High-temperature HEPA filtration is essential for maintaining sterility in pharmaceutical depyrogenation tunnels, where glassware must remain contaminant-free before entering aseptic filling operations. To comply with 21 CFR 211.94, all materials that contact the clean airstream—including media, frames, adhesives, and seals—must withstand elevated temperatures without degrading. However, prolonged heat exposure and rapid thermal cycling can stress these components, potentially causing warping, loss of structural integrity, or sealant breakdown that could release particles. Understanding these thermal and mechanical limitations is critical for ensuring long-term reliability, regulatory compliance, and consistent sterile performance in high-temperature manufacturing environments.