Sterile compounding: Regulations, best practices, and industry standards

December 10, 2015

Where things stand, where they're headed, and what you need to do now.

While sterile compounding in hospital and health-system pharmacies has long been a critical component of quality care delivery, the industry’s ability to mainstream and standardize best practices of these high-risk processes has faced ongoing challenges. However, several decades of effort are beginning to show promise as states increasingly adopt and mandate use of USP Chapter <797> (USP 797), the recognized industry standard, to improve the safety outlook for both patients and the staff who engage in compounding.

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Industry standards

USP 797 guidelines have gained some traction since their introduction in January 2004 as the first official and enforceable sterile preparation compounding requirement,1 but because it is up to each state’s board of pharmacy to adopt and enforce the standards, compliance and oversight have been inconsistent.2

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The culmination of a series of high-profile sterile compounding mishaps in recent years, including a deadly fungal meningitis outbreak in 2012 that resulted in 64 deaths,3 have changed the way federal and state regulators view compounding practices.

Recently, expectations and requirements have expanded at both the federal and state levels, and these trends are expected to continue in the coming years. Notably, 27 states have now adopted USP 797 standards and are enforcing them on some level.

While oversight was previously handled by the states, the federal government is now involved, through the introduction of the Drug Quality and Security Act.4  In fact, FDA conducted 148 inspections of compounding pharmacies between 2012 and 2014, uncovering safety problems in nearly nine out of 10 facilities.5

Regulatory developments

Alongside federal regulatory initiatives, pharmacy directors need to stay abreast of how their respective states are ratcheting up oversight of compounding regulations. Included here is a bird’s eye view of the evolving national landscape.

USP 797. The introduction of USP 797 in 2004 was an important step toward formalizing a national patient-safety standard for sterile compounding. A comprehensive standard addressing nearly every aspect of compounded sterile preparations, USP 797 details specific quality metrics of compounding processes, documentation of staff competencies, environmental testing and sampling protocols, and the architectural and environmental aspects of clean rooms and surrounding pharmacy areas.

USP 800. While USP 797 is comprehensive in its own right, the introduction of USP Chapter <800> (USP 800), which was initially published in draft form by USP in March 2014, details specific strategies necessary to protect employees and the environment from the occupational exposure to hazardous drugs while compounding preparations. This is an issue affecting approximately 80 million U.S. healthcare workers each year.6

Encompassing a broader scope than USP 797, USP 800 is designed to ensure that healthcare workers are exposed to amounts at “as low a limit as reasonably achievable” when handling sterile and nonsterile hazardous drugs, by focusing on:

  • Facility design. Hazardous drugs must be stored in negative pressure, and compounding must be completed in certified biological safety cabinets or compounding aseptic containment isolators in a separate room with negative pressure.

  • Garb. Details for personal protective equipment are based on the function being performed.

  • Cleaning and disinfection. Deactivation and disinfection must be done with an oxidizer, cleaning with a germicidal detergent, and disinfection with sterile alcohol.

  • Administration. Closed-system drug-transfer devices should be used when compounding and shall be used when hazardous drugs are administered.

CQA. Part of the Drug Quality and Security Act (DQSA) of 2013, CQA strengthens FDA oversight and creates a new category of facilities on the FDA Drug Shortage List (Section 506e) to better regulate entities that are engaged in compounding non-patient-specific medications. These entities, referred to as Outsourcing Facilities, can voluntarily register with the FDA as 503B entities.

The second provision of the DQSA gives FDA the authority to develop a national track-and-trace system to secure the supply chain and lessen opportunities for contamination, diversion, and counterfeiting. To clarify oversight responsibility between federal and state regulatory authorities, section 503A of the CQA dictates that traditional pharmacies providing patient-specific medications will be regulated by the state boards of pharmacy, and the entities that provide non-patient-specific medications or engage in compounding for office use will be regulated by FDA.

 

The future of USP 800

As the reality of USP 800 comes into focus, healthcare organizations will need to consider how to re-engineer processes to elevate staff competencies and promote standardization of an expanded set of industry best-practice guidelines.

The challenge lies not just in developing and implementing various quality metrics, but also in dedicating the resources required to maintain aggressive compliance schedules for USP 797 and USP 800.

Because of these challenges, adoption of USP 797 moved at a relatively slow pace until the fallout from recent sterile compounding incidents. Respondents to a 2014 USP 797 compliance study representing 525 hospital pharmacies noted that the primary challenges to compliance rested with financial constraints (27%), physical plant challenges (21%), and the time required to implement changes (16%).7 Other challenges named included access to training and competency resources, lack of knowledge and support from leadership, and staff resistance to change.

Trends suggest that states are continuing to up the ante on compliance with USP 797 and will follow suit with the introduction of USP 800. For instance, Massachusetts now requires that sterile compounding competencies be updated annually, prioritizing the need for more formal processes and better governance of staff education.

Act now

Healthcare organizations engaged in sterile compounding must design and deploy a comprehensive plan now to address compliance, staff competencies, facility needs, and environmental monitoring.

Setting a successful plan in motion necessitates buy-in from senior leadership and acknowledgement of the risks associated with sterile compounding practices. More important, it requires a willingness to dedicate the resources needed to make it happen.

One effective way of equipping resource-strapped pharmacy departments with the tools needed for long-term positioning is to make use of an electronic quality management system.

Capitalizing on advances in health IT has long been an effective strategy for improving pharmacy processes, and software solutions exist that can help pharmacies achieve a state of control with standardized training, demonstration of proper technique, quality assurance controls, standard operating procedures, and management oversight.

While challenging for today’s lean pharmacy environments, current movements to increase adoption and adherence to industry best practices for sterile compounding preparations represent a critical move towards enhancing patient safety and providing better care. With the right processes and governance in place, pharmacists will be in a position to promote the highest level of safety.

References

1. USP. The United States Pharmacopeia, 27th rev., and the National Formulary, 22nd ed. General Information Chapter. “Pharmaceutical Compounding–Sterile Preparations.” Rockville, MD: The United States Pharmacopeial Convention, 2003.

2. American Society of Health-System Pharmacists. “ASHP sterile compounding survey, executive summary.” Bethesda, Maryland: American Society of Health-System Pharmacists; 2013.

3. U.S. illnesses and deaths associated with compounded medications. The Pew Charitable Trusts. http://www.pewtrusts.org/en/about/news-room/news/2013/09/06/us-illnesses-and-deaths-associated-with-compounded-medications. Accessed June 23, 2015.

4. H.R.3204. H.R.3204 – Drug Quality and Security Act113th Congress (2013–2014). https://www.congress.gov/bill/113th-congress/house-bill/3204. Accessed June 23, 2015.

5. Inspection citations. U.S. Food and Drug Administration website. http://www.fda.gov/ICECI/Inspections/ucm346077.htm. Accessed June 23, 2015.

6. Hazardous drug exposures in health care. Centers for Disease Control and Prevention web site. http://www.cdc.gov/niosh/topics/hazdrug/. Accessed June 23, 2015.

7. Kastango, ES, Douglass, K. The 2014 USP 797 Compliance Study. Pharmacy Purchasing and Products Website. http://www.pppmag.com/article/1589/October_2014_Cleanrooms_Compounding/The_2014_USP_Chapter_797_Compliance_Survey/. Accessed July 16, 2015.

Christian Hartman is senior director, Clinical Quality and Patient Safety, Pharmacy OneSource (part of Wolters Kluwer), and founder of the Medication Safety Officers Society, now part of the Institute of Safe Medication Practices.