Inspectors from the National Association of Boards of Pharmacy (NABP) and state pharmacy boards descended on six compounding pharmacies in four states during the first two weeks of December as part of a broad, unified effort to bolster the safety of customized medicines being shipped across state lines.

The inspections were carried out in California, New Jersey, Texas and Utah as public and political pressure for increased federal and state regulation of pharmacy compounders continued to mount in the wake of the fungal meningitis outbreak that, by mid-December, had sickened more than 650 individuals in 19 states and claimed nearly 40 lives.

The dual inspection campaign is set to continue well into 2013. It is part of the association’s contractual agreement with the Iowa State Board of Pharmacy to strengthen surveillance of compounding pharmacies licensed by Iowa but located outside its borders.

“We’re moving full bore ahead,” Carmen Catizone, MS, RPh, DPh, the executive director of the association, told Pharmacy Practice News. “The response from the states has been incredible. They’ve said, ‘This is an issue we own and we’re going to move quickly on it.’”

Preliminary findings from the inspections suggest that the New England Compounding Center (NECC), whose tainted methylprednisolone was the source of the meningitis outbreak, is by no means the only pharmacy to compound drugs that are seldom if ever tied to a specific prescription. Four of the six compounders were found to distribute non-patient-specific, preservative-free sterile injectables, which can be at odds with “traditional” compounding—that is, the preparation of medications prescribed in small quantities for specific individuals. Two of the pharmacies produced very large volumes of non-patient specific sterile drugs, Dr. Catizone reported.

The findings have been sent to Iowa, he said, and the state “is going to be making some determinations.” Dr. Catizone praised Iowa’s “innovative” initiative. “They were able to think outside the box and say, ‘We can’t hire staff to do this, but we have the funding and we can use it in a way that gets the outcomes accomplished.’” He said other states were weighing similar agreements with NABP.

The NABP approach—to preserve individual states’ ownership of traditional pharmacy compounding oversight while broadening their ability to monitor nonresident compounders who ship product into their states—appears to cross over into FDA turf, which is oversight of interstate-shipped medications.

The FDA, meanwhile, is pressing Congress for new legislation that will reinforce the agency’s hand in policing practices that go beyond prescription-driven compounding. But some pharmacy sources worry that the FDA’s push for new authority may threaten states’ traditional role and raise the risk for a possible “federalization” of compounding practice. “I am absolutely terrified that the FDA is going to get in the middle of this, and more importantly, I’m more afraid that Congress is going to get into the middle of this and they’re going to muck this thing up,” said Eric Kastango, RPh, MBA, the president and the CEO of Clinical IQ, speaking at the American Society of Health-System Pharmacists’ Midyear Clinical Meeting last month.

Others have raised doubts about whether a budget-minded Congress would allocate funds that the FDA needs to hire more inspectors and expand its national oversight of compounders. The FDA has moved to ease these concerns. In December, agency officials met with pharmacy and health department regulators from all 50 states to solicit input on how federal and state agencies might work together to “close gaps” in the “regulatory framework,” as Margaret Hamburg, MD, the FDA Commissioner, put it.

Pharmacy board officials who spoke at the two-hour FDA public hearing that followed their early meetings at the agency’s headquarters in Silver Spring, Md., expressed confidence in their capacity to regulate compounding pharmacies in their own states, but some said that they were challenged by the difficulty of controlling nonresident compounders. “We know what happens in pharmacies in Arkansas,” said John Clay Kirtley, PharmD, the executive director of the Arkansas State Board of Pharmacy. “We don’t necessarily know about what is happening in specific pharmacies in other states that ship into our state.”

Several board officials noted that insufficient funding often hampers states’ regulatory efforts. Jay Campbell, RPh, JD, the executive director of the North Carolina Board of Pharmacy, said that whereas his board and others in the Southeast region generally have the resources to carry out their missions, others around the country “are dealing with revenue challenges.” He said it was important for state lawmakers to recognize that pharmacy boards must be adequately funded “and not simply be viewed as a revenue stream” for general purposes.

Despite concerns about the potential for federal encroachment on what traditionally has been state regulatory terrain, some board officials saw areas where federal and state collaboration might prevent future public health calamities like the one caused by NECC. Cody Wiberg, PharmD, MS, RPh, the executive director of the Minnesota Board of Pharmacy, suggested that “joint investigations” by the FDA and state boards might be a way to ensure better enforcement of federal and state compounding standards. In most states, he said, pharmacy boards “are regulatory licensing agencies. We’re not law enforcement agencies. We can’t initiate criminal proceedings; the FDA can. In some of these really horrible situations, [that may] get the attention of folks even more” than separate actions by federal or state regulators alone, he noted.

At the federal level, Senate and House committees have launched investigations into the causes of the NECC disaster, laying the groundwork for legislative remedies later in 2013. At least two bills have been introduced in the House. The one gaining the most attention was initiated by Rep. Edward J. Markey (D-Mass.), in whose district NECC’s manufacturing facility is located. Under the bill, most compounding pharmacies that engage in mass production would be regulated by the FDA as drug manufacturers.

ASHP’s Initial Take on Bills

The impact that the Markey bill or other legislative proposals might have on hospital pharmacy was a key point of focus during a late-breaking session at the ASHP’s Midyear Clinical Meeting, titled “A Compounding Tragedy—A National Response.” Joseph Hill, ASHP’s director of federal legislative affairs, said that although the Markey bill seems to provide the FDA with regulatory flexibility, the “core issue” is how to define the point on the continuum of compounding practice where state jurisdiction ends and federal authority kicks in. He said that it was “not so simple” to write legislation that clarifies the definitions of “compounding considered to be under state jurisdiction versus mass production—what people are calling manufacturing but may be potentially a third category.”

Mr. Hill emphasized that ASHP had not yet made any policy determinations. “We want to make sure that when we do go down the road of addressing any regulatory gaps, we don’t have a knee-jerk reaction” and “we’re not cutting off absolutely necessary practices going on in the health systems.”

One such necessary practice that concerns ASHP is anticipatory compounding—the preparation of sterile solutions in advance not for specific patients but based on known usage patterns—for example in a hospital operating room. Mr. Hill said the language in the Markey bill seems to define compounding “a bit more narrowly” when it limits the practice to being “pursuant to a patient prescription” and leaves out the phrase “or in anticipation of a prescription.”

If that definition were included in any final legislation, Mr. Hill said, anticipatory compounding “would not be automatically subject to state regulation,” with the possibility that it could come under FDA purview. However, he noted that the bill does grant the FDA some flexibility to issue waivers to entities to perform certain compounding activities, “such as in anticipation of a patient prescription.”

Addressing the issue of federal versus state jurisdiction, Christopher J. Topoleski, director of federal regulatory affairs at ASHP, said that it might be “useful for the FDA and state boards to collaborate further to identify entities that may be mass-producing and show they are licensed properly and to share information about enforcement actions or disciplinary procedures” not just between themselves but also with the general public.

Mr. Topoleski noted that the agency had asked to be given “full authority to collect test samples of compounded products and ... records in compounding pharmacies, such as prescriptions received, volume of operations and product test results.” He said ASHP was concerned “this new authority would essentially federalize regulation of traditional pharmacy compounding. We believe that this should remain within the jurisdiction of state boards of pharmacy.”

He also said that the FDA “quite frankly does not have the capacity to inspect all compounding pharmacies. Agency collaboration with state boards will be necessary to identify entities engaged in these activities.”

Mr. Hill said that it was vital for ASHP to continue “talking to Congress as well as other stakeholders to ensure that we’re moving forward.” From a lobbyist’s perspective, he added, “one of the things we say a lot is ‘You want to be on the train rather than under it.’”

Who Is To Blame?

As for who is to blame for the NECC disaster, Dr. Catizone said it’s easy to point fingers. However, “every single one of us was responsible for this tragedy,” he stressed. “The regulatory system broke down, the pharmacy compounding system broke down, [and] the collaboration between FDA and the states broke down.” Because methylprednisolone purchasers failed to exercise due diligence, he added, “those transactions [also] broke down.”

In terms of next steps, Dr. Catizone cautioned again focusing too much on the nuances of regulatory policy. “We can’t argue [over the definition of compounding versus manufacturing] for 20 more years,” he said. “Too many patients have been killed. We have to act.” 

Massachusetts Governer Takes Action

The state of Massachusetts is doing its part by proposing tighter regulations on sterile compounding. On Jan. 4, Gov. Deval Patrick said he will be presenting legislation that would include several provisions designed to bolster compounding safety. Under the bill, he noted, compounding pharmacies would have to obtain a special state license that would make the firm's operations more transparent to regulators. Out-of-state pharmacies that ship compounded products into Massachusetts would also have to obtain a state license in order to continue operation, Patrick said. Firms that are found to be in violation of the bill would face stiff fines and penalties. And the bill would include whistleblower protection for workers who come forward with evidence of safety violations.

—Bruce and Joan Buckley