A story in last Thursday’s Washington Post, “Compounding pharmacies have been linked to death, illnesses and safety failures for years,”investigated the track records at three large-scale compounding facilities, two of which compound and repackage sterile medications for hospitals.
Like many stories in the months since the October 2012 meningitis outbreak, this one emphasizes a lack of oversight of compounding pharmacies. The story gives less attention, however, to such facilities’ role in the health care system; practical reasons these facilities don’t adhere to the same regulations as drug manufacturers; and feasible solutions to undeniable problems.
“Sterile compounding pharmacies meet a very practical need of smaller hospitals by aggregating demand and meeting all patient safety requirements,” said Thomas E. Menighan, BSPharm, MBA, ScD (Hon), FAPhA, APhA Executive Vice President and CEO. “There is little disagreement in the pharmacy profession that greater clarity and regulatory oversight are important to protect public health as the primary objective.”
“It’s not a question of if we need [outside compounding facilities]. It’s a question of how we apply the oversight,” said Cynthia Reilly, BSPharm, Director of the Medication Safety and Quality Division of the American Society of Health-System Pharmacists (ASHP).
That’s “the million-dollar question,” Reilly said. “Should these facilities comply with USP [United States Pharmacopeia] <797> or something more like current Good Manufacturing Practices? I don’t think we have all the answers for that yet, but there is a sense that more oversight will be needed on a federal level.”
As described in the Post, hospitals came to outsource sterile compounding after new safety standards proved to be extremely costly.
USP <797> standards require, first, that sterile compounding take place in a clean room—a controlled environment that, when used and maintained correctly, ensures sterile medications remain so. Standards also include environmental testing and specially trained personnel. Hospitals that fail to comply risk lawsuits and loss of accreditation.
Many hospitals find it more cost-effective to outsource sterile compounding—which includes, for example, the preparation of I.V. solutions—to companies whose sole enterprise is sterile compounding than to invest hospital dollars in building, staffing, and maintaining their own clean room.
“A lot of the reason that people turn to external companies is the standards set in USP <797>,” Reilly told pharmacist.com. “You can’t just set up a USP <797>–compliant clean room. It’s physically and financially a challenge, so there is a place for external compounders who have dedicated resources to prepare these products.”
While recent scrutiny of compounding facilities may push some large hospitals to reconsider outsourcing, smaller hospitals are likely to remain reliant on the facilities.
“A small critical-access hospital may not have a pharmacist at night. Outsourcing to a company that is professional and for whom compounding is really their bread and butter may be safer than asking a nurse to prepare something that they don’t normally compound,” said Garrett Eggers, PharmD, who manages inpatient pharmacy operations at Cleveland Clinic.
“For large institutions equipped to do this like the Cleveland Clinic, compounding in-house may be a better option,” he added. “That’s where you have to do a cost-benefit analysis.”
Many hospitals struggle to meet safety standards, according to a 2012 survey on USP <797> compliance in Pharmacy Purchasing & Products. While hospital respondents were found to be 76% compliant overall, a number failed to meet some individual <797> requirements. Tests that ensure staff can don latex gloves without contaminating them occurred at less than half of hospitals. Filter integrity tests were conducted at just 16.7%.
Compounding facilities are not required to test their products in the same way that major manufacturers do because they don't make the same products.
While pharmaceutical manufacturers make mass quantities of drugs that may not expire for 2 years, compounding facilities may produce a single dose of a drug at a time with a shelf life ranging from several hours to months depending on the drug and the formulation.
“If you’re going to do a 14-day sterility test on every single lot of such small batch sizes, you could end up making twice as many doses and reducing the shelf life significantly while you wait for results,” said Mike Koch, BSPharm, MBA, Vice President for Marketing and Support Services at Central Admixture Pharmacy Services (CAPS)—one of the biggest suppliers of outsourced sterile products in the United States. “We use sterility testing in combination with other tests, such as container closure integrity testing and comprehensive clean room and employee environmental monitoring, to prove our processes are capable and in control.”
CAPS was identified in the Post article as being under investigation at its Massachusetts facility by FDA.
There is a nationwide effort to better regulate and understand the activities within compounding pharmacy. What these regulations will look like remains to be seen.
A number of proposals, such as Rep. Ed Markey’s (D-MA) proposed Verifying Legality and Authority in Drug Compounding Act (H.R. 6584), acknowledge the need to distinguish small community compounders—those dispensing directly to individual patients—from large facilities dispensing to hospitals and across state lines, which some consider manufacturing.
“The line has become blurred between compounding and manufacturing,” Eggers said. “Once that line is drawn, the manufacturing side needs to be regulated by the FDA, and if you fall on the compounding side, holding those sites to USP <797>, having more frequent inspections and tighter regulations is important to make sure that the level of quality is there.”