The design, installation, commissioning and qualification of clean rooms heating, ventilation and air conditioning (HVAC) systems is often one of the largest considerations in the design of a new pharmaceutical or biotechnology manufacturing facility. With high running costs (energy associated with the movement, cooling and heating of air) and the potential to impact upon safety and product quality, getting them right
The design of the HVAC system will be based upon the clean room suite that it serves, and will be affected by factors such as the number of rooms served, the layout of the rooms, the equipment within the rooms and, most critically from a qualification perspective, the environmental conditions that the rooms must achieve.
BackgroundThe air handling unit helps maintain each room's clean environment by providing an appropriate volume of clean air to each room at the correct temperature and humidity.
The air is filtered by pleated paper filters called high efficiency particulate air (HEPA) filters which, depending upon the classification of the rooms, are located either within the air handling unit or where the air enters each room. Cooling and heating coils are also located within the air handling unit, increasing or decreasing the air temperature to ensure that the room temperatures remain within specification.
Reliable operation of the air handling unit within established limits is critical,1 not only to prevent product quality from
Defining the Requirements
What are the problems?
If the design phase is completed without considering the compliance aspects of the clean rooms, then there is a high likelihood of incurring significant time delays and costs during the validation period, as a result of having to make mechanical changes to the installation or revisiting some of
Some typical examples of areas where problems can occur as a result of not designing for compliance are highlighted below, together with suggested actions to try to avoid these problems from occurring.
Operating tolerances. Design, commissioning and validation criteria must be determined for GMP-critical parameters such as air change rates, room differential pressures, temperature and humidity.1 For example, different tolerances may need to be applied at commissioning and validation to ensure that the facility will operate reliably within the validation acceptance criteria limits.
Air filtration. The level of air filtration will vary depending upon the classification of the clean rooms being served. For example, an ISO Class 5 room (Class 100) will require terminal HEPA filters, whereas an ISO Class 8 environment (Class 100000) may be achieved by using a high-grade (non-HEPA) filter within the air handling unit.2 To avoid failures during validation integrity testing it is important for the validation and design teams to discuss the in situ test requirements, and to agree upon appropriate grades of air filtration.