USP 797: Contamination sources—control and remediation


By Douglas Theobald, CFM

Even the most excellent compounding room design cannot compensate for the one factor that has the greatest impact on a controlled environment—the human factor. Recently as I was greeting a group of people for training on "Correct Cleanroom Behavior," I made a point to greet each person with a deliberate handshake and introduction. As the training began, I introduced myself and the topic of discussion. Directing my focus to a few people in the audience whose names I remembered, I said, "thank you for coming and congratulations because you have now come into contact with me and whatever I have handled since the last time I washed my hands!" The statement drew some odd looks and a few laughs. Of course, I quickly re-assured everyone that I had washed my hands just prior to starting the training. My point was to illustrate how we assume everything is OK based on appearance and perception. I cannot stress enough the importance of hygiene and current Good Manufacturing Practices (cGMP) when working in a controlled environment.


The term "human factor" refers to an awareness of how our activities either enhance or devalue the quality of a compounded sterile preparation (CSP) and/or product in a controlled environment. The USP 797 calls for stricter adherence to personnel hygiene, additional gowning components, gowning procedures, standard operating procedures (SOPs) and documentation verifying training and adherence to protocol. It is essential that all personnel working in the environment or coming in contact with the "product" are thoroughly trained in correct behavior and product handling. The training elements will vary slightly based on product, material flow, equipment and room design.

The basics

There are some basic elements to controlling potential contamination that we can consider. As I have referenced in previous articles, low-, medium- or high-risk activities all require some kind of ante area. The purpose is to control access to the compounding room as well as prevent the migration of contamination into the aseptic environment. This is also where the proper gowning and sequence of donning garments comes into play. The 797 guidelines state that, "Compounding personnel are (must be1) adequately skilled, educated, instructed and trained to correctly perform and document the following activities in their sterile compounding duties:

  1. Perform antiseptic hand cleansing and disinfection of nonsterile compounding surfaces;
  2. Select and appropriately don protective gloves, goggles, gowns, masks, and hair and shoe covers;
  3. Use laminar flow clean-air hoods, barrier isolators, and other contamination control devices that are appropriate for the risk level;
  4. Identify, weigh, and measure ingredients; and
  5. Manipulate sterile products aseptically, sterilize high-risk level CSPs and label and quality inspect CSPs."2

The key is that the personnel are trained for, and aware of, the critical nature of their interaction with the CSP process and the necessity to maintain the integrity of the controlled environment.

Reviewing the "hardscape"

In construction terms "hardscape" typically refers to concrete walls, decks, columns and so on—in essence, those items that are not movable. Let's assume that we have a room that has been designed to minimize the potential of contamination; we have set our equipment in the room to be as efficient as possible in our process and we have a good idea of what our process entails. I like to view this as the hardscape. If you want to change something it is probably more than just a simple solution. Now the next critical step is to assess any residual opportunities for development or migration of contamination in the controlled environment. Look for design or construction deficiencies, equipment that should not be located in the environment or "gaps" in the process and handling of the preparation or product. I highly recommend performing a complete survey prior to changing anything in an existing room. Then you can take an abrogated approach to mitigating any deficiencies.

Dress for success

In addition to properly donning the correct apparel for a specific process (the object of which is to protect the product from you), there are a few other considerations. If you are using reusable garments that are worn for a period of time and then laundered for use again, it is advisable to have the garments checked periodically for integrity. In short, the garments wear out and can become part of the problem rather than the solution. There are several companies that will perform periodic random inspections for you.

There is a whole host of integrity tests for a garment monitoring program. All of the tests are based on industry-standard metrics, that is ASTM or IEST RP. Some basics are: Particulate Enumeration, Barrier Integrity and Surface Sensitivity. Even if you are using a professional laundering service or disposable garments, always check with the vendor to confirm they have a regular, documented quality method of testing with results you have access to. You may need the information if you have an "incursion" or failure due to contamination.

Cleaning up

As part of the quality program it is necessary to have SOPs delineating the methods and frequencies of cleaning and sterilization of the room and its' components. USP 797 includes "Suggested Standard Operating Procedures." The operative word is "suggested." The important thing is to consider what tasks are critical enough to be "standardized." The old adage "document what you do and do what you document" definitely applies.

It is recommended that, although the each person working in the environment will as a matter of course clean his work area(s), thorough periodic cleanings should be performed by individuals specifically trained for the comprehensive cleaning. This even applies to equipment supplying conditioned air to your environment. Preventative maintenance and filter changes should be scheduled and documented to affirm completion on a regular frequency. Depending on where you are located the outdoor air quality can be a factor in what comes in via the air supply and what we bring in on our clothes and bodies.

Moving on

Now that we have discussed the issue of the human factor and established the variables in controlling our CSP environment, the next installment of this column will begin to address matters pertaining to compliance and documentation.

Notes: 1 Words in Parenthesis mine, 2 USP General Chapter 707 Pharmaceutical Compounding – Sterile Preparations

DOUGLAS THEOBALD is a certified facilities manager and is the Orange County-Los Angeles general manager of Controlled Contamination Services LLC (Anaheim, Calif). He can be reached at: