UNIVERSITY PARK, Pa. — Manufacturing modern medicines is a multi-stage process, and each step introduces the opportunity for contamination, which can be both deadly and expensive . Recently, epinephrine injections, used for severe allergic reactions, were recalled due to lack of assurance of sterility, according to the U.S. Food and Drug Administration .
Penn State chemical engineering doctoral candidate Shreya Kapila is working to improve the sterilization process by surface-modifying the membranes used to sterile filter pharmaceutical products and remove bioburden. She conducts research in the laboratory of Andrew Zydney , Bayard D. Kunkle Chair and professor of chemical engineering at Penn State.
In this Q&A, Kapila discussed the importance of drug sterilization, the findings of her research related to sterilizing drugs and the opportunities she has had to contribute to pharmaceutical safety as a graduate student at Penn State.
Kapila: Pharmaceutical products can potentially become contaminated with microorganisms such as bacteria and fungi, particulate matter and other impurities introduced during different steps involved in manufacturing. For injectable drug products, maintaining sterility is especially important because the product is administered directly into the patient’s body, where microbial contamination can have serious consequences.
Drug manufacturers use multiple layers of control to prevent contamination and maintain product quality. These include controlled manufacturing environments, sterilized equipment, validated cleaning procedures and processes designed to prevent or remove microorganisms. At the same time, manufacturers ensure that processing does not adversely affect the product. The goal is therefore not only to achieve sterility, but also to maintain the chemical, physical and functional properties — including purity, potency, physical stability and particle or droplet size — of the pharmaceutical product.
Kapila: Time and cost can vary greatly; some sterilization processes can be completed relatively quickly, while others require extended processing, preparation and validation.
Sterilization can become particularly challenging when the drug product is sensitive to heat or other processing conditions. Manufacturers may need specialized equipment, additional processing steps or more complex aseptic processing. In an aseptic process, different activities and materials may require separate facilities or controlled areas, making it a particularly expensive manufacturing approach. Another important consideration is product loss. If a sterilization or filtration process causes a portion of the drug product to be retained or damaged, manufacturers can lose valuable product. For example, filtration may result in some product remaining in the filter or tubing, and a low-yield process can be especially costly when the active pharmaceutical ingredient is expensive or available only in limited quantities. Improving these processes can therefore have both safety and economic benefits.
Kapila: Sterilization is a crucial step in the manufacture of parenteral drug products, meaning medicines delivered by injection, infusion or implantation. Its purpose is to ensure sterility, defined as the complete absence of viable microorganisms. The appropriate method depends on the formulation, packaging and stability of the pharmaceutical product.
Traditional methods include heat sterilization and gamma irradiation. Heat can rapidly and effectively destroy microorganisms, but it is unsuitable for products that are sensitive to elevated temperatures. Gamma irradiation offers strong penetration and can be useful for certain heat-sensitive materials; however, it may degrade some formulations, including nanoemulsions — liquid formulations containing extremely small oil droplets, typically ranging from approximately 20 to 200 nanometers — by increasing droplet size or otherwise affecting product stability.
Aseptic processing is another way to produce sterile drug products. This approach requires extensive facility validation, specialized equipment and strict personnel procedures to prevent contamination. Because these requirements increase manufacturing complexity and cost, aseptic processing is generally used as “the last resort.”
Sterile filtration is widely used for vaccines and other injectable liquid formulations that have sensitive active pharmaceutical ingredients. In this process, the drug product is passed through a sterilizing-grade membrane. The membrane is designed to retain microorganisms while allowing the pharmaceutical product to pass through. Other methods, including chemical sterilization, may be appropriate for specific materials and applications. The overall goal is to select a sterilization strategy that provides an appropriate level of sterility assurance without compromising the product’s chemical, physical or functional integrity.
Kapila: My work examines different strategies to improve the design and operation of sterile filtration processes by developing a fundamental understanding of the factors governing nanoemulsion filtration through sterilizing-grade filters, that can then be used to improve existing manufacturing practices and address emerging challenges in the production of nanoemulsion-based vaccines and other therapeutic products.
Through our work with one specific strategy of prewetting membrane surfaces to increase surface hydrophilicity, we found that pore blockage was reduced, nanoemulsion flow through the membrane was improved and filter capacity increased substantially, by more than 100-fold in some cases. These findings show that relatively simple surface modification strategies can remarkably improve filtration efficiency and product yield.
Kapila: When I joined Dr. Andrew Zydney’s research group at Penn State, I had the opportunity to work as part of the group’s collaboration with Merck on a real-world challenge in pharmaceutical manufacturing, connecting fundamental chemical engineering with an industry-relevant problem. Through this work, I was able to study membrane filtration from both a scientific and applied perspective and contribute to research directly relevant to pharmaceutical development.
I also completed a five-month co-op at GlaxoSmithKline (GSK), which gave me valuable experience applying my technical knowledge in an industry setting and strengthened my understanding of pharmaceutical manufacturing.
Graduate school also gave me opportunities to communicate this work beyond the laboratory. I presented my research at various symposia hosted by Penn State’s J. Jeffrey and Ann Marie Fox Graduate School and the Robert V. Waltemeyer Department of Chemical Engineering, where I interacted with researchers from academia and industry. I also had the opportunity to present my research at several international conferences, where I shared my work with researchers and professionals from around the world. I also served as a teaching assistant, which helped me develop important soft skills, including communication, organization, time management and collaboration. In addition, I had the opportunity to mentor various undergraduate students, support their research experiences and motivate them to pursue opportunities in science and engineering. These experiences helped me develop my scientific communication, teaching and mentorship skills and understand how fundamental research can ultimately contribute to making pharmaceutical manufacturing more efficient, reliable and capable of delivering safe products to patients.
Biotechnology Journal
Experimental study
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Modulating Membrane Surface Properties via Prewetting With Polysorbate 20 to Improve Sterile Filtration of Nanoemulsions
9-Jul-2026