Development and Implementation of a Standardized Sterile Compounding Training Program

Abstract

Purpose: The purpose of the study is to develop and implement a standardized sterile compounding training program in a multihospital system that incorporates sterile compounding best practice recommendations and ensures compliance with United States Pharmacopeia (USP) Chapters 797 and 800 standards. Methods: Baseline sterile compounding training data were collected and reviewed for sterile compounding facilities across a multihospital health system, which included 37 distinct sterile compounding operations. Current sterile compounding personnel across the system completed preintervention assessments consisting of a written, knowledge-based exam; media-fill challenge test; and an observed assessment of aseptic technique. The personnel then completed refresher training of sterile compounding concepts by completing online and in-person courses. A postintervention assessment was then conducted to evaluate training methods and topics. Based on the intervention data, a training program for new sterile compounding personnel was developed and implemented. A program to provide annual, ongoing training to existing sterile compounding personnel was also developed and implemented. Results: There was a statistically significant improvement in sterile compounding written exam scores (P < .0001) and aseptic technique observation scores (P < .0001) after implementation of refresher training. The validated training program was then included in the development and implementation of standardized training for all new and existing sterile compounding personnel across a multihospital health system. Conclusion: A standardized and consistent, sterile compounding training program was developed for all new and existing sterile compounding personnel incorporating a live, in-person training course, as well as online and hands-on training.

The United States Pharmacopeia (USP) General Chapter 797 was first introduced in 2004 to provide guidance to pharmacies on quality standards for compounding sterile preparations.¹ The purpose of the chapter is to promote safety and prevent patient harm by ensuring sterility and accuracy of all compounded sterile preparations (CSPs). Failure of compounding personnel to follow quality standards and best practice recommendations introduces the greatest risk of contamination and therefore appropriate training of personnel is of high importance.^1-4 With increased scrutiny and focus on sterile compounding training with the anticipated release of updated USP Chapter 797 and USP Chapter 800,^1,5 sterile compounding facilities are required to develop and implement robust tools, processes, and assessments to ensure safe and adequate training of compounding personnel. A critical component of any sterile compounding operation is the design and implementation of a comprehensive, didactic, and hands-on instruction and assessment of personnel involved in compounding sterile preparations.⁴

Background

Published reports describe fatal and nonfatal consequences resulting from contamination or accuracy errors during compounding of sterile preparations.^6-9 Trissel and colleagues found the contamination rate of media-fill simulations done by pharmacists and technicians was 4.4% and 6.2%, respectively, likely through inadvertent touch contamination.¹⁰ Flynn and colleagues conducted an observational study of the accuracy of intravenous (IV) admixture compounding at 5 US hospital pharmacies which resulted in a mean overall error rate of 9%.¹¹ From this study, a CSP was deemed to have been prepared in error if it met any of the following criteria: use of an unauthorized drug, wrong dose, wrong base solution content or volume, omission of a component, wrong form of delivery, incorrect reconstitution procedure, or wrong preparation technique. Sterile compounding requires highly skilled and knowledgeable compounders; thus, pharmacies must ensure adequate and sufficient training is provided to all personnel.³

Most colleges of pharmacy do not provide sufficient sterile compounding didactic or laboratory training for pharmacy students.^3,4 A 2005 survey studied the extent of didactic and laboratory instruction related to CSPs. A total of 53 responses from US school of pharmacy deans showed only 70% of those schools required students to compound individually and only 21% offered a stand-alone sterile compounding course.¹² Pharmacy technicians also must be trained sufficiently in sterile compounding. Currently, some, but not all, pharmacy technicians may graduate from a pharmacy technician training program, which may include sterile compounding education.³ Sterile compounding training done within the workplace is usually more skill-focused rather than knowledge-based.³ External vendor resources such as training videos, workbooks, online and in-person learning courses and certificates are available to aid facilities in training.^13-20 These resources, however, lack the organization-specific training processes required for compounders to fully achieve competency and safe practices within an organization’s daily practice. In addition, these can be cost-prohibitive for training all sterile compounding personnel. Therefore, each facility typically develops and implements an internal training program that recognizes all skill sets and educational levels.^1,3

USP Chapter 797 requires sterile compounding training programs to include (1) didactic review with written examination, (2) a media-fill assessment, and (3) competency-based skill assessments of sterile compounding duties, such as accurate garbing and aseptic technique.^1,4 Previous literature on school of pharmacy curriculums describe topics of sterile compounding instruction to include (1) hand-hygiene and garbing; (2) determination of beyond-use dating (BUD) and labeling; (3) calculations; (4) requirements of USP Chapters 797 and 800; (5) engineering controls, facility design, and cleaning; (6) working with syringes and needles; (7) preparation of parenteral nutrient solutions, hazardous drugs (HDs), and ophthalmic compounding; (8) documentation; (9) environmental monitoring; (10) proper use of tubing, pumps, and technology; and (11) theory and practice of aseptic technique.^12,21,22 Proper aseptic technique instruction is fundamental in preventing contamination of CSPs but requires practice and repetition to master.⁴

Aurora Health Care (AHC) recognized a need to provide a standardized sterile compounding training program across the health system, which included 37 distinct and dispersed sterile compounding operations. A standardized training program could streamline the approach for training to create efficiencies and improve outcomes in each site’s process with the goal to reduce staff practice variability. In addition, a standardized method provides system-focused guidance on tool development and implementation to promote advancement of a sterile compounding safety culture. The objective of this initiative was to develop and implement a standardized and validated sterile compounding training program across a multihospital health system that incorporates sterile compounding best practice recommendations and ensures compliance with USP Chapter 797 and 800 standards.

Methods

Setting

This work was conducted within AHC, an integrated health care system located in eastern Wisconsin. Sterile compounding occurs at 15 of the 16 hospitals and within 22 specialized cancer-care clinics. Previously, each facility developed and implemented their own sterile compounding training for personnel at their site, including development and execution of ongoing competency assessments. In 2016, a system-wide work group was established to address the needs and resources required for AHC compounding facilities to achieve compliance with the new USP Chapter 800 standards and review compliance with USP Chapter 797 standards. The work group reviewed data provided by all sterile compounding facilities and completed site walk-throughs to analyze current processes and methods for compliance with USP Chapters 797 and 800.

Baseline data on each sterile compounding facility’s training were collected and reviewed and revealed different methods, tools, and time frames used for training. Observations and data suggested that training among sterile compounders was inconsistent and, therefore, skills and knowledge varied across sites. Providing consistent training to personnel would ensure essential knowledge is delivered and that proficient aseptic technique skills are consistently performed. The institutional review boards from AHC and Concordia University Wisconsin reviewed this study and considered it exempt.

From June through September 2016, each facility identified site-specific sterile compounding super-users. The assigned super-users attended a live, 1-day refresher course to review key concepts related to USP Chapters 797 and 800 and sterile compounding best practices outlined per recommendations provided by American Society of Health-System Pharmacists,^23,24 Institute for Safe Medication Practices,²⁵ CriticalPoint® Sterile Compounding Boot Camp and pearls, and sterile compounding texts.^26-28 The course also provided a review and practice of aseptic technique skills. The super-users received, reviewed, and discussed expectations associated with completion of an aseptic technique rubric and media-fill challenge test. Once back to their respective sites, super-users were to distribute information and perform evaluations of sterile compounding personnel within their facility.

Preintervention

From August through November 2016, sterile compounding personnel completed 3 preintervention assessments: (1) written, sterile compounding knowledge-based exam; (2) media-fill challenge test; and (3) an observation assessment of aseptic technique utilizing an aseptic technique rubric (done in conjunction with the media-fill challenge test). The written assessment comprised of 30 questions related to 5 topics: sterile compounding calculations (n = 5), compounding equipment and supplies (n = 6), facilities (n = 9), aseptic technique (n = 7), and assignment of BUD (n = 3). The media-fill challenge test procedure was developed to create complexity and repetition, ultimately requiring the compounder to complete a series of 14 steps. As AHC also utilizes closed system transfer devices in HD sterile compounding, a HD media-fill challenge test was also required for HD personnel. Personnel responsible for both HD and non-HD sterile compounding completed both types of media-fill challenge tests. Observation of aseptic technique was completed by a super-user utilizing an aseptic technique rubric. The aseptic technique rubric was completed during each media-fill challenge test and consisted of 14 different competency criteria marked as pass, fail, or not applicable. The aseptic technique rubric is available in Supplemental Appendix A and the written exam is available in Supplemental Appendix B.

Refresher Training Intervention

Following completion of the preintervention assessments, current sterile compounding personnel participated in the refresher training intervention, which was completed November 2016 through February 2017. The purpose of refresher training was to review pertinent sterile compounding information and proper aseptic technique to standardize sterile compounding knowledge and expertise across the health system. Refresher training required completion of a 1-hour online review of sterile compounding-related calculations, a 30-minute online review of BUD assignment, and a 1-day, in-person refresher training course which included hands-on review of aseptic technique and major knowledge-based concepts within USP Chapter 797. For personnel practicing at sites with a compounding aseptic isolator (CAI), there was an alternative 75-minute online refresher training course in place of the in-person training course. Personnel responsible for HD sterile compounding reviewed additional material specific to USP Chapter 800 content. All online training modules were developed for and completed through AHC’s electronic teaching platform software. The activities and requirements of refresher training interventions are summarized in Table 1.

Table 1.

Summary of Refresher Training Interventions.

Topic	Required for	Method	Content	Duration
Calculations	All sterile compounding personnel (n = 262)	Online	Ratios/proportions, dosage calculations, dilution, concentration and percentage strength, displacement volume, flow rates, and alligations	1 hour
Beyond-use dating	All sterile compounding personnel (n = 246)	Online	Risk levels, expiration date, beyond-use date, stability, immediate-use products	30 minutes
Refresher training course	Sterile compounding personnel who compound in a CAI (n = 199)	Online	General: Introduction to parenteral preparations, influences of contamination, compounding environment and engineering controls, compounding equipment, garbing and gloving, aseptic technique, and quality assurance	1.25 hours
			CAI specific: Parts of the CAI (gloves, sleeves, airlock chamber, inner chamber, pressure gauge), filtration, cleaning, and disinfecting
Refresher training course	Sterile compounding personnel who compound in laminar flow hoods (n = 90)	In-person	General: Introduction to parenteral preparations, influences of contamination, compounding environment and engineering controls, compounding equipment, garbing and gloving, aseptic technique, and quality assurance	4-6 hours
			Activities: Sterile compounding practice questions and example calculations, product manipulation with demo vials and ampules, aseptic technique validation
			HD specific: Introduction to USP Chapter 800, exposure risk, engineering controls and compounding environment, garbing and gloving, and storage

Note. CAI = compounding aseptic isolator; HD = hazardous drug; USP = United States Pharmacopeia.

Postintervention

From March through June 2017, after completion of refresher training interventions, postintervention assessments were completed. Postintervention assessments consisted of the same 3 assessments conducted during the preintervention phase including (1) written, knowledge-based exam; (2) media-fill challenge test; and (3) an observed assessment of aseptic technique.

Results from preintervention and postintervention assessments were collected and scored. The 30-question, written exam was graded with a total score of 30 and final scores represented as percentage correct. A passing score was that of 80% or greater. In addition, results were separated and analyzed based on question-specific topics. Media-fill challenge test results were documented as either positive or negative based on evidence of microbial contamination after incubation. To pass, the test had to be negative or clear of any microbial contamination. The aseptic technique rubric utilized during the media-fill challenge test was marked with pass, fail, or not applicable for each of the 14 competency criteria listed. The rubric must have had a total of zero fail marks to successfully pass. The media-fill results and aseptic technique rubrics were collected with individual personnel identification. If available, media-fill results were matched accordingly with individual aseptic technique rubrics.

Statistical Analysis

A chi-square test was used to determine whether there was a difference in the written exam pass rate preintervention and postintervention for the overall exam, as well as within each subsection of questions. In addition, the average percentage of correct answers was examined preintervention and postintervention using the t test. Again, this was conducted for the overall exam and within each subsection of questions. For the 51 matched pairs, McNemar test was utilized to determine whether there was a difference in the preintervention and postintervention pass rates for the media-fill challenge test and aseptic technique observation combined. Finally, the chi-square test was used to determine whether there was a difference in pass rates preintervention and postintervention for aseptic technique observation, including those that were nonmatched. The priori level of statistical significance for all comparisons and hypothesis tests was 0.05.

Results

A total of 236 written exams were collected and scored during the preintervention phase and 150 exams in the postintervention phase. The average percentage correct on the written exams for the preintervention and postintervention phase was 65.2% and 74.8%, respectively (P < .0001). The overall exam scores, as well as scores in each question category, showed a statistically significant improvement, demonstrating increased retention of sterile compounding knowledge (Table 2). The number of personnel with passing scores in the preintervention phase was 46 (19.6%) and in the postintervention phase was 68 (45.3%; P < .0001) (Table 3). A passing score was that of 80% or greater on the written exam.

Table 2.

Preintervention and Postintervention Written Exam Scores, Including by Question Subsection.

	Average percentage correct, % (95% CI)		P
	Pre (n = 236)	Post (n = 150)
Overall	65.2 (63.3-67.1)	74.8 (72.7-77.0)	<.0001
Calculations	73.7 (70.3-77.1)	84.9 (81.1-88.7)	<.0001
Compounding equipment and supplies	71.6 (68.8-74.3)	79.3 (76.1-82.5)	.0004
Facilities	56.7 (54.5-59.0)	63.6 (60.9-66.3)	.0001
Aseptic technique/compounding	68.8 (66.1-71.4)	76.1 (73.2-79.0)	.0004
Assignment of BUD	55.2 (51.9-58.4)	79.8 (75.8-83.8)	<.0001

Note. CI = confidence interval; BUD = beyond-use dating.

Table 3.

Preintervention and Postintervention Written Exam Pass Rates, Including by Question Subsection.

	Pass rate (%)		P
	Pre (n = 236)	Post (n = 150)
Overall	19.6	45.3	<.0001
Calculations	55.7	80.0	<.0001
Compounding equipment and supplies	46.8	65.3	.0005
Facilities	6.0	10.7	.1182
Aseptic technique/compounding	38.7	51.3	.0157
Assignment of BUD	11.9	52.0	<.0001

Note. BUD = beyond-use dating.

The media-fill challenge test was completed by 144 sterile compounding personnel in the preintervention phase and 70 in the postintervention phase. There was 1 media-fill test result from the preintervention phase and 3 results from the postintervention phase that had evidence of microbial contamination. Along with these media-fill challenge tests, there was a total of 133 aseptic technique rubrics collected in the preintervention phase and 64 in the postintervention phase. There was a statistically significant increase in pass rates on the aseptic technique rubrics between the preintervention and postintervention data (32.3% and 89.1%, respectively; P < .0001) (Table 4).

Table 4.

Preintervention and Postintervention Pass Rate of Aseptic Technique Observation.

	Pre (n = 133)	Post (n = 64)	P
Pass rate (%)	32.3	89.1	<.0001

There were a total of 51 matched pairs between the preintervention and postintervention group, meaning that 51 individuals completed media-fill with aseptic technique observation for both preintervention and postintervention phases with results appropriately documented and collected. A combined passing result consisted of no evidence of microbial growth and zero fail marks on the aseptic technique rubric. There was a statistically significant difference between preintervention and postintervention pass rates between the matched pairs (56.9% and 88.2%, respectively; P = .0002) (Table 5).

Table 5.

Results of Media-Fill With Aseptic Technique Evaluation for Matched Pairs Only.

		Post			P
		Fail	Pass	Total
Pre	Fail	6 (11.8%)	16 (31.4%)	22 (43.1%)	.0002
	Pass	0 (0%)	29 (56.9%)	29 (56.9%)
	Total	6 (11.8%)	45 (88.2%)	51

New Sterile Compounding Training Program

Based on preintervention and postintervention data, a new sterile compounding training program was developed, incorporating aspects from refresher training such as an in-person, interactive training course; new online learning modules; and repeated evaluations of proper aseptic technique. New sterile compounding personnel will be trained through this program with the focus on their repeated demonstration of skills rather than the amount time spent in training.

Training begins (step 1) with the new sterile compounder attending a 2-day, in-person, interactive training course that provides information from USP Chapters 797 and 800 and sterile compounding best practices. The didactic instruction includes topics in (1) background and purpose of USP Chapters 797 and 800, (2) dosage form review, (3) importance of sterility, (4) environment, (5) aseptic technique, (6) compounding equipment, (7) cleaning and disinfecting, (8) garbing, (9) stability considerations, (10) quality assurance, (11) calculation review, and (12) handling of HDs. In addition, the training course provides hands-on practice of aseptic technique fundamentals. Once this training course is completed, all further training is completed at the respective site utilizing standardized training tools and assessments. To progress through training, the new compounder must consistently demonstrate proper knowledge and skills necessary to perform aseptic manipulations independently.

The first part of site-based training (step 2) begins with peer observation; this is to gain an understanding of workflow and staffing responsibilities. This is an appropriate time to complete introductory competencies, online learning modules, and competency-based requirements, as dictated per USP Chapter 797, such as gloved fingertip sampling and media-fill challenge test. When successfully completed, the compounder begins compounding preparations by practicing proper aseptic technique with constant observation and assistance offered by the site trainer.

While under observation, the compounder must successfully compound 80 preparations utilizing vials in the compounding recipe and 20 preparations utilizing ampules. The compounder must demonstrate proper aseptic technique with each individual manipulation. In this step, the trainer would offer assistance or advice throughout each manipulation and product preparation. Once the new compounder has successfully completed the specified number of manipulations and properly prepared products for patient use, it is appropriate to move onto the more advanced level of training.

The next step (step 3) is designed for the compounder to gain independence in sterile compounding practices. During this step, all compounding is assessed, again utilizing the aseptic technique rubric; however, the trainer is no longer allowed to offer assistance or suggestions during the compounding process. The compounder must independently and successfully compound 20 preparations with vials and 10 preparations with ampules, demonstrating proper aseptic technique with each CSP. If there is concern at any point during training over preparation sterility or aseptic technique, the CSP will not be dispensed for patient use. Once the new compounder has successfully completed the specified number of CSPs and has consistently received passing marks on the aseptic technique rubric, it is appropriate to move onto the final step of training.

The final step (step 4) of training is staffing a minimum of 2 work shifts with the designated site trainer offering observation and assistance as needed. The compounder will also need to complete the written assessment with a passing score of 80% or greater. The completion of training will then allow the new sterile compounding personnel to staff without trainer supervision and continue to demonstrate learned knowledge and skills on all annual reassessments thereafter.

The newly developed training program also outlines annual requirements for assessment, evaluation, and training as required per USP 797 and 800 for current sterile compounding personnel. Annual competencies include a didactic review and assessment, media-fill challenge test, observation of aseptic technique, garb and hand hygiene, and gloved fingertip sampling. All personnel must undergo annual assessment to continue compounding sterile preparations for patient use. Also described are expectations on how to properly retrain and reevaluate any personnel in the event of a failed attempt of the required annual assessments.

Discussion

The majority of existing sterile compounding training typically focuses more on skill rather than knowledge.³ The development of this training program focused on both skill and knowledge because sterile compounding practices require highly skilled and knowledgeable compounders; failure of compounding personnel to follow quality standards and best practice recommendations introduces the greatest risk of contamination.^1-4 Inconsistencies in training are seen across sterile compounding facilities, and this was evident within a large, integrated health system. The development of a standardized training program helped to streamline training, as well as provide guidance, tools, and continued focus on advancing sterile compounding safety.

Training programs must ensure consistent, initial, and ongoing instruction of sterile compounding personnel. There is currently a lack of sufficient literature on the development of sterile compounding training programs; therefore, further guidance, support, and innovation are necessary to ensure safe sterile compounding practices. Previous studies demonstrated that repeated testing improves retention and skills,^29,30 which may help aid in aseptic technique training and retention. Begley and colleagues studied repeated testing of skill-based activities essential to professional practice in pharmacy students. Student scores on sterile product verification improved significantly over 3 assessments but then plateaued, demonstrating the students’ mastery of the skill.²⁹ Larsen and colleagues demonstrated that repeated testing with feedback resulted in significantly greater long-term retention of medical education compared with repeated, spaced study.³⁰

With increased scrutiny and focus on sterile compounding training with the anticipated release of revised USP Chapter 797 and USP Chapter 800,^1,5 this newly developed training program meets all necessary and required components to properly train and assess sterile compounding personnel. This training, most importantly, places a renewed focus on patient safety. In addition, the emphasis on training was to assess knowledge and skill repetitively with movement to the next training level dependent on these assessments, rather than on time spent in training.

The preintervention and postintervention phases assess 3 key elements USP Chapter 797 requires for sterile compounding training programs: (1) didactic review with written examination, (2) media-fill assessment, and (3) competency-based skill assessments (ie, aseptic technique).¹ The 5 main topics of the written exam were all reviewed in the didactic portion of refresher training and are in line with topics within USP Chapter 797 and sterile compounding texts.^1,26-28 The media-fill challenge test and aseptic technique observation were evaluated to determine whether the hands-on training was valuable to sterile compounding personnel. Because scores overall were low in the preintervention phase and significantly improved during the postintervention phase, topics and techniques covered in refresher training were considered beneficial and, therefore, incorporated into the new training program.

There are limitations to discuss in relation to this study. It was challenging to monitor and track the status of each compounder throughout the training process due to the size of AHC and the large volume of sterile compounding personnel across the system. This was further complicated by the short completion time frame window for each step and assessment to be accomplished. All site directors were consistently made aware of each phase of the intervention and were given approximately 3 months to complete each (preintervention, refresher training, and postintervention). Depending on priorities within each site, this may have affected the total completion rate, which was noticeable during the postintervention time window.

Ideally, each media-fill challenge test would have had an aseptic technique rubric completed in conjunction with it and those results should have been submitted together for each individual. There may have been a misunderstanding across sites as to what exactly was required to be completed and submitted for data collection. Looking at the overall results of media-fill challenge tests, it was evident that there were more failed media-fill challenge tests in the postintervention phase compared with the preintervention phase. A few of the failed tests did not have observation rubrics submitted with them to determine whether a breach in aseptic technique or other factors contributed to the failed result. Also, 2 of the media-fill test failures in the postintervention phase did not have a matched pair in the preintervention phase to compare.

Observation of aseptic technique with the validation rubric was completed by various personnel across the system and within each site, although it was set up to done by the site super-user previously trained. As this assessment was evaluated by multiple users, this may have led to inconsistencies in how each individual was evaluated. However, as the pre-aseptic and post-aseptic technique observation results were so dramatically different, it is unlikely this affected the validity of the results.

Conclusion

A standardized and consistent, system-wide sterile compounding training program was developed for all new and existing AHC personnel incorporating a live, in-person training course; online; and hands-on training. This training program has demonstrated improvement in sterile compounding knowledge and skills across the system.