Enforcing adequate aseptic procedures will ensure patient and personnel safety

By Fran McAteer, Microbiology Research Associates

Compounding sterile preparations (CSPs) are made utilizing aseptic technique. Aseptic technique is a microbiological term referring to the prevention of microorganism contamination. The procedure involves the use of specialized equipment, sterile apparel, meticulous processing, and continuous cleaning.

Historically, asepsis was a startling revelation and was demonstrated in the work of great scientists such as Lister and Pasteur. Over time, aseptic technique has been developed, improved, specialized, and harmonized. Today, aseptic technique is the basis of good manufacturing practices (GMP), quality system regulations (QSR), and USP Chapter <797>, “Pharmaceutical Compounding-Sterile Preparations.”

In sterile compounding, aseptic technique is contributing to the prevention of nosocomial infections and thereby improving patient care. It is providing sterility, safety, and efficacy to CSPs, especially various aqueous injections for patients. Due to the routes of administration of these injections directly into the bloodstream, microbial contamination has a more deleterious effect on this target population and these preparations represent the greatest risk to patients from potential contamination. CSPs produced using meticulous technique, personnel gowning, and repetitive cleaning procedures dramatically reduce the opportunity for potential contamination.

Competent aseptic technique compounding procedures reduce contamination risks. The technique is divided into several general categories.

1. Controlled environments
2. Personal gowning
3. Visual inspection
4. Cleaning/sanitization
5. Procedural manipulation
6. Disposal

Aseptic technique is performed in a controlled area such as a cleanroom, laminar flow hood, and/or isolator. Each type of environment reduces both surface and air contamination to minimum levels. These environments are encased with smooth surfaces such as stainless steel and/or Lexan. Surfaces that are easily cleaned and composed of a material such as 316 stainless steel show a higher imperviousness to scratches, which provide a good hiding spot for microbes. The critical environments are equipped with high efficiency particulate air (HEPA) filters that remove 99.9 percent of microorganisms by continuous filtration. The higher air velocity moving through the filter and the number of air changes reduce bacterial levels. These controlled areas provide the foundation for successful aseptic processing.

Personal gowning specifies the type of garb worn by personnel while performing aseptic processing. This can refer to bouffants, booties, gloves, sleeves, hoods, masks, glasses, goggles, boot covers, suits, aprons, lab coats, beard covers, and scrubs, to name a few. The exact items and gowning sequence needed to successfully perform asepsis in various compounding activities should be specified in the standard operating procedures (SOPs). The SOP will stipulate types of acceptable gowning, frequency of changes, and garbing sequence. Some procedures will also specify a gowning certification in which the pharmacist or technician must demonstrate proficiency in donning cleanroom apparel before being permitted to work in the clean zone. This type of proficiency-based training further enhances meticulousness of personnel in complying with cleanroom gowning procedures. Certification testing is accomplished by utilizing contact TSA plates to test hands, forearms, and shoulders after gowning. This certification process helps exhibit aseptic competency to regulators.

Personal gowning also includes hand washing and hand disinfection. Remove jewelry, watches, bracelets, etc., before cleansing. Wash hands, up to the elbow, with an antibacterial soap, scrubbing to remove dirt-especially under fingernails-and ensure a good contact time (30 seconds). Be careful not to touch the face, clothing, or surroundings. Many compounding sinks are set up with knee or foot pedals to eliminate a potential touch contamination. If applicable, immediately put on gloves as specified in SOPs. Gloves should be frequently sanitized with 70 percent isopropyl alcohol (IPA) during aseptic processing.

Visual inspection is another integral part of aseptic technique. Pharmacists and technicians should visually inspect their work zone, gowning, equipment, vial closures, IV bags, syringes, needles, and so on for clutter, debris, trash, vial defects, septum penetration, and disposable package integrity. If there is an out-of-specification observation, then remove the impediment and resanitize the work area. If it is a vial closure issue, then inform the supervisor and obtain a new vial. Visual inspection of the admixture preparation for particulates is very important. Precipitate, flakes, and dust particles can indicate potential hazards in the medication. Visual inspection should be emphasized during new hire training and upon media proficiency requalification. Visual inspection should also play a role in personal gowning. A mirror in the anteroom will let technicians observe and inspect for proper attire.

Aseptic technique is enforced by strong cleaning and sanitization procedures. It is critical to disinfect the work area on a daily basis, if not more frequently. This cleaning and sanitization should be documented in datasheets or logbooks to demonstrate compliance. Using 70 percent IPA is the easiest choice. It is effective against most bacteria but not spore forms such as gram-positive rods. Adding a second sanitizer such as peracetic acid, hydrogen peroxide, quaternary ammonium, or phenol will provide more robustness to the cleaning efficacy. A rotation of these sanitizers is certainly a suitable strategy.

Procedural manipulation is a term indicating preciseness and meticulousness in performing compounding procedures. It refers to manipulations that minimize contact with critical product surfaces such as septums and needles. When contact is made, the surface should be immediately wiped with 70 percent IPA. The preciseness of procedures limits movement, which reduces particle generation and contamination potential. Procedural manipulation is best done through repetition and demonstrated by media proficiency testing.

Disposal and cleanup of the work area after completion of the admixture is critical in maintaining asepsis. If spillage is not wiped up immediately, it can create both a safety and contamination hazard for the immediate compound and other CSPs made in that work area. When compounders’ hands leave the sterile field, it is imperative that they are resanitized with IPA before re-entering the laminar flow hood. For disposal, spent materials used in the preparation of sterile compounds should be removed and the work area resanitized with IPA before leaving the area. Datasheets showing the date and workers’ initials are a good way to demonstrate compliance.

Aseptic technique is a process limiting potential contamination in the compounding process. However, it is very subjective and a function of the skills of the pharmacist, which should be reinforced with education, training, and proficiency.

Fran McAteer is vice president of quality at Microbiology Research Associates, Inc., an FDA-registered contract microbiology testing laboratory specializing in USP testing for pharmaceuticals, biologics, and medical devices. The author has expertise and experience in implementation of USP <797> programs for hospital pharmacies and acts as a consultant for many hospitals.