1. Introduction

AHU zoning in Pharmaceutical Plants is one of the most important HVAC engineering drawings to be released in earlier stages such as concept design. It will determine the number of Air Handling Units of the plant to satisfy the GMP requirements.

In this article, we are going to evaluate the critical aspects to assign Air Handling Units for all the spaces. We will have to balance in terms of quality and cost:

• Maximum segregation: a large number of units fully accomplishing GMP, containment, and other requirements, but expensive and with space limitations.
• Minimum segregation: less number of units, with less cost but with risk of cross-contamination that should be assessed.

Within these two extremes, there is an optimization process to assure that the number of units is enough to satisfy the following:

• Process constraints
• Room classification
• Containment requirement (if any)
• ATEX constraints
• Energy
• Decontamination process
• Engineering

Let´s discuss each point below.

Typical colored drawing showing AHU zoning. Each color identify an Air Handling Unit serving different spaces

1.1. Process constraints

The main objective is to avoid cross-contamination, either products or subprocesses. We shall consider if the facility is a single product or multiproduct and what type of product is. We must ask ourselves how the product or the process would be affected if recirculated air from a room went into another of the same system. A risk analysis approach would guide us to the right decision.

Different processes are usually segregated, i.e.:

• upstream and downstream in biological production
• product dedicated rooms
• support areas (corridors, janitors, storage areas)
• lockers
• cell culture
• critical process equipment (freeze dryers, autoclaves)
• filling rooms
• cleaning and washing rooms
• …others

1.2. Room classification

Although there is no regulatory requirement to segregate AHUs depending on the room classification areas, it is a good practice to observe the following premises.

• Classified rooms (ISO8, ISO7, ISO5, and ISO5 unidirectional flow) should not share the same unit with non-classified areas. A designer could be tempted to share a large corridor ISO 7 with a few non-classified rooms next to it, to save some ductwork. The reason why not should take such a decision is that there are terminal HEPA filters in the ISO7 corridor (as usual). Then, when we balance the system, we should compensate the high-pressure drop of the HEPA filter with a balancing damper in the non-classified rooms. That causes a significant operational cost.

• You can share some spaces with the same AHU with different classifications if there are no process constraints. A typical example is PAL/MAL ISO8 with PAL/MAL ISO7 and distribution corridors.

• Otherwise, you can share within an AHU the complete suite including a single process (PALs, MALs, and production area)

• We normally apply special considerations about classifications ISO5 in sterile production facilities, with a separated AHU. These areas are often decontaminated, and it is common to isolate them from the rest of the systems to facilitate this.

• We can bear on the same approach for unidirectional flows (also ISO5) systems by supplying to a fan filter set per room.

1.3. Temperature requirements

This is another factor that could suggest we have different AHU zoning. If all the above factors are satisfied (process, classification), then probably we could use the same AHU for one area. But, if the heat gains are significantly higher in one room, that will force us to lower the air supply temperature to the value that will remove heat gains for that room. Consequently, we should install reheaters to keep the temperature values within the margins for all the remaining rooms. In the example below, we could take the decision to assign one AHU only for room 2, and another AHU for rooms 1, 3, and 4.

We should study such a situation because probably is economically a better solution to split the units depending on the heat gains.

In our past post Heat Gains, you can find more information about that.

1.4. Humidity requirements

In this case, different humidity areas should be handled with separated units. Reducing the main airflow humidity to the room with less humidity and increasing locally the humidity in those rooms which require a higher value (in a similar way to the reheater seen above) is not practical and operationally expensive.

We find low humidity requirements in hygroscopic product presence areas, cold rooms, lyophilization areas, etc.

In most cases, humidity is affected only by the makeup air water content, so a specific control for that unit provides air that will satisfy the hygrometric room conditions. We can use this makeup air handling unit to provide air with low water content to other units (i.e. a cold room) by taking advance of the preliminary cooling. In this example, the zoning will help us to optimize the energy consumption:

1.5. Containment requirements

For biological containment, we recommend that the rooms with the same level (BLS1, BSL2, BSL3, and BLS4) are grouped in the same AHU. Moreover, we should define clearly areas with live viruses and deactivated viruses, or pathogenic and non-pathogenic areas with different AHUs.

For chemical containment (i.e. HPAPI) we will follow the same approach.

1.6. ATEX constraints

Usually, the dilution of explosive or flammable substances requires large air volume AHUs. In such a manner, different ATEX classification areas will not share the same AHU.

ASHRAE published a guide for HVAC in hazardous spaces. You can find it here: https://www.ashrae.org/news/ashraejournal/designing-operating-safe-hvac-systems-for-hazardous-spaces

1.7. Energy Use

As explained above, concerning the temperature and humidity requirements, the use and optimization of the energy can provide a direction about how to group different air handling units for different spaces.

We have to explore the possibility of heat recovery (see our post Energy Savings in Pharmaceutical HVAC Design), especially in those systems using a high percentage of makeup air.

1.8. Decontamination Process

Decontamination processes are very common in biological and or sterile facilities. It consists of propelling a disinfectant product into the room atmosphere using a diffuser that saturates the room air so that the product is deposited everywhere (wall, ceiling, floor, work surfaces…)

This particular system requires that when the decontamination is over, we have to remove the disinfectant product existing in the room releasing it to the atmosphere. That means that the HVAC system shall be able to supply 100% fresh air and completely exhaust this air.

Therefore, those rooms requiring decontamination shall be separated from others non-requiring.

1.9. Engineering

There are other reasons not related to quality or performance, that the engineer could decide to adopt a different AHU zoning, based on engineering constraints. One of the most usual is the lack of space. We can find some examples in the following typical situations.

• AHU footprint too large could lead us to split the unit into a few smaller
• Not enough space to pass ductwork from levels could make us think about using a large AHU with reheaters
• Lead time for specific units
• …and more

In any case, based engineering zoning decisions shall not compromise GMP requirements!