Among the many surprises that have emerged since a Framingham pharmacy was implicated in a national fungal meningitis outbreak is this one: Hundreds of US hospitals, including most of those in Massachusetts, bought medications from the lightly regulated New England Compounding Center.
Unlike major drug manufacturers, the specialty pharmacy was not regularly inspected or monitored by the Food and Drug Administration, yet prestigious hospitals from Massachusetts General to Yale-New Haven were among its customers, according to a list posted online by the FDA.
Hospitals and pharmacists say companies such as New England Compounding play a critical role in supplying scarce drugs, specialized medications, and individually packaged doses. But over the years, some companies have grown so large that they quietly crossed a line, acting more like drug manufacturers than pharmacies that prepare drugs for individual patients.
"We do think we need to clarify some of the regulations and who is doing the regulation," said Dr. Elizabeth Mort, interim senior vice president of quality and safety at Massachusetts General Hospital. "We want to be part of that conversation, because we're at the delivery end. We want to make sure we have continuous, uninterrupted, high-quality drugs delivered to our patients."
More stringent standards for preparing sterile drugs, which can include everything from injections to eyedrops, helped build demand for compounding pharmacies that specialized in such drugs. Problems at big drug makers have caused shortages of many of the injectable medications hospitals commonly need. And manufacturers do not always make drugs in the individual doses that hospitals prefer to use to reduce the risk of medication errors and contamination.
As a result, hospital pharmacies prepare many of their own drugs, but they also outsource some of the work to pharmacy companies that are licensed and regulated as manufacturers by the FDA, a fact underscored by the flurry of activity to come up with alternate suppliers after Ameridose, the much larger sister company of New England Compounding, recalled all its products this week.
Some hospitals also turn to compounding pharmacies that are not licensed manufacturers for a small portion of their medications.
The reasons include textbook cases of what compounding is: making specialized medicines fine-tuned to the needs of an individual, such as an intravenous medication that could ease the pain of a terminally ill patient. For example, Mass. General would place individual orders with New England Compounding for patients who needed high doses of pain medication, Mort said.
But among the products New England Compounding shipped since May 21 were many that were delivered to hospitals in quantities of dozens to hundreds, according to company records released by the FDA.
At Baystate Medical Center, which regularly ordered injectable drugs in quantities of several dozen at a time, chief pharmacy officer Gary Kerr said it placed orders and would receive drugs the next day. The company, he said, had an uncanny ability to get scarce medications.
"It is difficult for us to understand, us being pharmacy leaders, how they were able to procure particular drugs that I was not able to procure," Kerr said. "But the fact remained they did have things I could not buy."
A 2011 survey by the American Society of Health-System Pharmacists found that 71 percent of the more than 500 hospitals that responded said they outsourced some or all of their drug preparation activities, although it did not ask whether they used compounding pharmacies or manufacturers.
Several local hospitals reported that they relied on compounding pharmacies for only a small number of drugs.
Brigham and Women's Hospital outsources 20 percent of its sterile drugs. Of those, less than 2 percent were outsourced to New England Compounding; the rest were bought from Ameridose and CAPS, another company licensed as a manufacturer.
Tufts Medical Center said that about 1 percent of 2 million doses of medication administered annually are procured from a compounding pharmacy.
Many hospitals turn to such pharmacies because they can prepare doses of a drug that can sit on the shelf longer. Compounding pharmacies are more likely to invest in testing intended to ensure the potency and sterility of a drug over a long time span.
Tufts and Brigham and Women's said they both used New England Compounding's cardioplegic solutions, used in cardiac surgery, because of their longer expiration dates.
A shift in recent years to using drugs in single-dose packaging and with barcodes, both designed to reduce medication errors and contamination, contributed to hospitals' need to outsource drugs.
Strict guidelines for preparing sterile drugs, written in 2004 by the US Pharmacopeial Convention, a nonprofit that sets requirements for drug compounding, also led hospitals to rely on external companies.
Hospitals also said they use compounding pharmacies to fill drug shortages, which have increased in number and length.
"The irony is you have these people who are subject to far less stringent regulation jumping into the breach and producing . . . an inferior product," said Frances Miller, a professor at Boston University School of Law, referring to the New England Compounding injectable steroid blamed for the meningitis outbreak.
When hospitals ordered in bulk from New England Compounding, they were not always required to provide individual patient prescriptions. A Mass. General pharmacist said the hospital was told by New England Compounding to order cardioplegia solution and retain the names of individual patients who received the drug.
"We would have them on file, ready at any time to send" to the company or to regulators, said Margaret Clapp, chief pharmacy officer at Mass. General. To avoid patient privacy and confidentiality issues, the information would not be transferred unless it was requested.
Kerr of Baystate said his hospital complied with the requirements set forth by New England Compounding, which did not demand prescriptions for each dose.
"This is where you run into a grey area in the law," said Bona Benjamin, director of medication use quality improvement at the health system pharmacists group. Pharmacies are allowed, she said, to make a small amount of extra drug in anticipation of patient need, so that there is sufficient drug on hand for patients.
But, she added, "when you get into preparing thousands and thousands of prescriptions in anticipation, then you run into problems with mass production and inadequate quality control. I think it's here where we need some clarification around where you cross the line between compounding and manufacturing."