06 May Cleanroom Requirements for Pharmaceuticals: A Short Guide

To create a compliant cleanroom, it takes more than simply air filters. These spaces are highly engineered environments with very strict rules and regulations, especially when it comes to pharmaceuticals. In fact, the cost of getting things wrong is so dangerous that one design mistake could create product recalls, legal troubles, or worse. In this guide, we’ll cover some of the most important cleanroom requirements for pharmaceutical manufacturing, and dig into topics such as classifications, environmental controls, materials, personnel protocols, and more.

Cleanroom Classifications and Regulatory Standards

The pharmaceutical industry often has to follow several overlapping guidelines, each of which depends on what country you’re in and what types of product you’re making, as well as the vulnerability of such manufacturing processes to contamination.

In the United States, the most widely used standards include ISO 14644, the FDA’s current Good Manufacturing Practices (cGMP) and Good Manufacturing Practices (GMP) regulations, and USP <797> / <800> for compounding.

ISO Cleanroom Classes

The ISO 14644-1 standard classifies cleanrooms by the size and number of particles per cubic meter of air. According to it, cleanrooms are classified from ISO 1 (the cleanest) to ISO 9 (the “dirtiest”). However, for pharmaceuticals, typically only ISO 5–ISO 8 are used:

• ISO 5: Allows up to 3,520 particles ≥0.5 μm and 29 particles ≥5.0 μm. Used in applications such as aseptic filling and other sterile processes.
• ISO 6: Allows up to 35,200 particles ≥0.5 μm and 293 particles ≥5.0 μm. Occasionally used for transitional areas or buffer zones.
• ISO 7: Allows up to 352,000 particles ≥0.5 μm and 2,930 particles ≥5.0 μm. Often used in weighing, dispensing, and formulation areas; also, typically used as a buffer zone.
• ISO 8: Allows up to 3,520,000 particles ≥0.5 μm and 29,300 particles ≥5.0 μm. Typically used in gowning rooms, staging areas, and packaging rooms.

Environmental and Air Quality Requirements

Cleanrooms, in order to stay pristine, have to keep air quality throughout the space, and in some places more than others. To do this, pharmaceutical operations have to make use of special filtration devices, pressure control, and environmental monitoring.

HEPA Filtration and Air Changes

Most pharmaceutical cleanrooms use HEPA filters, which remove 99.97% of particles that are 0.3 microns or larger. These filters help keep air clean and pristine, and are also installed in laminar airflow hoods or fan filter units, especially in strict spaces like ISO 5.

The number of air changes per hour, or ACH, can vary depending on the cleanroom classification. ISO 5 cleanrooms, which are used for the most critical processes like aseptic filling, require anywhere from 240 to 360 air changes per hour to keep particle levels low. ISO 7 cleanrooms, which, as we’ve discussed, often serve as buffer zones, typically require much fewer, around 60 air changes per hour.

In general, more frequent air changes (though not a perfect metric) help prevent particle buildup and are an absolute necessity for creating a sterile environment, especially in manufacturing stages where products are exposed.

Pressure Differentials

Further, pharmaceutical cleanrooms often make use of pressure differences to control how air moves between rooms. Most cleanrooms are kept at positive pressure, which means clean air is pushed out of the room to keep contaminants from coming in. This is standard in sterile manufacturing, where the goal is to protect the product from outside contamination.

In contrast, cleanrooms that handle hazardous drugs are kept under negative pressure. This means air flows into the room rather than out of it, which helps protect workers and the surrounding areas by containing any hazardous particles from the drugs. This approach is required under USP <800>.

The type of pressure used depends on whether you’re protecting the product, the personnel, or even both.

Temperature and Humidity Control

When manufacturing medicines, keeping temperature and humidity steady and within range is imperative. If the room gets too humid, it can encourage bacteria or mold growth. If too dry, static electricity (and therefore electro-static discharge) can build up, making particles move around more easily, and also making electrical equipment more vulnerable. A balanced environment helps protect both the product and the process.

Monitoring Systems

Finally, cleanrooms need to be monitored constantly to make sure everything stays within the required limits. A little slip up here can lead to disaster in the form of spoiled batches, product recalls, legal trouble, and even harm to consumers.

Environmental monitoring can help track particle levels in the air, checking that the airflow is moving in the right direction, and making sure temperature and humidity stay stable.

Pressure is also another factor that is carefully watched over, as air needs to move in certain directions for the space to work properly. Having real-time data makes rectifying any issues a much quicker affair.

Cleanroom Design Features

Furthermore, pharmaceutical cleanrooms must be built from materials and parts that support the whole operation, whether that’s to help resist contamination, make cleaning easy, or something else entirely. Here are a few essential considerations in pharmaceutical cleanroom design.

Modular vs. Traditional Cleanroom Construction

The first and perhaps biggest choice when deciding to build pharmaceutical cleanrooms is whether to use modular methods or traditional ones.

Modular cleanrooms are often faster to install, and much easier to expand in the future. Panels are pre-engineered off-site and assembled with few interruptions to your operation. These systems can be either post-and-panel or seamless, which gives drug manufacturers greater control over cleanroom design and compliance.

Traditional cleanrooms, on the other hand, are built entirely on-site, and the process is much slower. It can be disruptive to your operations, assuming they’ve already begun in some form. In addition, with traditional construction any changes to layout will require a lot more work (and demolition).

Often, they are less practical for pharmaceutical companies that need to adapt quickly.

Cleanroom Surfaces & Materials

Additionally, the surfaces inside a pharmaceutical cleanroom need to be tough, easy to clean, and designed to prevent contamination.

Walls and ceilings are usually made from powder-coated steel, aluminum, or fiberglass-reinforced plastic, each of which is non-porous and resistant to harsh cleaning agents.

Floors are typically finished with seamless, coved vinyl or epoxy resin, which makes them easy to disinfect and leaves no gaps for microorganisms to collect and grow. Urethane coatings are sometimes used as well, especially in areas exposed to frequent chemical cleaning. Corners are often rounded (with coving) rather than sharp, which also prevents particle buildup.

Ceiling panels are flush-mounted and gasketed, often with built-in lighting, to maintain a smooth, sealed surface. Some systems use aluminum-framed ceiling grids with gel-sealed or gasketed panels to ensure an airtight fit.

Cleanroom doors and windows are also flush and tightly sealed. This helps eliminate ledges, gaps, and other surfaces where dust or microbes could potentially accumulate.

Other Design Features

Pharmaceutical cleanrooms also have a few other design features that are necessary to keep the space clean and within regulations. Though not always used, pass-through chambers are important to help transfer materials in and out cleanrooms without the risk of introducing new contamination.

Gowning rooms are also common, with clearly separated zones (often a long line within the space itself) to help personnel move from “dirtier” areas into cleaner ones in a controlled way.

Ductwork should in general be sealed and made from smooth, easy-to-clean materials to prevent dust buildup and microbial growth.

Every one of these elements is there to support contamination control and to keep the cleanroom in line with ISO classification requirements.

Personnel Protocols

Finally, even the cleanest environments can be compromised if the people working inside it don’t follow the right rules. (In fact, people are often the biggest source of contamination in cleanrooms!)

Gowning Requirements

As a result, cleanroom staff must wear proper gowning, and what that is will depend on the exact environment, but can include items like coveralls, hoods, face masks, goggles, boot covers, sterile gloves, and more, especially in the stricter areas.

Once inside the cleanroom, personnel should reduce unnecessary talking and movement, avoid sudden motions, and never wear cosmetics or perfumes. Hands should be kept away from the face at all times, and these behavior standards should be reinforced through regular training. The exact protocols, will of course, vary.

Disinfection

Cleaning and disinfection routines will also depend on the cleanroom class, but generally involve daily floor and surface cleaning, weekly attention to ceilings and walls, and occasional full-room decontamination using approved disinfectants. All tools and supplies should be rated for cleanroom use, including low-lint wipes and sterile mops.

Anything brought into the cleanroom should be wiped down and passed through designated transfer hatches or airlocks. Cardboard and wood should be avoided, as they tend to shed particles.

Training

Last but not least, all personnel should receive regular training on cleanroom protocols, and spaces must keep detailed logs of cleaning schedules, environmental monitoring, gowning compliance, and equipment maintenance.

These steps aren’t just best practices; they’re an absolute necessity in keeping pharmaceutical operations on the right track.

The Bottom Line

In pharmaceutical manufacturing, cleanrooms are a necessity to create safe and effective products. With such a long list of regulations and requirements, every detail matters in pharmaceutical cleanroom design, whether it’s to aid particle control, support pressure management, reduce contamination risks, or enable systems that help keep medicines safe.

Interested in setting up modular cleanrooms at your location? Reach out to the experts at Allied Cleanrooms to get a quote on new spaces today:

FAQs About Cleanroom Requirements for Pharmaceuticals

1. Can cleanrooms be relocated or reconfigured if pharmaceutical production changes?

Yes, absolutely. This is one of the biggest benefits of modular cleanrooms; they are designed to be flexible. You can relocate, expand, or adjust them with minimal downtime, which makes them great for pharmaceutical companies that need to adapt to new production requirements.

2. Do pharmaceutical cleanrooms require antimicrobial finishes/coating?

In many cases, yes, but such coatings are not always required; they are commonly used to reduce microbial growth on walls, floors, and other surfaces, especially in sterile processing areas.

3. What is the difference between a cleanroom and a controlled environment?

A cleanroom is a type of controlled environment with strict limits on airborne particles. A controlled environment is a broader term that means a space that manages conditions, whether that’s light, temperature, humidity, or something else. Cleanrooms, though they also often control temperature and humidity, focus mostly on controlling particles.