1. ISSUE: JUNE2014|VOLUME: 41
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Technology
Insourcing IV Sterile Compounding
by SteveFrandzel
Lorraine Lee,
MHA, BS Pharm
Determined to cement access to reliable and safe sources for crucial IV drug admixtures, a
growing number of hospitals are bringing production of compounded sterile products (CSPs)
in-house and turning their backs on external compounding pharmacies. Such far-reaching
decisions reflect the lingering distrust of outsourced CSPs, according to several
administrators from hospitals that have made this move.
“People were really pulled up short by the events related to the New England Compounding
Center [NECC],” said Eric Kastango, MBA, RPh, FASHP, the president and CEO of Clinical IQ
and formerly a member of the United States Pharmacopeial Convention’s (USP) Compounding
Expert Committee. “Warnings issued by the FDA to other compounding pharmacies have
brought to light a lot of the ugly stuff that was going on.”
That “ugly stuff” included a wide range of manufacturing and quality control issues that
resulted in a nationwide outbreak of severe meningitis cases caused by tainted steroid
injections. To date, about 750 people have developed the infections; 64 have died, according
to federal health officials.
As a result of this massive breakdown in drug safety, Mr. Kastango noted, “hospitals are
looking for strategies to become self-sufficient and vertically integrated, and to decrease
reliance on these vendors.”
A Wake-Up Call To Gain More Control
For some hospitals the decision was, by necessity, sudden. In March 2013, Yale-New Haven
Hospital, in Connecticut, received contaminated magnesium sulfate from a compounding
pharmacy. No patients were harmed, but the incident was a wake-up call, according to
Lorraine Lee, MHA, BS Pharm, the director of pharmacy. “It was much too real because it
happened here, we didn’t just read about it,” Ms. Lee said. “Something had to change.”
The hospital’s multiphase transition to insourcing—still a work in progress—began with cutting
off the pharmacy responsible for the contaminated drugs. Producing enough CSPs internally
then required a 260% increase in staff hours and far greater use of existing infrastructure.
“The bulk of the CSP deficiencies were counteracted without the acquisition
of additional equipment,” Ms. Lee said. Other adjustments included re-
evaluating the use of previously outsourced CSPs. For example, tightening
use restrictions for magnesium sulfate, as recommended by a group of
physicians at the hospital, reduced demand for the drug by 30%. Help also
came from nursing, which increased its use of closed systems that allow
nurses to reconstitute IV drugs in patient care areas safely. Ideally, the
second phase will be to divest all third-party CSPs, including total
parenteral nutrition (TPN) products. The hospital is considering
construction of a new 5,000- to 8,000-square-foot cleanroom at a cost
upward of $1 million. Phase 3 would be construction of a centralized
compounding service to supply all three of the system’s hospitals.
Ms. Lee noted that insourcing changes the equation for beyond-use dating (BUD). One
attraction of outsourcing has been that compounding pharmacies offered extended BUD for
the drugs they ship to the hospital, which potentially reduces wasted doses and allows
hospitals to stock up on high-volume admixtures. But Ms. Lee became skeptical after her
experience with contaminated products. “They tell you they can provide CSPs that have
extended beyond-use dates [without compromising stability or sterility of the products] and
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2. Erasmo A.
Mitrano, RPh, MS
Bill Churchill,
MS, RPh
they have the studies to back that up, but do they really? That’s a big red flag to me now,” she
said.
Hospitals that decide to do a higher percentage of sterile compounding in-house must be
ready to commit to the added time, training and testing necessary to comply with USP
standards for BUD, Ms. Lee stressed. “Operationally, it’s hard to manage and comes at a high
cost, and that’s why hospital pharmacies typically don’t put beyond-use dates on the drugs
they make,” she noted.
Mass General Pivots Quickly
Massachusetts General Hospital (MGH), in Boston, decided to fast-track
CSP insourcing after the FDA shut down Ameridose (a sister company of
NECC) for multiple manufacturing violations in fall 2012. The company,
which delivered about 68,000 doses to MGH monthly, had been the
hospital’s primary CSP supplier, according to Erasmo A. Mitrano, RPh, MS,
MGH’s associate chief of pharmacy. “We needed very quickly to change
gears to take care of patients,” he said.
In the year before the Ameridose closing, the hospital produced about
200,000 CSPs. The following year, insourced production reached 320,000
—a 150% increase, according to Nathan Van Allen, PharmD, the pharmacy
compounding manager. The hefty increase was made possible through increased staffing
(including pharmacy students, overtime and outside agency help) and around-the-clock
operation of compounding facilities. “We’re still using an additional 10 to 12 full time–
equivalent staff positions than we were before,” Dr. Van Allen said, noting that the added
stress on the pharmacy staff has meant increased sensitivity to burnout and health problems.
“We’re still in the middle of this; it hasn’t eased up,” added Mr. Mitrano.
Just as at Yale-New Haven Hospital, the pharmacy leadership at MGH reached out to other
services, particularly nursing and anesthesia, to help fill the vast shortfall. Systems such as
Mini-Bag Plus (Baxter) allowed drugs to be reconstituted safely by nurses outside of a
cleanroom. Anesthesia providers, who had been receiving 13,000 syringes monthly from
Ameridose, began drawing up their own syringes in preparation for—and during—surgery.
“That type of help had an enormous impact and took a lot of weight off our shoulders,” Mr.
Mitrano said.
Making such a titanic transition—either under the gun or more deliberately—requires
tremendous support from hospital administration, Mr. Mitrano stressed. “You must have their
total commitment that this is the way the institution wants to go; it can’t be a partial effort,” he
said.
To keep up the momentum, the pharmacy is undergoing a build-out of its current facility and
has acquired additional IV workstations and robotics, Mr. Mitrano noted. He predicted that
automated production eventually will account for 75% of CSP preparation. “We’ll essentially
have our own compounding facility within the hospital.” Self-sufficiency is getting closer, added
Dr. Van Allen. The hospital now produces about 90% of its CSPs; for now, it will continue to
outsource TPN products.
BWH a Fan of ‘Re-Insourcing’
At Brigham and Women’s Hospital (BWH) in Boston, CSP supply lines were
disrupted to a lesser extent than at other facilities during the IV compounding
crisis, because the hospital had already begun the process of ramping up
internal compounding of IV sterile products, according to Bill Churchill, MS,
RPh, the chief of pharmacy services. Although quality and safety were major
driving forces for “re-insourcing” (the term Mr. Churchill prefers for describing
the hospital’s new direction), so were financial implications. The hospital
projected, and realized, major savings (estimated at $1.5 million; sidebar)
over the past few years, which it attributes to the strategic shift. “Bringing
production inside and having control of our own environment with our own
staff was a much better way for us to go,” Mr. Churchill said.
The hospital also hired a microbiologist to work in the pharmacy department to coordinate all
IV compounding quality assessment, including end-product testing, staff testing and facility
testing, and to assure compliance with USP Chapter <797> standards. All CSP batches are
tested and quarantined until they are confirmed sterile and stable.
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3. “Only after they pass muster with my microbiologist do they move into circulation for patients,”
Mr. Churchill explained. BWH also invested in upgrading on-site cleanroom facilities. Once a
new negative-pressure cleanroom is completed, the existing main cleanroom will be upgraded
and renovated to further increase capacity. BWH also has purchased four IV compounding
robots. A fifth one, dedicated to oncology, is expected in June.
New workflow patterns and staff responsibilities also emerged. The changes were heavily
influenced by lean process redesign, a method for streamlining processes or systems by
eliminating as much waste and unnecessary work as possible. Some pharmacy technicians,
for example, have become automation experts, expanding their skill sets well beyond more
traditional tasks, like drawing up syringes in a laminar flow hood. Additionally, the BWH
pharmacy used to produce CSPs in batches to cover the following 18 hours of use, but that
was not efficient. “Drug regimens change, orders get discontinued, doses get changed. A lot
of the labor and materials expended for long batch runs were being wasted,” Mr. Churchill
said. Now, the restructured workflow, supported by newer technology and greater staff
expertise, allows batches to be produced every four hours. “That was a huge step forward for
us.”
Centralized Compounding?
The pharmacy now produces about 70% of the CSPs used at the hospital—up from about
40% two years ago. Going forward, Partners HealthCare, the umbrella system for both BWH
and MGH, is contemplating the feasibility of a centralized compounding facility to supply all 13
of its hospitals. In the interim, the steps taken have been challenging and progress gradual.
“It’s an ongoing process where you take things in bite sizes that you feel comfortable with,” Mr.
Churchill said. “To make the change, operationalize that change, go back and re-evaluate it,
then continue to evolve your process with the next change until you finally get it where you
want it, takes time and patience. The process simply cannot be rushed.”
—Steve Frandzel
Mass General’s Growing Menu Of Sterile Compounding Technology
Nathan Van Allen, PharmD, the pharmacy compounding manager at Massachusetts General
Hospital, in Boston, offered additional details on the type of sterile compounding technologies in
play at the facility. The systems are ones “we have either added to our operation, are in the midst of
adding or investigating for the future,” he noted:
i.v. Station (Health Robotics). “These will be used for automated mixing and packaging either
by mixing each individual dose separately or repackaging a premixed solution in a repeatable
and controlled environment,” Dr. Van Allen said.
i.v. Soft (Health Robotics). This technology can be used for documenting and verifying the
contents of compounded solutions.
Barcode scanning and point-of-service software. These programs allow for checking of
ingredients before preparation and stepwise checks throughout the compounding process.
Mini-Bag Plus(Baxter). Proprietary system allowing for powdered vial to be attached to diluent
bag on patient floor.
DoseEdge (Baxter). Dr. Van Allen and his colleagues are investigating this for documentation
and verification of solutions.
Biological Safety Cabinets(Baker Co.). Preparation of sterile solutions for packaging,
syringes for robotics automation, specialty preparations, etc.
Baxa Repeater Pump. Semi-automated syringe filler.
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4. At Brigham and Women’s, ASuite Of Robots Lends a Helping Hand
The Pharmacy Department at Brigham and Women’s uses a variety of robotic technologies to
assist in its transition toward bringing sterile compounding in-house. Bill Churchill, MS, RPh, the
hospital’s chief of pharmacy services, said the technologies have significantly boosted workplace
efficiency and patient safety—and saved scarce health care dollars in the process.
Until the latter part of 2013, three primary robotics systems were in use at Brigham and Women’s,
Mr. Churchill noted: Health Robotics’ i.v. Station, which is used to compound batch-prepared drugs,
as well as patient-specific IV bags and syringes; an Intellifill syringe robot, from Baxter, that
prepares bulk batches of ready-to-use syringes (primarily for anesthesia and nursing staff); and
Health Robotics’ CytoCare robot for preparing chemotherapy products.
Bill Churchill observes the IntelliFill robot sort syringes.
Since that time, “in our efforts to continually evaluate our technology, BWH has moved toward
standardizing our robotic technology,” Mr. Churchill said. As a result, “we’ve moved away from the
Intellifill and the CytoCare units, by bringing in two additional i.v. Station robots, and we are awaiting
delivery of an i.v. Station Onco robot that will replace the CytoCare [unit].”
He added that BWH also is using Aesynt’s i.v. Soft Assist system to streamline workflow related to
manual compounding. “This basically helps us to supplement robotic production with manual
processes as efficiently as possible,” Mr. Churchill explained.
The gain in volume and efficiency that occurred as a result of these technologies has been
significant, Mr. Churchill noted. The systems can aid in the preparation of more than 400,000 doses
annually, all of which were previously done off-site and shipped to the hospital at significantly higher
costs, he noted. Moreover, the robots have contributed to approximately $1.5 million in savings, Mr.
Churchill said. The cost savings, he noted, were largely a result of shifting from higher-cost
outsourced products to less expensively prepared products made at the hospital. “The calculation
was a straightforward business analysis that was performed to get approval for the robotic devices,
and then revalidated to prove ROI [return on investment] savings,” he said.
Mr. Churchill stressed, however, that the importance of cost savings pales in comparison to the
safety gains that occur as a result of increased automation. “IV medications that are prepared by
humans are approximate—USP standards allow a range of plus or minus 10% of what the label
amount says, but there can be much greater range of variability in the accuracy of preparation.” He
added that the robots measure these medications not only by volume, but also by specific gravity,
with an accuracy of plus or minus 5%.
“That higher level of accuracy makes a difference for many patient populations, including elderly
[patients], patients with renal or liver disease, as well as neonates and pediatric patients, to name a
few.”
—Steve Frandzel, David Bronstein
More on the Web
To read an expert’s take on the pros and cons of insourcing, “To Insource or Outsource? That Is the
Question!”, visit http://bit.ly/​1lnKIiD.
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