Keeping drugs free of contaminants – pharmaceutical manufacturers filter medications through tiny pores to keep them sterile and safe

Every year, the global pharmaceutical industry produces trillions of doses of medications. Manufacturing these drugs involves several stages, and the chance of contamination increases with every step.

Thus, before a single drop of any drug can be given to a patient, it must be sterilized. In my work as a researcher in pharmaceutical manufacturing, I investigate how the properties of different drugs and filters affect how well medications are sterilized through certain methods. Ensuring drug safety while maintaining product integrity remains a persistent and technically nuanced challenge, even on a good day.

As medical therapies become increasingly complex, however, the goal to keep these drugs safe from bacterial contamination is facing unprecedented bottlenecks, including global drug shortages due to fragile materials, regulatory pressures and strained supply chains.

From contamination to crisis

Sterile filtration acts as a shield between a manufactured drug and a patient. When this shield fails, contamination is costly for both patients and manufacturers.

In 2012, a large-scale fungal meningitis epidemic broke at the New England Compounding Center. Epidural injections were contaminated at the pharmacy with the fungus Exserohilum rostratum due to inadequate sterilization and poor aseptic conditions during manufacturing. This oversight caused over 750 infections and more than 60 deaths.

In 2021, the contamination of one manufacturer’s multiuse gel for ultrasounds led to outbreaks of Burkholderia stabilis bacterial infections across 10 American states. Around 14 deaths were linked to the manufacturer’s inappropriate testing of the finished product, inadequate inspection of raw materials and lack of environmental controls.

Beyond the legal consequences of harming patients, pharmaceutical companies also face massive financial risks when filtration fails.

While there are costs to maintaining a sterilization process during manufacturing, producing products that are insufficiently sterile imposes the highest costs. If a filter fails a routine check to confirm its ability to remove impurities, the entire batch of the drug product has to be discarded. This results in huge losses to the company.

Industry reports note that contamination-related batch failures can lead to millions of dollars in losses from not only discarded product, but also from investigation costs and manufacturing downtime.

How sterile filtration works

Sterile filtration involves forcing a drug product through a microscopic filter to remove contaminants such as bacteria and other dangerous microorganisms. This filter, also called a membrane, is extremely thin. It typically has a thickness between 105 and 170 micrometers, which is roughly that of a sheet of paper.

These membranes operate through a mechanism called size exclusion. Pores allow small drug molecules to pass through the membrane, while larger particulates are retained. The chemical properties of the membrane, which affects how molecules interact with it, can also determine what it catches.

The use of semipermeable membranes for removing bacteria dates back over 100 years to the early work of Nobel Prize winner Richard Zsigmondy on nitrocellulose membranes. The pharmaceutical industry began using these membranes as sterile filters after they were commercialized in the 1920s. However, after scientists found that Pseudomonas diminuta bacteria could pass through these membranes, even smaller pore sizes became the standard.

The U.S. Food and Drug Administration and European Medicines Agency considers filtration an appropriate method to sterilize highly sensitive drugs.

Pores and other methods

Why force drugs through microscopic pores instead of other sterilization methods?

Although techniques like heat sterilization or gamma radiation are highly effective for surgical tools or certain older drugs, they are often destructive to sensitive modern drugs. Many drugs consist of delicate proteins and genetic material that can be easily degraded or altered in ways that render the medication useless.

Another alternative to sterilization is aseptic processing, which involves assembling presterilized components in a completely sterile environment. However, this approach is expensive and highly prone to human error.

Sterile filtration emerges as a reliable method to process drugs without destroying their active ingredients.

Engineering better filtration strategies

Despite its widespread use, sterile filtration has certain limitations. Many new and promising approaches to drug delivery – such as mRNA technology and nanotechnology, monoclonal antibodies and cell and gene therapies – also introduce new challenges for sterile filtration and drug manufacturing.

For example, nanoemulsions are a mixture of oil and water commonly used to help drugs travel through the body when they don’t easily dissolve in water. These particles are similar in size to the membrane pores; if they clump together, they can block the pores so nothing passes through the filter. When the pores are completely clogged, no more material can pass through the filter.

Think of this process like trying to push a crowd of people wearing large backpacks through a single, narrow doorway. If a few people get stuck, they block the door for everyone else.

Moreover, when these particles get stuck on the surface of the filter, the expensive drug products they’re carrying are also trapped and lost. Losing these particles in the filter results in huge economic losses. For high-value biopharmaceutical products, a single failed or rejected batch may cost millions of dollars in raw materials, processing, investigation and production downtime.

My team and I examined different techniques to help find solutions to these challenges. We found that dual-layer membranes – where the top layer has larger pores and the bottom has smaller pores – can increase a filter’s capacity by more than 50% in some cases and increase yield to over 94%.

We also found that choosing the right prefilter by considering pore size and distribution, as well as the chemical properties of its surface, can reduce yield loss by over 10%. Additionally, pre-wetting filters with a specific chemical can increase the amount of nanoemulsions passing through pores before they clog.

Securing the batch

The global market for sterile filtration is estimated to grow from over US$5 billion in 2026 to nearly $13 billion by 2035.

As the pharmaceutical industry continues to develop complex therapies, keeping these drugs safe and affordable requires sterilization methods to evolve. Understanding the intricate interactions between drug molecules and membrane filters can help researchers find ways to keep the manufacturing pipelines flowing while safeguarding the batch.

Securing these microscopic gates helps ensure that the next generation of lifesaving medicines will be safe, reliable and accessible to the patients who need them most.