At Penn State, chemical engineering doctoral candidate Shreya Kapila, working in the laboratory of Andrew Zydney, Bayard D. Kunkle Chair and professor of chemical engineering, is tackling the problem at the level of the membrane surface itself. Her approach is deceptively simple: she modifies the surface properties of the membranes used to sterile filter pharmaceutical products and remove bioburden, the population of living microorganisms that must be eliminated before a drug can be considered safe. The work, published in Biotechnology Journal under the title Modulating Membrane Surface Properties via Prewetting With Polysorbate 20 to Improve Sterile Filtration of Nanoemulsions, demonstrates that a modest change in how a membrane is prepared can yield improvements in filtration capacity of more than a hundredfold in some cases.

To understand why that matters, it helps to consider what pharmaceutical products are actually up against. As Kapila explains, drug products can become contaminated with microorganisms such as bacteria and fungi, particulate matter, and other impurities introduced at different steps in manufacturing. For injectable drug products, sterility is especially critical because the product is administered directly into the patient’s body, bypassing nearly every natural defense the human body possesses. Microbial contamination in an injection can have serious, sometimes fatal, consequences, which is why regulators treat parenteral products, medicines delivered by injection, infusion or implantation, with exceptional scrutiny.

Achieving that level of safety, however, cannot come at the expense of the medicine itself. Manufacturers rely on multiple layers of control: controlled manufacturing environments, sterilized equipment, validated cleaning procedures, and processes specifically designed to prevent or remove microorganisms. At the same time, processing must not damage the product. The goal, Kapila emphasizes, is not only to achieve sterility but to preserve the chemical, physical and functional properties of the drug, including its purity, potency, physical stability, and particle or droplet size. A sterilization process that destroys every microorganism but degrades the active ingredient, or alters the size distribution of droplets in a formulation, has failed on its own terms.

The menu of available sterilization methods reflects this tension. Traditional heat sterilization can rapidly and effectively destroy microorganisms, but it is unsuitable for products that are sensitive to elevated temperatures, an increasingly common problem as biotechnology-derived medicines proliferate. Gamma irradiation offers strong penetration and can be useful for certain heat-sensitive materials, but it may degrade some formulations, including nanoemulsions, liquid formulations containing extremely small oil droplets typically ranging from roughly 20 to 200 nanometers, by increasing droplet size or otherwise destabilizing the product. Chemical sterilization may be appropriate for specific materials and applications. Aseptic processing, in which the drug is assembled from sterile components in a sterile environment, requires extensive facility validation, specialized equipment and strict personnel procedures, making it so complex and costly that manufacturers generally treat it as the last resort.

That leaves sterile filtration as the workhorse for many sensitive liquid products, including vaccines and injectable formulations with fragile active pharmaceutical ingredients. In this process, the drug product is passed through a sterilizing-grade membrane engineered to retain microorganisms while letting the therapeutic molecules or droplets pass through. The method sounds elegant, but it carries its own economic hazards. Some product inevitably remains trapped in the filter or the tubing, and when the active ingredient is expensive or available only in limited quantities, even modest losses translate into substantial financial cost. Time and cost also vary greatly across sterilization approaches; some processes are completed relatively quickly while others demand extended processing, preparation and validation, and heat-sensitive products may require specialized equipment or multi-facility aseptic operations that drive expenses higher still.

Kapila’s research focuses on the intersection of these problems: understanding, at a fundamental level, the factors that govern how nanoemulsions behave as they pass through sterilizing-grade filters. Nanoemulsions are increasingly important as platforms for vaccines and other therapeutic products, yet their tiny oil droplets are vulnerable to fouling phenomena that conventional filtration models do not fully capture. By developing a mechanistic understanding of droplet-membrane interactions, her group aims to improve existing manufacturing practices and address emerging challenges in the production of nanoemulsion-based medicines, connecting fundamental chemical engineering directly to an industry-relevant problem.

The centerpiece of the published work is a strategy that could hardly be easier to implement: prewetting the membrane surface with polysorbate 20, a common surfactant, to increase its hydrophilicity. The results were striking. Prewetting reduced pore blockage, improved the flow of nanoemulsion through the membrane, and increased filter capacity substantially, by more than 100-fold in some cases. In an industry where a single batch of a biologic can be worth millions of dollars, an intervention that multiplies the volume of product a single filter can process, while simultaneously reducing product retained in the filter, represents both a safety and an economic win. As Kapila notes, these findings show that relatively simple surface modification strategies can remarkably improve filtration efficiency and product yield.

The research also illustrates how academic-industrial collaboration can accelerate solutions to manufacturing problems. Kapila joined Zydney’s group at a time when it was working with Merck on a real-world challenge in pharmaceutical manufacturing, an experience she credits with allowing her to study membrane filtration from both a scientific and an applied perspective and to contribute to research directly relevant to pharmaceutical development. She later completed a five-month co-op at GlaxoSmithKline, gaining hands-on experience applying technical knowledge in an industry setting and deepening her understanding of how pharmaceutical manufacturing actually operates at scale.

Beyond the laboratory and the plant floor, Kapila has presented her work at symposia hosted by Penn State’s J. Jeffrey and Ann Marie Fox Graduate School and the Robert V. Waltemeyer Department of Chemical Engineering, and at several international conferences, sharing her findings with researchers and professionals from around the world. She has served as a teaching assistant and mentored undergraduate researchers, experiences she says sharpened her communication, organization and collaboration skills while reinforcing how fundamental research can ultimately make pharmaceutical manufacturing more efficient, more reliable and more capable of delivering safe products to patients. In a field where the difference between a clean membrane and a fouled one can be measured in lives as well as dollars, that pipeline from bench science to bedside safety has rarely mattered more.

Subject of Research: Surface modification of sterilizing-grade filtration membranes to improve sterile filtration of pharmaceutical nanoemulsions

Article Title: Q&A: The safety and sterilization of pharmaceuticals manufacturing

Article References: Q&A: The safety and sterilization of pharmaceuticals manufacturing. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: sterile filtration, pharmaceutical manufacturing, membrane technology, nanoemulsions, polysorbate 20, aseptic processing, bioburden, drug safety, vaccines, surface modification, Biotechnology Journal, Penn State