1. Introduction

The Grade C cleanroom air change rate is still one of the most debated topics in pharmaceutical HVAC design. In many projects, 20 air changes per hour are treated almost as a default value for ISO 7 / Grade C cleanrooms, even though the real airflow requirement may depend strongly on the process, room layout, occupancy and contamination risk.

One of the best ways to stay current in pharmaceutical HVAC is to read technical papers, not just guidelines, habits and inherited design rules. A single paper may not change the whole industry. But it can force us to ask better questions. A good example is the paper “Effects of different air change rates on cleanroom ‘in operation’ status” by Detlef Behrens, Jens Schaefer, Cornelia M. Keck and Frank E. Runkel, published in Drug Development and Industrial Pharmacy in 2022 (link here). The paper is interesting for one simple reason: it challenges a very common assumption in cleanroom HVAC design.

In pharmaceutical projects, that number appears everywhere. It is repeated in specifications and design criteria. Very often, it is treated as a minimum requirement. However, the paper reminds us that the FDA wording says that 20 ACH is “typically acceptable”. That is not the same as saying that it is always required. This distinction matters. In practice, “typically acceptable” is often interpreted as a fixed design rule. That can lead to oversized HVAC systems and unnecessary energy use.

2. What the paper studied

The authors performed an experimental study in a pharmaceutical cleanroom under “in operation” conditions. They simulated operation with a process unit and two operators inside the room, and they tested four different air change rates: 20, 15, 12 and 10 ACH. They also varied operator garments, from proper cleanroom clothing to deliberately poor clothing, in order to understand how much contamination was driven by gowning practice and operator behavior. In total, they carried out 32 trials, measuring both non-viable particles and viable contamination using calibrated particle counters and microbial air samplers.

The test room itself was not some abstract model. It was a typical pharma cleanroom with a floor area of 38.4 m², a volume of 99.8 m³, two H13 terminal filters with swirl diffusers in the ceiling and two low-level exhaust grilles on the wall. That point is important, because the paper is not purely theoretical. It is based on a realistic room and measured results.

Related to this topic you can find this related post interesting Airflow Reduction in Cleanrooms Operations HVAC Optimization

3. Why the topic matters

This discussion is not only about compliance. It is also about energy. The paper points out that pharmaceutical cleanrooms can consume dramatically more energy than normal rooms, and that HVAC systems in these environments may have up to 25 times higher energy demand than standard spaces. In many facilities, cleanrooms are operated continuously and often with more airflow than they really need, simply because designers and operators prefer to stay on the safe side. That conservative approach is understandable, but it has a cost.

This is why the question is so relevant: if a room can still meet cleanliness requirements at a lower ACR, then blindly sticking to 20 ACH may no longer be good engineering. It may just be habit.

4. The main result

The strongest conclusion of the paper is very clear: 20 ACH was not required in the tested setup, and 10 ACH was sufficient without compromising the demanded air quality. That is the headline result, and it is the part that will attract most attention from HVAC engineers.

For 0.5 µm particles, the results were especially striking. Even at 10 ACH, the measured values during normal “in operation” activity stayed far below the ISO 7 / Grade C limits. In fact, the authors point out that the measured values were even below the ISO 7 / Grade C “at rest” limit in their normal operating simulations. That means the offset between real measured values and regulatory limits was extremely large.

For 5 µm particles, the margin was smaller, but still comfortable in normal operation. The only exceedance of the “in operation” limit happened in a deliberately exaggerated test scenario with poor clothing and intentionally bad operator movements such as running and waving. During normal operation, the limits were still met at all tested ACRs.

The viable results follow the same general trend. Better garments and higher airflow reduced contamination, as expected, but even at lower ACRs the microbiological performance remained generally within the regulatory expectations. The worst results appeared in the deliberately poor garment scenarios, which underlines a point that HVAC engineers sometimes forget: airflow is only one part of contamination control. Clothing, behavior and operational discipline matter just as much.

5. What this means for HVAC engineers

From an HVAC point of view, this paper is valuable because it supports a much more rational design philosophy. Instead of asking, “What ACR do people usually use for Grade C?”, we should be asking, “What ACR is actually required for this room, this process and this operating condition?”

That is a much better engineering question.

The paper supports the idea that air change rate should be justified by actual contamination risk, room function, garment standard, operator activity and recovery requirement, not just by tradition. This is also consistent with the wider direction of the industry, where fixed generic ACR values are increasingly being replaced by more risk-based and process-specific approaches.

6. The role of garments

One of the most practical observations in the paper is the impact of operator clothing. With proper cleanroom garments, the room performed extremely well. With street clothes or very poor garments, particle and viable contamination increased significantly. In one summary of the “in operation” phase at 10 ACH, the poor-garment cases produced roughly 2 to 3 times more particles than the proper cleanroom garment case.

That is an important lesson. If a room struggles to meet its performance targets, the answer is not always “more air.” Sometimes the real problem is poor gowning, poor room behavior, unnecessary movement or process-related emissions. Higher ACR can hide these problems, but it does not solve them.

7. The uncomfortable message behind the paper

The paper does not stop at saying that 10 ACH worked in the tested room. The authors go further and argue that the current Grade C / ISO 7 limits may be so generous that they create an excessive buffer between what is required and what is actually measured. In their view, that large gap can mask real operational problems in aseptic manufacturing. Whether one agrees fully with that argument or not, it is a provocative and useful point. If the allowed limit is extremely high, then a room may remain “compliant” even when its performance has noticeably deteriorated.

8. A necessary note of caution

As interesting as the paper is, it should not be overused. This was still one experimental setup. The room had a specific size, layout, diffuser arrangement, filtration concept, heat load and occupancy. The paper itself acknowledges that real rooms may contain more equipment, more heat generation and more process complexity than the study room. That means the conclusion should not be simplified into “10 ACH is always enough for Grade C.” That would be just another design myth.

9. Final thought

For me, the value of this paper is not that it gives us a new universal number. Its value is that it pushes us to think properly. It reminds us that good cleanroom design should be based on measured contamination risk, real room behavior and technical justification, not on repeating old numbers without questioning them.

That said, the paper should also be read with some caution. It is based on one specific cleanroom setup, with a defined room size, diffuser arrangement, filtration concept, process unit and operator load. This makes it very useful for challenging the automatic use of 20 ACH, but not sufficient to claim that 10 ACH is always enough for every Grade C / ISO 7 room.

In other words, the paper is a strong argument against blind overdesign, but it is not a license to generalize without engineering judgement.

And that is exactly why reading technical papers still matters.

References:

Behrens, D., Schaefer, J., Keck, C. M., & Runkel, F. E. (2021). Effects of different air change rates on cleanroom ‘in operation’ status. Drug Development and Industrial Pharmacy, 47(10), 1643–1655.

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