, performing health screenings, providing education and helping patients navigate vision or dental care needs that they may have neglected. “Ninety percent of the U.S. population lives within five miles of a pharmacy,” said Dr. Emily Flores, associate professor of pharmacy practice. “The accessibility of a pharmacist is there. We’re trying to get our pharmacy students to help bridge gaps in rural healthcare and the disparities that exist.”

Since ETSU initiated the program, students have increasingly served hundreds of hours in rural underserved areas, she said. Even dealing with COVID-19 this past year, “our students served over 900 hours—and that’s just what they logged, they probably did more,” Flores said. “We’re making strategic partnerships and more specialized opportunities for students. All of our students have a set of competencies that they should achieve for rural care.”

About 97 percent of the pharmacy school’s APPE students completed at least “one rural and/or underserved experience” in 2019-20, Flores and her colleagues wrote in a poster describing the program. Each student completes a rural service IPPE of at least two hours in each of the first three years. Through its diverse programs, which include 15 health professional degrees within the school’s Academic Health Sciences Center, “we have an environment that expects collaboration,” said Dr. Brian Cross, associate professor and vice chair in the Department of Pharmacy Practice and associate professor in the Department of Family Medicine at the James H. Quillen College of Medicine.

Despite COVID-19, “we’re still committed to the rural healthcare settings. The pharmacies and critical access hospitals in these rural areas are important partners for our educational programs.” —Dr. Renae Chesnut

A national pipeline is growing to develop educational programs in rural America. The Area Health Education Centers (AHEC) work to train students and healthcare professionals in locations across the country, while developing healthcare workers in the nation’s rural and underserved populations, according to Dwain Harris, CEO of the National AHEC Organization. There are AHECs in 300 locations in 46 states and each state has an AHEC program office that is typically housed in a university medical school with regional AHECs that cover the state, Harris said. The regional AHEC centers “are a connection between the academic institutions and their rural communities,” he noted.

The National AHEC Organization, developed by Congress in 1971 to recruit, train and retain health profession workforce members committed to underserved populations, serves more than 85 of the nation’s counties. “The advantage of AHEC continuing education is that it is typically designed to respond to the local communities served by the AHEC,” Harris explained. In each area—such as Harris’s home base in southern Kentucky, which has a high rate of heart disease—“AHECs can provide education that is more specific to that area, perhaps delivered by a local or regional cardiologist,” he continued. “These events also allow for local informal networking among providers, decreasing the sense of isolation some providers may be experiencing when working in rural or remote areas.” AHEC Scholars is a two-year longitudinal program that provides 80 hours per year of supplemental education to health professional students from multiple disciplines. “All experiential or clinical training must be conducted in rural and/ or underserved settings,” he added. In 2018 the AHEC Scholars Program was introduced in AHECs across the country, creating a large cohort of health professions and students becoming more prepared to care for rural and urban underserved patients in small interprofessional teams. “AHEC Scholars provides students with the opportunity to go above and beyond, equipping themselves with added knowledge and training ultimately to be better at what they do and to be more responsive to patients in rural and underserved healthcare settings,” Harris said. It’s important that students interact with many disciplines, and “cultural competency is another hallmark of the program.” “The opportunity to train and interact, for example, with students in other disciplines provide them with a more indepth understanding of the advantages of a team approach to healthcare,” he continued. “Through their training, AHEC Scholars are likely to gain insights into health disparities and understand how health status may be affected by culture, race or socioeconomic status.”

In October, six student pharmacists from the East Tennessee State University Bill Gatton College of Pharmacy were accepted into the Tennessee AHEC Scholars Program. “We are so proud of these students for earning this honor,” said Dr. Debbie Byrd, Gatton College of Pharmacy dean, in a statement. “The AHEC Scholars Program is directly in line with our values and mission at the college to prepare progressive, team-oriented pharmacists who improve healthcare, focusing on rural and underserved communities. I look forward to seeing the impact these students make in their pharmacy careers in the Appalachian Highlands and beyond.”

Learn more: www.nationalahec.org

“We prepare the students to be service leaders in their communities. Some of these students want to return to their home communities. Others want to serve underserved populations and without this program they don’t really know how to get started—the program teaches them to make the connections possible.” —Dr. Kevin O. Rynn

Cross also helped establish a program with his wife, Dr. Patricia Amadio, a professor at the medical school, to carry out a “grassroots initiative from the students” to help the homeless population get flu shots and clothing, as well as prepare for COVID-19 vaccinations as they become available. “We need to be on the front line with our team. That’s not to say we are cavalier and do not protect our students and ourselves,” Cross added. “For us to go into a bunker and wait for COVID-19 to be over would mean that we had an opportunity to help and we did not.”

Dr. Jessica Robinson, assistant professor, pharmacy practice, a member of the college’s community pharmacy initiative, said she knows firsthand the contributions that ETSU is delivering to the rural environment and the potential it offers students. “I was a student here and I was from a rural area,” Robinson said. “I don’t know if I would have gone to pharmacy school if this college wasn’t here for me at the time. I couldn’t imagine practicing anywhere else other than with the folks who got me where I am today.”

While more highly populated areas have seen more chains, South Central Appalachia has a greater concentration of independent pharmacies, which offers additional opportunities for community-based innovations as well as hands-on learning. Through the college’s participation in the Flip the Pharmacy grant program (Community Pharmacy Foundation, 2019), Robinson and other faculty, along with students, work with more than 120 pharmacies to evaluate their business and clinical workflow and provide ongoing support to help pharmacies meet their unique business, social and demographic needs, she said.

As part of their pharmacy education, students participate in nine monthlong rotations during their APPE year, many of which are in rural communities, “which gives them the skills they need to jump into that environment when they graduate,” said Dr. Susie Crowe, director of experiential education. That experience not only encompasses the work of community pharmacies, but also in hospitals, ambulatory care settings and primary care, all within the rural environment, Crowe said. “If a career in a rural setting is something [students] want to pursue, then they have plenty of opportunities to develop and practice those skills while on APPEs.”

As the school develops its programs, it also is focusing on research to evaluate how patients are impacted by rural healthcare teams, said Dr. Karilynn DowlingMcClay, assistant professor of pharmacy practice. A major multidisciplinary effort is examining “the intersection of health policy and care, including pharmacy-based care, through the newly formed Rural Health Equity Research Center, a collaboration among the ETSU Addiction Science Center, the ETSU Center for Rural Health Research and the NORC Walsh Center for Rural Health Analysis,” she said.

Having academic programs that involve pharmacy practice along with other professions is standard in much of the work at ETSU and also is reflected in programs at the University of Illinois Chicago and Drake University. Giving student pharmacists the opportunity to work interprofessionally with medical and nursing students is paramount in UIC’s rural health professions program, said Rynn, the vice dean. During their four years in the program, they complete a rural community capstone project with a medical student partner. In early years pharmacy, nursing and medical students learn together how to conduct a needs assessment and work with local community organizations, hospitals, clinicians and community leaders to develop their project. The RPHARM program culminates with students spending 18 weeks on three APPE rotations in a rural community. During this time, they work with their medical student partner to implement

UIC’s rural health professions program includes a “no harm on the farm” visit to a farm to allow students to discuss potential emergencies with first responders and farmers.

and measure the outcomes of their project, later presenting results at the campuses research day.

“We prepare the students to be service leaders in their communities,” Rynn said. “Some of these students want to return to their home communities. Others want to serve underserved populations and without this program they don’t really know how to get started—the program teaches them to make the connections possible.” Part of UIC’s program includes a “no harm on the farm” visit to a farm where students discuss with first responders and farmers potential emergency situations that pharmacists and other health professionals may encounter, whether it’s “a pesticide exposure, tractor rollovers or grain bin entrapment,” Rynn said.

Even though Drake University doesn’t have its own medical school, the school partners with other institutions in the area so student pharmacists and occupational therapy students can work with doctors of osteopathic medicine, in addition to physician assistants, and physical therapy students through the Rural Health Initiative Program. Students can complete one year of the program or continue to a second year to earn the Rural Health Initiative Program Certificate. The program includes didactic coursework with hands-on interactive group work and site visits to healthcare practices in rural communities.

The Rural Health Initiative Program has been an option available to student pharmacists at Drake for the past five years. More than 30 students have finished the program, and the school expects even more interest. Despite COVID-19, “we’re still committed to the rural healthcare settings,” Chesnut said. “The pharmacies and critical access hospitals

Student pharmacists at UIC spend 18 weeks on three APPE rotations in a rural community.

in these rural areas are important partners for our educational programs.” Drake is expanding its rural healthcare education opportunities in the pharmacy program, she said. Among those is “Cultivate,” a high school internship program that seeks to heighten interest in the pharmacy field.

At ETSU, the community expressed a need and desire for a pharmacy school more than 15 years ago, said Byrd. In 2004, the nearest pharmacy school in the state was more than 500 miles away and there were calls in the community to have its own. The state wasn’t willing to fund one—but then-Gov. Phil Bredesen offered a challenge. He said if the community and region could raise $5 million in 90 days, they could have their school. “I think it was meant to be the end of the story, but this is a group of people up for a challenge,” Byrd recalled. With many people just donating dollar bills at local grocery store collections, the community raised more than $5 million in 58 days, setting the stage for the Gatton College of Pharmacy. “We feel a sense of responsibility to this community,” Byrd said. “We wouldn’t be here without them.” P

For more coverage of rural health initiatives, including information about the University of Wisconsin-Madison School of Pharmacy Rural Pharmacy Practice concentration, visit www.aacp. org/article/care-encompasses-every-community