Sterilization Processes in the Pharmaceutical Industry

Introduction

Sterilization is an important process in pharmaceutical production that ensures the safety, effectiveness, and quality of medication products. Microbial contamination in pharmaceutical goods can pose serious health risks, including infections, treatment failure, and even death (Cundell, 2013). According to the World Health Organization (WHO), microbial contamination remains a major global concern, with injectable medications being particularly susceptible due to their direct injection into the human body (WHO, 2010).

Sterile pharmaceutical goods include injectables, ophthalmic preparations, surgical irrigants, and some topical treatments. Sterilization kills or inactivates all microbiological life, such as bacteria, viruses, fungus, and spores (Patel, 2025). To address these difficulties, pharmaceutical producers use stringent sterilization processes governed by regulatory bodies such as the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and WHO.

Advances in technology and regulatory standards have resulted in the development of dependable sterilization processes customized to various pharmaceutical goods and container formats. In this post, we'll look at the numerous sterilization techniques utilized in the pharmaceutical sector, as well as their uses and benefits in terms of product safety and regulatory compliance.

Heat Sterilization

Moist Heat Sterilization (Autoclaving)

Moist heat sterilization is one of the most used sterilization methods in the pharmaceutical business (Moll, 2023).  It uses saturated steam under pressure to destroy microbes.  The most prevalent method is autoclaving, which exposes items to temperatures ranging from 121°C to 134°C for a set amount of time, usually 15 to 30 minutes (CDC, 2023b).

This approach is highly effective against bacteria, fungi, and spores, and it is commonly employed in aqueous preparations, surgical tools, and rubber seals. Autoclaving is a terminal sterilization process, which indicates that sterilization takes place after the product has been sealed in its final container, lowering the risk of post-sterilization contamination.

Limitations: Moist heat sterilization is ineffective for heat-sensitive pharmaceuticals, proteins, some polymers, and oils (Admin, 2021).

Dry Heat Sterilization

Dry heat sterilization employs hot air that is either static or circulated in a sterilizing oven. It needs higher temperatures (160°C to 180°C) for longer lengths of time (usually 2 hours at 160°C or 30 minutes at 180°C) than wet heat sterilization.

This process is used for materials that cannot tolerate moisture but can withstand high temperatures, such as metal instruments, and certain powders.

Limitations: The extended exposure to high temperatures restricts its use to thermostable items, which excludes many plastic materials (Admin, 2021).

Filtration Sterilization

Filtration is a physical sterilizing technique used on thermosensitive pharmaceutical items such as protein solutions, vaccinations, ophthalmic solutions, and injectable medications. It entails passing the liquid through a membrane filter with a particle size of 0.22 microns or less, which captures bacteria and other microbes (Admin, 2021).

Advantages: Filtration preserves the physicochemical properties of heat-sensitive materials, can remove viruses as well as bacteria, and is faster than thermal sterilization (Johnson, 2022).

Limitations: Standard size exclusion filtration cannot remove bacterial endotoxins. Therefore, it is often paired with a charged PES Filter in controlled environments to ensure endotoxin-free product sterility (CPF, 2023).

Gas Sterilization

Gas sterilization is appropriate for heat- and moisture-sensitive items. The most often utilized gases are ethylene oxide (EtO) and hydrogen peroxide vapor. Around half of all sterile medical devices in the US are sterilized using EtO (CDRH, 2024).

Ethylene Oxide (EtO) Sterilization

EtO is a powerful sterilizing agent that kills bacteria and fungi while inactivating viruses and spores. EtO sterilization is effective because it may alkylate proteins, DNA, and other macromolecules. It is used to sterilize surgical tools, medical devices, plastic gadgets, and some pharmaceutical packaging materials.

Advantages: Effective at relatively low temperatures (37-63°C) and suitable for heat- and moisture-sensitive items (CDC, 2023a).

Limitations: EtO is an irritant, flammable, and requires aeration post-sterilization to remove residues, increasing process time and cost.

Vaporized Hydrogen Peroxide (VHP) Sterilization

VHP is an environmentally safe alternative to EtO that is mostly used in isolators and cleanrooms for surface sterilization (Jones, 2024).

Advantages: Rapid cycle time, no harmful residues, and efficient against a broad variety of bacteria.

Limitations: Limited penetration into porous surfaces and possible compatibility concerns with some polymers (Steris, 2024).

Radiation Sterilization

Radiation sterilization is the process of destroying bacteria by exposing pharmaceutical items to ionizing radiation. Gamma rays and electron beams are the two most common forms of radiation employed.

Gamma Radiation

Gamma radiation generated by cobalt-60 or cesium-137 sources may penetrate deep into materials, making it excellent for sterilizing pre-packaged medical equipment, implants, and some medications (PRO-TECH, 2023).

Advantages: Highly effective, suitable for terminal sterilization, and compatible with a variety of materials.

Limitations: Potential deterioration of certain polymers, glass discolouration, and changes in drug stability (Hasanain, 2014).

Electron Beam (E-Beam) Radiation

E-beam radiation sterilizes products by exposing them to high-energy electrons. It has faster processing speeds and requires less energy than gamma radiation (NextBeam, 2025).

Advantages: Rapid procedure, no radioactive source, and appropriate for surface and shallow-depth sterilization.

Limitations: Limited penetration depth, making it less suitable for bulk or densely packed products.

Sterilization by Chemical Liquids

This procedure entails immersing heat-sensitive instruments or equipment in liquid chemical agents, such as glutaraldehyde or peracetic acid for a set duration. (Malchesky, 1993).

Advantages: Ideal for fragile equipment and goods that are incompatible with heat, gas, or radiation.

Limitations: Requires rigorous washing to eradicate remaining chemicals, which limits its direct usage for medicines.

Regulatory Framework and Validation

The pharmaceutical sector closely regulates its sterilization methods. The US FDA, United States Pharmacopeia Chapter 71, European Pharmacopoeia, and ISO 11135 all provide regulatory recommendations that describe criteria for sterilization validation and routine monitoring.

Validation of sterilization methods is required to guarantee that they consistently fulfill a predefined Sterility Assurance Level (SAL). A SAL of 10-6 means that there are fewer than one live microbe per million units and is used in surgically implanted devices, sutures, and intraocular lenses, for example. A SAL of 10-3 is necessary for devices that are not intended to come into contact with breached skin or compromised tissue, such as topical devices, surgical drapes, or gowns (Meghavaram, 2020).

Validation includes microbiological testing, physical performance certification, and biological indicators.

Conclusion

Sterilization is a critical and strictly controlled procedure in pharmaceutical production that ensures patient safety and product performance.  The optimal sterilization procedure is determined by the product's kind, packaging, and susceptibility to heat, moisture, or chemicals.

Advancements in sterilizing technology and equipment, together with developing regulations, continue to improve sterility assurance and industrial efficiency. As pharmaceutical goods become increasingly complex, incorporating novel sterilizing technologies while adhering to high quality requirements will remain critical to protecting public health globally.

Sources：

Admin. (2021, November 13). Types of pharmaceutical sterilization method - the pharmapedia. thepharmapedia.com. https://thepharmapedia.com/sterilization-method-pharmaceutics/pharmacy-notes/pharmaceutics/

CDC. (2023a, November 28). Ethylene oxide “gas” sterilization. cdc.gov. https://www.cdc.gov/infection-control/hcp/disinfection-sterilization/ethylene-oxide-sterilization.html

CDC. (2023b, November 28). Steam sterilization. cdc.gov. https://www.cdc.gov/infection-control/hcp/disinfection-sterilization/steam-sterilization.html

CDRH. (2024, November 26). Sterilization for medical devices. fda.gov. https://www.fda.gov/medical-devices/general-hospital-devices-and-supplies/sterilization-medical-devices

CPF. (2023, October 21). The difference between sterilizing fluids and endotoxin removal. criticalprocess.com. https://www.criticalprocess.com/blog/the-difference-between-sterilizing-fluids-and-endotoxin-removal

Cundell, T. (2013, December 15). Microbiology: Mould contamination in pharmaceutical drug products. europeanpharmaceuticalreview.com. https://www.europeanpharmaceuticalreview.com/article/23351/microbiology-mould-contamination-pharmaceutical-drug-products-medical-devices/

Johnson, S. A., Chen, S., Bolton, G., Chen, Q., Lute, S., Fisher, J., & Brorson, K. (2022). Virus filtration: A review of current and future practices in bioprocessing. Biotechnology and Bioengineering, 119(3), 743-761. https://doi.org/10.1002/bit.28017

Jones, B. (2024, December 3). VHP sterilization: Precision cleanliness for isolators and hatches. youthfilter.com. https://youthfilter.com/news/vhp-sterilization-precision-cleanliness-for-isolators-and-hatches/

Hasanain, F., Guenther, K., Mullett, W. M., & Craven, E. (2014). Gamma sterilization of pharmaceuticals--a review of the irradiation of excipients, active pharmaceutical ingredients, and final drug product formulations. PDA journal of pharmaceutical science and technology, 68(2), 113–137. https://doi.org/10.5731/pdajpst.2014.00955

Malchesky, P. S. (1993). Peracetic acid and its application to medical instrument sterilization. Artificial Organs, 17(3), 147–152. https://doi.org/10.1111/j.1525-1594.1993.tb00423.x

Meghavaram, M. (2020, May 4). Sterility Assurance Level 10-6 and sterilization process. i3cglobal.com. https://www.i3cglobal.com/sterility-assurance-level/

Moll, F., Bechtold-Peters, K., & Friess, W. (2023). Impact of autoclavation on baked-on siliconized containers for biologics. European Journal of Pharmaceutics and Biopharmaceutics, 187, 184-195. https://doi.org/10.1016/j.ejpb.2023.04.018

NextBeam. (2025, January 6). E-beam vs. Gamma Sterilization - which is right for you?. nextbeam.com. https://nextbeam.com/irradiation-illuminated/e-beam-vs-gamma-sterilization-which-is-right-for-you/

Patel, Y., & Patel, V. (2025, January 6). 11 key contributing factors for maintaining sterility assurance. pharmaceuticalonline.com. https://www.pharmaceuticalonline.com/doc/11-key-contributing-factors-for-maintaining-sterility-assurance-0001

PRO-TECH . (2023, December 6). The role of gamma sterilization in medical devices - PRO-TECH design. protechdesign.com. https://protechdesign.com/articles/the-role-of-gamma-sterilization-in-medical-devices/

Steris. (2024, January 12). Vaporized hydrogen peroxide (VHPTM) Biodecontamination: Ensuring Operator Safety. sterislifesciences.com. https://www.sterislifesciences.com/resources/documents/articles/vaporized-hydrogen-peroxide-vhp-biodecontamination---ensuring-operator-safety

WHO. (2010, January 3). WHO best practices for injections and related procedures toolkit. who.int. https://www.who.int/publications/i/item/who-best-practices-for-injections-and-related-procedures-toolkit