Safer Sterile Compounding: Choosing and Using Disinfectants for the Cleanroom.

Compounders worldwide are responsible for ensuring that the sterile preparations they dispense are pure, potent, and safe. To achieve that result, proper cleaning and disinfection of International Organization for Standardization controlled environments must occur. Because those tasks must be performed according to established standards, the compounding pharmacist must research regulatory requirements and appropriate products for use. In this report, we focus on U.S. regulations, guiding entities, and effective products that enable compliance with the increasingly stringent procedures required for pharmaceutical compounding. We also review cleaning and disinfecting processes, discuss the importance of correctly choosing and using disinfectants and/ or sporicidal disinfectants with surface claims in the cleanroom, and provide answers to questions frequently asked by staff who use those agents. In addition, we profile specific disinfectants that are compliant with United States Pharmacopeia Chapter <797> and current good manufacturing practice standards. Biological safety cabinets and compounding aseptic containment isolators must undergo an additional process that deactivates hazardous drug residues and removes them from the interior surfaces of those devices before they are cleaned and disinfected, but that discussion is beyond the scope of this article.

Evaluation of the Quality of Sterile Compounding Videos Available on the YouTube Video-sharing Website.

The objective of this study was to evaluate the quality of instructional sterile compounding videos posted on a popular video-sharing website (YouTube). YouTube was systematically searched using relevant terms (aseptic compounding, sterile compounding) to identify all videos demonstrating aseptic manipulations of compounded sterile preparations in a cleanroom. Promotional videos, news stories, interviews, and videos with manipulations performed outside a cleanroom, without audio or spoken in a language other than English, were excluded. Three experts independently reviewed each video and assessed the quality of key sterile compounding processes, information delivery, and overall suitability for workforce training using a standardized assessment tool. Kendall's coefficient of concordance (W) was calculated to assess agreement. Included were 66 videos with a median of 839 (IQR 62-3935) views. There was moderate to substantial agreement among assessors when determining the quality of each step of the compounding process (W 0.48 to 0.72; all P<0.002). Only one in five videos demonstrated an acceptable standard of gloving and garbing, while product inspection and waste disposal processes were more likely to be appropriately demonstrated. Most videos had acceptable sound/image quality and English pronunciation, but not all videos had a comprehensive narration. Six videos (9%) were recommended for training compounding personnel by two assessors and a further 17 (26%) videos were recommended by one assessor. No videos were recommended by all three assessors. The conclusions of this study are: 1) there is considerable variation in the quality of instructional sterile compounding videos available on the YouTube website; 2) few videos are suitable for training compounding personnel.

SAFER STERILE COMPOUNDING: Choosing and Using Disinfectants for the Cleanroom.

Compounders worldwide are responsible for ensuring that the sterile preparations they dispense are pure, potent, and safe. To achieve that result, proper cleaning and disinfection of International Organization for Standardization controlled environments must occur. Because those tasks must be performed according to established standards, the compounding pharmacist must research regulatory requirements and appropriate products for use. In this report, we focus on U.S. regulations, guiding entities, and effective products that enable compliance with the increasingly stringent procedures required for pharmaceutical compounding. We also review cleaning and disinfecting processes, discuss the importance of correctly choosing and using disinfectants and/ or sporicidal disinfectants with surface claims in the cleanroom, and provide answers to questions frequently asked by staff who use those agents. In addition, we profile specific disinfectants that are compliant with UnitedStates Pharmacopeia Chapter <797> and current good manufacturing practice standards. Biological safety cabinets and compounding aseptic containment isolators must undergo an additional process that deactivates hazardous drug residues and removes them from the interior surfaces of those devices before they are cleaned and disinfected, but that discussion is beyond the scope of this article.

Outbreak of Serratia marcescens bloodstream infections in patients receiving parenteral nutrition prepared by a compounding pharmacy.

BACKGROUND: Compounding pharmacies often prepare parenteral nutrition (PN) and must adhere to rigorous standards to avoid contamination of the sterile preparation. In March 2011, Serratia marcescens bloodstream infections (BSIs) were identified in 5 patients receiving PN from a single compounding pharmacy. An investigation was conducted to identify potential sources of contamination and prevent further infections. METHODS: Cases were defined as S. marcescens BSIs in patients receiving PN from the pharmacy between January and March 2011. We reviewed case patients' clinical records, evaluated pharmacy compounding practices, and obtained epidemiologically directed environmental cultures. Molecular relatedness of available Serratia isolates was determined by pulsed-field gel electrophoresis (PFGE). RESULTS: Nineteen case patients were identified; 9 died. The attack rate for patients receiving PN in March was 35%. No case patients were younger than 18 years. In October 2010, the pharmacy began compounding and filter-sterilizing amino acid solution for adult PN using nonsterile amino acids due to a national manufacturer shortage. Review of this process identified breaches in mixing, filtration, and sterility testing practices. S. marcescens was identified from a pharmacy water faucet, mixing container, and opened amino acid powder. These isolates were indistinguishable from the outbreak strain by PFGE. CONCLUSIONS: Compounding of nonsterile amino acid components of PN was initiated due to a manufacturer shortage. Failure to follow recommended compounding standards contributed to an outbreak of S. marcescens BSIs. Improved adherence to sterile compounding standards, critical examination of standards for sterile compounding from nonsterile ingredients, and more rigorous oversight of compounding pharmacies is needed to prevent future outbreaks.

Compounding USP <797>: inspection, regulation, and oversight of sterile compounding pharmacies.

Using USP Chapter <797> Pharmaceutical Compounding-Sterile Preparations (CSP) is now considered the standard for sterile compounding practice and safety in the United States. This is particularly important in compounding the complex formulation of parenteral nutrition.

Hygrometers and thermohygrometers: environmental monitoring ensures the potency and stability of compounding agents.

Although the terms humidity and relative humidity are often used interchangeably, they are not synonymous. Humidity is the amount of water in the air, and relative humidity is the ratio of the amount of water vapor in the air at a specific temperature to the maximum possible amount of water vapor in the air at that temperature. Thus humidity and temperature are inextricably bound in their effects on the environment. In a compounding pharmacy, humidity can affect the stability and quality of the compounds prepared, as well as equipment, chemicals, and polymers. Devices that measure relative humidity (hygrometers) or humidity and temperature (thermohygrometers) are essential instruments in a compounding pharmacy. They must be chosen carefully, however, to ensure that the measurements they yield are accurate, that they are reliable over time. Most desirable are devices that alert the pharmacist immediately at any time if levels of humidity or temperature at a designated site differ from a specific norm. In this report, we discuss the effects of humidity on the process of compounding and on the agents used in customized preparations. A Table that lists essential features of a variety of hygrometers and thermohygrometers appropriate for use in a compounding pharmacy is presented for easy reference.

Generation of particulate matter during handling of needle and syringe packaging.

PURPOSE: Generation of airborne particulate matter during the handling and opening of various syringe and needle packages in a laminar-airflow workbench (LAFW) and in a biological safety cabinet (BSC) was measured to compare the effects on air cleanliness conditions (International Organization for Standardization [ISO] class 5 within the LAFW or BSC and ISO class 7 in buffer areas). METHODS: Twenty-five to 50 packages of each of 12 needle or syringe products were opened. Probes were configured to count airborne particles during the separation of strip packages and the opening of packages by peeling back the top web or pushing the device through the packaging (for soft packages) or by twisting apart hard packages. RESULTS: The numbers of particles were not significantly different between the LAFW and BSC. The separation of strip packages generated visible particles and raised airborne particle counts. Peeling open plastic film packages and opening hard plastic packages generated fewer airborne particulates than did pushing devices through the packaging. For all methods of package opening, average counts downstream from the direct compounding area exceeded ISO class 5 conditions. Counts in the LAFW buffer area did not exceed ISO class 7. CONCLUSION: All methods of separating and opening the packaging of needles and syringes generated particles. The peel-and-present technique generated the lowest particulate volume. The LAFW and BSC were equally effective in maintaining low particle counts.

Microbial air-sampling equipment, part 1: meeting United States pharmacopeia chapter 797 standards.

The most recent changes to Chapter 797 of the United States Pharmcopeia-National Formulary initiated an intense controversy about the frequency of cleanroom air sampling that is required to prevent the contamination of sterile preparations. For compounders who must purchase an air sampler to use in the cleanroom, choices abound. Included in this article are a review of United States Pharmacopeia-National Formulary requirements that pertain to air sampling, a discussion of how recent revision to Chapter 797 affect air sampling and patient safety, and, for easy reference, a table that features specifications for various models of microbial air samplers.

Basics of compounding: United States pharmacapeia general chapter 797 pharmaceutical compounding-sterile preparations, part 10: first revision: the main changes, events, and rationale.

From 2005 to 2007, the United States Pharmacopeia's Sterile Compounding Committee revolutionized sterile preparation practices with a thorough revision to a monumental standard. By revising United States Pharmacopeia General Chapter 797, they defined safe procedures for compounded sterile preparations in profound detail. From proper hygiene to air quality control, the revised Chapter 797 aims to reduce complications related to treatment with compounded sterile preparations, offers invaluable information to those involved in the compounding process, and establishes standards to improve the quality of the compounding process. The vast intellect, innovative review process, and dedicated research incorporated into this revision have assisted those involved with compounding pharmacy around the world.

Pharmacy compounding urban legends.

This article reviews and clarifies a small sampling of the myths, or urban legends, about compounding. Included are comments on United sTates Pharmacopeia Chapter 797, environmental issues related to sterile compounding, and suggested resources for clarification of some of these myths. This article recommends a knowledge-based partnership between compounding pharmacists and pharmaceutical manufacturers to improve compounding activities and quality assurance methods to ensure that compounded medications are safe.

Putting the science back into the "art and science" of compounding.

Acceptance of the revised standards for compounding sterile preparations published as United States Pharmacopeia Chapter 797 has met with a significant amount of resistance, mainly owing to the expense of compliance. These standards owe much to the expanded perspective of the United States Pharmacopeia Council of Experts Sterile Compounding Committee, which was responsible for the revision. Because it is widely accepted by those in the pharmaceutical industry that compounding facility design, environmental control, and personnel have direct effects on the sterility of aseptically compounded preparations, the committee drew from expertise in pharmacy as well as fields outside pharmacy, such as microbiology, infection control, and engineering controls. How "science" from other disciplines has been incorporated into the in-process revision of United States Pharmacopeia Chapter 797 is reviewed.

Blueprint for implementing USP chapter 797 for compounding sterile preparations.

PURPOSE: Guidelines for adopting and successfully implementing the requirements of the United States Pharmacopeia (USP) chapter 797 for compounding sterile preparations are presented. SUMMARY: The quality of a compounded sterile preparation (CSP) is directly related to the methods used to ensure that the CSP achieves the desired goal of purity, potency, and sterility. A properly designed, constructed, and maintained cleanroom contributes to the quality of CSPs. Design criteria of a sample clean-room are supplied, as are a summary and comparison of the liquid disinfectants that can be used to clean and sanitize the facility and maintain environmental controls. All activities associated with cleaning the cleanroom, including air and surface sampling, must be properly documented in logs, examples of which are provided. A robust employee-training program for properly teaching aseptic technique and a method to verify that personnel have successfully completed the program are integral to compliance with chapter 797 and thoroughly discussed herein. Emerging compounding and testing technology is also discussed. CONCLUSION: Although the task of compliance with the requirements of USP chapter 797 may appear overwhelming, complicated, expensive, and even unattainable, quality can be established via a methodical and organized approach. After the systems have been implemented, maintaining them requires vigilance and follow-up. Compliance with chapter 797 involves up-front and ongoing costs associated with establishing these systems, but the time, energy, and cost required to maintain them are far less than those of retrospective or manual systems of collecting, reviewing, and collating quality assurance data on a monthly basis.