Stepping up drug development. Oh yes, there’s that pandemic, too.

from my story at Academic Pharmacy Now

https://www.aacp.org/article/thriving-innovation

Talk to academics involved in The National Institute for Pharmaceutical Technology & Education (NIPTE) and they will tell you it’s about striving and thriving in innovation—inside and outside the walls of academia. NIPTE has collaborated with industry, academia and government, particularly the Food and Drug Administration (FDA), to identify and help solve the world’s pharmaceutical challenges, which are far-reaching and keep growing. NIPTE scientists are exploring more effective methods for the characterization of active pharmaceutical ingredients and drug products. They are identifying strategies to prevent drug opioid addictions. They are charting ways to improve dosage form design and manufacturing. They are exploring how to determine the quality of pharmaceuticals.

In addition, they are creating education and training programs that focus on evolving technology in pharmaceutical science and engineering with an eye on thwarting future workforce shortages. And they are part of the conversation in Washington on accelerated drug development plans in light of pandemics such as the coronavirus.

Most recently, NIPTE is studying plans to essentially overhaul the process for bringing generic medicines to market that its scientists say could take dramatic steps to improve safety and quality while enhancing pharmaceutical production in the U.S. “We define ourselves as a community of pharmaceutical knowledge and the scientific home for academic pharmaceutical sciences,” said Dr. Vadim J. Gurvich, executive director of NIPTE and research associate professor of medicinal chemistry at the University of Minnesota College of Pharmacy. The organization, established in 2005 and based in Minneapolis, is a coalition of academic scientists from pharmacy, education, engineering and chemistry and includes 16 universities with pharmaceutical education and research programs and one medical school. Each university member’s representative serves on the NIPTE board of directors, providing leadership and financial oversight.

“From our perspective, there is a tremendous potential to draw together subject matter experts in the academic world and being able to connect those experts to either industry or other regulatory agencies, such as the Food and Drug Administration, to address some of the grand challenges as we move forward,” said Dr. Eric Barker, dean of the Purdue University College of Pharmacy and secretary of the NIPTE board. “We’re able to have collaborations and partnerships with members to draw together on their collective expertise.”

The mission: increase science and engineering-based understanding that can lead to new drug products to move to market faster with less variability and higher predictable performance at a lower cost, said Gurvich. For example, researchers are studying abuse-deterrent protocols, intervention-based opioid technology, nanotechnology, advanced manufacturing methods and the formulation of new drug products, “which is extremely challenging, cutting-edge science that addresses a huge societal need,” he added.

Preparing the Workforce

Education and skills development in pharmaceutical science are essential elements in preparing a new workforce, according to Gurvich. At NIPTE, courses are taught based on what the organization calls a “quality and integrated review concept” involving product development, delivery, manufacturing and outcome—with collaboration as a key with schools of pharmacy and engineering. Chemistry and materials science are also included in NIPTE’s strategic roadmap.

NIPTE said its scientists organize into centers of excellence and focus groups to “more efficiently collaborate and integrate their expertise across member organizations.” The focus groups target advanced manufacturing, biologics and biosimilars, nanotechnology and translational biomarkers. The idea is to link all areas within the scope of pharmaceutical production, from development to manufacturing.

“Large data has advanced more quickly than our ability to analyze the data and that’s a challenge,” said Barker. “That we cannot go alone. We can draw and tap into (NIPTE’s) tremendous expertise in engineering and even agriculture. That’s a factor for both basic knowledge and having a program to train data scientists to upskill the existing workforce—not expecting them necessarily to be experts but competent enough to work with the data.”

NIPTE’s examination of dosages (i.e., dosage forms) and complex molecules and specialty drug technology ties into Purdue’s strategic initiatives to expand its area of pharmaceutical and biotechnology instruction from basic science to clinical science for “cutting-edge educational programming,” Barker said. NIPTE has a collection of “a close-knit group of deans,” he said.

Pharmacy a Key Component in FDA’s Drug Manufacturing Strategy

Federal officials are enlisting academia as they look toward a new generation of pharmaceutical manufacturing methods to overcome the country’s reliance on drugs produced overseas. While the U.S. is a leader in drug discovery and development, it relies heavily on drugs made in China and India. As a result, the Food and Drug Administration is encouraging investments in advanced manufacturing technology and establishing quality management systems to improve the quality of pharmaceuticals.

“FDA believes that advanced manufacturing can help regain its competitiveness with China and other foreign countries and potentially ensure a stable supply of drugs critical to the health of U.S. patients,” said Dr. Janet Woodcock, director of the FDA Center for Drug Evaluation and Research in testimony late last year before the House Committee on Energy and Commerce, subcommittee on Health.

Between 70 and 80 percent of active pharmaceutical ingredients and 40 percent of finished products are made outside the U.S. The FDA reported last year that 18 percent of Active Pharmaceutical Ingredients (API) manufacturing facilities are located in India and 13 percent in China. The number of Chinese manufacturing facilities has doubled since 2010. As of late 2019, only 28 percent of manufacturing facilities making APIs that supply the U.S. market are based in this country.

Vulnerable Supplies

“The fact that so many of our drug products are made overseas creates a vulnerability in the U.S. supply,” said Dr. Fernando J. Muzzio, director, National Science Foundation/Engineering Research Center on Structured Organic Particulate Systems, and distinguished professor, chemical and biochemical engineering, Rutgers University. “The supply chain can be disrupted for lasting shortages. This is a real issue both with shortages caused by emerging quality problems and with the ability to respond quickly to emerging threats.”

Muzzio has worked for years with the National Institute for Pharmaceutical Technology & Education, a proponent of the advanced manufacturing processes with one key purpose in mind: improving the amount and quality of the U.S. drug supply. Proponents of advanced manufacturing say innovative technologies ranging from 3D printing to continuous manufacturing methods also can quickly move drugs to market. The continuous production method stands in contrast to the current predominately used batch method of drug production, which is considered inefficient and involves “breaks” or “stops” in the process.

“Advanced manufacturing offers many advantages over traditional pharmaceutical manufacturing and if the U.S. invests in this technology, it can be used to reduce the nation’s dependence on foreign sources of APIs to increase the resilience of our document manufacturing base and reduce quality issues that trigger drug shortages or recalls,” Woodcock said. Advanced manufacturing has been widely used in automotive, aerospace and semiconducting.

“The continuous state of control enables the continuous monitoring and assurance of product quality,” Muzzio told Congress. Continuous manufacturing has been embraced to replace traditional and inefficient batch methods in an era of “unprecedented innovation” following “decades of near stagnation,” Muzzio said.

Academia is playing a large role with industry and other regulatory agencies to help the FDA identify potential regulatory hurdles to adopt advanced manufacturing, according to Woodcock. In 2018, the FDA awarded eight grants to universities and nonprofit organizations to “study and recommend improvements for the continuous manufacturing of drugs and biological products as well as similar innovative monitoring and control techniques,” she said.

The FDA is working with academia and industry to identify new research areas for advanced manufacturing. FDA laboratories also have conducted advanced manufacturing research and established a Center of Excellence for Manufacturing Science and Innovation to coordinate internal advances in manufacturing research for both small molecules and biologics.

There is a tremendous potential to draw together subject matter experts in the academic world and being able to connect those experts to either industry or other regulatory agencies…to address some of the grand challenges as we move forward. We’re able to have collaborations and partnerships with members to draw together on their collective expertise.D

“Many of the NIPTE labs are doing dosage design research, and some of the information we are generating with prior knowledge may not be seen as cutting-edge research, but for pharmaceutical analysis and formulations and master’s and Ph.D. level students, this is an invaluable learning experience, both in mastering techniques and formulation design,” said Dr. Kenneth Morris, professor and director of Lachman Institute for Pharmaceutical Analysis at the Long Island University Pharmacy, which is a NIPTE member. NIPTE is also working to identify the next compounds and products likely to be important targets for the generic industry, Morris said.

As NIPTE collaborates with the FDA, the organization is also emphasizing the need to overcome workforce shortages in pharmaceutical sciences, according to Gurvich. “That was a big concern for the FDA several years ago and they couldn’t find enough qualified people with appropriate training in pharmaceutical sciences,” Gurvich recalled. “That led them to us, and they approached us to develop a training and certification program, which is very much a work in progress.”

There is irony in the work. As Gurvich and his team strive to improve pharmaceutical manufacturing in this country, “if it starts coming back to the U.S., the industry will face shortages in the workforce and that is another concern,” he said. “At NIPTE we discussed the situation, and (seek) to recalibrate education programs to solve that problem.”

More Accessible Generic Drugs

Even before the alarm over the spread of coronavirus throughout the world this past winter, NIPTE researchers began stepping up their research into improved mechanisms to manufacture and deliver generic drugs into the U.S. market. That market has been saddled by regulatory woes and much production overseas.

“The efficiency of the generic drug product system is quite low,” Gurvich said. “We noticed that about 60 percent of the drugs that are marketed by brand companies are not making it to generics. And that has caught our attention. That feeds into our priorities. It’s extremely important. It affects the drug supply, the quality of drugs, all sorts of things.”

Part of the organization’s strategy to improve access to generic drugs is wrapped around the words “new” and “prior knowledge.” Gurvich said NIPTE is pushing to highlight the distinction between the information that may involve proprietary and trade secrets and available knowledge in the public domain. Using that prior knowledge, he noted, can accelerate development and commercialization of generic drugs.

As an example of “new” and “old,” NIPTE published a paper last year titled “Pharmaceutical New Prior Knowledge: Twenty-First Century Assurance of Therapeutic Equivalence” that referred to manufacturer Apotex’s formulation of a nasal spray product, which used a different drug formulation so as not to infringe on a previous product’s unexpired patent. Years later, the situation changed: The FDA approved the generic version of the drug after the patent’s expiration. “Clearly during this review process, the FDA had access to previously disclosed” information, the paper states. Ultimately, it points to a “need for NPK (new prior knowledge) efforts to bridge the gaps between research to policy and policy to practice,” according to the authors.

Using the terms “new” and “prior knowledge,” Gurvich said, “sounds like an oxymoron. It may be a little bit provocative or paradoxical. But it needs to be taken up by public-private partnerships. NIPTE can be a partner and we had this discussion and talked to the FDA and the idea is we will have the scientific firepower to make a significant impact.”

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