By Eden M. Venti, ASQ CQA
WHILE THE USP STERILE COMPOUNDING COMMITTEE COMPLETES ITS review of comments received in response to the proposed changes to Chapter <797>, pharmacies across the country are beginning to identify the potential financial, procedural, and operational impact some of these changes may have on their operations. Perhaps one of the most significant revisions is an addition to the “Environmental Monitoring” section that will require gloved fingertip sampling of operators compounding preparations in an ISO Class 5 environment.1 This sampling may be new to Chapter <797>, but it has roots within many of the current standards and guidelines around monitoring personnel in cleanroom environments. As your pharmacy prepares for this change, there are several key items to consider when revising your environmental monitoring plan.
Why This Addition?
All of the references cited in this article, including <797>, speak to the fact that operators pose the highest risk of introducing to a cleanroom the microbial contaminants that could make their way into a sterile preparation. Operators whose hands are contaminated can compromise the sterility of a preparation by directly touching any surface that comes into contact with the drug or its components.
Many of the current global standards and guidelines on environmental monitoring of cleanrooms address gowning qualification and procedures for operators, including selection and donning of cleanroom garb, operator behavior, and routine fingertip and garb testing of operators to show continued compliance with these procedures. Adding gloved fingertip sampling to the environmental monitoring section of USP Chapter <797> aligns USP more closely with the standards referenced within its pages. More importantly, it provides pharmacies with an additional quality control mechanism to ensure its cleanroom environment remains in a state of control. The following sections will give you an idea of some of the expectations set forth by the revisions, as well as considerations that may need to be made as your pharmacy plans to implement the changes outlined.
The distinction between low-, medium-, and high-risk compounding in the proposed revisions is reflected in the minimum sampling frequencies proposed. High-risk level compounding will require daily sampling, while lowto medium-risk level compounding will require weekly sampling. In all of the risk levels, the proposed changes require that at least one operator or 10% of all compounding operators in the shift (whichever number is greater) complete sampling.1 While not expressly addressed in the USP chapter, pharmacies with more than one aseptic operator should have a schedule that allows each operator to perform testing on a routine basis, in order to establish the baseline data needed to trend operator sampling results.
Sampling may be best performed with the assistance of another operator waiting outside of the ISO Class 5 area, and should occur after the last compounded medication has been made. If your pharmacy’s operators will be performing self sampling, they should be trained on proper self-sampling using aseptic sampling technique and should be closely monitored (e.g. direct observation during sampling) to ensure they perform sampling correctly.
Current guidance for environmental monitoring includes garb testing of operators.
Media Selection and Additional Resources to Consider
A trypticase soy agar (TSA) contact plate ranging from 24 to 30 cm2 is recommended for sampling. It is best to select media with ingredients to neutralize any residual surface disinfectants that may be on the fingertips, in order to reduce the likelihood of a false result.1
Each lot of medium should be accompanied by a certificate of analysis (C of A) showing it has passed growth promotion tests for the prescribed microorganisms that can grow in TSA. The C of As should be retained in your pharmacy’s environmental monitoring documentation for the time prescribed by applicable local and federal regulations, accrediting bodies, or other standards your pharmacy is required to follow.
Pharmacies should determine, in advance of the publication of the revised chapter, how many additional plates will be required for their operations, as well as any other resources they may need. Depending on the size and scope of your pharmacy’s operations, it may be necessary to purchase additional incubators to house samples.
Pharmacies considering outsourcing this testing should have procedures developed to address how the samples will be prepared for and preserved during transportation to the testing laboratory.
Prior to use in sampling activities, contact plates should be visually inspected for signs of contamination or dryness. The manufacturer, lot number, and expiration date of the plates should be recorded in the pharmacy’s environmental monitoring log. Before sampling, the bottom of each plate should be labeled with a plate number, operator name or initials, the sampling date, and sampling location (ie, right or left hand). Your pharmacy may also want to consider retaining a positive and a negative control for this sampling period.
Operators should exit the ISO Class 5 area to complete the sampling. Aseptic technique should be used to remove the lids of each plate. It is important to remember that gloves should not be disinfected prior to sampling as this activity may generate false negative results.1,2 The four fingers and thumbs for each hand should be pressed into their respective contact plates.
If another operator is assisting with the sampling, he or she should hold each plate at an angle that will easily allow the operator being tested to first press his or her four fingers of one hand and then thumb into the first plate, and repeat with the opposite hand for the second plate. When done correctly, a visible impression of each finger will be present. Lids should be carefully replaced when finished, again using aseptic technique, so as not to inadvertently contaminate the samples.
Plates should be inverted and incubated according to Chapter <797> between 33°o and 37°o for two days. Results should be read, recorded, and trended in the pharmacy’s environmental monitoring log.
Action and Alert Levels
Action and alert levels will be triggered when a sample shows greater than or equal to three colony-forming units (CFUs).3 Results exceeding the established action and alert levels should prompt the retraining of personnel in hand hygiene and garbing procedures, as well as glove and surface disinfection procedures and cleanroom behavior.3 In addition, your pharmacy’s policies and procedures should require full retraining and/or recertification of technicians who have repeated excursions from established limits.2
Operator sampling results should be trended to provide a picture of which aseptic operators may pose higher risks as “shedders,” as some staff members may tend to emit large numbers of particles and microcontaminants, even if they are appropriately certified and properly garbed. If trending data for a particular operator continues to come close to or exceed the established three-CFU limit, it may be prudent to remove the operator from cleanroom operations altogether.2
Proposed fingertip sampling is just one addition within the revised USP Chapter <797> that will have a direct impact on many areas of your pharmacy. Performing operational and financial impact analyses now will allow your pharmacy to properly address what will be required to comply with the chapter when it is released.
Eden M. Venti, ASQ CQA, is a quality assurance and regulatory affairs specialist for Wedgewood Pharmacy in Swedesboro, New Jersey. Prior to joining Wedgewood Pharmacy in 2004, Venti worked for Bristol-Myers Squibb and DuPont Pharmaceuticals. She is currently pursuing her master’s degree in quality assurance and regulatory affairs from Temple University School of Pharmacy and is a senior member and certified quality auditor with the American Society for Quality. She is also affiliated with the International Society for Pharmaceutical Engineering, Parenteral Drug Association, and Regulatory Affairs Professionals Society, and is a member of IEST (Institute of Environmental Sciences and Technology).
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