Corporate Partner Spotlight: EMD Millipore Corporation
Author: Karen Chronholm
Director Regional Marketing
EMD Millipore Corporation
290 Concord Road
Billerica, MA 01821 USA
Phone: +1 978-715-1748
Ensuring the Highest Level of Microbiological Quality and Patient Safety
As the regulatory environment for compounding pharmacies continues to evolve, facilities can take immediate steps to strengthen their microbiological testing and environmental monitoring programs. Robust programs that are timely, comprehensive, and effective will minimize risk and help support patient safety and positive outcomes. This article is the first in a series that will outline strategies to increase control in the sterile compounding process, identify contamination faster, and improve the sterility testing of final products.
Testing and microbiological quality measures for sterile, compounded drugs conducted by US and Canadian facilities are addressed by the United States Pharmacopeial Convention’s USP <797>, Pharmaceutical Compounding – Sterile Preparations. This chapter provides guidelines for facilities in which compounded sterile preparations are prepared, stored and dispensed. However, several US states do not have laws providing guidance for sterile compounding, and USP <797> guidelines were written to allow for flexibility, which can be challenging when an organization is trying to define the right approach.
In response to recent well-publicized contamination events, compounding pharmacies and the regulations governing them are coming under intense scrutiny, with regulations likely to evolve in the coming months and years.
Earlier in 2013, FDA officials reported results of their inspection of over 30 compounding pharmacies that mix sterile drugs. Federal inspectors observed “concerning sterility practices, inappropriate conditions for sterile processing and other practices that create risk of contamination”. 1 This report further galvanized the effort to reform the industry.
The US Senate Health, Education, Labor, & Pensions (HELP) Committee recently introduced the Pharmaceutical Compounding Quality and Accountability Act (S. 959). The act would create a boundary between traditional pharmacy compounding and a new category of businesses called "compounding manufacturers," which are defined as facilities that: 1) make sterile products without a prescription and sell those products across state lines, or 2) repackage preservative free sterile products. The bill also seeks to make clear the oversight responsibilities of state and federal authorities.2
Individual states are also evaluating their regulations. The Massachusetts Joint Committee on Public Health is proposing legislation that will require pharmacists who mix injectable and other sterile medications to take continuing education classes. It would also introduce random inspections of facilities and the sterile drugs they produce. Pharmacists and pharmacies would face fines for not complying with the new rules.3 In Idaho, there have been discussions about implementing rules for compounding pharmacies where none have previously existed.4
The Iowa Board of Pharmacy is inspecting more than 80 U.S. compounding pharmacies that do business in its state. The Wall Street Journal reported this initiative as, “the most aggressive and comprehensive effort by any federal or state agency to inspect compounding pharmacies in the wake of the outbreak”.5 Charges resulting from the inspections would carry a maximum fine of $25,000 and could cause the offending pharmacy to lose their license in Iowa.The article further notes that “Other state boards of pharmacy are closely watching the outcome of Iowa's move.The Iowa board is using an authority rarely invoked by a state pharmacy board to inspect any compounding pharmacy that sells products in its state, whether that pharmacy is physically located there or not.”
Independent of existing and changing regulations, quality microbiological testing and safety are crucial to prevent future instances of contamination and potential deaths. Sterility testing and environmental monitoring are measures that compounding facilities can utilize to minimize the risk of contamination.
Establishing a robust, compliant microbiology sampling and testing program in any environment is no small task, and yet the stakes are high. Knowing exactly how to become compliant with USP <797> can be a challenge as there are many options, no prescribed route, and evolving regulations. Even if home states have no laws regarding governing sterile compounding, facilities must meet the requirements of the states to which they may be shipping their drugs. As a result, it would be in the best interests of an organization to identify and then adhere to the most stringent requirements possible.
As is typical in USP chapters, the content is basic enough to allow for flexibility. While the information is subject to many interpretations, it can be relied on as guidance for decision making and validation of a process. It is, however, ultimately up to the person or people responsible for the final product to make the determination that their process and product is in a state of control.
An optimal microbiological testing program is one that incorporates knowledge not only of microbiology, but also aseptic practices and leverages well-trained operators, established and robust technology and systems, and thorough validation programs. When operating in such 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
A robust microbiological testing program should encompass all of these requirements to ensure products are manufactured to the desired specifications. As part of the program, a formal risk assessment identifies where in the process is there a risk, whether to the product or the patient. In order to conduct a thorough risk assessment, one must know every detail about the product and process and where possible exposure to contamination might come from. The assessment includes knowing the facility, the utilities, the raw materials and how training is being executed and documented. The topics bulleted above will be discussed in greater detail in part two of this series.
Part three of the series will detail environmental monitoring, another essential component of a compounding pharmacy’s microbiology program. Environmental monitoring is used to determine the microbial and particulate content of cleanroom air and surfaces. Results are used to identify conditions contributing to excessive microbial and particulate levels, and alert personnel to conditions exceeding classification. This monitoring not only helps avoid risks to consumers and producers, but also saves time and reduces costs by preventing the release of potentially contaminated products.
The final installment in the series will discuss implementation of a sterility testing program products.
The compounding pharmacy industry is facing unprecedented scrutiny and increased regulation. Organizations can prepare for coming changes by reassessing their quality systems and standard operating procedures. When applied in a proactive, timely manner, a controlled process, robust microbiological testing program, environmental monitoring and sterility testing can improve patient safety by identifying risk before a contamination event occurs.
1] Proactive Inspections Further Highlight Need for New Authorities for Pharmacy Compounding. http://blogs.fda.gov/fdavoice/index.php/2013/04/proactive-inspections-further-highlight-need-for-newauthorities-for-pharmacy-compounding/
Accessed August 6, 2013.
 Lazar, K. (2013, July 9). Bill aims to increase pharmacy oversight in Mass. Boston Globe. Retrieved from http://www.bostonglobe.com/lifestyle/health-wellness/2013/07/09/bill-unveiled-strengthen-oversight-compounding-pharmacies/U9FWWW1Tz4YYsjIwLd5tQM/story.html
Dutton, A. (2013, July 9). Idaho's few compounding pharmacies face new rules and a changing industry. Idaho Statesman. Retrieved from http://www.idahostatesman.com/2013/07/09/2647443/idahos-few-compounding-pharmacies.html
 Martin, T.W. (2013, March 16-17) Pharmacies feel more heat: Iowa takes lead inspecting compounding facilities after meningitis outbreak. The Wall Street Journal.