Designing Efficient Layouts for Pharmaceutical Production Facilities

The layout of a pharmaceutical facility should help manufacturing run smoothly, from the entrance to the most critical areas, while minimising contamination. Designing efficient layouts that fit a required process within the available space can be challenging. By taking a systematic approach, cleanroom designers can create layouts that accommodate a logical flow through multiple ISO class cleanrooms, with appropriate anterooms, airlocks and HVAC equipment.

Core Principles of Layout Design

The basis of designing cleanroom layouts is to balance a logical, linear flow through the space with appropriate zones to prevent cross-contamination.

Zones

Cleanroom specialists build in various zones to facilitate the segregation of activity such as API extraction, manufacturing processes, cleaning equipment, and packaging. There are also appropriate ways to zone storage to separate raw materials and finished products, used items that require cleaning and clean items that require sterilisation, for example.

Flow

The movement of materials, personnel, and products should be a logical, linear process. If possible, everything should move in one direction, from unclassified areas through areas of various classes up to the highest required. There should also be a separate route to exit through these areas, scaling down one at a time so that no critical, aseptic area is exposed directly to an unclassified area. Once in a high-grade cleanroom, personnel should not need to exit until the critical stages are finished. All the equipment and materials required should either move with them or be available in the space where it is needed.

Cleanroom Zoning: What is it and why is it so important

Zoning divides a pharmaceutical manufacturing space into separate areas based on their function, cleanliness requirements, and the level of contamination control needed. For pharmaceutical cleanrooms, we typically discuss zones in terms of GMP grades, which correspond to ISO classifications. These grades also include stipulations such as whether or not sinks and drains should be present, particle monitoring is required, and different limits for when at rest and in operation, and so on.

GMP Grade A

Grade A is often a local zone, provided by a laminar air flow system at a given work station. This is the cleanest area, used for aseptic operations for filling ampoules, making aseptic connections, replenishing sterile bulk product, staging and conveying of sterile primary packaging components, etc. These operations pose a high risk for product quality, e.g. filling, closing, ampoule and bottle opening zones.

GMP Grade B

Grade A zones are surrounded by Grade B zones when an isolator is not used. Both have air quality equivalent to ISO 5 when at rest, while B may drop to ISO 7 in operation. Grade B zones are for transporting equipment and components into the A zone, while protecting them from the surrounding environment.

GMP Grade C

Grade C zones are separated from B and D zones by air locks and are classed as ISO 8 when in operation. They are used for preparing solutions to be filtered and filling products for terminal sterilisation.

GMP Grade D

The lowest grade offered by GMP, equivalent to ISO 8, is used for cleaning equipment, handling and assembling components and equipment after washing, prior to sterilisation.

Appropriately zoning cleanrooms physically and environmentally separates clean areas from general-purpose areas such as offices. It also controls who and what travels between zones, with gowning rooms, airlocks and clean corridors minimising the contaminants that may enter with personnel.

A Systematic Approach to Zoning

When we design layouts for pharmaceutical facilities, we begin by setting out the number of zones. Each zone should be supported by one of the class below, so the highest class dictates the number of zones. If the highest cleanroom class required is GMP Grade C, then 2 controlled zones are required: D and C.

Accessing Clean Areas from Less Clean Areas

Moving personnel and materials from an unclassified area to grade D, or from one class to a higher class, requires passing through an airlock.All Grade D, C and B clean zones are supported by 3 air locks:

Materials In
Materials Out
Personnel Airlock

Using two materials airlocks is standard practice and means there is no need for procedural separation of incoming and outgoing items. These airlocks may be small pass-boxes set one above the other, or may be larger, depending on the types of materials.

The personnel airlock will include handwashing facilities and gowning areas, a stepover bench and gowning storage.Once the zones are known, we plan the layout to include the position of walls and doors, observation zones and air locks. It is crucial to consider HVAC at this stage.

HVAC Integration

We consider HVAC needs right at the beginning of the design phase so that all zones have an appropriate amount of room for the equipment. Each grade has a limit on particulate matter allowable, which can be achieved with HEPA filtration and ventilation systems. This hardware is set up to change the air in the cleanroom a certain number of times per hour to maintain cleanliness.

Air pressure differs between spaces

During the cleanroom design, the desired air pressure in each zone is decided, relative to the outside area. This means that from the beginning, we know what level of positive air input is required in each zone.

Air pressure will always be higher inside a cleanroom than in the non-classified area. This prevents contaminants and particulate matter from flowing into the clean area. In general, there should be a difference of at least 10pa between GMP grades, so it’s worth aiming for 15pa differentials to provide tolerance when air locks are open. Within hatches and anterooms, the air pressure is set at an intermediate differential, allowing the air pressure to cascade down.

This means that when a door is opened, air escapes out of the higher grade, not into it, reducing contamination risks.

Environmental Controls

Pharmaceutical cleanrooms require precise controls of humidity and temperature to maintain personnel comfort and drug storage conditions. Each cleanroom zone is fitted with monitors, dehumidifiers, air conditioning and control panels as needed.

Common Design Mistakes to Avoid

Sometimes our team is called on to upgrade an older cleanroom, and the cleanroom layouts we see share some features that need to change. These errors or outdated layouts are unsuitable because they make the cleanroom less effective, require operators to work less efficiently, or are not suitable for new processes or equipment.

Inadequate Space for Air Handling and Ductwork

Cleanrooms should be constructed with a double wall, fitting air handling, ventilation units and ductwork in the space between. Ductwork also needs a clear path from machinery to the building exterior. The space will also house cabling that leads to sockets on the interior, and provide maintenance access on the exterior.

Failure to plan this space effectively leads to ducts and cabling fitted inside the cleanroom, creating opportunities for particulates to accumulate. It also requires any maintenance to happen inside the cleanroom, which must then be decontaminated afterwards.

Poor Zoning And Air Pressure Mismanagement

Poor zoning is usually the result of changes in workflow that require operators to move between zones too frequently. This means airlocks are opened more often, work slows down as operators need to wash their hands and gown more frequently.

Overlooking Flexibility

A modern cleanroom installation should be designed with room to manoeuvre. When a business invests in new machinery, changes processes or needs to expand, a poorly designed cleanroom will have to be rebuilt from scratch. A well-designed cleanroom will have the flexibility needed to adapt to changes over time.

How Airology Can Help

At Airology, we specialise in designing bespoke cleanrooms and laboratories for pharmaceutical manufacturing and other industries. We work with companies to understand the needs of their facility and design a space that has a strong flow and appropriate zoning. We consider the space as a whole, incorporating offices, stairways, security access points, PPE preparation areas and sterilising stations, as well as designated areas for machinery and quality control. Our plans can include custom furniture and trolleys to support manufacturing efficiency.

For assistance with designing cleanroom layouts, contact Airology today.