Brigham and Women’s Hospital (BWH) in Boston, Massachusetts, is a leader in the use of bar code verification and automation to enhance quality, safety, and cost-efficiency. In 2008, the BWH pharmacy department became one of the first in the nation to begin using IV robotics technology in the preparation of IV chemotherapy. Thereafter, BWH evolved to a more comprehensive robotics platform and quality framework to insource the compounding of sterile products.
At the present time, BWH prepares about 600,000 sterile products annually; epidural admixtures, TPNs, and some miscellaneous PCA admixtures are outsourced. Our platform includes multiple robotic systems and workflow assistance devices. The shift toward robotic compounding has significantly improved the accuracy of compounded sterile products (CSPs), and the decision to insource certain products has resulted in significant cost savings and a reduction in overall waste.
Introducing a Quarantine Program
Building upon this foundation, the BWH pharmacy department implemented an official CSP quarantine program, monitored by our full-time microbiologist, in August 2013. A key goal of the quarantine program is to safely extend the beyond-use-date (BUD) of certain CSPs to exceed the recommended BUDs in USP <797>; to accomplish this, per USP <71>, all CSP batches must be tested for sterility. A passing sterility test is one that does not incur microbial growth after 14 days of incubation. If a positive sample is identified within the 14-day quarantine period, pharmacy can rest assured that none of the questionable CSPs were administered to patients.
BWH keeps a log of each CSP batch to record the date and time the batch was compounded, the names of the staff members who performed the compounding and verification check, the primary engineering control used, and the lot numbers and expiration dates of the products used, to enable a root cause analysis in the event of a positive sample. With the robust QA program for CSPs at BWH, the failure rate has been maintained at <1%. Albeit a rare occurrence, a root cause analysis and corrective action is performed every time a failed sterility test occurs. It also is important that the personnel or lab performing the sterility tests employ similar quality controls to determine the cause of the contamination if it was not due to a lab error or other human error.
Designating Products for Quarantine
Determining which products can be batch-prepared in advance depends on the needs of the organization’s patient population. BWH primarily includes three types of CSPs in the quarantine program:
To address these three scenarios, it would be appropriate to conduct the testing necessary to support an extended stability BUD. Should the data exist to support an extended chemical and physical BUD, each batch then requires sterility testing per USP <71> stipulations. Currently, USP <797> and <71> do not require quarantining and delaying the use of CSPs prior to receiving the results of the batch sterility tests; however, it is fundamental to understand the implications if any CSP batch is released for patient use before the sterility tests are rendered.
BWH compounds only low– and medium-risk CSPs, and tests every batch that has an extended BUD surpassing the limits outlined in USP <797>. An FDA-registered, ISO 17025 and 9001:2008-certified contract laboratory tests each of these batches for sterility per USP <71>. Then, the products are placed in a controlled quarantine area where they are held until confirmed passing results are published by the contract testing laboratory. BWH pharmacy strongly supports the quarantine process as best practice; it is an added safety check, and it ensures that products are never used before sterility is confirmed.
At the inception of the quarantine program, BWH tested about 20 products on a routine basis, which encompassed about 75 to 100 CSP batches each week. Since then, many changes have been made to optimize the program and to reduce waste as we frequently adjust our processes to better serve patient needs. Currently, we test approximately 40 CSP batches per week.
Multiple staff training sessions and discussions designed to ease the process of integrating the quarantine program into our workflow took place prior to and during program implementation. The quarantine program required significant changes to pharmacy workflow, as pharmacists and pharmacy technicians had to be able to identify the products that required testing, follow the correct process for pulling samples from each batch, and maintain proper documentation. Implementing the quarantine program added approximately 15 minutes per batch to the workflow for non-controlled substances.
Quarantining controlled substances is a more intricate process due to the increased documentation and accountability requirements for these drugs. Further complicating the system is the fact that, due to our space limitations, the secure space we utilize for storing the quarantined products is located on a different floor than the pharmacy. Ultimately, the need to coordinate between the pharmacist, pharmacy technician, and QA microbiologist adds an additional 30 minutes to the process for each batch of controlled substances.
To ensure program success, we determined that a minimum of 2 weeks’ worth of products must be on hand to meet our inventory needs. The USP <71> sterility tests require a 14-day incubation period. As such, we must plan 2 to 3 weeks ahead, since the products are not available for release for at least 2.5 weeks. Key to efficient ordering is purchasing sufficient inventory for both quarantined CSPs and patient-specific orders.
It is not uncommon for space to be at a premium in hospitals, and BWH is no exception; identifying a location to store quarantined products was a significant challenge. Ideally, the quarantined products should be stored in a location completely separate from the released drug products in the pharmacy. To accomplish this, we had to commandeer a coat closet and take down some countertop storage to arrange sufficient quarantine space. Also, because there was insufficient space for additional refrigerators, only room-temperature products currently are included in the quarantine program.
Any organization considering implementing a quarantine program for CSPs produced in-house must consider the costs and benefits of such a program. For example, quantify the volume of products prepared, the number of batches that will be sent out for testing, and the cost of testing. It also might be prudent to compare the cost of testing with an outsourcer’s price per unit; in some cases, outsourcing might be preferable.
Pharmacists need to be able to justify the increased costs of a quarantine program with the decrease in potential waste due to short-dated products. If your institution is close to just-in-time administration for all CSPs, the need for extended BUDs and quarantining may be minimal. However, if you work at a busy institution with limited resources that needs to prepare inventory well in advance, extending BUDs for CSPs might be the best choice to optimize pharmacy operations and decrease waste due to outdated product.
There are countless benefits to implementing a CSP quarantine program, especially at an institution as large as BWH. Although the program has added time and required changes to workflow, the benefits far outweigh the risks. Quarantining CSPs in a controlled quarantine area until confirmed passing results are received gives us control over when a batch is released for patient use, and reassurance that the batch is indeed sterile and safe for administration. If a sterility test should come back positive, we have peace of mind knowing that we can track, trace, and recall every unit produced from that batch and that no patient received the potentially compromised product.
Caryn Domenici Belisle, RPh, MBA, is the director of pharmacy regulatory compliance, quality, and safety at Brigham and Women’s Hospital (BWH). Caryn received her BS in pharmacy from the Massachusetts College of Pharmacy and her MBA from the University of Massachusetts. She is the current president of the Massachusetts Society of Health-System Pharmacists. Caryn’s areas of expertise include USP <797>, sterile product robotic and workflow technology, regulatory compliance, patient safety, and pharmacy operations.
Keely K. Kwok, BS, is the quality assurance coordinator at BWH. She received her BS in both microbiology and food science and technology from the University of Massachusetts Amherst. Keely has an extensive microbiology background, with a strong knowledge in cGMP, GLP, Code of Federal Regulations, and USP chapters <797>, <800>, <71>, <85>, and <1116>. Her expertise also includes cleanroom and aseptic gowning, garbing, and processing standards.