USP 797: Compliance and documentation



With a higher level of scrutiny comes a more intense means of tracking or documenting every aspect of personnel training, material handling and environmental monitoring. USP 797 clearly defines criteria beyond the traditional standards of training and documentation for compounded sterile preparations (CSPs) and aseptic techniques. This is where we really want to pay attention: USP 797 states, "The pharmacy should have written, properly approved, standard operating procedures (SOPs) designed to ensure the quality of the environment in which a CSP is prepared." As we have discussed previously, regardless of whether the pharmacy is located in a state that has adopted USP 797 as written or in a state that is still drafting a response, there are some things that are critical in current Good Manufacturing Practices (cGMP).

Quality documentation

The various "recommended procedures" that we are focusing on both affirm some of the issues we have already addressed and prepare us for future discussions. Let me say up front that the information here is in no way comprehensive. The purpose is to crack the surface and get a good look at what's inside. The critical types of documentation we are currently addressing include SOPs, Standard Operating Forms (SOFs), Work Instructions (WINs), Training Records, Environmental Monitoring Records and Equipment Calibration Records. Regardless of the "risk level" or the size of the compounding operation, each of these types of documentation is relevant and necessary.

Critical documentation should always be controlled with standard formats, control numbers, revision dates and so on and stored in an accessible location for use and inspection. Larger drug manufacturers already have this in place (due to regulatory requirements) and even the small corner pharmacy has some form of controlled documentation. Take some time to look at your system to verify that you have a system that will continue to work as you expand the number and types of documents we are talking about. Regardless of the size of the operation, a good quality system is essential, and documentation is an integral part. I recommend that the "Suggested Standard Operating Procedures" section in USP 797 be used as a guideline for working clean and in a clean environment.

Common denominator

The common denominator of the SOPs, SOFs, WINs and other documents is that they reference each other. That is good because they work like pieces of a puzzle to form a clear picture. Conversely, if one is changed they all should be reviewed and updated. The simplest rule of thumb is summed up in two age-old phrases, "keep it simple" and "document what you do and do what you document." Training goes beyond the basic training to perform tasks or manipulations; it also includes training on the understanding, use and frequent review of documentation up to and including "how to correct an error in documentation."

SOPs are general instructions on various activities such as gowning, aseptic techniques, cleaning and frequencies, personnel/equipment and material flow, equipment maintenance/calibration and so on. Work instructions are typically more detailed step-by-step instructions on performing a certain task or a critical portion of a larger task. SOFs are often used in both cases to record that an SOP or WIN has been performed as per instructions.

Believe it or not

Implementing or enhancing the documentation and the document control program can actually be rewarding in several ways. Over the years, I have worked with various companies to draft documentation for everything from gowning procedures to the flow of materials in the manufacturing process. This has afforded the opportunity to learn about technologies and processes that are "made for the movies." For the individual that uses the same documentation on a daily basis it grants the comfort of working in a framework or structure that can be a breath of fresh air compared to the dynamics of the uncontrolled aspects of "real" life. For both the short and the long term, the benefits are control through standardization, safety through verification and compliance through documentation. You can have the best practices and the most qualified personnel, but as they say, "if it isn't written down, it never happened."

Some specifics

In addition to a "Written Quality Assurance Procedure," as described in the USP 797 section "Responsibility of Compounding Personnel," we are also given the instruction to perform "routine disinfection and air quality testing of the direct compounding environment to minimize microbial surface contamination…" as well as "visual confirmation that compounding personnel are properly donning and wearing appropriate items." This applies to all risk levels.

Media fill tests are to be performed on an annual basis for low- and medium-risk CSPs, while high-risk fill tests are performed on a semi-annual basis. Under the heading of "Personnel Training and Evaluation In Aseptic Manipulation Skills" the requirement is stated that, "Personnel who prepare CSPs must be provided with appropriate training from expert personnel [what constitutes an expert is not clearly defined], audio-video instruction sources, and professional publications in the theoretical principles and practical skills of aseptic manipulations before they begin to prepare CSPs." These are all operations that would have SOPs, SOFs, WINs and a documented "specific training and performance evaluation program…"

Clearing the air

Environmental monitoring is not just testing the air for particulate contamination. The environment in a cleanroom comprises the quality of air, the cleanliness of surfaces, the performance and condition of equipment, the performance and cleanliness of personnel, the quality and integrity of materials introduced into and manipulated within the clean environment, and even the quality of the garments that are used. For now let's talk a bit about documentation relative to environmental monitoring.

Again, as stated in USP 797, "a written plan and schedule for the environmental monitoring procedures for airborne microorganisms must be established and followed." This is one of the few times the word must is used so it must be important. In regard to the air quality, we need to test not only for particulates but also viable microorganisms. In a way, some of the testing we used to perform only on the product has now moved out in a larger scope. Certification of LAFWs (I would include gloveboxes and barrier isolators) must be performed by qualified professionals "at least every six months or whenever an LAFW or barrier isolator is moved." Interestingly enough the larger scope here also extends to the air quality of the buffer areas, clean areas and anteroom as well. These areas should be "evaluated at least every six months or when renovations occur." I hate to throw this in at the end, but here's the fun part; "These records are maintained and reviewed by the supervising pharmacist or other designated employee."

Fear not. Help is on the way. We will dig into this a little deeper in my next column when we address Compliance and Testing. You're in for a treat.

Douglas Theobald is a consultant and general manager with Controlled Contamination Services LLC (San Clemente, Calif.). He can be reached at