Wednesday, 23 August 2017

Aging pharmaceutical facilities

The aging facility presents various microbiological contamination risks (and some more recent pharmaceutical product recalls associated with microbial contamination have related to older facilities). These risks include:

Poor facility management

General poor upkeep, leading to peeling paint or torn lagging, presents opportunities for microbial contamination to occur. Risks are more acute for spore forming organisms, such as Bacillus and related genera and with fungal spores.

Changes to facility use

Changes to facility use, in terms of people and equipment, present potential risks. For example, if a facility was designed for a specific number of personnel and the operational level increases, this could present new challenges for contamination control, especially where cleanroom occupancy rates increase (given that people are the primary contamination source within cleanroom environments).

Furthermore, changes to production equipment and layouts can affect airflow directions, especially in relation to aseptic processing. The addition of more equipment to a working space can cause greater heat generation, placing a greater heat load upon air conditioning. If environments are not suitably controlled, this can cause personnel to shed higher levels of skin and thus increase the microbial load into the cleanroom. Additionally, as amounts of equipment increase this can make areas more difficult to clean and disinfect simply because operators cannot maneuver around the equipment footprint. Poor air circulation also brings with it other risks, such as undetected fungal growth A related area is with the air supply system from variable air volume boxes. Here the air volumes supplied into cleanrooms may not be as originally designed. This not only affects air supply volumes but also air exchange rates and clean-up times. These physical parameters are essential for keeping particles (viable and inert) in suspension and for removing them from cleanrooms. This factor can be overlooked because most cleanroom monitoring systems assess pressure differentials rather than air supply volumes.

Degradation to fabric

Cracks in walls, tears to vinyl, and the degradation of construction joints can lead to microbial contamination events. Here unclean areas can become exposed to cleanrooms and microorganisms can reside in cracks. Where cracks occur, cleaning solutions will often not be able to penetrate.

A further risk with weakened or broken joints is that high airflow velocities can drag unsuitable air into cleanrooms from plant areas. This can lead to turbulent mixing and the potential entailment of contamination. This can be assessed through airflow visualization.

Regular inspection and a sound repair program can overcome these problems, together with the fitting of high quality seals such as compressed rubber gaskets.

Building void spaces

The voids between adjacent cleanrooms or between cleanrooms and the outside environment will accumulate dust, and within the dust there will be spore-forming microorganisms. Such environments will not have any impact unless they are disturbed. Here contamination will arise when facilities are modified, such as knocking through a wall in order to expand a cleanroom. Good control measures should be in place when modifications take place including partitioning off areas, vacuuming dust and regular cleaning followed by sporicidal disinfection.

Excerpted from the chapter: Risk Considerations for Aging Pharmaceutical Facilities:

Sandle, T. (2017) Risk and Microbiological Contamination, PDA Letter, Volime LIII (7),  (July 2017, pp8 at:

Posted by Dr. Tim Sandle