Designing Low-RH Cleanrooms – Overcoming the Challenges for Precision Pharma Manufacturing

It was in the midst of a global shutdown when Fabtech was entrusted with a pivotal project for Navesta, Sri Lanka. The project was to build Sri Lanka’s first facility for granulation in tablets and capsules, with ultra-low relative humidity (RH) levels.

Challenges lie in every project, but this time, it was the timing of the project that we had to sail through. Nevertheless, we navigated all along, securing special travel permissions for chartered flights, maintaining strict social distancing and safety protocols, coordinating with global suppliers during major disruptions and ensuring team safety with quarantine measures and RT-PCR testing. 

The facility today operates smoothly and efficiently, and has been successful in achieving quality benchmarks for advanced manufacturing and research in challenging low-RH conditions.

Between the initial pandemic challenges and the successful outcome were the key considerations to establish the Low RH cleanroom facility. 

Understanding low RH level cleanrooms

Low RH environments are typically defined as those operating below 20% RH and, in some cases, as low as 1–5%. They are essential when working with hygroscopic materials that readily absorb moisture from the air. In tablet and capsule manufacturing, for example, excess humidity can compromise product integrity, affect uniformity and dissolution rates, and lead to microbial growth. Even packaging integrity can be compromised if moisture enters the process at any stage.

 In such cases, a low RH cleanroom is not just a design preference, but a compliance and quality necessity.

Design Considerations for Low-RH Cleanrooms

1. HVAC & Dehumidification

Standard cooling coils can manage moderate humidity control, but cannot achieve ultra-dry conditions on their own. Therefore, Desiccant Dehumidification Systems become a preferred choice. These systems use hygroscopic materials, often in a rotating wheel format, to capture moisture from the air before it enters the cleanroom. The captured moisture is then removed through a regeneration process, allowing the desiccant to maintain its drying efficiency.

In some facilities, these systems work alongside dual HVAC Systems to control temperature and humidity separately in different zones. This separation ensures that adjustments in one parameter do not affect the other. Air balancing is also critical here as enough air changes per hour (ACH) must be maintained to meet ISO cleanroom classification without disturbing RH stability.

2. Air Filtration

HEPA or ULPA filters keep airborne particles in check, but in a low-humidity environment, even the filter materials must be chosen carefully to avoid cracking or degradation. The filters must maintain cleanliness without adding moisture to the air stream and withstand very dry conditions without cracking. 

3. Building Envelope

The building envelope is equally critical and must be completely sealed against moisture ingress. Vapour barriers, insulation, and careful sealing of wall, floor, and ceiling penetrations are essential. Any compromise in the barrier can result in humidity spikes that are costly and time-consuming to correct.

4. Materials & Finishes

Materials must have low moisture permeability (e.g., PUF or PIR panels with aluminium/SS skins). The flooring must be non-porous, resist static buildup and be easy to clean. Hygroscopic materials such as untreated wood and paper must be avoided within the cleanroom environment.

Operational Challenges

1. Energy Consumption

Achieving and sustaining ultra-low humidity (<20%) demands significant energy, and continuous regeneration of desiccant wheels adds to operational costs. Facilities often mitigate this by maintaining ultra-low RH only in critical zones, while surrounding support areas operate at standard humidity levels.

2. Worker Comfort

Very low humidity can cause dry skin, eye irritation, and dehydration, which can affect productivity. Clearly defined work protocols help keep teams productive while minimising fatigue and discomfort in the ultra-dry conditions. This may sometimes require installing hydration stations and localised humidification at specific workstations, without affecting overall room conditions.  

3. Equipment Stress

Certain equipment, like electronics, seals, and some plastics, may be stressed by extremely dry conditions and behave differently in ultra-dry air. Static charge buildup also becomes a constant threat if proper grounding is not in place. Therefore, conductive flooring and anti-static garments become imperative. 

Monitoring, Control, and Compliance

In a low RH cleanroom, constant monitoring is essential. A small fluctuation in outside air temperature, a leaky seal, or an HVAC fault can cause rapid changes in humidity. Modern facilities use calibrated sensors tied into automated building management systems (BMS) that can trigger alarms and corrective actions the moment parameters drift outside set points.

Compliance with ISO 14644 standards for particulate control remains mandatory, as does adherence to Good Manufacturing Practices (GMP). Documentation and validation become even more critical in a low RH environment. Humidity control systems must be qualified, calibrated, and maintained according to strict schedules to ensure consistent performance.

Planning and Execution

Coordination for RH level cleanrooms extends beyond design and construction. Many components for dry environments have long lead times, and logistics can be complex, requiring close coordination between civil, MEP, and process teams. In some cases, site conditions may require special importation, handling, or installation protocols to protect sensitive components from humidity before they are operational.

Training is another area that can’t be overlooked. Operators and maintenance staff need to understand not just how to work in the environment, but also how their actions can impact the delicate humidity balance. Maintenance can become demanding as filters, desiccant beds, and seals degrade faster in low-RH setups.

Predictive maintenance helps prevent costly downtime. Even something as simple as leaving a door open for too long can set off a chain reaction of humidity spikes, production delays, and costly revalidation. They should be adept in handling static-sensitive processes and respond quickly if humidity levels fluctuate.

Balancing Sustainability 

Being thoughtful in designing a low RH cleanroom balances performance with efficiency. Strategies such as zoning, heat recovery systems, variable speed fans, and advanced control algorithms can reduce energy consumption without compromising environmental stability.

Projects such as Navesta, Sri Lanka, made it possible to manufacture sensitive drugs and develop advanced therapies with the precision and stability that modern healthcare demands. For Fabtech, such projects are both a challenge and an opportunity as they give us a chance to push the boundaries of environmental control and deliver manufacturing spaces that safeguard the integrity of life-saving medicines.

Let us engineer your next low-RH facility with precision, compliance, and reliability. Connect with Fabtech’s experts and turn your vision into a controlled, high-performance reality.

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