A firsthand look at successful USP 797 compliance
Implementation of a compliance program improves pharmacy compounding quality at a major Boston hospital
By Fran McAteer, Microbiology Research Associates; William Churchill, John Fanikos, Michael Cotugno, and Caryn Domenici, Brigham and Women’s Hospital
The pharmacy services department of Brigham and Women’s Hospital (BWH), a major urban hospital in Boston, MA, has initiated a comprehensive USP <797> compliance program, the experiences of which stand to greatly benefit many other hospital pharmacy facilities and managers.
The BWH project began with the development of a detailed project management plan, called a GAP analysis, detailing myriad compliance issues and resulting in the decision by senior management to pursue a proactive strategy for USP <797> implementation. The project set out multiple phases and included a nonbiased expert audit of the hospital’s existing operation. This audit included:
- a comprehensive review of quality documentation
- interviewing compounding personnel
- testing for viable particles
- observing aseptic processing
- monitoring the cleanroom environment
- assessing the facility design
- inspecting training records
- reviewing quality management
Based on the results of the audit, a detailed project list was developed that further subdivided all compliance issues by size, scope, quality impact, and time of implementation. This was then developed into a project management plan and uploaded into the existing GAP analysis, making it a more proactive and focused document, and giving the pharmacy management team an overall customized assessment and implementation plan.
Turning words into action
The first step in the implementation phase was the establishment of environmental monitoring (E/M) capability within the sterile cleanroom where the compounding of sterile preparations (CSPs) would take place. Environmental monitoring standard operating procedures (SOPs) were also developed, including location-specific, sampling-site maps. The maps clustered sampling points around product critical areas.
Microbiological sampling utilized specific media to exhibit both bacterial and fungal contamination, and sampling techniques and frequency were also delineated. Not only did environmental monitoring provide a feedback loop for overall cleanliness and sanitization of the cleanroom, it also provided trending data, which gave BWH pharmacy managers quantifiable performance management tools to help ascertain the quality of the sterile CSP area (see Fig. 1).
One immediate benefit of the environmental monitoring data was the clear demonstration that a stricter gowning policy for CSPs was needed. As a result, in addition to scrubs, booties, bouffants and gloves, gowning was upgraded to sterile, disposable, one-piece cleanroom coveralls. This proved to be a dramatic improvement over the ubiquitous blue scrubs and the new gowning requirements were stipulated in formal quality standard operating procedures.
The CSP staff were trained in the new gowning procedures and gowning proficiency was tested using contact plates at multiple gown sites (hands, forearms, chest). Staff members who passed the gowning tests were certified to work in the sterile CSP cleanroom. The change in gowning procedures immediately impacted the viable particle environmental monitoring and a decrease in microbiological colony forming units (CFU) was observed (see Fig. 2).
In compliance with USP <797>, a formal quality unit for the pharmacy operation was established consisting of the associate director of pharmacy and the sterile product manager. The responsibilities of the quality unit include add-mixture review, environmental monitoring, documentation control, personnel training, final drug testing, and quality procedure enforcement. The quality unit has senior management approval and support, and multiple quality management procedures have been developed for documentation change control, review and approval. The quality unit is responsible for the review and approval of documentation, including all standard operating procedures, add-mixture records, and USP testing results. The quality unit also enforces gowning procedures, cleaning procedures, and environmental monitoring.
Another important element of the compliance program was the requirement that the pharmacy staff undergo USP <797> education and training. On-site training seminars were therefore conducted specific to CSPs and a 24-hour, 7-days-a-week operation. Topics included USP <797> compliance, aseptic processing, cleanroom gowning and environmental monitoring. The seminars are required before compounding activities may begin, and there are periodic updates for new personnel.
A formal cleanroom cleaning and sanitization program was also initiated. Since an outside vendor was used for this service, SOPs were developed for them, which included approved BWH sanitizers, appropriate dilutions, specific contact times for cleaners, application procedures, frequency of sanitizations, and a list of equipment and materials to be sanitized. The validation of the cleaning was conducted at both pre- and post-clean scenarios by environmental monitoring to demonstrate microbial reductions of various areas such as floors, walls, ceiling, laminar flow hoods, and equipment used in preparing sterile preparations. The validation demonstrated a successful cleaning process that adhered to BWH procedures and met acceptance criteria for microbial reduction.
Drug testing of CSPs to strict current USP <71> sterility testing requirements and current USP <85> bacterial endotoxin testing were also initiated. This will be required for CSP in batch sizes greater than 25. Both outside and internal microbiological testing laboratories must also be compliant with GLP/GMP as well as USP <797>. Inhibition/enhancement testing per CSP formulation for USP <85> should be performed initially to validate test results, as well as bacteriostasis and fungistasis validation testing for USP <71> compliance.
Looking ahead, Brigham and Women’s Hospital will continue to build on compliance activities. For example, media fill validation testing has been performed on initial fill equipment (i.e., TPN) to demonstrate consistent sterility, and calibration of monitoring devices such as thermometer and chart recorders will be implemented to show traceability to USP standards.
In summary, the implementation of a USP <797> compliance program has improved overall pharmacy compounding quality. The improvements in technique, training, staff education, standard operating procedures, daily sanitization, and environmental monitoring have created a quality program with proactive performance feedback that enables Brigham and Women’s Hospital pharmacy to provide meticulous patient care in a fast-pace, high-volume setting.
Fran McAteer, MS, MBA, is vice president of Microbiology Research Associates (Acton, MA), a consulting laboratory for USP <797> compliance. He can be contacted at firstname.lastname@example.org.
William Churchill, MS Hospital Pharmacy, is director of pharmacy services at Brigham and Women’s Hospital.
John Fanikos, MBA, is assistant director of pharmacy services at Brigham and Women’s Hospital.
Michael Cotugno is the pharmacy manager at Brigham and Women’s Hospital.
Caryn Domenici, RPh, is the sterile products room supervisor at Brigham and Women’s Hospital.
- United States Pharmacopeia. USP 29, Chapter 797: Pharmaceutical Compounding-Sterile Preparations. Rockville, MD, 2004.