Microbiological testing programs are a vital part of any compounding pharmacy’s operation. When applied in a timely, comprehensive, and effective manner, they help minimize risk and support patient safety and positive outcomes.
The United States Pharmacopeial Convention’s (USP) <797> addresses testing and microbiological quality measures for sterile, compounded drugs produced by U.S. and Canadian facilities. USP <797> Pharmaceutical Compounding – Sterile Preparations provides guidelines for areas in which compounded sterile drugs are prepared, stored, and dispensed. Additionally, USP <797> includes guidance on cleanrooms, where the concentration of airborne particles is controlled to meet a specified airborne particulate cleanliness class. Microorganisms in cleanrooms should be monitored so that microbial counts for air, surface, and personnel are not exceeded beyond the specified level. In addition, access to cleanrooms should be limited to personnel trained and authorized to perform sterile compounding and facility cleaning.1
Although USP <797> guidelines are in place, they were written to allow for flexibility and several U.S. states do not have laws providing guidance for sterile compounding. Such flexibility can make it challenging for an organization to define the best approach to testing. Adding to the challenge, regulations are likely to change in coming months and years as compounding pharmacies and the regulations governing them are coming under intense scrutiny, in response to recent, well-publicized contamination events.
Despite existing and changing regulations, quality microbiological testing and safety are crucial to prevent future instances of contamination, as well as potential deaths. As such, compounding facilities should establish a robust, compliant microbiological sampling and testing program consisting of various measures, such as sterility testing and environmental monitoring to minimize the risk of contamination. This is no small task and yet the stakes are high. Knowing exactly how to become compliant with USP <797> can be difficult as there are many options, no prescribed route, and evolving regulations.
While the information in USP <797> can be relied on as guidance for decision making and validation of process, it is also important to note that some states do not have laws governing sterile compounding. Facilities must also meet the requirements of the states to which they may be shipping their drugs. Thus, as best practice, organizations should identify and then adhere to the most stringent requirements possible.
An optimal microbiological sampling and testing program incorporates knowledge of microbiology, aseptic practices, well-trained operators, established and robust technology and systems, and thorough validation programs. When operating in an uncertain, evolving environment, a number of factors must be considered to establish and ensure a robust, successful program, including:
• A formal risk assessment program
• Intimate knowledge of the product and processes
• An effective operator training program
• Standard operating procedures
• Validation protocols
• Environmental monitoring trending data
• Corrective actions/preventative actions (CAPA) and investigation protocols
• Personnel with microbiological experience or training
• High quality products that are compounded to your tightest specifications
As part of these requirements, a robust microbiological sampling and testing program should include formal risk assessment to identify where in the process there is a risk to the product or the patient. In order to conduct a thorough risk assessment, it is important to understand every detail about the product and process and identify where possible exposure to contamination could come from. Proper risk assessment requires knowing the facility, utilities, raw materials, and how training is being executed and documented.
Once an assessment is complete, companies can mitigate exposure to risk through implementation of appropriate environmental monitoring technologies, which are used to determine the microbial and particulate content of cleanroom air and surfaces. Environmental monitoring is an essential component of any robust QC program because it determines the microbial and particulate content of air and surfaces and operators. Identifying and addressing contamination in compounding pharmacy production is critical since it can damage product, lead to product recall, slow product’s time to market, and compromise consumer safety.
A variety of approaches and new technologies for surface monitoring and air monitoring exist to help identify conditions contributing to excessive microbial and particulate levels. Data collected from environmental monitoring are a vital component of a compounding pharmacy’s microbiological testing program. Results are used for quality assurance, identifying conditions contributing to excessive microbial and particulate levels, as well as to alert personnel to conditions exceeding classification, which can save time and reduce costs.
In addition to environmental monitoring, sterility and media fill testing should be performed on all final products that are purported to be sterile or need to be qualified for beyond-use-dating. The tests help ensure the final product is contaminant-free before it is released to market.
Ultimately, it is up to the company responsible for the final product to comply with laws and regulations, and observe industry standards. By establishing a more robust QC microbiology program, from identifying requirements through implementing environmental monitoring and sterility testing, companies can effectively increase control in the sterile compounding process. This will help identify contamination faster and improve the sterility testing of final products. When applied in a proactive, timely manner, such controlled processes can improve patient safety by identifying risk before a contamination event occurs.
1. The United States Pharmacopeial Convention (2008). 797〉 Pharmaceutical Compounding—Sterile Preparations. Retrieved from http://www.doh.wa.gov/Portals/1/Documents/2300/USP797GC.pdf
Anne Connors is a Regional Marketing Manager at EMD Millipore, specializing in Environmental Monitoring and Media Fill applications. She holds a B.S. in Biology and has over eight years of experience in the pharmaceutical industry. She can be reached at email@example.com.
This article appeared in the June 2014 issue of Controlled Environments.