Controlling what enters the environment

A complete system starts with controlling what enters the facility. Most GMP operations struggle with this task each and every day. Simple reasoning tells us that if one reduces contamination entering the controlled environment, then its presence doesn’t have to be addressed. If contamination is controlled, the cleaning and disinfection process becomes much simpler since, as existent particulates and microbes are reduced, cleaning and disinfection efforts can also be reduced. Although it’s a simple concept, it’s more difficult to implement than it sounds.

However, on a scale of importance, the control of particulates and microbes entering a controlled environment is probably the most critical area of concern in the entire cleaning and disinfection process. Controlling contamination from introduced components, personnel, carts, tanks, tools and other sources is also important. Lack of control over the cleanliness and sterility of items entering the clean space can compromise the environmental conditions during manufacturing, particularly as relates to the introduction of particulates and microbes, and the remains of dead organisms, or pyrogens.

In the industry, pyrogens have proven to be an equal threat to live cells. Fevers and even death have been attributed to their presence. There are two ways to eliminate a pyrogen: disintegrate it at high temperatures using a dry-heat process called depyrogenation, or clean it. Depyrogenation of cleanroom surfaces is not possible, so pyrogens must be cleaned from the surface like a particulate.

There are two high-risk time periods when contamination enters the cleanroom. The most critical time is after disinfection and prior to the beginning of manufacturing. Production personnel enter the just-cleaned facility and riddle it with particulates and microbes that may shed from their entry and whatever components they bring into the room. Such particulates and bioburden will now exist in the area during manufacturing.

Although it is well understood in the industry that, because it is an aseptic process and not a sterile process, the area will always have some level of particulates and bioburden in it, the goal in the aseptic cleanroom is to reduce bioburden to its lowest level.

The other high-risk time is after manufacturing and before cleaning. In general, we are less conscious of cleanliness after the manufacturing is complete. And so, breaches tend to occur during this time.

To reduce particulates and microbes, we must first define the cleanliness and sterility (or disinfection when sterilization is not an option) of what we bring into the environment. Those responsible for developing disinfection systems need to first make a list of every item and/or person that enters the controlled area, then evaluate each to determine whether it is clean and appropriately sterilized (or disinfected) prior to entry. Organizations that institute a very strict entry system for all items and personnel have fewer excursions.

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