A short history of cleanrooms

Do you know where it all started for cleanrooms?

We've come a long way when it comes to scientific and medical impovements. But everything has to start somewhere. The modern cleanroom has only existed for about 65 years, but even before that, we have looked for ways to minimalize contamination!

From ancient Roman hospitals to modern-day life sciences, in less than 5 minutes, we'll take a dive into our history, and the evolution of the cleanrooms we know today!

Recap! A cleanroom is a special environment that is isolated and monitored to maintain a minimal concentration of airborn particle and avoid contamination. They are used in several industries, including but not limited to: pharmaceutical and biotechnology, aerospace and electronics manufacturing.

Before cleanrooms

Initially, hospitals attempted to regulate the air quality in areas where the patients where staying. Already in first-century Rome's military hospitals, the hospital space ventilation was manipulated. Hospitals, called valetudinaria, had roofs meant to provide cooling, because of the hot weather, and ventilation for fresh air. Military hospitals also stressed hygiene, cleanliness and sanitation in general.⁽¹⁾⁽²⁾

Eighteen centuries later, many new developments progressed us towards more contamination control. For example, Florence Nightingale, the Italian statistician and nurse famous for challenging the status quo of health care and women's education, made progress to reduce the mortality rate of injured soldiers. She implemented reforms, such as washing linens regularly, improving ventilation, and ensuring access to clean water. As a result, the mortality rate in her hospital dropped from 42% to 2% within six months.⁽³⁾

Around the same time, French chemist Louis Pasteur also made discoveries that improved our understanding of contamination. He designed a series of experiments to demonstrate that micro-organisms can't develop without contamination. Pasteur boiled a broth to sterilize it, before pouring it into sealed and unsealed flasks. This showed that growth of micro-organisms only occurred in the unsealed flasks, where airborne particles could contaminate the broth, and confirmed that micro-organisms cannot emerge from non-living matter.⁽⁴⁾

1883

Surgeon Gustav Neuber pioneered the use of non-porous surfaces, glass and metal furniture, and equipment for sterilizing the room, to improve the cleanliness of pharmaceutical environments. Neuber was insistent that every item used in surgery had to be sterilized, from surgical tools to linens and towels. He designed and operated the very first aseptic operating theatre in 1886, in Germany. ⁽⁵⁾

20th century

A first concept for the cleanroom was developed during World War II, driven by the need to improve the reliability of instruments used in manufacturing military equipment. Manufacturing issues caused by airborne particles, like dust  and micro-organisms, were leading to critical failures in sensitive electronic components. This pushed military and research institutions to find new ways to control environmental contamination at an industrial scale.

In 1960, physicist Willis Whitfield invented the modern cleanroom to solve contamination control issues. Earlier cleanrooms struggled to keep out dust and micro-organisms, because they often recirculated (contaminated) air and used inconsistent filtration.

The new laminar-flow cleanroom model revolutionized manufacturing in pharmaceuticals. In this model, filtered air flows in a uniform stream in one direction, from the ceiling to the floor, flushing particles away from the processes. HEPA filters (High-Efficiency Particulate Air) clean the incoming air, while positive air pressure prevents contaminated air from entering from outside. This controlled airflow reduced particle counts in cleanrooms from millions of particles per cubic foot to just a few hundred.⁽⁶⁾

During the years that follow, more and more pharmaceutical and industrial plants install cleanroom facilities, known as "White rooms", "Clean rooms" or "Dust-free rooms". His design remains the industry standard, still forming the basis for today’s ultra-clean environments.

Today

Modern cleanrooms are designed to maintain the highest standards of contamination control. This means they are characterized by many features and regulations to attain these high standards⁽⁷⁾:

• HEPA filtration
  HEPA filters are used to effectively remove particles as small as 0.5 microns from the air.
• Cleanroom standards
  Specific industry standards and guidelines apply, such as ISO 14644, to ensure a controlled environment with clearly defined cleanliness levels, like the maximum permissible concentrations of airborne particles.
• Cleanroom garments
  Cleanroom operators have to go through strict gowning procedures and wear specialized cleanroom garments, such as coveralls, masks or shoe covers, to prevent the shedding of particles and micro-organisms.
• Controlled airflows
  Air flows in a controlled pattern, including laminar or unidirectional flow, to minimize the movement of contaminants and reduce particle accumulation. Because of appropriate pressure, air flows from cleaner to less clean areas. For example, when doors open, the air flows out of the cleanroom.
  
  

Looking ahead

From ancient Roman hospitals to high-tech pharmaceutical facilities, the evolution of contamination control was shaped by centuries of innovation, experimentation, and necessity. The modern cleanroom may be a relatively recent invention, but the principles behind it have been thousands of years in the making: cleanliness, ventilation, and precision.

As industries continue to push the boundaries of precision and safety, cleanroom technology will remain central to ensuring quality and compliance at the highest level. Whether it's developing life-saving vaccines, assembling microchips, or preparing components for space missions, cleanrooms remain critical to some of the most important breakthroughs of our time. So next time you see a vial of medicine, a smartphone, or even a satellite launch: remember the hidden, spotless rooms behind them.

References

1. Belfiglio, V. (2015). Sanitation in Roman military hospitals. International Journal Of Community Medicine And Public Health, 462–465. https://doi.org/10.18203/2394-6040.ijcmph20151030 

2. Wesselingh, A. R. (2023, 31 mei). From Milites Medici to Army Medics - A two thousand year tradition of military medicine - JMVH. JMVH. https://jmvh.org/article/692/ 

3. Visser, Y. (2021, 16 oktober). Florence Nightingale (1820-1910) - De vrouw met de lamp. Historiek. https://historiek.net/florence-nightingale-vrouw-met-de-lamp/70027/ 

4. Libretexts. (2024, 23 november). 1.1C: Pasteur and Spontaneous Generation. Biology LibreTexts. https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/01%3A_Introduction_to_Microbiology/1.01%3A_Introduction_to_Microbiology/1.1C%3A_Pasteur_and_Spontaneous_Generation#:~:text=By%20sterilizing%20cultures%20and%20keeping,life%20does%20not%20arise%20spontaneously.

5. Joseph Lister’s antisepsis system. (2018, 14 oktober). Sciencemuseum.org.uk. https://www.sciencemuseum.org.uk/objects-and-stories/medicine/listers-antisepsis-system

6. Willis Whitfield: A simple man with a simple solution that changed the world. (2024, 4 april). LabNews. https://www.sandia.gov/labnews/2024/04/04/willis-whitfield-a-simple-man-with-a-simple-solution-that-changed-the-world/

7. WHO Good Manufacturing Practices for Sterile Pharmaceutical Products. (2011). Docslib. https://docslib.org/doc/193932/who-good-manufacturing-practices-for-sterile-pharmaceutical-products?