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Brian D. Stump, PharmD, BCCCP
Earnest Alexander, PharmD, BCCCP, FCCM
Jennifer L. Morris, PharmD, BCPPS, BCPS
In an era fraught with drug shortages, hospitals are faced with limited options for some vital admixtures. When manufacturers have limited supplies or products are no longer available, hospital pharmacies may be faced with admixing these agents or outsourcing to compounding facilities. Preparation of admixtures is regulated in terms of sterility and stability for optimal patient safety. Providing appropriate drug therapy for patients in the intensive care unit can become problematic when medication supplies run short. Medication compounding may be offered as a method of drug shortage management.
The U.S. Pharmacopeial Convention (USP) is an organization that sets standards for the quality and purity of medications. These standards are enforced by the U.S. Food and Drug Administration and are considered best practice. Two sets of USP standards exist for the preparation and dispensing of nonsterile and sterile admixtures. Nonsterile compounding is the focus of USP Chapter 795, while USP Chapter 797 focuses on sterile compounds, primarily intravenous (IV) administration.
Nonsterile compounding is divided into three categories related to the intricacy of the preparation.1 Simple and moderate compounding are easily performed. Examples include making suspensions from solid oral dosage forms or making a topical steroid ointment from powdered drug and petroleum jelly. Complex compounding that necessitates mixing powdered drug and weighing out individual doses requires assessments of products for factors such as weight, clarity, color, etc. Hospital pharmacies without dedicated compounding facilities may not be able to perform these functions. Often, hospital pharmacies resort to compounding simple and moderate nonsterile admixtures when faced with medication shortages. However, depending on the specific drug or dosage form required, compounding nonsterile admixtures may not be feasible.
Sterile compounding is divided into low-, medium-, and high-risk categories related to the potential for bacterial contamination. This risk is of major concern when preparing IV admixtures and can be mitigated by improving the air quality of the compounding environment. Air quality is improved by decreasing the air particle size, which increases the compounding capability of the environment under Chapter 797 guidelines. International Organization for Standardization (ISO) standards are used to classify the quality of air within the clean room. Lower numbers indicate better air quality. Most hospital pharmacies in the United States have an ISO Class 8 anteroom, ISO Class 7 clean room, and ISO Class 5 laminar flow hood for compounding low- and medium-risk admixtures. This meets the needs of the typical hospitalized patient, but may fall short during drug shortages.2
High-risk sterile compounding uses nonsterile products such as oral dosage forms, sterile ingredients or components that have been exposed to air quality inferior to an ISO Class 5 environment. Terminal sterilization is required either through steam autoclaving or filtering, and products must undergo extensive sterility testing. Systems require frequent quality assurance testing, which is not only complicated but time intensive. High-risk compounding requires better-quality air and additional training and evaluation of personnel.2 When IV drug shortages emerge, making IV formulations from oral dosage forms or powdered drug appears to be promising. However, because of the sterility requirements, this type of compounding is impractical even for an equipped pharmacy. Thus, hospital pharmacies will seek to outsource admixing to compounding pharmacies.
In September 2012, an outbreak of meningitis occurred in the United States secondary to contaminated parenteral compounded products prepared at a compounding pharmacy in Massachusetts. Since then, hospitals have maintained a heightened scrutiny of outsourcing facilities and rigorous vetting processes to ensure that products obtained from these facilities are sterile and safe. This has resulted in a shrinking list of outsourcing facilities, which is further strained by ongoing challenges with shortages.
The American Society of Health-System Pharmacists (ASHP) has published “Guidelines on Outsourcing Sterile Compounding Services,” which provides an overview of factors important to hospitals in the approval process.3 This process requires time and attention, evaluated over a course of weeks, including on-site visits to the facility, review of processes, compounding practices, certifications, etc. For that reason, outsourcing facilities that have not been previously approved at an institution are not viable options for immediate patient care needs. Tools have been developed through the ASHP Research and Education Foundation based on the guidelines to aid in outsourcing facility assessment and the approval process.4
Compounding as a management strategy for a drug shortage can have direct and indirect impact on a hospital pharmacy budget. Direct impact occurs when IV admixtures from an outsourcing facility are used to bridge drug supply for a shortage. These are often costlier and have a shorter expiration date than the commercially manufactured product. When interfacility compounding is used to mitigate a drug shortage, indirect costs from the increased manpower required to identify recipes and to compound must be taken into consideration. Financial effects of drug shortages, specifically those secondary to increased acquisitions costs, should be reported through budgetary channels.
With an understanding of regulatory issues and adequate planning, use of compounded drug products may be a reasonable management strategy for drug shortages. Hospitals and health systems should proactively develop policies and procedures on how both interfacility and outsourced compounded products should be used during periods of drug shortages.
1. U.S. Pharmacopeial Convention. General Chapter 797. Pharmaceutical compounding—sterile preparations. In: United States Pharmacopeia and the National Formulary. 31st ed. Rockville, MD: United States Pharmacopeial Convention; 2013.
2. U.S. Pharmacopeial Convention. General Chapter 795. Pharmaceutical compounding—nonsterile preparations. In: United States Pharmacopeia and the National Formulary. 31st ed. Rockville, MD: United States Pharmacopeial Convention; 2013.
3. [No authors listed]. ASHP guidelines on outsourcing sterile compounding services. Am J Health-Syst Pharm. 2015 Oct 1;72(19):1664-1675.
4. American Society of Health-System Pharmacists Research and Education Foundation. Outsourcing sterile products preparation: contractor assessment tool. Bethesda, MD: American Society of Health-System Pharmacists Research and Education Foundation; 2017. http://www.ashpfoundation.org/SterileProductsTool. Accessed January 19, 2017.