USP releases sterile compounding regulations

01/01/2004

By Mark A. DeSorbo

ROCKVILLE, Md.—Using syringes free of contamination to transfer sterile drugs and manually measuring and mixing no more than three products to compound drug admixtures and nutritional solutions must be done in an air quality of ISO Class 5 or better, according to newly released guidelines from the United States Pharmacopeia.

Along with the guidance to prevent microbial contamination under ISO Class 5 laminar flow hoods and in cleanrooms, USP 797, which became effective Jan. 1, also requires that cleanrooms in any facility where sterile products are prepared meet an ISO Class 8 rate or better, have an ante area "that need no be separated with a physical wall," and meet the construction requirements of ISO 14644-4. [See "Step 1: Familiarize yourself with ISO 14644-4," Cleanroom standards, CleanRooms June 2000.]

The USP 797 chapter and its predecessor USP 1206 were once just used as informational guidance, but have now evolved into a mandatory regulation, USP officials say.

"The Food and Drug Administration can enforce this chapter, and state boards of pharmacy can adopt it, too," says Frank Barletta, a USP scientist, who helped formulate the USP 1206, the predecessor to 797.

The ability to enforce the regulations points to the important role of compounding in the healthcare arena, says Roger Dabbah, USP's director of the complex active division.

"There is a lot of compounding being done now, and there are a lot of prescriptions that need to be compounded," he says. "If I am a physician, the correct dosage that I need to treat my patient may not be available, or I may need a combination that is not available or has been discontinued. So, there are a lot of reasons for compounding."

The overall intent of USP 797, Barletta adds, applies to all types of pharmaceutical compounding.

"The chapter was intended for hospitals, home healthcare environments—any pharmacy that is compounding, even the corner pharmacy in your neighborhood," he says.

USP 797 addresses a number of other contamination-control topics, including personnel training, gowning, barrier isolators, environmental monitoring and cleaning and sanitizing workspaces.

The reason, Dabbah says, is the risk involved in compounding sterile products. "It's not just about microorganism anymore. It's about particles, too," Dabbah says. "You don't want a preparation to have any particulates. Ten percent of the population is allergic to penicillin, so you don't want to compound it at the same time you are compounding something else. There could be cross-contamination."

According to a summary of USP 797, personnel must be professionally trained, perform didactic reviews, pass written and media fill tests, and be reviewed at least annually for low- to medium-risk compounding and semi-annually for high-risk level preparations.

The regulation also stipulates that personnel must remove outer lab coats, make-up and jewelry, and thoroughly scrub hands and arms to the elbow.

"After drying hands and arms, they should don non-shedding uniforms consisting of hair covers, shoe covers...coveralls or knee-length coats, appropriate gloves. Facemasks should be put on after entering the cleanroom," the summary says.

Environmental monitoring

A well-designed barrier isolator, according to USP, is an alternative to an ISO Class 5 laminar flow hood. And while it does not need to be located in an ISO Class 8 area, personnel working with the minienvironment must wear head and shoe covers as well as lab coats and facemasks (for covering facial hair).

Barrier isolators are also subject to the overall environmental monitoring program and validation requirements, according to USP.

Cleaning and sanitization for workspaces requires a written standard operating procedure that is executed at the beginning of each shift. For environmental monitoring, the regulation calls for verification of sterile compounding equipment through a written plan and schedule for monitoring airborne contaminants and verifying particle and viable microorganisms.

Validation under USP 797 requires three consecutive media fills without contamination in order to validate personnel. Revalidation would require one media fill run per quarter without contamination.

"Failure of revalidation; three consecutive media runs without contamination," the summary says.

In higher risk factions, the process must also have three consecutive runs without contamination, and one media-fill run annually for revalidation. Failure would require three runs without contamination.

Following 797, USP is expected to release a new guidance on cross-contamination, while the National Institute for Occupational Safety and Health (NIOSH) will issue new regulations on the handling of hazardous drugs.

"I've been getting a lot of calls about it," Barletta says of USP 797. "There are a heck of a lot of people out there who say they can't meet these requirements. I tell them they should submit their comments to the committees for consideration. The USP is always evolving."