By Yarisi M. Valero, RPh

WHEN COMPOUNDING STERILE PREPARATIONS, ONE OF THE MOST IMPORtant factors to consider is the quality of the environment in which the preparation is being compounded. In addition, good documentation and validated processes are imperative to comply with the regulations set forth in USP Chapter <797>. Developed by Grifols, the Gri-fill System is a closed system that can be used in the preparation of compounded sterile preparations (CSPs) and may assist pharmacists in complying with USP Chapter <797>.

AnazaoHealth Corporation conducted a study to observe the Grifill System’s process of mixing sterile preparations with eight manipulations per admixture in a non-controlled environment. We used tryptic soy broth (TSB) media fill to validate this process, and to monitor the room’s environment, we used contact plates and agar settling plates.

The Gri-fill System was programmed to compound 325-mL units. Fifty mL of TSB were withdrawn from a 1-liter bag (simulating the diluent) and 275 mL of TSB were withdrawn from six glass vials (simulating the drug additive) into a 500-mL Gri-Bag. The entire solution was filtered through the Gri-fill system via a 0.22-micron filter pre-attached to the 500-mL GriBag. The Gri-fill System also performs an integrity test of the filter. The units that failed the integrity test were discarded and not included in the total number of units. A total of 600 units were compounded and stored for seven days at room temperature, followed by seven days incubated at 30 to 35 ?C. Three vials containing TSB were inoculated with Bacillus subtilis, Candida albicans, and Aspergillus niger as a growth promotion test
to demonstrate that the media would support bacterial and fungal growth. All three vials were found to have evidence of bacterial or fungal growth.

The contact and settling plates used to monitor the environment in which the Gri-fill system was being used revealed the presence of bacterial contaminants. The room where the Gri-fill System was used was not a cleanroom, had no special controls, and also contained items not suitable for controlled environments, such as cardboard. We created the worst-case scenario for the Gri-fill System to perform in. However, none of the media fill units compounded by the Gri-fill System exhibited signs of bacterial or fungal growth. It is reassuring to know that even in a worst-case scenario, the Grifill System can compound sterile solutions. However, according to USP Chapter <797>, all compounding must take place in an ISO Class 5 environment, and the Gri-fill System 3.0 is compact enough to be used conveniently within a laminar air flow hood.

Due to the requirements of <797>, we must now be able to prove that we follow procedures, monitor our cleanroom, test our preparations, and that our compounding personnel are properly validated. The Gri-fill System documents the integrity test of its filter and gives you duplicate printed labels that you can use for your files and/or affix to the preparation. It can measure volumes of 1 mL to 3000 mL plus or minus 2%, which is highly accurate. The system also offers the option to use computer software that allows you to print activity reports.

In addition, the statistical analysis of our media fill supports a 95% confidence that the Gri-fill System contamination rate is less than 0.5%. In fact, while we can’t measure the exact contamination rate with 0 media positives, according to the statistical analysis, the positive rate must be less than 0.0085% to give a result such as this with reproducibility.

As pharmacists, we must use our professional judgment to determine if we have control of our practice. Using a system that documents our processes, as the Gri-fill System does, can help us make that determination and support our judgment. The validated process of this system is a wonderful tool. The system can be used for all types of medium-risk compounding, such as pain management bags, PCAs, epidurals, IVIG, and the pooling of TPN components. Furthermore, the Gri-fill System is very easy to use, and to train a pharmacy technician to use it takes less than one hour.

While important news and discoveries related to the compounding of sterile preparations and the overall practice of pharmacy continue to come to light, devices like the Gri-fill System can help pharmacists—in conjunction with our increasing knowledge—to ultimately improve patient care.

Yarisi M. Valero, RPh, is the pharmacist in charge at Tampa, Floridabased AnazaoHealth Corporation. She can be reached at yvalero@anazaohealth.com.