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Pauletti Receives $1.2 Million FDA Contract

Published on 15 October 2020

Giovanni Pauletti, M.Pharm., Ph.D., Gustavus and Henry Pfeiffer Chair in Pharmacy, professor of pharmaceutics and associate dean of graduate studies at University of Health Sciences and Pharmacy in St. Louis, 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.

“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 the GastroPlus® 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.

“The current state-of-the-art Oral Cavity Compartmental Absorption and Transit™ module in GastroPlus® was created several years ago in collaboration with a large pharmaceutical company using limited in vitro data,” said Viera Lukacova, chief scientist at Simulations Plus Inc. “Using the novel database generated by University of Health Sciences and Pharmacy in St. Louis, the improved machine learning and physiologically-based biopharmaceutics/physiologically-based pharmacokinetic models will provide a better characterization of formulation effects and enhance regulatory assessments for innovator and generic products.”

Utilizing this novel simulation tool that is informed by results from in vitro experiments, Pauletti says 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 non-generic versions of the drugs.

“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,” Pauletti 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.”

Pauletti’s research efforts are now underway, and will last until September 2023.

“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 work is just one example of the many innovative and groundbreaking research projects happening across the University of Health Sciences and Pharmacy campus.

To learn more about the exciting projects happening at the University, visit uhsp.edu/research.

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