Hospital pharmacies face a stiff challenge as the fallout over the recent meningitis outbreak caused by tainted compounding continues: As scores of other vendors shut their doors because they failed FDA inspections, how does a hospital ensure the adequate flow of crucial admixtures?
One solution is to bring more of the sterile compounding workload back into the hospital. But this strategy has its own risks and challenges, including ensuring United States Pharmacopeia (USP) <Chapter 797> compliance, adjusting staffing and workflow, and building expensive new clean rooms and buying other high-ticket equipment and technologies. Another roadblock: steering clear of the regulatory minefield surrounding beyond-use dating (BUD).
“We all learned from the New England Compounding Center’s situation not to max out beyond-use dates,” said Bernadette Ellegard, RPh, MBA, principal at Ellegard Pharmacy Consulting, LLC, in Kent, Conn. “Hospital pharmacies should take control of batch sizes, make what’s needed for periods of time and not extend use dates as far as possible. Also, account for time out of refrigeration during delivery.”
Such a strategy makes sense, given the increased regulatory scrutiny of compounding that already has been brought to bear. The New York State Board of Pharmacy, for example, has ended batch outsourcing. An established but newly enforced requirement for true patient-specific prescriptions aims to end the practice of pharmacies supplying fake names to outsource centers as placeholders to get product in advance, and later sending in actual patient names, according to Ms. Ellegard. Moreover, the New York board wants the FDA to inspect manufacturers before they can operate in the state, she noted.
For resource-strapped hospitals that decide to meet at least some of the resulting compounding gap by doing the mixing in-house, help is at hand. Ms. Ellegard noted that it is possible to bring in relatively affordable technologies such as semi-automated compounding devices that can be used safely within an ISO Class 5 hood, making it easier for directors to balance patient needs with limited budgets. Such a strategy can help a hospital maintain a viable mix of batch and patient-specific in-house and outsource preparations, she noted.
Ms. Ellegard said she has worked with semi-automated compounding technology for a decade in posts as an assistant director for sterile products and repackaging at Mount Sinai Medical Center, New York City, and until 2012 as a Cardinal Health–contracted pharmacy director at Sharon Hospital, in Sharon, Conn.
Focus on Sterility, Not Production Speed
The more prepared solutions that a pharmacy has on hand with BUD, the more stable its supply and the better it can schedule to maximize workflow. This is necessary with the Gri-fill System 3.0 Compounder (Grifols), for instance, because its deliberate filling processes to ensure sterility take at least a couple of minutes per bag. The 282-bed Sentara Virginia Beach General Hospital, in Virginia, uses the compounder during evenings when the clean room is less hectic. This scheduling also enables technicians to perform required cleaning or do other simple tasks to be productive; they set up each bag and do other tasks while the semi-automated compounder works, explained Rich Grasmick, RPh, the pharmacy manager.
Similarly, Healix ambulatory infusion centers, in Sugar Land, Texas, have “improved staff efficiency by allowing our clinicians to perform other duties while the product is being compounded,” said Brenda Parker, RN, the vice president of nursing. Healix, which has used Gri-fill technology since 2010, now has 15 of the compounders in different sites and plans to add 30 more in the next 18 months. “Using our anti-infective formulary with [Grifols’] Mix Manager software, we consistently produce the same sterile product from one clinician to the next. The technology’s simplicity has streamlined order entry and decreased risk of calculation errors.”
The Gri-fill System meets the USP sterility standard with a 0.22-micron filter pre-attached to a proprietary polyvinyl chloride bag. According to Grifols, it “maintains sterility through media fill validation under worst-case conditions, with over 3,150 prepared doses with no microbiological growth.” The company states that there is “95% confidence the contamination rate is no greater than 0.095%.” For items prepared aseptically with the filter, the probability is one in 1,000 of a nonsterile item “making it through the validated sterilization process.”
Match Extended-Use Dates To Usage Forecasts
The Gri-fill system tests each bag for sterility integrity, indicates immediately if it passes (for BUD) or fails (for short-term use only), and prints a label to be affixed to each bag. Safe usage dates for compounded solutions depend on the inherent stability of the medications and the containers used, as well as the sterility levels achieved during preparation, Ms. Ellegard explained.
Although the system is established for up to a 60-day BUD (in normal room temperature or refrigerated), individual pharmacies may elect not to maximize the shelf life of their products and use the added BUD to enhance the rotation of batch-prepared doses, Ms. Ellegard noted. “Doses stored on shelves maximizing the BUD is passé, and will be frowned upon by inspectors,” she stressed. By comparison, the USP Chapter <797> standard is 30 hours in normal room temperature and nine days refrigerated for medium-risk preparations. Longer dates help pharmacies match supply to usage forecasts.
During her hospital tenure, Ms. Ellegard has used Gri-fill technology across many drug classes such as electrolytes, antibiotics, oncology and controlled substances—about 30 to 40 different medication combinations in all. The Mount Sinai Medical Center pharmacy used it to pool electrolytes from as many as a half-dozen source containers for total parenteral nutrition, to serve an average of 70 adults and 20 neonates daily. “Each bag we pooled was guaranteed sterile,” she said. “This practice enabled us to use one supply container per electrolyte, with the possibility of one change on a busy day … rather than changing a source bag 10 or more times daily. We greatly lessened the chance of introducing contamination.”
Drug Shortage a Factor
At the 73-bed Sharon Hospital, the pharmacy regularly replaced ambulance drivers’ kits. These included dextrose 50% solution (D50) for stat use in diabetes patients with hypoglycemia. During a drug shortage that lasted about two months, the pharmacy used Gri-fill to compound the D50 from D70 and sterile water they had on hand to supply 100% of its needs—not only for the kits, but also for hospital code carts. “That was a big save; we helped about 25 patients with that,” Ms. Ellegard said.In her experience, a fentanyl epidural solution in normal saline that passes the integrity test could be used safely for 30 days at normal room temperature, and so could bupivacaine 0.125% solution in normal saline.
Sentara uses Gri-fill two to three times monthly to batch the sedative midazolam for intensive care trauma patients and fentanyl/bupivacaine bags for postoperative pain management; the preparations can be used safely because of the BUD, so more frequent scheduling isn’t necessary, Mr. Grasmick said. “We always keep most IV technicians trained on the Gri-fill as an advantage.” If not for Gri-fill, technicians would need to replenish the preparations every few days.
Sentara compounds another 70% in-house, up to 150 to 200 compounds daily. These are patient-specific bags that are used quickly. It outsources the rest to PharMEDium, which picked up the slack from Ameridose and, like many large-scale pharmacy compounders, has undergone federal and state inspections in recent months.
Mr. Grasmick said he is concerned that his facility may reach a point where, due to increased regulatory oversight of compounders, their sterile compounding needs from outsourcers may not be fully met. In such a scenario, he said, “we may have to choose between compounding in-house to USP <797> standards or using Gri-fill; we may choose the latter.”
According to Grifols, the Gri-fill system costs about $32,000, and four- and five-year leases are available. Part of its worth is in less medication waste: Products don’t expire as fast because they’re sterile, and technicians don’t have to manually test samples for sterility and then discard the samples. Ms. Ellegard pointed out that “those costs add up with narcotics and oncology products.”