Purdue University, in collaboration with Eli Lilly and Merck & Co., launched the Young Institute Pharmaceutical Manufacturing Consortium in January to pioneer advances in making medicines, with a focus on sterile injectables and innovative aseptic manufacturing technology. Leading this consortium is Elizabeth Topp, a professor in the Purdue University Department of Industrial and Molecular Pharmaceutics and the Davidson School of Chemical Engineering, and expert in solid state chemistry. We asked her about the benefits and challenges of industrial and academic collaboration.
What led you to specialize in the chemistry of solids, and how does this focus contribute to the development of more stable pharmaceuticals?
I started my career at the University of Kansas, where I had the privilege of working with three outstanding pharmaceutical chemists: Ron Borchardt, Val Stella, and Dick Schowen. At the time, I had some background in pharmaceutical solids, and they were kind enough to include me in new projects and proposals that merged their expertise in stability and drug degradation with my interests in the solid state.
Most drugs degrade in some way. Understanding how they degrade – and how fast – can help us design formulations that protect the drug until it can be administered to the patient. Many orally delivered drugs are formulated as solid tablets or capsules. Drugs for injection are usually administered as liquids but can be formulated as solids that are re-dissolved (reconstituted) before use. The extra steps to dry and re-dissolve are often needed because the drug is unstable in solution.
Given the challenges with mRNA degradation, what innovative approaches is your team exploring to enhance the stability of mRNA-based vaccines and therapeutics?
The mRNA-based COVID-19 vaccines are shipped and stored at ultracold temperatures (down to -80°C) because mRNA is very unstable. In a sense, mRNA is set up to fail. mRNA is a linear polymer make up of monomers called nucleotides, each containing a phosphate group, a ribose (a type of sugar), and a nucleobase.
Degradation occurs when part of the ribose (the “R” in “mRNA”) attacks the nearby bond linking two nucleotides together (a phosphodiester bond), so that the chain falls apart. Steven Ferguson and our team at the National Institute for Bioprocessing Research and Training (NIBRT) in Dublin are working on chemical modifications of mRNA that would make that degradation reaction impossible. Our group is also working on improving our fundamental understanding of the factors that affect mRNA degradation, so that we know, for example, which parts of the molecular are the most vulnerable.
Can you explain the significance of understanding reactions in the amorphous solid state and how this knowledge impacts drug formulation and shelf life?
Most drugs are unstable in some way – and it’s a good thing! We’d like medicines to get into our bodies, treat medical problems, and then go away by degrading into harmless, inactive compounds. Problems occur when the drug degrades before it does its job rather than after – in the vial or on the shelf, rather than after providing treatment. To minimize reactions “on the shelf”, many drugs are formulated in solid forms, such as tablets, capsules, powders, or frozen solutions. That often works because most reactions are much slower in solids than in solution. Just making a solid doesn’t guarantee that degradation will be slow enough, though. If we can’t slow down degradation enough by making a solid, we’re often out of tactics – and a very promising drug candidate can’t become a product that reaches patients.
What’s the story behind the Young Institute Pharmaceutical Manufacturing Consortium?
Our Institute is named for Purdue alumnus William D. (“Bill”) Young and his wife Sherry. Bill graduated from Purdue in 1966 and, after a stint at Eli Lilly, took a job with Genentech, a company that was just a start-up at the time. While at Genentech, Bill and his team developed the manufacturing process for Humulin®, the first recombinant human insulin and the product that launched the biotech revolution in pharma.
Our mission as the Young Institute is simple: to honor Bill and his family by starting the next revolution in pharmaceutical manufacturing. It’s important to do that in collaboration with industry because they know what their pain points are, and because they’re the ones doing the manufacturing. We’re thrilled that both Lilly and Merck have agreed to join us on this journey – and we’re keen to have other pharma companies join us, as well as those in related sectors.
Could you elaborate on the specific advanced aseptic manufacturing technologies the consortium aims to develop?
Specific technologies that we’re interested in include:
- New unit operations for drug product manufacturing. For example, Young Institute Co-Director Alina Alexeenko and her team are developing radiofrequency assisted lyophilization as a way of making lyophilization much faster while maintaining product quality.
- Applications of artificial intelligence to enable real-time process control to optimize efficiency or manage supply chains.
- Development of digital twins and other computational models of manufacturing processes, enabling process changes and deviations to be simulated without using physical equipment.
- Robotics to remove humans from sterile manufacturing environments, protecting drug products from human-borne bacteria, and protecting human operators from exposure to high potency drugs.
- Automated visual inspection of vials, enabling injectable drug products to be inspected for particles and microbial contamination, a process currently done largely by human operators.
- Development of in-line sensors, enabling product quality to be assessed in real-time and reducing reliance on off-line testing.
In what ways will the consortium contribute to the education and training of the next generation of pharmaceutical scientists and engineers?
We’re involved in many exciting initiatives on the Purdue campus, designed to engage students with pharmaceutical manufacturing at many different levels. For example, in summer 2025, we’ll host a week-long introduction to pharma manufacturing for college students. The program is sponsored by NIIMBL (the National Institute for Innovation in Biopharmaceutical Manufacturing) and will involve Ivy Tech Community College, Eli Lilly, Simtra, and Biocrossroads. We’re also a partner in Heartland BioWorks, which aims to transform Central Indiana into a global leader in biotechnology and biomanufacturing. Training is an integral part of that mission.
Are there plans to involve other stakeholders, such as additional pharmaceutical companies or startups, in the consortium's initiatives?
Yes, absolutely! We’re actively recruiting companies across the value chain to join the Young Institute consortium. We have a tiered membership structure that encourages participation at different levels by a variety of stakeholders. Founding members make a significant investment and help to set the direction and focus areas for the consortium. Tier 1 members participate in our pre-competitive research programs, working together with one another and with founding members to select research projects. Tier 2 members have a low barrier to entry, enabling participation by start-ups, non-profits, and other academic institutions. We’re also actively working to engage with federal agencies because regulatory oversight is so important to all aspects of pharma manufacturing.
What inspired you to lead this consortium, and what do you envision as its long-term impact on the pharmaceutical industry?
A big part of my inspiration has been the three Co-Directors of the Young Institute, Purdue faculty members Alina Alexeenko (College of Engineering), Eric Munson (College of Pharmacy), and Garth Simpson (College of Science). Over several years, they conceived the idea of a pharmaceutical manufacturing institute and then invited me to serve as the director. Additional inspiration has come from our colleagues in the pharmaceutical industry who’ve talked to us about manufacturing opportunities and challenges. In addition, Bill Young and the other members of our Advisory Council have been tremendous sources of advice and encouragement.
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