CONTINUING EDUCATION Understanding Medication Compounding Issues
2.2
RODNEY W. HICKS, PhD, RN, FNP-BC, FAAN, FAANP
www.aorn.org/CE Continuing Education Contact Hours
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indicates that continuing education (CE) contact hours are available for this activity. Earn the CE contact hours by reading this article, reviewing the purpose/goal and objectives, and completing the online Examination and Learner Evaluation at http://www.aorn.org/CE. A score of 70% correct on the examination is required for credit. Participants receive feedback on incorrect answers. Each applicant who successfully completes this program can immediately print a certificate of completion.
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Event: #14510 Session: #0001 Fee: Members $17.60, Nonmembers $35.20 The CE contact hours for this article expire April 30, 2017. Prices are subject to change.
Purpose/Goal To provide learners with knowledge specific to the use of compounded medications in the OR.
Objectives
Approvals This program meets criteria for CNOR and CRNFA recertification, as well as other CE requirements. AORN is provider-approved by the California Board of Registered Nursing, Provider Number CEP 13019. Check with your state board of nursing for acceptance of this activity for relicensure.
Conflict of Interest Disclosures Rodney W. Hicks, PhD, RN, FNP-BC, FAAN, FAANP, has no declared affiliation that could be perceived as posing a potential conflict of interest in the publication of this article. The behavioral objectives for this program were created by Helen Starbuck Pashley, MA, BSN, CNOR, clinical editor, with consultation from Susan Bakewell, MS, RN-BC, director, Perioperative Education. Ms Starbuck Pashley and Ms Bakewell have no declared affiliations that could be perceived as posing potential conflicts of interest in the publication of this article.
Sponsorship or Commercial Support
1. Describe the threats to patient safety that compounded medications pose. 2. Define pharmaceutical compounding. 3. Identify resources to help nurses understand medication compounding. 4. Explain the themes of successful compounding. 5. Discuss considerations for contracting with external compounding services.
No sponsorship or commercial support was received for this article.
Disclaimer AORN recognizes these activities as CE for RNs. This recognition does not imply that AORN or the American Nurses Credentialing Center approves or endorses products mentioned in the activity.
http://dx.doi.org/10.1016/j.aorn.2013.07.021
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Ó AORN, Inc, 2014
Understanding Medication Compounding Issues RODNEY W. HICKS, PhD, RN, FNP-BC, FAAN, FAANP
2.2 www.aorn.org/CE
ABSTRACT The potential for contamination of compounded products and the resulting infections are a serious threat to patient safety. Immediate use products are used frequently in the perioperative department, and perioperative nurses should be familiar with the guidelines and practices that aim to reduce the contamination that can occur during the sterile compounding process. Four common themes lead to successful compounding: quality (eg, product identification, purity, stability, compatibility, risk level assessment), the environment (eg, using a segregated compounding area with specialized airflow capabilities, reducing particulate matter, practicing proper hand hygiene, performing gloved fingertip sampling, properly cleaning equipment and work areas), personnel activities (eg, familiarity with types of containers used and how often they can be accessed, following expiration dates and the number of times containers can be accessed), and the control process (eg, process monitoring, quality improvement). If a third-party vendor is contracted to handle compounding for a facility, perioperative personnel should be aware of the responsibilities for the facility and the vendor to ensure a quality compounding program. AORN J 99 (April 2014) 467-476. Ó AORN, Inc, 2014. http://dx.doi.org/10.1016/j.aorn.2013.07.021 Key words: medication compounding, compounding, perioperative practice standards, contamination, immediate use products.
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uch of preoperative, intraoperative, and postoperative care could not be achieved without the use of compounded pharmaceutical products. Recently, media headlines have brought to light the risks associated with compounded products and focused renewed attention on the roles and responsibilities of health care professionals who work with these products. In 2012 and 2013, there were an abundance of media headlines on the issues of compounding (Table 1). The untoward outcomes of compounding is not a new issue, however, and case reports of patient
harm and death that implicate compounded products go back more than 20 years. Harm from compounded medications can result from microbial or physical contamination, the presence of bacterial endotoxins, and variations in product strength or quality. In response to this long-standing threat to patient safety, the US Pharmacopeia (USP), a nongovernmental standards setting organization based in Rockville, Maryland, published what is known as Chapter .1 Chapter has many far-reaching components that direct many aspects of sterile
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TABLE 1. Recent National Headlines Regarding Compounding Issues n n
n n
n n
Eisler P. Deaths, infections tied to “compounding” drug. USA Today. October 12, 2012. http://www.usatoday.com/story/ news/nation/2012/10/11/compounding-pharmarcies-deaths/1626753. Accessed August 8, 2013. Wallack T. Grand jury sets sights on compounding pharmacy. Boston Globe. December 1, 2012. http://www.bostonglobe .com/business/2012/12/01/federal-grand-jury-investigating-new-england-compounding-meningitis-outbreak/IlRHC3wOchna S188UB7EyN/story.html. Accessed August 8, 2013. Sack K, Williams T. Death of 9 Alabama patients tied to intravenous supplement. New York Times. March 30, 2011; A20. http://www.nytimes.com/2011/03/31/us/31intravenous.html?_r¼0. Accessed August 8, 2013. Crime time. Dallas compounding pharmacy faces charges in three deaths. Fort Worth Star Telegram. February 10, 2012. http://blogs.star-telegram.com/crime_time/2012/02/dallas-compounding-pharmacy-faces-charges-in-three-deaths.html. Accessed August 8, 2013. Safety news: another compounding pharmacy in trouble. Outpatient Surgery Magazine. November 12, 2012. http://www.out patientsurgery.net/news/2012/11/10-Another-Compounding-Pharmacy-in-Trouble. Accessed August 8, 2013. Perrone M. FDA inspection triggers recall by Florida compounding pharmacy. Associated Press. May 8, 2013. http://bigstory .ap.org/article/fda-inspection-triggers-recall-florida-pharmacy. Accessed August 8, 2013.
compounding, all aimed at reducing opportunities for harm. Chapter provides a multifactorial guideline to the preparation of sterile compounds.2 It addresses conditions and practices that reduce the likelihood of harm, including death, associated with compounded products. The current version of Chapter , which became effective on June 1, 2008, is organized with a revised introduction, new definition section, descriptions of compounding personnel responsibilities, a list of microbial contamination risk levels, training and evaluation requirements, discussion of environmental quality and control, criteria for a robust quality assurance program, and several other sections.1 Understanding, following, and enforcing these recommendations helps to ensure public health safety,2 and perioperative nurses should familiarize themselves with the full chapter. AORN has discussed information about compounding from the viewpoint of perioperative care in the AORN Journal “Clinical Issues” column3 and in its “Recommended practices for medication safety.”4 The purpose of this article is to provide the perioperative nurse with information about compounding and how it relates to perioperative patient safety by defining and reviewing components of compounding and discussing the applications and 468 j AORN Journal
implications of compounding for the perioperative care provider. This article focuses only on the preparation of compounded sterile products intended for human use. COMPOUNDING Compounding has its roots in the pharmacy profession,5 so some perioperative personnel may not recognize the scope and breadth of all that is included in the term compounding. Pharmaceutical compounding is the creation of custom-made medications. Compounding encompasses a triad that includes the patient, practitioner, and pharmacist (Figure 1). According to the USP, a compounded product is a sterile product that includes preparations prepared according to the manufacturer’s labeled instructions and other manipulations when preparing sterile products that expose the original contents to potential contamination, as well as preparations that contain non-sterile ingredients or employ non-sterile components and devices that must be sterilized before use.1(p2) According to the American Pharmacists Association (APhA), compounding is the mixing of ingredients, including dilution, admixture, repackaging, reconstitution, and other manipulations of sterile products,
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Figure 1. Compounding encompasses a triad that includes the patient, practitioner, and pharmacist.
to prepare a medication for patient use.6 Although the USP does not define compounding this specifically, the APhA’s definition allows for products to be made in anticipation of routine prescribing patterns.6 Furthermore, compounding is said to occur when a medicine has to be created because the strength, concentration, or dosage that is needed for a specific patient varies from what is commercially available.7 These definitions highlight the intent of compounding to prepare a small quantity of a US Food and Drug Administration (FDA)eapproved medication based on a practitioner’s prescription. The APhA’s definition allows for products to be made in anticipation of routine prescribing patterns (eg, ophthalmology),6 and the USP’s narrower definition signals the intent for compounding medications for a specific patient population. Pharmaceutical manufacturing, by contrast, is where a commercial vendor with FDA approval uses mass production to compound a bulk quantity of medication without regard to a specific patient population or prescription. Before November 2013, state boards of pharmacy had authority over compounding (eg, mixing one medication for one patient) and for compliance with meeting Chapter standards,7 while the FDA had oversight of commercial manufacturing (ie, bulk production without regard to the specific patient). The differentiation between compounding and manufacturing was sometimes unclear and,
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when problems were identified, this lack of clarity led to the identification of deficits in various parties’ accounting and responsibility. With the recent passage of HR 3204, the Drug Quality and Security Act,8 there is now clarification of the existing laws and improvements in accounting and responsibilities of the various parties. Furthermore, the bill clarifies the authority of the FDA to broaden its scope in the regulation of compounded products and to further promote patient safety along the pharmaceutical supply chain. Physician and advance practice nurse practitioners have professional autonomy to make ordinary medical care decisions, and those decisions may lead to an order for a compounded product. Respective licensing boards regulate health professions because it is not the role of the federal government to determine medical care.5 Similarly, the state boards that regulate pharmacists have important roles in regulating the practice of compounding given that schools of pharmacy provide specialized training in sterile compounding,9 and as a result, pharmacists are recognized as having specialized skills and knowledge in this area. Pharmacists have expertise in a product’s absorption, distribution, metabolism, and excretion. Additionally, pharmacists have knowledge about product compatibility, stability, changes in pH, humidity, osmolarity, and other factors that influence a product. Successful Compounding There are four common themes that lead to successful compounding: quality, the environment, personnel activities, and the control process. Interruption of any areas related to these can adversely affect compounding outcomes. Quality. Quality begins with the product, including product identification, purity, stability, and compatibility. Errors in product identification can occur because of sound-alike or look-alike product names or when products have similar packaging. Purity refers to the absence of bacterial, viral, or physical contamination in the compounding AORN Journal j 469
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TABLE 2. Classifications of Risk Assessment Levels of Compounded Sterile Products Requirementsa
Classification Immediate use
n n n
Low risk
n n n
Low risk < 12 hours beyond use date
n n
Medium risk
n n n n
High risk
n n n
Emergent use, administer < 1 hr after preparation No storage or batch compounding Aseptic technique Simple admixture compounded using closed system transfer Prepared in ISO Class 5 laminar airflow workbench Located in ISO Class 7 buffer with ISO Class 8 anteroom area (eg, OR anteroom in substerile corridor) Simple admixture compounded using closed system transfer Prepared in ISO Class 5 primary engineering controlled area Admixture compounded using multiple additives Batch preparation Complex manipulations Prepared in ISO Class 5 conditions Nonsterile (bulk powders) ingredients Open system transfers Prepared in ISO Class 5 conditions
ISO ¼ International Standards Organization. a Requirements listed are not all inclusive. Adapted with permission from the American Society of Health-System Pharmacists. The ASHP Discussion Guide on USP Chapter for Compounding Sterile Preparations. Bethesda, MD: American Society of Health-System Pharmacists; 2008.
process. Stability means that there is no less than 10% degradation of product(s). Factors that affect stability include changes in pH, humidity levels, or exposure to light. Compatibility refers to the interaction between two or more products being mixed together. Each of these quality control areas support the value of having a pharmacist involved in the compounding process. Another aspect of quality is the risk level assessment of the compounding process and the medications created, which is obtained through a formal process known as a gap analysis. According to Chapter , practitioners should identify risk level contamination categories (eg, immediate use, low risk, low risk < 12 hours beyond use date, medium risk, high risk).1 Each risk level contamination category requires that different conditions1 are satisfied to minimize the potential for contamination (Table 2). Some of the factors that affect risk level include the environment (ie, where the products are physically compounded), temperature storage (when applicable), type of product, and 470 j AORN Journal
when the product will be used. The American Society of Health-System Pharmacists (ASHP) has a tool kit to assist those conducting the gap analysis.2 This tool kit focuses on determining the risk level, developing an action plan to reduce risks that are identified, implementing and monitoring the action plan, and continually monitoring the process for improvement. Environment. Chapter provides technical specifications for constructing a suitable work environment in which to compound medications. Perioperative personnel should be familiar with various inherent environmental threats to sterility, including the leading threats to compounding, which come from microbial contamination and contamination from particulate air matter measuring 0.5 mm and larger per cubic meter. Ways to reduce opportunities for contamination of the environment include segregating compounding to areas with specialized airflow capabilities, reducing particulate matter to the extent possible, practicing
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TABLE 3. ISO Classification of Particulate Matter in Room Air Class name1 ISO class
US Federal Standard 209E for clean room
3 4 5 6 7 8
Class Class Class Class Class Class
1 10 100 1,000 10,000 100,000
Particle count1 ISO, m3
Federal Standard 209E, ft3
35.2 352 3,520 35,200 352,000 3,520,000
1 10 100 1,000 10,000 100,000
Perioperative examples
IV room OR OR anteroom in substerile corridor
ISO ¼ International Standards Organization. 1. United States Pharmacopeia Convention. Committee of Revision. Pharmaceutical compoundingdsterile preparations. In: The United States Pharmacopeia. 27th ed. Rockville, MD: United States Pharmacopeial Convention, Inc; 2009:318-354.
proper hand hygiene, performing gloved fingertip sampling, and helping to ensure proper cleaning of equipment and work areas. To achieve the lowest risk of contamination, Chapter recommends that low-risk, medium-risk, or high-risk sterile products be compounded in segregated compounding areas with specialized airflow capabilities. This type of environment is commonly referred to as an International Standards Organization (ISO) Class 5 setting, which is attained by achieving a level of air cleanliness. For example, ORs have 10 times or more the number of particles per cubic meter than are present in ISO Class 5 settings. Table 3 shows the requirements and particulate matter thresholds for various volume levels of air cleanliness. Older literature may sometimes refer to Federal Standard 209E as the clean room standard; however, this standard is obsolete. Having the least amount of particles per square foot reduces the opportunity for contamination during the compounding process. Particulate matter is inherent throughout the environment, but there are ways to reduce it. For example, wearing street clothes is associated with estimates of 10 to 30 million particles per square foot, and laundered hospital garments can have 1 million particles per square foot.10 Wearing cover attire, such as a standard coverall, along with limiting physical
movement, reduces particulate matter counts to 50,000 particles per square foot.10 Hand hygiene practices reduce opportunities for contamination as well. Organizations that support compounding services are expected to have policies and procedures in place that address hand washing techniques and enforce compliance of these policies.2 In an ISO Class 5 setting, compounders should wear sterile gloves. It is important to note that handling nonsterile vials and ampules results in glove contamination; therefore, the compounder should disinfect his or her gloves by applying sterile 70% isopropyl alcohol to the fingertips between each handling of a product container. Glove integrity should be maintained and monitored throughout the compounding process.1 For low-, medium-, and high-risk compounding, compounders working in an ISO Class 5 setting are also required to conduct gloved fingertip sampling.1,2 Policies and procedures should direct the frequency of fingertip sampling (eg, with new hires versus ongoing monitoring) as well as the expected outcomes; for example, the absence of growth on bacterial cultures suggests compliance with adequate disinfecting practices. The concept of the environment also must address cleaning, equipment, and personnel responsibilities. Cleaning includes the type of cleaning agent used as well as the schedule of cleaning the AORN Journal j 471
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various surfaces in the location where compounding occurs. Disinfectants can be applied to work surfaces to decrease microbial contamination in the environment. Steam sterilization is another process for disinfecting objects used for compounding. Equipment pertains to the various types of equipment used, including laminar flow hoods, specifications for air exchanges, and smaller pieces of adjunct equipment (eg, filter needles, syringes).
HICKS
Some considerations to which personnel contribute that are important to compounding include the type of containers used, the expiration date of contents of containers, and the number of times a container can be accessed. The type of container refers to vials (either single dose or multidose) or ampules. A single-dose vial’s contents are to be used within an hour of opening, and partial vials cannot be stored.1,2 The single-dose vial can be accessed twice to withdraw contents. Multidose 2 1 Personnel activities. The ASHP and the USP vials are to be handled per the manufacturer’s recognize that there are threats to the compounding policy and generally are discarded by the end-ofprocess other than contamination. For example, use date. However, facility policy can direct a more mental calculations frequent discard polassociated with medicy; in fact, facilities ication preparation often require that such A single-dose vial’s contents are to be used are threats that may vials be discarded within an hour of opening, and partial vials result in the wrong cannot be stored. The single-dose vial can be within 28 days. This accessed twice to withdraw contents. concentration of the 28-day period begins final product. Another on the day of the first area of concern pervial puncture. Multitains to switching between metric and nonmetric dose vials must contain bacteriostatic properties, system measurements. The majority of pharmaand it is these properties that distinguish a multiceutical products are expressed in metric system dose vial from a single-use vial. If there is gross units of measurement; however, converting becontamination of the contents or process, the multween systems may be needed (eg, converting tidose vial should be discarded immediately. a patient’s weight from pounds to kilograms). Personnel should decontaminate the exterior of Another area pertains to total vial content versus ampules using 70% isopropyl alcohol and open them product concentration. For example, there could be carefully to avoid contaminating the product with confusion between the intended 10 mg/mL conmicroshards of glass. Contents should be removed centration and the delivery of a 100-mL bottle by one entry (ie, single draw) into the ampule with containing a total vial content of 1,000 mg. The a syringe that has a filter needle. The filter needle compounder bears responsibility for ensuring acmust be discarded and replaced with a sterile needle. curacy across these risk areas. Ampules cannot be stored for any time period.1 In addition, according to Chapter , compounding personnel are responsible for ensuring Control. Part of complying with Chapter that compounded sterile products are accurately is implementing ongoing quality improvement identified, measured, diluted, and mixed and are processes.1,7 Perioperative managers should colcorrectly purified, sterilized, packaged, sealed, laborate with members of the quality and safety 1 labeled, stored, and distributed. The ASHP has department and the pharmacy in designing, implementing, and evaluating a robust quality imidentified 14 achievable objectives that direct comprovement plan. Such a plan also should include pounding personnel activities; these can be found patient monitoring and adverse event reporting.2 in The ASHP Discussion Guide on USP Chapter for Compounding Sterile Preparations.2 Perioperative leaders should recognize the 472 j AORN Journal
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immediately administered) and requires that peradministrative burden of record keeping (eg, recorsonnel use aseptic technique to transfer or measure ding of lot numbers, maintaining the appropriate no more than three nonhazardous products or environmental conditions, staff testing, transporperform no more than two entries into a sterile tation guidelines) associated with the compounding container.1 Any need for product preparation outprocess. The perioperative setting should have established relationships with the pharmacy side the immediate use period must be handled by department if these basic compounding practices the pharmacy department. cannot be maintained. This is why a compounding To adhere to the quality aspect of the compharmacist is needed; the rules and documentation to pounding process, the perioperative nurse should meet the regulation are extensive and a burden that begin by correctly identifying all products; confirm goes well beyond the that he or she has the role of perioperative right product, concennurses. A nurse tration, and strength; The perioperative compounder should ensure manager, however, and confirm that the that the surface area where the compounding should be aware will occur is decontaminated. If the area is not, product has not passed the person preparing the medication should of the rules for its expiration date. clean it and apply a disinfectant to the surface. After the nurse has compliance. If a facility outsources retrieved the products its compounding, the from their storage burden grows exponentially. If the surgery setting is location and gathered any needed supplies, he in a facility that has outsourced sterile compounding, or she should perform appropriate hand hygiene the ASHP provides operational guidelines that propractices before beginning the compounding mote adherence to Chapter .11 process. Donning sterile gloves is not required for preparing immediate use products; however, wearing artificial nails, overlays, or extenders and IMMEDIATE USE PREPARATIONS IN jewelry is prohibited for all individuals working THE OR with compounded products.1 The nurse’s skin In the OR, practitioners work only with immediate should be intact and free of rashes, sunburns, use products. Chapter does not speak speor other conditions that could cause shedding. cifically to compounding in the OR, just the nature To adhere to the environmental aspects of the of “low-risk level” compounded productsdthose process, the perioperative compounder should products that have minimal (ie, less than three) ensure that the surface area where the compounding manipulations (eg, transfers, measuring, mixing) will occur is decontaminated. If the area is not, the and for which the final compounded product can person preparing the medication should clean it and begin to be administered in less than 1 hour. This apply a disinfectant to the surface.1 The perioperrestriction is noted in light of the understanding that ative nurse also should consider decontaminating if compounding occurs in an environment greater the products’ vials or ampules as described in the than ISO Class 5, the likelihood of microbial preceding text. This step would be followed by contamination or clinically significant microbial using aseptic technique to transfer the contents to colonization increases. the final container, bearing in mind that there are There are many areas from Chapter limits to the number of times the container can standards that should be considered routine practice be accessed. An additional environmental considto minimize patient risk. The most important coneration is that perioperative personnel must mainsideration begins with the definition of immediate tain appropriate air pressure with the use of the use products (ie, products that are prepared and AORN Journal j 473
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Ambulatory Takeaways Considerations for Using Compounded Medications in the Ambulatory Setting Freestanding ambulatory surgery centers (ASCs) typically contract with a third-party compounding pharmacy that can provide compounded medications ready for patient use. Recently, new federal legislation expanded the authority of the US Food and Drug Administration (FDA) to strengthen the rules that govern compounding pharmacies to further promote patient safety.1 In other instances, ASCs obtain medications for compounding at the patient’s bedside to meet patient care needs. The US Pharmacopeia (USP) Chapter provides a multifactorial guideline for the preparation of sterile compounds.2 The USP considers OR compounding to be low risk, because fewer medications are typically used and the compounding is performed using sterile medications, syringes, and needles. Higher risks include mixing compounds with nonsterile products, such as nonsterile powders and solutions, and then sterilizing. In outpatient ophthalmology settings, for example, many compounded medications are not made commercially and are compounded either by a compounding pharmacy or in the surgical area before use. Ambulatory surgery centers should consider only using compounded medications that are manufactured, because these are required to undergo sterility testing. There have been outbreaks of endophthalmitis linked to the compounding of antibiotics, dyes, and irrigation solutions for ophthalmic procedures. More concerning than this, perhaps, are inaccuracies in dilution and dosage, which have resulted in devastating patient outcomes, including loss of vision or enucleations.3 If medications are compounded in the ASC environment, meticulous hand hygiene and a clean, decontaminated workspace should be used for preparing and compounding medications. The majority of infections occur because of poor technique used in the preparation. Additionally, safe injection practices (ie, one syringe, one needle for one patient) should be used at all times. To help guide ASCs in selecting a compounding pharmacy, the Ambulatory Supplement to the AORN “Recommended practices for medication safety” includes the International Academy of Compounding Pharmacy Assessment Questionnaire (CPAQTM). The CPAQ provides a comprehensive checklist of what to look for in a pharmacy compounding practice and is based on USP standards.4,5 Editor’s note: The Compounding Pharmacy Assessment Questionnaire (CPAQ) is a trademark of IACP, Missouri City, TX. Terri Link, MPH, RN, CNOR, CIC, is an ambulatory education specialist at AORN, Inc. Ms Link has no declared affiliation that could be perceived as posing a potential conflict of interest in the publication of this article. 1. 2. 3. 4. 5.
Compounding: Compounding Quality Act. US Food and Drug Administration. http://www.fda.gov/drugs/GuidanceComplianceRegu latoryInformation/PharmacyCompounding. Accessed January 16, 2014. United States Pharmacopeia Convention. Committee of Revision. Pharmaceutical compoundingdsterile preparations. In: The United States Pharmacopeia. 27th ed. Rockville, MD: United States Pharmacopeial Convention, Inc; 2009:318-354. Lockington D, Flowers H, Young D, Yorston D. Assessing the accuracy of intracameral antibiotic preparation for use in cataract surgery. J Cataract Refract Surg. 2010;36(2):286-289. Compounding Pharmacy Assessment Questionnaire (CPAQ)TM. IACP. http://www.iacprx.org/displaycommon.cfm?an¼1&subarticle nbr¼47. Accessed January 16, 2014. Ambulatory supplement: medication safety. In: Perioperative Standards and Recommended Practices. Denver, CO: AORN, Inc; 2014:316-320.
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MEDICATION COMPOUNDING facility’s heating, ventilation, and air conditioning system. The doors to the OR should be closed, and there must be a deliberate effort to minimize traffic to reduce contamination from particulate matter. As part of the control aspect of the compounding process, the entire process should be performed without interruption, and administration of the final compounded products must begin within one hour. Complying with this one-hour time limit means that compounded products should not be prepared ahead of time in the OR setting. If an RN circulator performs the compounding, the person administering the preparation should have observed the entire process. If the person administering the product did not observe the process, the compounder should label the final products. Appropriate labeling is an important aspect of compliance.1 VENDOR-CONTRACTED COMPOUNDING FACILITIES Facilities can use vendor-based compounding services (eg, outsourcing). If a facility uses an external partner, there are reasonable expectations for each party. Beginning with the perioperative facility, the leadership team should identify what products are going to be needed. With that information, the leadership team can communicate with potential vendors and ultimately create the statement of work and contract. The plan should include the management and disposal of infectious waste as well as cytotoxic products. Because compounding is a pharmacy function, it is most prudent to engage pharmacists in all discussions with third-party vendors. Perhaps one of the most important aspects to be mindful of when contracting with external vendor-based compounding services is that the compounding pharmacy must have state-granted permission to cross jurisdiction boundaries. In other words, no compounding product can cross state lines until appropriate licensing has occurred. For example, if a pharmacist in Colorado wants to ship compounded medications to New Mexico, then the New Mexico Board of Pharmacy also must approve the Colorado pharmacist. Facility managers are
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highly encouraged to verify compounding pharmacies through their respective state boards of pharmacy. Likewise, there are vendor responsibilities. Vendors must supply the customer with all packaging and handling instructions. If the vendor prepares a product that is “chilled,” the receiving facility must be prepared to handle and safeguard temperature requirements. Compliance with this expectation can be documented through temperature logs. Vendors must provide adequate labeling of the products, including their beyond-use date. Vendors bear responsibility for all training and quality improvement efforts and for sterility testing of their staff members (eg, fingertip sampling) and the vendor site. In the best case scenario, the vendor’s compounding pharmacist should be available to facility personnel to review orders and offer product information. CONCLUSION Medication compounding is an essential part of providing care to many perioperative patients. Awareness of national standards and following recommended practices will decrease the likelihood of an adverse event. Perioperative personnel should collaborate early and often with pharmacy representatives, either within the facility or at the thirdparty vendor facility, to ensure the highest standard of care.1,2
References 1. United States Pharmacopeia Convention. Committee of Revision. Pharmaceutical compoundingdsterile preparations. In: The United States Pharmacopeia. 27th ed. Rockville, MD: United States Pharmacopeial Convention, Inc; 2009:318-354. 2. The ASHP Discussion Guide on USP Chapter for Compounding Sterile Preparations. Bethesda, MD: American Society of Health-System Pharmacists; 2008. 3. Denholm B. Policies for using multidose liquid medications in the OR; clarifying the definitions of and the practices for compounding sterile solutions; storage of emergency medications [Clinical Issues]. AORN J. 2012; 96(2):206-214. 4. Recommended practices for medication safety. In: Perioperative Standards and Recommended Practices. Denver, CO: AORN, Inc; 2013:255-294.
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5. Riley RJ. The Regulation of Pharmaceutical Compounding and the Determination of Need: Balancing Access and Autonomy with Patient Safety. Cambridge, MA: Harvard Law School; 2004. 6. Allen LV. Guidelines for Compounding Practices. Washington, DC: American Pharmacists Association; 2012. 7. Model state pharmacy act and model rules. 2012. National Association of Boards of Pharmacy. http://www .nabp.net/publications/model-act. Accessed August 8, 2013. 8. HR 3204 Drug Quality and Security Act. http://beta .congress.gov/bill/113th/house-bill/3204. Accessed February 17, 2014. 9. Kastango ES. Blueprint for implementing USP chapter 797 for compounding sterile preparations. Am J Health Syst Pharm. 2005;62(12):1271-1288. 10. Kastango ES, Bradshaw BD. USP chapter 797: establishing a practice standard for compounding sterile
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HICKS preparations in pharmacy. Am J Health Syst Pharm. 2004;61(18):1928-1938. 11. American Society of Health-System Pharmacists. ASHP guidelines on outsourcing sterile compounding services. Am J Health Syst Pharm. 2010;67:757-765.
Rodney W. Hicks, PhD, RN, FNP-BC, FAAN, FAANP, is a professor and assistant director of the Doctor of Nursing Program at Western University of Health Sciences College of Graduate Nursing, Pomona, CA. Dr Hicks has no declared affiliation that could be perceived as posing a potential conflict of interest in the publication of this article.
EXAMINATION
2.2
CONTINUING EDUCATION
Understanding Medication Compounding Issues
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PURPOSE/GOAL To provide learners with knowledge specific to the use of compounded medications in the OR.
OBJECTIVES 1. 2. 3. 4. 5.
Describe the threats to patient safety that compounded medications pose. Define pharmaceutical compounding. Identify resources to help nurses understand medication compounding. Explain the themes of successful compounding. Discuss considerations for contracting with external compounding services.
The Examination and Learner Evaluation are printed here for your convenience. To receive continuing education credit, you must complete the online Examination and Learner Evaluation at http://www.aorn.org/CE.
QUESTIONS 1.
Harm from compounded medications can result from microbial or physical contamination, the presence of bacterial endotoxins, and variations in product strength or quality. a. true b. false
2.
Chapter is a multifactorial guideline that 1. addresses conditions and practices that reduce the likelihood of harm associated with compounded products. 2. describes the responsibilities of compounding personnel. 3. discusses environmental quality and control. 4. lists microbial contamination risk levels. 5. describes criteria for a quality assurance program. a. 1 and 3 b. 2 and 4 c. 1, 2, 3, and 4 d. 1, 2, 3, 4, and 5
Ó AORN, Inc, 2014
3.
Pharmaceutical compounding is the creation of a. mass-made medications. b. custom-made medications. c. large volumes of medications. d. medications made only for the OR.
4.
According to the American Pharmacists Association, compounding is the mixing of ingredients, including 1. admixture. 2. dilution. 3. reconstitution. 4. repackaging. a. 1 and 3 b. 2 and 4 c. 1, 2, and 4 d. 1, 2, 3, and 4
5.
Pharmacists play an important role in medication compounding because they have expertise in a product’s
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1. 2. 3. 4. 5.
6.
7.
8.
create a robust quality improvement plan that includes 1. patient monitoring. 2. staff monitoring. 3. adverse event reporting. 4. collaborating with members of the quality and safety department and the pharmacy. a. 1 and 3 b. 2 and 4 c. 1, 3, and 4 d. 1, 2, 3, and 4
absorption and distribution. cost and marketability. metabolism and excretion. compatibility and stability. humidity and osmolarity. a. 1, 2, and 4 b. 2, 3, and 5 c. 1, 3, 4, and 5 d. 1, 2, 3, 4, and 5
The theme of quality of successful compounding begins with the product and includes disinfection, purity, stability, and dosage. a. true b. false The theme of environment of successful compounding includes ways to reduce opportunities for contamination by 1. segregating compounding to areas with specialized airflow capabilities. 2. practicing proper hand hygiene. 3. performing gloved fingertip sampling. 4. helping to ensure proper cleaning of equipment and work areas. a. 1 and 3 b. 2 and 4 c. 1, 2, and 4 d. 1, 2, 3, and 4 The theme of control of successful compounding describes how perioperative managers should
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9.
10.
Wearing artificial nails, overlays, or extenders and jewelry is prohibited for all individuals working with compounded products. a. true b. false One of the most important aspects to be mindful of when contracting with external vendor-based compounding services is that the compounding pharmacy must have a. only certified pharmacy technicians on staff. b. state-granted permission to cross jurisdiction boundaries. c. a vast supply of composite agents. d. documented cleaning of multimodal hood apparatuses.
LEARNER EVALUATION
2.2
CONTINUING EDUCATION PROGRAM
Understanding Medication Compounding Issues
T
his evaluation is used to determine the extent to which this continuing education program met your learning needs. The evaluation is printed here for your convenience. To receive continuing education credit, you must complete the online Examination and Learner Evaluation at http://www .aorn.org/CE. Rate the items as described below. OBJECTIVES To what extent were the following objectives of this continuing education program achieved? 1. Describe the threats to patient safety that compounded medications pose. Low 1. 2. 3. 4. 5. High 2. Define pharmaceutical compounding. Low 1. 2. 3. 4. 5. High 3. Identify resources to help nurses understand medication compounding. Low 1. 2. 3. 4. 5. High 4. Explain the themes of successful compounding. Low 1. 2. 3. 4. 5. High 5. Discuss considerations for contracting with external compounding services. Low 1. 2. 3. 4. 5. High CONTENT 6. To what extent did this article increase your knowledge of the subject matter? Low 1. 2. 3. 4. 5. High 7. To what extent were your individual objectives met? Low 1. 2. 3. 4. 5. High
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8. Will you be able to use the information from this article in your work setting? 1. Yes 2. No 9. Will you change your practice as a result of reading this article? (If yes, answer question #9A. If no, answer question #9B.) 9A. How will you change your practice? (Select all that apply) 1. I will provide education to my team regarding why change is needed. 2. I will work with management to change/ implement a policy and procedure. 3. I will plan an informational meeting with physicians to seek their input and acceptance of the need for change. 4. I will implement change and evaluate the effect of the change at regular intervals until the change is incorporated as best practice. 5. Other: ________________________________ 9B. If you will not change your practice as a result of reading this article, why? (Select all that apply) 1. The content of the article is not relevant to my practice. 2. I do not have enough time to teach others about the purpose of the needed change. 3. I do not have management support to make a change. 4. Other: ________________________________ 10. Our accrediting body requires that we verify the time you needed to complete the 2.2 continuing education contact hour (132-minute) program: _________________________________
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RODNEY W. HICKS, PhD, RN, FNP-BC, FAAN, FAANP
www.aorn.org/CE Continuing Education Contact Hours
Accreditation
indicates that continuing education (CE) contact hours are available for this activity. Earn the CE contact hours by reading this article, reviewing the purpose/goal and objectives, and completing the online Examination and Learner Evaluation at http://www.aorn.org/CE. A score of 70% correct on the examination is required for credit. Participants receive feedback on incorrect answers. Each applicant who successfully completes this program can immediately print a certificate of completion.
AORN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.
Event: #14510 Session: #0001 Fee: Members $17.60, Nonmembers $35.20 The CE contact hours for this article expire April 30, 2017. Prices are subject to change.
Purpose/Goal To provide learners with knowledge specific to the use of compounded medications in the OR.
Objectives
Approvals This program meets criteria for CNOR and CRNFA recertification, as well as other CE requirements. AORN is provider-approved by the California Board of Registered Nursing, Provider Number CEP 13019. Check with your state board of nursing for acceptance of this activity for relicensure.
Conflict of Interest Disclosures Rodney W. Hicks, PhD, RN, FNP-BC, FAAN, FAANP, has no declared affiliation that could be perceived as posing a potential conflict of interest in the publication of this article. The behavioral objectives for this program were created by Helen Starbuck Pashley, MA, BSN, CNOR, clinical editor, with consultation from Susan Bakewell, MS, RN-BC, director, Perioperative Education. Ms Starbuck Pashley and Ms Bakewell have no declared affiliations that could be perceived as posing potential conflicts of interest in the publication of this article.
Sponsorship or Commercial Support
1. Describe the threats to patient safety that compounded medications pose. 2. Define pharmaceutical compounding. 3. Identify resources to help nurses understand medication compounding. 4. Explain the themes of successful compounding. 5. Discuss considerations for contracting with external compounding services.
No sponsorship or commercial support was received for this article.
Disclaimer AORN recognizes these activities as CE for RNs. This recognition does not imply that AORN or the American Nurses Credentialing Center approves or endorses products mentioned in the activity.
http://dx.doi.org/10.1016/j.aorn.2013.07.021
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Understanding Medication Compounding Issues RODNEY W. HICKS, PhD, RN, FNP-BC, FAAN, FAANP
2.2 www.aorn.org/CE
ABSTRACT The potential for contamination of compounded products and the resulting infections are a serious threat to patient safety. Immediate use products are used frequently in the perioperative department, and perioperative nurses should be familiar with the guidelines and practices that aim to reduce the contamination that can occur during the sterile compounding process. Four common themes lead to successful compounding: quality (eg, product identification, purity, stability, compatibility, risk level assessment), the environment (eg, using a segregated compounding area with specialized airflow capabilities, reducing particulate matter, practicing proper hand hygiene, performing gloved fingertip sampling, properly cleaning equipment and work areas), personnel activities (eg, familiarity with types of containers used and how often they can be accessed, following expiration dates and the number of times containers can be accessed), and the control process (eg, process monitoring, quality improvement). If a third-party vendor is contracted to handle compounding for a facility, perioperative personnel should be aware of the responsibilities for the facility and the vendor to ensure a quality compounding program. AORN J 99 (April 2014) 467-476. Ó AORN, Inc, 2014. http://dx.doi.org/10.1016/j.aorn.2013.07.021 Key words: medication compounding, compounding, perioperative practice standards, contamination, immediate use products.
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uch of preoperative, intraoperative, and postoperative care could not be achieved without the use of compounded pharmaceutical products. Recently, media headlines have brought to light the risks associated with compounded products and focused renewed attention on the roles and responsibilities of health care professionals who work with these products. In 2012 and 2013, there were an abundance of media headlines on the issues of compounding (Table 1). The untoward outcomes of compounding is not a new issue, however, and case reports of patient
harm and death that implicate compounded products go back more than 20 years. Harm from compounded medications can result from microbial or physical contamination, the presence of bacterial endotoxins, and variations in product strength or quality. In response to this long-standing threat to patient safety, the US Pharmacopeia (USP), a nongovernmental standards setting organization based in Rockville, Maryland, published what is known as Chapter .1 Chapter has many far-reaching components that direct many aspects of sterile
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TABLE 1. Recent National Headlines Regarding Compounding Issues n n
n n
n n
Eisler P. Deaths, infections tied to “compounding” drug. USA Today. October 12, 2012. http://www.usatoday.com/story/ news/nation/2012/10/11/compounding-pharmarcies-deaths/1626753. Accessed August 8, 2013. Wallack T. Grand jury sets sights on compounding pharmacy. Boston Globe. December 1, 2012. http://www.bostonglobe .com/business/2012/12/01/federal-grand-jury-investigating-new-england-compounding-meningitis-outbreak/IlRHC3wOchna S188UB7EyN/story.html. Accessed August 8, 2013. Sack K, Williams T. Death of 9 Alabama patients tied to intravenous supplement. New York Times. March 30, 2011; A20. http://www.nytimes.com/2011/03/31/us/31intravenous.html?_r¼0. Accessed August 8, 2013. Crime time. Dallas compounding pharmacy faces charges in three deaths. Fort Worth Star Telegram. February 10, 2012. http://blogs.star-telegram.com/crime_time/2012/02/dallas-compounding-pharmacy-faces-charges-in-three-deaths.html. Accessed August 8, 2013. Safety news: another compounding pharmacy in trouble. Outpatient Surgery Magazine. November 12, 2012. http://www.out patientsurgery.net/news/2012/11/10-Another-Compounding-Pharmacy-in-Trouble. Accessed August 8, 2013. Perrone M. FDA inspection triggers recall by Florida compounding pharmacy. Associated Press. May 8, 2013. http://bigstory .ap.org/article/fda-inspection-triggers-recall-florida-pharmacy. Accessed August 8, 2013.
compounding, all aimed at reducing opportunities for harm. Chapter provides a multifactorial guideline to the preparation of sterile compounds.2 It addresses conditions and practices that reduce the likelihood of harm, including death, associated with compounded products. The current version of Chapter , which became effective on June 1, 2008, is organized with a revised introduction, new definition section, descriptions of compounding personnel responsibilities, a list of microbial contamination risk levels, training and evaluation requirements, discussion of environmental quality and control, criteria for a robust quality assurance program, and several other sections.1 Understanding, following, and enforcing these recommendations helps to ensure public health safety,2 and perioperative nurses should familiarize themselves with the full chapter. AORN has discussed information about compounding from the viewpoint of perioperative care in the AORN Journal “Clinical Issues” column3 and in its “Recommended practices for medication safety.”4 The purpose of this article is to provide the perioperative nurse with information about compounding and how it relates to perioperative patient safety by defining and reviewing components of compounding and discussing the applications and 468 j AORN Journal
implications of compounding for the perioperative care provider. This article focuses only on the preparation of compounded sterile products intended for human use. COMPOUNDING Compounding has its roots in the pharmacy profession,5 so some perioperative personnel may not recognize the scope and breadth of all that is included in the term compounding. Pharmaceutical compounding is the creation of custom-made medications. Compounding encompasses a triad that includes the patient, practitioner, and pharmacist (Figure 1). According to the USP, a compounded product is a sterile product that includes preparations prepared according to the manufacturer’s labeled instructions and other manipulations when preparing sterile products that expose the original contents to potential contamination, as well as preparations that contain non-sterile ingredients or employ non-sterile components and devices that must be sterilized before use.1(p2) According to the American Pharmacists Association (APhA), compounding is the mixing of ingredients, including dilution, admixture, repackaging, reconstitution, and other manipulations of sterile products,
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Figure 1. Compounding encompasses a triad that includes the patient, practitioner, and pharmacist.
to prepare a medication for patient use.6 Although the USP does not define compounding this specifically, the APhA’s definition allows for products to be made in anticipation of routine prescribing patterns.6 Furthermore, compounding is said to occur when a medicine has to be created because the strength, concentration, or dosage that is needed for a specific patient varies from what is commercially available.7 These definitions highlight the intent of compounding to prepare a small quantity of a US Food and Drug Administration (FDA)eapproved medication based on a practitioner’s prescription. The APhA’s definition allows for products to be made in anticipation of routine prescribing patterns (eg, ophthalmology),6 and the USP’s narrower definition signals the intent for compounding medications for a specific patient population. Pharmaceutical manufacturing, by contrast, is where a commercial vendor with FDA approval uses mass production to compound a bulk quantity of medication without regard to a specific patient population or prescription. Before November 2013, state boards of pharmacy had authority over compounding (eg, mixing one medication for one patient) and for compliance with meeting Chapter standards,7 while the FDA had oversight of commercial manufacturing (ie, bulk production without regard to the specific patient). The differentiation between compounding and manufacturing was sometimes unclear and,
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when problems were identified, this lack of clarity led to the identification of deficits in various parties’ accounting and responsibility. With the recent passage of HR 3204, the Drug Quality and Security Act,8 there is now clarification of the existing laws and improvements in accounting and responsibilities of the various parties. Furthermore, the bill clarifies the authority of the FDA to broaden its scope in the regulation of compounded products and to further promote patient safety along the pharmaceutical supply chain. Physician and advance practice nurse practitioners have professional autonomy to make ordinary medical care decisions, and those decisions may lead to an order for a compounded product. Respective licensing boards regulate health professions because it is not the role of the federal government to determine medical care.5 Similarly, the state boards that regulate pharmacists have important roles in regulating the practice of compounding given that schools of pharmacy provide specialized training in sterile compounding,9 and as a result, pharmacists are recognized as having specialized skills and knowledge in this area. Pharmacists have expertise in a product’s absorption, distribution, metabolism, and excretion. Additionally, pharmacists have knowledge about product compatibility, stability, changes in pH, humidity, osmolarity, and other factors that influence a product. Successful Compounding There are four common themes that lead to successful compounding: quality, the environment, personnel activities, and the control process. Interruption of any areas related to these can adversely affect compounding outcomes. Quality. Quality begins with the product, including product identification, purity, stability, and compatibility. Errors in product identification can occur because of sound-alike or look-alike product names or when products have similar packaging. Purity refers to the absence of bacterial, viral, or physical contamination in the compounding AORN Journal j 469
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TABLE 2. Classifications of Risk Assessment Levels of Compounded Sterile Products Requirementsa
Classification Immediate use
n n n
Low risk
n n n
Low risk < 12 hours beyond use date
n n
Medium risk
n n n n
High risk
n n n
Emergent use, administer < 1 hr after preparation No storage or batch compounding Aseptic technique Simple admixture compounded using closed system transfer Prepared in ISO Class 5 laminar airflow workbench Located in ISO Class 7 buffer with ISO Class 8 anteroom area (eg, OR anteroom in substerile corridor) Simple admixture compounded using closed system transfer Prepared in ISO Class 5 primary engineering controlled area Admixture compounded using multiple additives Batch preparation Complex manipulations Prepared in ISO Class 5 conditions Nonsterile (bulk powders) ingredients Open system transfers Prepared in ISO Class 5 conditions
ISO ¼ International Standards Organization. a Requirements listed are not all inclusive. Adapted with permission from the American Society of Health-System Pharmacists. The ASHP Discussion Guide on USP Chapter for Compounding Sterile Preparations. Bethesda, MD: American Society of Health-System Pharmacists; 2008.
process. Stability means that there is no less than 10% degradation of product(s). Factors that affect stability include changes in pH, humidity levels, or exposure to light. Compatibility refers to the interaction between two or more products being mixed together. Each of these quality control areas support the value of having a pharmacist involved in the compounding process. Another aspect of quality is the risk level assessment of the compounding process and the medications created, which is obtained through a formal process known as a gap analysis. According to Chapter , practitioners should identify risk level contamination categories (eg, immediate use, low risk, low risk < 12 hours beyond use date, medium risk, high risk).1 Each risk level contamination category requires that different conditions1 are satisfied to minimize the potential for contamination (Table 2). Some of the factors that affect risk level include the environment (ie, where the products are physically compounded), temperature storage (when applicable), type of product, and 470 j AORN Journal
when the product will be used. The American Society of Health-System Pharmacists (ASHP) has a tool kit to assist those conducting the gap analysis.2 This tool kit focuses on determining the risk level, developing an action plan to reduce risks that are identified, implementing and monitoring the action plan, and continually monitoring the process for improvement. Environment. Chapter provides technical specifications for constructing a suitable work environment in which to compound medications. Perioperative personnel should be familiar with various inherent environmental threats to sterility, including the leading threats to compounding, which come from microbial contamination and contamination from particulate air matter measuring 0.5 mm and larger per cubic meter. Ways to reduce opportunities for contamination of the environment include segregating compounding to areas with specialized airflow capabilities, reducing particulate matter to the extent possible, practicing
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TABLE 3. ISO Classification of Particulate Matter in Room Air Class name1 ISO class
US Federal Standard 209E for clean room
3 4 5 6 7 8
Class Class Class Class Class Class
1 10 100 1,000 10,000 100,000
Particle count1 ISO, m3
Federal Standard 209E, ft3
35.2 352 3,520 35,200 352,000 3,520,000
1 10 100 1,000 10,000 100,000
Perioperative examples
IV room OR OR anteroom in substerile corridor
ISO ¼ International Standards Organization. 1. United States Pharmacopeia Convention. Committee of Revision. Pharmaceutical compoundingdsterile preparations. In: The United States Pharmacopeia. 27th ed. Rockville, MD: United States Pharmacopeial Convention, Inc; 2009:318-354.
proper hand hygiene, performing gloved fingertip sampling, and helping to ensure proper cleaning of equipment and work areas. To achieve the lowest risk of contamination, Chapter recommends that low-risk, medium-risk, or high-risk sterile products be compounded in segregated compounding areas with specialized airflow capabilities. This type of environment is commonly referred to as an International Standards Organization (ISO) Class 5 setting, which is attained by achieving a level of air cleanliness. For example, ORs have 10 times or more the number of particles per cubic meter than are present in ISO Class 5 settings. Table 3 shows the requirements and particulate matter thresholds for various volume levels of air cleanliness. Older literature may sometimes refer to Federal Standard 209E as the clean room standard; however, this standard is obsolete. Having the least amount of particles per square foot reduces the opportunity for contamination during the compounding process. Particulate matter is inherent throughout the environment, but there are ways to reduce it. For example, wearing street clothes is associated with estimates of 10 to 30 million particles per square foot, and laundered hospital garments can have 1 million particles per square foot.10 Wearing cover attire, such as a standard coverall, along with limiting physical
movement, reduces particulate matter counts to 50,000 particles per square foot.10 Hand hygiene practices reduce opportunities for contamination as well. Organizations that support compounding services are expected to have policies and procedures in place that address hand washing techniques and enforce compliance of these policies.2 In an ISO Class 5 setting, compounders should wear sterile gloves. It is important to note that handling nonsterile vials and ampules results in glove contamination; therefore, the compounder should disinfect his or her gloves by applying sterile 70% isopropyl alcohol to the fingertips between each handling of a product container. Glove integrity should be maintained and monitored throughout the compounding process.1 For low-, medium-, and high-risk compounding, compounders working in an ISO Class 5 setting are also required to conduct gloved fingertip sampling.1,2 Policies and procedures should direct the frequency of fingertip sampling (eg, with new hires versus ongoing monitoring) as well as the expected outcomes; for example, the absence of growth on bacterial cultures suggests compliance with adequate disinfecting practices. The concept of the environment also must address cleaning, equipment, and personnel responsibilities. Cleaning includes the type of cleaning agent used as well as the schedule of cleaning the AORN Journal j 471
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various surfaces in the location where compounding occurs. Disinfectants can be applied to work surfaces to decrease microbial contamination in the environment. Steam sterilization is another process for disinfecting objects used for compounding. Equipment pertains to the various types of equipment used, including laminar flow hoods, specifications for air exchanges, and smaller pieces of adjunct equipment (eg, filter needles, syringes).
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Some considerations to which personnel contribute that are important to compounding include the type of containers used, the expiration date of contents of containers, and the number of times a container can be accessed. The type of container refers to vials (either single dose or multidose) or ampules. A single-dose vial’s contents are to be used within an hour of opening, and partial vials cannot be stored.1,2 The single-dose vial can be accessed twice to withdraw contents. Multidose 2 1 Personnel activities. The ASHP and the USP vials are to be handled per the manufacturer’s recognize that there are threats to the compounding policy and generally are discarded by the end-ofprocess other than contamination. For example, use date. However, facility policy can direct a more mental calculations frequent discard polassociated with medicy; in fact, facilities ication preparation often require that such A single-dose vial’s contents are to be used are threats that may vials be discarded within an hour of opening, and partial vials result in the wrong cannot be stored. The single-dose vial can be within 28 days. This accessed twice to withdraw contents. concentration of the 28-day period begins final product. Another on the day of the first area of concern pervial puncture. Multitains to switching between metric and nonmetric dose vials must contain bacteriostatic properties, system measurements. The majority of pharmaand it is these properties that distinguish a multiceutical products are expressed in metric system dose vial from a single-use vial. If there is gross units of measurement; however, converting becontamination of the contents or process, the multween systems may be needed (eg, converting tidose vial should be discarded immediately. a patient’s weight from pounds to kilograms). Personnel should decontaminate the exterior of Another area pertains to total vial content versus ampules using 70% isopropyl alcohol and open them product concentration. For example, there could be carefully to avoid contaminating the product with confusion between the intended 10 mg/mL conmicroshards of glass. Contents should be removed centration and the delivery of a 100-mL bottle by one entry (ie, single draw) into the ampule with containing a total vial content of 1,000 mg. The a syringe that has a filter needle. The filter needle compounder bears responsibility for ensuring acmust be discarded and replaced with a sterile needle. curacy across these risk areas. Ampules cannot be stored for any time period.1 In addition, according to Chapter , compounding personnel are responsible for ensuring Control. Part of complying with Chapter that compounded sterile products are accurately is implementing ongoing quality improvement identified, measured, diluted, and mixed and are processes.1,7 Perioperative managers should colcorrectly purified, sterilized, packaged, sealed, laborate with members of the quality and safety 1 labeled, stored, and distributed. The ASHP has department and the pharmacy in designing, implementing, and evaluating a robust quality imidentified 14 achievable objectives that direct comprovement plan. Such a plan also should include pounding personnel activities; these can be found patient monitoring and adverse event reporting.2 in The ASHP Discussion Guide on USP Chapter for Compounding Sterile Preparations.2 Perioperative leaders should recognize the 472 j AORN Journal
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immediately administered) and requires that peradministrative burden of record keeping (eg, recorsonnel use aseptic technique to transfer or measure ding of lot numbers, maintaining the appropriate no more than three nonhazardous products or environmental conditions, staff testing, transporperform no more than two entries into a sterile tation guidelines) associated with the compounding container.1 Any need for product preparation outprocess. The perioperative setting should have established relationships with the pharmacy side the immediate use period must be handled by department if these basic compounding practices the pharmacy department. cannot be maintained. This is why a compounding To adhere to the quality aspect of the compharmacist is needed; the rules and documentation to pounding process, the perioperative nurse should meet the regulation are extensive and a burden that begin by correctly identifying all products; confirm goes well beyond the that he or she has the role of perioperative right product, concennurses. A nurse tration, and strength; The perioperative compounder should ensure manager, however, and confirm that the that the surface area where the compounding should be aware will occur is decontaminated. If the area is not, product has not passed the person preparing the medication should of the rules for its expiration date. clean it and apply a disinfectant to the surface. After the nurse has compliance. If a facility outsources retrieved the products its compounding, the from their storage burden grows exponentially. If the surgery setting is location and gathered any needed supplies, he in a facility that has outsourced sterile compounding, or she should perform appropriate hand hygiene the ASHP provides operational guidelines that propractices before beginning the compounding mote adherence to Chapter .11 process. Donning sterile gloves is not required for preparing immediate use products; however, wearing artificial nails, overlays, or extenders and IMMEDIATE USE PREPARATIONS IN jewelry is prohibited for all individuals working THE OR with compounded products.1 The nurse’s skin In the OR, practitioners work only with immediate should be intact and free of rashes, sunburns, use products. Chapter does not speak speor other conditions that could cause shedding. cifically to compounding in the OR, just the nature To adhere to the environmental aspects of the of “low-risk level” compounded productsdthose process, the perioperative compounder should products that have minimal (ie, less than three) ensure that the surface area where the compounding manipulations (eg, transfers, measuring, mixing) will occur is decontaminated. If the area is not, the and for which the final compounded product can person preparing the medication should clean it and begin to be administered in less than 1 hour. This apply a disinfectant to the surface.1 The perioperrestriction is noted in light of the understanding that ative nurse also should consider decontaminating if compounding occurs in an environment greater the products’ vials or ampules as described in the than ISO Class 5, the likelihood of microbial preceding text. This step would be followed by contamination or clinically significant microbial using aseptic technique to transfer the contents to colonization increases. the final container, bearing in mind that there are There are many areas from Chapter limits to the number of times the container can standards that should be considered routine practice be accessed. An additional environmental considto minimize patient risk. The most important coneration is that perioperative personnel must mainsideration begins with the definition of immediate tain appropriate air pressure with the use of the use products (ie, products that are prepared and AORN Journal j 473
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Ambulatory Takeaways Considerations for Using Compounded Medications in the Ambulatory Setting Freestanding ambulatory surgery centers (ASCs) typically contract with a third-party compounding pharmacy that can provide compounded medications ready for patient use. Recently, new federal legislation expanded the authority of the US Food and Drug Administration (FDA) to strengthen the rules that govern compounding pharmacies to further promote patient safety.1 In other instances, ASCs obtain medications for compounding at the patient’s bedside to meet patient care needs. The US Pharmacopeia (USP) Chapter provides a multifactorial guideline for the preparation of sterile compounds.2 The USP considers OR compounding to be low risk, because fewer medications are typically used and the compounding is performed using sterile medications, syringes, and needles. Higher risks include mixing compounds with nonsterile products, such as nonsterile powders and solutions, and then sterilizing. In outpatient ophthalmology settings, for example, many compounded medications are not made commercially and are compounded either by a compounding pharmacy or in the surgical area before use. Ambulatory surgery centers should consider only using compounded medications that are manufactured, because these are required to undergo sterility testing. There have been outbreaks of endophthalmitis linked to the compounding of antibiotics, dyes, and irrigation solutions for ophthalmic procedures. More concerning than this, perhaps, are inaccuracies in dilution and dosage, which have resulted in devastating patient outcomes, including loss of vision or enucleations.3 If medications are compounded in the ASC environment, meticulous hand hygiene and a clean, decontaminated workspace should be used for preparing and compounding medications. The majority of infections occur because of poor technique used in the preparation. Additionally, safe injection practices (ie, one syringe, one needle for one patient) should be used at all times. To help guide ASCs in selecting a compounding pharmacy, the Ambulatory Supplement to the AORN “Recommended practices for medication safety” includes the International Academy of Compounding Pharmacy Assessment Questionnaire (CPAQTM). The CPAQ provides a comprehensive checklist of what to look for in a pharmacy compounding practice and is based on USP standards.4,5 Editor’s note: The Compounding Pharmacy Assessment Questionnaire (CPAQ) is a trademark of IACP, Missouri City, TX. Terri Link, MPH, RN, CNOR, CIC, is an ambulatory education specialist at AORN, Inc. Ms Link has no declared affiliation that could be perceived as posing a potential conflict of interest in the publication of this article. 1. 2. 3. 4. 5.
Compounding: Compounding Quality Act. US Food and Drug Administration. http://www.fda.gov/drugs/GuidanceComplianceRegu latoryInformation/PharmacyCompounding. Accessed January 16, 2014. United States Pharmacopeia Convention. Committee of Revision. Pharmaceutical compoundingdsterile preparations. In: The United States Pharmacopeia. 27th ed. Rockville, MD: United States Pharmacopeial Convention, Inc; 2009:318-354. Lockington D, Flowers H, Young D, Yorston D. Assessing the accuracy of intracameral antibiotic preparation for use in cataract surgery. J Cataract Refract Surg. 2010;36(2):286-289. Compounding Pharmacy Assessment Questionnaire (CPAQ)TM. IACP. http://www.iacprx.org/displaycommon.cfm?an¼1&subarticle nbr¼47. Accessed January 16, 2014. Ambulatory supplement: medication safety. In: Perioperative Standards and Recommended Practices. Denver, CO: AORN, Inc; 2014:316-320.
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MEDICATION COMPOUNDING facility’s heating, ventilation, and air conditioning system. The doors to the OR should be closed, and there must be a deliberate effort to minimize traffic to reduce contamination from particulate matter. As part of the control aspect of the compounding process, the entire process should be performed without interruption, and administration of the final compounded products must begin within one hour. Complying with this one-hour time limit means that compounded products should not be prepared ahead of time in the OR setting. If an RN circulator performs the compounding, the person administering the preparation should have observed the entire process. If the person administering the product did not observe the process, the compounder should label the final products. Appropriate labeling is an important aspect of compliance.1 VENDOR-CONTRACTED COMPOUNDING FACILITIES Facilities can use vendor-based compounding services (eg, outsourcing). If a facility uses an external partner, there are reasonable expectations for each party. Beginning with the perioperative facility, the leadership team should identify what products are going to be needed. With that information, the leadership team can communicate with potential vendors and ultimately create the statement of work and contract. The plan should include the management and disposal of infectious waste as well as cytotoxic products. Because compounding is a pharmacy function, it is most prudent to engage pharmacists in all discussions with third-party vendors. Perhaps one of the most important aspects to be mindful of when contracting with external vendor-based compounding services is that the compounding pharmacy must have state-granted permission to cross jurisdiction boundaries. In other words, no compounding product can cross state lines until appropriate licensing has occurred. For example, if a pharmacist in Colorado wants to ship compounded medications to New Mexico, then the New Mexico Board of Pharmacy also must approve the Colorado pharmacist. Facility managers are
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highly encouraged to verify compounding pharmacies through their respective state boards of pharmacy. Likewise, there are vendor responsibilities. Vendors must supply the customer with all packaging and handling instructions. If the vendor prepares a product that is “chilled,” the receiving facility must be prepared to handle and safeguard temperature requirements. Compliance with this expectation can be documented through temperature logs. Vendors must provide adequate labeling of the products, including their beyond-use date. Vendors bear responsibility for all training and quality improvement efforts and for sterility testing of their staff members (eg, fingertip sampling) and the vendor site. In the best case scenario, the vendor’s compounding pharmacist should be available to facility personnel to review orders and offer product information. CONCLUSION Medication compounding is an essential part of providing care to many perioperative patients. Awareness of national standards and following recommended practices will decrease the likelihood of an adverse event. Perioperative personnel should collaborate early and often with pharmacy representatives, either within the facility or at the thirdparty vendor facility, to ensure the highest standard of care.1,2
References 1. United States Pharmacopeia Convention. Committee of Revision. Pharmaceutical compoundingdsterile preparations. In: The United States Pharmacopeia. 27th ed. Rockville, MD: United States Pharmacopeial Convention, Inc; 2009:318-354. 2. The ASHP Discussion Guide on USP Chapter for Compounding Sterile Preparations. Bethesda, MD: American Society of Health-System Pharmacists; 2008. 3. Denholm B. Policies for using multidose liquid medications in the OR; clarifying the definitions of and the practices for compounding sterile solutions; storage of emergency medications [Clinical Issues]. AORN J. 2012; 96(2):206-214. 4. Recommended practices for medication safety. In: Perioperative Standards and Recommended Practices. Denver, CO: AORN, Inc; 2013:255-294.
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5. Riley RJ. The Regulation of Pharmaceutical Compounding and the Determination of Need: Balancing Access and Autonomy with Patient Safety. Cambridge, MA: Harvard Law School; 2004. 6. Allen LV. Guidelines for Compounding Practices. Washington, DC: American Pharmacists Association; 2012. 7. Model state pharmacy act and model rules. 2012. National Association of Boards of Pharmacy. http://www .nabp.net/publications/model-act. Accessed August 8, 2013. 8. HR 3204 Drug Quality and Security Act. http://beta .congress.gov/bill/113th/house-bill/3204. Accessed February 17, 2014. 9. Kastango ES. Blueprint for implementing USP chapter 797 for compounding sterile preparations. Am J Health Syst Pharm. 2005;62(12):1271-1288. 10. Kastango ES, Bradshaw BD. USP chapter 797: establishing a practice standard for compounding sterile
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HICKS preparations in pharmacy. Am J Health Syst Pharm. 2004;61(18):1928-1938. 11. American Society of Health-System Pharmacists. ASHP guidelines on outsourcing sterile compounding services. Am J Health Syst Pharm. 2010;67:757-765.
Rodney W. Hicks, PhD, RN, FNP-BC, FAAN, FAANP, is a professor and assistant director of the Doctor of Nursing Program at Western University of Health Sciences College of Graduate Nursing, Pomona, CA. Dr Hicks has no declared affiliation that could be perceived as posing a potential conflict of interest in the publication of this article.
EXAMINATION
2.2
CONTINUING EDUCATION
Understanding Medication Compounding Issues
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PURPOSE/GOAL To provide learners with knowledge specific to the use of compounded medications in the OR.
OBJECTIVES 1. 2. 3. 4. 5.
Describe the threats to patient safety that compounded medications pose. Define pharmaceutical compounding. Identify resources to help nurses understand medication compounding. Explain the themes of successful compounding. Discuss considerations for contracting with external compounding services.
The Examination and Learner Evaluation are printed here for your convenience. To receive continuing education credit, you must complete the online Examination and Learner Evaluation at http://www.aorn.org/CE.
QUESTIONS 1.
Harm from compounded medications can result from microbial or physical contamination, the presence of bacterial endotoxins, and variations in product strength or quality. a. true b. false
2.
Chapter is a multifactorial guideline that 1. addresses conditions and practices that reduce the likelihood of harm associated with compounded products. 2. describes the responsibilities of compounding personnel. 3. discusses environmental quality and control. 4. lists microbial contamination risk levels. 5. describes criteria for a quality assurance program. a. 1 and 3 b. 2 and 4 c. 1, 2, 3, and 4 d. 1, 2, 3, 4, and 5
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3.
Pharmaceutical compounding is the creation of a. mass-made medications. b. custom-made medications. c. large volumes of medications. d. medications made only for the OR.
4.
According to the American Pharmacists Association, compounding is the mixing of ingredients, including 1. admixture. 2. dilution. 3. reconstitution. 4. repackaging. a. 1 and 3 b. 2 and 4 c. 1, 2, and 4 d. 1, 2, 3, and 4
5.
Pharmacists play an important role in medication compounding because they have expertise in a product’s
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CE EXAMINATION
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1. 2. 3. 4. 5.
6.
7.
8.
create a robust quality improvement plan that includes 1. patient monitoring. 2. staff monitoring. 3. adverse event reporting. 4. collaborating with members of the quality and safety department and the pharmacy. a. 1 and 3 b. 2 and 4 c. 1, 3, and 4 d. 1, 2, 3, and 4
absorption and distribution. cost and marketability. metabolism and excretion. compatibility and stability. humidity and osmolarity. a. 1, 2, and 4 b. 2, 3, and 5 c. 1, 3, 4, and 5 d. 1, 2, 3, 4, and 5
The theme of quality of successful compounding begins with the product and includes disinfection, purity, stability, and dosage. a. true b. false The theme of environment of successful compounding includes ways to reduce opportunities for contamination by 1. segregating compounding to areas with specialized airflow capabilities. 2. practicing proper hand hygiene. 3. performing gloved fingertip sampling. 4. helping to ensure proper cleaning of equipment and work areas. a. 1 and 3 b. 2 and 4 c. 1, 2, and 4 d. 1, 2, 3, and 4 The theme of control of successful compounding describes how perioperative managers should
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9.
10.
Wearing artificial nails, overlays, or extenders and jewelry is prohibited for all individuals working with compounded products. a. true b. false One of the most important aspects to be mindful of when contracting with external vendor-based compounding services is that the compounding pharmacy must have a. only certified pharmacy technicians on staff. b. state-granted permission to cross jurisdiction boundaries. c. a vast supply of composite agents. d. documented cleaning of multimodal hood apparatuses.
LEARNER EVALUATION
2.2
CONTINUING EDUCATION PROGRAM
Understanding Medication Compounding Issues
T
his evaluation is used to determine the extent to which this continuing education program met your learning needs. The evaluation is printed here for your convenience. To receive continuing education credit, you must complete the online Examination and Learner Evaluation at http://www .aorn.org/CE. Rate the items as described below. OBJECTIVES To what extent were the following objectives of this continuing education program achieved? 1. Describe the threats to patient safety that compounded medications pose. Low 1. 2. 3. 4. 5. High 2. Define pharmaceutical compounding. Low 1. 2. 3. 4. 5. High 3. Identify resources to help nurses understand medication compounding. Low 1. 2. 3. 4. 5. High 4. Explain the themes of successful compounding. Low 1. 2. 3. 4. 5. High 5. Discuss considerations for contracting with external compounding services. Low 1. 2. 3. 4. 5. High CONTENT 6. To what extent did this article increase your knowledge of the subject matter? Low 1. 2. 3. 4. 5. High 7. To what extent were your individual objectives met? Low 1. 2. 3. 4. 5. High
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8. Will you be able to use the information from this article in your work setting? 1. Yes 2. No 9. Will you change your practice as a result of reading this article? (If yes, answer question #9A. If no, answer question #9B.) 9A. How will you change your practice? (Select all that apply) 1. I will provide education to my team regarding why change is needed. 2. I will work with management to change/ implement a policy and procedure. 3. I will plan an informational meeting with physicians to seek their input and acceptance of the need for change. 4. I will implement change and evaluate the effect of the change at regular intervals until the change is incorporated as best practice. 5. Other: ________________________________ 9B. If you will not change your practice as a result of reading this article, why? (Select all that apply) 1. The content of the article is not relevant to my practice. 2. I do not have enough time to teach others about the purpose of the needed change. 3. I do not have management support to make a change. 4. Other: ________________________________ 10. Our accrediting body requires that we verify the time you needed to complete the 2.2 continuing education contact hour (132-minute) program: _________________________________
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