Cleaning Compounding Aseptic Isolators

 

Using the right techniques and procedures can make cleaning sterile compounding areas a matter of routine.

Since the June 1, 2008 revision of USP general chapter 797, pharmaceutical compounding personnel have been held responsible for the cleanliness of their sterile compounding areas, including biosafety cabinets (BSCs), compounding aseptic isolators (CAIs), compounding aseptic containment isolators (CACIs), and laminar airflow workbenches (LAFWs), as well as their buffer areas, ante-areas, and segregated compounding areas. Cleaning and disinfecting these controlled environments is required to minimize the risk of environmental contact as a source of microbial contamination of compounded sterile preparations (CSPs).1

WHAT HAS TO BE CLEANED AND WITH WHAT FREQUENCY?
All of the surfaces of the sterile compounding areas must be cleaned regularly and frequently. It is required that the surfaces of BSCs, CAIs, CACIs, and LAFWs be cleaned and disinfected at the beginning of each shift, before each batch of product is compounded, not longer than 30 minutes following the previous surface disinfection when ongoing compounding activities are occurring, after spills, and when surface contamination is known or suspected.

In addition to the sterile compounding areas, counters and easily cleanable work surfaces shall be cleaned and disinfected daily. Floors in all areas, including the buffer area, anteroom, and compounding area, are to be cleaned and disinfected daily. All mopping should take place when no compounding is in progress.

All other surfaces, walls, ceilings, carts, and storage area shelving, should be cleaned and disinfected at least monthly, again when no compounding is in progress.

HOW SHOULD THE CLEANING OCCUR AND WHAT SHOULD BE USED?
USP Chapter 797 requires written standard operating procedures (SOPs) and cleaning logs to ensure the quality of the environment for the preparation of CSPs. SOPs for cleaning should include a procedure (how to clean), as well as the frequency (when to clean), and the supplies (what to clean with). Charts, checklists, and training posters for cleaning are useful tools for ensuring compliance with cleaning SOPs.

In general, cleaning should be done from the cleanest area to the dirtiest area. To minimize crosscontamination, cleaning should also be done from top to bottom. For example, in a monthly cleaning, the order would be: ceilings; walls and windows; exteriors of process equipment and cabinets; countertops and other horizontal surfaces; and at last, floors.

Surfaces within arm’s reach can be cleaned using wipers and solutions (such as 70% isopropyl alcohol (IPA) or a disinfectant) appropriate to the environment. Wipers should be “low-linting” — that is, wipers should not leave particles and fibers behind when they are used to clean surfaces. In an ISO Class 5 area, a non-woven polyester/cellulose wiper can be used. However, in areas where a more stringent environment is necessary (such as the interiors of BSCs, CAIs, CACIs, and LAFWs), a knit polyester wiper is suggested.

Wipers can be purchased either pre-wetted with 70% IPA or they can be wetted at the time of use with the solution of choice. Be sure wipers are not dripping with solution — an overly wet wiper can redisperse contaminants and can increase the chances of the solution itself becoming a contamination source.

Wipers should be folded so that the entire surface of the wiper can be used. Typically wipers are quarter folded, and then refolded after every wipe of the surface, to contain and remove the contamination. In this manner, there are eight different surfaces of the wiper exposed and able to be used for wiping. Wiping should be done in overlapping linear strokes from clean to dirty or dry to wet.2 After all eight surfaces have been used, the wiper (and its captured contamination) should be discarded in an appropriate container (Figure 1).


(Click Image For A Larger Version)

For the floor, string mops made of tubular knitted yarn with captured ends to minimize release of particles and fibers are considered ideal. String mops should be rinsed frequently using two to three buckets to accomplish thorough rinsing. The mop should first be dunked into the “dirty” bucket, agitated, and then wrung out. Then the process should be repeated with the second (and third, if present) buckets to ensure the dirt that the mop has just picked up is not re-deposited. The bucket water/cleaning solution or disinfectant should also be changed frequently to avoid reintroducing contamination.

Floors can also be cleaned using flat mops with a bucketless system where mop covers are either prewetted with the cleaning or rinsing solutions, or the operator sprays the mop covers with a cleaning solution after the covers have been placed on the mop head. The mopping should be done in linear overlapping strokes from clean to dirty, dry to wet, the same procedure that is recommended for wiping. In a cleanroom, the corners furthest away from the entry doors are usually the cleanest areas since they have the least foot traffic. Aisles and entry doors sustain the greatest traffic and are usually the dirtiest areas. So mopping is done from far corners to aisles and entry doors (cleanest to dirtiest).

Some spaces can be difficult to reach with wipers, such as back walls and far corners of the deck in minienvironments. In such cases an isolator cleaning tool (a small mop) with replaceable mop covers is employed (Figure 2).

Swabs wetted with a cleaning solution, IPA, or sterile water can be used to address very tight areas. Some possible candidates for swab cleaning are: vents in the back wall or front surface, the junction of the walls with the floor and ceiling of the cabinet, surface dimples surrounding rivets or screws, connectors to hoses or filters, etc. (Figure 3).

TRAINING
Training, based on written protocols, is essential for proper cleaning of a cleanroom.3 Cleanroom personnel should have a good understanding of how and what they are to clean and why. They will perform much better if they know what they are expected to do.

Written protocols define the SOPs describing cleaning methodology. SOPs tell personnel what needs to be cleaned, what tools (wipers, mops, swabs, cleaning agents) are to be used, how often to clean, and how to do the cleaning.

Personnel need to be trained using these SOPs, and then tested to ensure proficiency in cleaning and maintenance procedures. Plus, personnel should be retrained on a regular schedule. The written SOPs should be available at all times; visual aids, such as posters or graphs, can be used to reinforce the training.4

CONCLUSION
USP general chapter 797 has mandated that pharmaceutical compounders must maintain the cleanliness of their sterile compounding areas. Cleaning these areas should become a matter of routine, following written SOPs developed specifically for these areas. Training personnel is essential and must be continual, assisted by charts, graphs, and other visual aids. Cleaning logs with check-offs for daily, weekly, and monthly cleaning can assist in ongoing training.

References:

  1. USP 797 Pharmaceutical Compounding — Sterile Preparations, Revision Bulletin, The United States Pharmacopeial Convention, 2007.
  2. Douglas Cooper, “Wipe First, Clean Later,” A2C2 Magazine [now Controlled Environments Magazine], June 1998.
  3. “Cleanroom Housekeeping — Operating and Monitoring Procedures,” Document IEST-RP-CC018.2, Institute of Environmental Science and Technology, Rolling Meadows, IL.
  4. Howard Siegerman, “Is This A Convenient Time to Clean?” Controlled Environments, January 2007.

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