When FDA inspectors made a surprise visit to AnazaoHealth Corporation in Tampa, FL, in February and announced they would be conducting a cGMP (current Good Manufacturing Practices) audit, AnazaoHealth employees were puzzled.
“All pharmacies—and especially pharmacies that do compounding like we do and like most of those other pharmacies that have been investigated—do not follow cGMP regulations; they follow state regulations, which for the most part are driven by USP <795> and USP <797>, which we follow rigorously,” David Joseph, BSPharm, AnazaoHealth’s Director of Pharmacy and Regulatory Compliance and Quality, said in an interview with pharmacist.com.
AnazaoHealth is one of the compounding pharmacies FDA inspected in February through April after the deadly October 2012 fungal meningitis outbreak was traced to tainted steroid injections distributed by the New England Compounding Center (NECC) in Framingham, MA. In response to the media furor and public outcry that followed, FDA conducted surprise inspections and made “observations” related to cGMP requirements at AnazaoHealth and 47 other compounding pharmacies. In April, Rep. Ed Markey (D-MA) released the report “State of Disarray: How States’ Inability to Oversee Compounding Pharmacies Puts Public Health at Risk,” and proposed legislation giving FDA greater authority over compounding pharmacies is currently wending its way through Congress.
All compounding pharmacies, which are regulated by state boards of pharmacy, are required to adhere to the guidelines laid out in the U.S. Pharmacopeia (USP), whereas cGMP standards apply to large-scale drug manufacturers. “One standard is not more rigorous than the other; they’re just different standards,” said Natarsha D. Nesbitt, JD, AnazaoHealth’s Corporate Counsel. On the same inspection visit, noted Samantha Dangler, AnazaoHealth’s Marketing and Public Relations Manager, state authorities accompanying the FDA inspectors did not find any safety deficiencies or issue any warnings.
To AnazaoHealth, the cGMP-based inspections revealed a lack of understanding about the crucial role of compounding pharmacies, which make one prescription at a time for individual patients with special needs—for example, a patient who is allergic to a drug ingredient or an infant who can’t be given the full strength of a drug. “Where are they supposed to get that care if it’s not from us?” asked Dangler.
“We fill a need that can’t be filled by an off-the-shelf product. … [Our] Tampa pharmacy … provides refill medications for people with implanted pain pumps all over the country,” Joseph explained. “These are custom-made cocktails, [and] physicians decide what percentages of certain drugs [go] in these sterile cocktails. They actually go in people’s spinal columns via a pump. So, this isn’t something that a manufacturer could do in any way, shape, or form.”
“We simply can’t automate that process for a one-off,” Nesbitt added. “FDA [is] looking at safety, but they’re also looking to make sure that every time that manufacturer makes that product, that product is the same no matter what. … Those standards can’t in principle or practicality apply to us.”
Joseph explained that the inspection focused on the creation of the preparations and not on “patient care, interaction with patients, drug utilization review, all those things that make a pharmacist a pharmacist and a pharmacy a pharmacy.” AnazaoHealth wants to preserve these functions, Joseph said, because “that’s the key to protecting patients—not only dispensing a safe medication, but all the steps that go behind that in dealing with physicians and patients.”
AnazaoHealth does not operate like some compounding pharmacies that have been dispensing thousands of doses without patient prescriptions and shipping them across state lines, Joseph stressed. “We dispense a lot of prescriptions, and I guess to FDA that might be a problem,” he explained. “We certainly don't fill anything near the prescriptions that a large mail-service or even a CVS or Walgreens fills, but for a compounding pharmacy, we have a fairly large operation. But those orders are custom-compounded medications for individual patients.” Volume parameters should not be the determining factor in oversight decisions, Joseph continued; what should matter is that protocols are in place to protect patients.
“USP <797> is designed to ensure patient safety and still allow those one orders at a time to get out of our pharmacies on a timely basis,” Joseph said, noting that the distinction between cGMP and USP <797> standards isn’t included in the inspection reports.
Dangler and Joseph cited the need for more funding to hire and train qualified inspectors, pointing out that most states have adopted USP <797> standards but require adequate funding to enforce the standards more effectively.
“To be in [the compounding business] successfully, you have to be very highly trained, and you have to have a really good understanding of protocols and how to maintain a facility. [I]n general, [it has been difficult for some] states [to keep] up with this level [of understanding]. Compared to a retail drugstore operation, this is much more sophisticated, so they need to step up and fund inspectors to learn more about this so some of these bad players can be noticed,” Joseph said. “I strongly believe that if [NECC], even at the level they were producing, had been following USP <797> standards, this tragedy would not have happened.”
Joseph emphasized that AnazaoHealth cooperated fully with FDA and has reexamined its operations, including making several improvements as a result of the agency’s inspection.