Know What You’re Buying? The Messy World of Compounding Pharmacies.: Paulick Report 7/28/16

By: Natalie Voss

From Dec. 28 to Dec 30, 2015, inspectors from Florida’s Department of Health observed business at Ergogenic Labs in Wellington, Fla., where pharmacist Scott Mangini oversaw the compounding of human and animal drugs. The inspectors were not happy with what they found.

In a subsequent report dated Jan. 5, 2016, they “noted serious deficiencies of state and federal law,” including “filthy conditions in the pharmacy’s clean room,” mislabeled or unidentified drugs on the shelves, and several substances in bottles labeled “Not intended for humans or animals” and “Not for Drug, Household, or Other Uses.” The floor of the pharmacy was so filthy that one inspector was able to write the initials “DOH” with an alcohol swab. The pharmacy, the inspectors wrote, was not conducting tests for sterility or for endotoxin contamination of their products. One report from the Florida Department of Health said employees were washing their hands in a bucket in lieu of a working sink.

“This may present conditions that can affect the safety and well-being for citizens and animals in Florida,” the report concluded. “Severity of the violations listed and the extent of the deficiencies warrant evaluation for emergency action.”

Compounding pharmacies are often used by veterinarians to provide a form of medication that’s commercially unavailable by changing the route of administration (like making an oral paste version of a drug that’s typically injected), adding flavoring, or producing a drug during a manufacturing shortage. Many humans and animals use compounded drugs without incident, but some pharmacies have made headlines in recent years for recurring neglect or making drugs outside the bounds of federal law.

In mid-February, the Florida Department of Health filed a report calling for an emergency restriction on Mangini’s license to operate the pharmacy. Their December inspection convinced them that Mangini had failed in his capacity as the pharmacy’s Prescription Department Manager. Not only had he overseen the shoddy conditions, but he was in charge while the pharmacy compounded an illegal omeprazole drug called UlcerRX using ingredients labeled “not for drug, household or other uses.” The department also alleged he failed to keep a proper audit trail of drugs like furosemide, sildenafil, Procrit, Aranesp, among other substances.

Weeks later, Mangini, a longtime owner in both the Standardbred and Thoroughbred racing worlds, voluntarily surrendered Ergogenic’s Special P/E license, which allowed sterile compounding at the facility, to avoid further sanctions from the Florida Board of Pharmacy. Among other items in the agreement Mangini signed was a promise that Ergogenic would never reapply for a Special P/E license in Florida, and that Ergogenic “agrees to voluntarily cease operating as a pharmacy immediately upon executing this Voluntary Relinquishment.” The surrender was accepted on April 20.

During Kentucky Derby week, Kentucky Horse Racing Commission officials received a report that a non-veterinarian representing Ergogenic on the backstretch at Churchill Downs, hoping to interest trainers in purchasing a compounded ulcer medication, allegedly without requiring them to obtain a prescription.

Despite the filthy conditions described in reports to the Florida Department of Health after the December inspection, Ergogenic Labs remains in operation. The pharmacy still holds a clear community pharmacy license in Florida, which according to state codes, allows it to dispense and sell drugs, and make non-sterile compounds (like oral powders and pastes). The surrender of its P/E license prevents it from legally being able to produce sterile compounds, which include injectable drugs, but does not require the business to close. On May 16, an Ergogenic Labs employee who identified herself only as “Amy” informed the Paulick Report that the pharmacy is operating as normal, and “our license is fine.”

Voicemails left at the pharmacy’s main number requesting additional details about its operation were unreturned.

A troubling history

The pharmacy’s surrender of its Special P/E license wasn’t the first time Ergogenic had been under fire for its practices. In 2014, trainer Bruce Levine filed a civil suit against Ergogenic along with other co-defendants when Levine claimed an over-the-counter paste he purchased to treat exercise-induced pulmonary hemorrhage caused a drug positive. Court documents reveal Levine had the paste tested and found sildenafil in the product, which was not listed as an ingredient on the label. Not only should Ergogenic have known about the presence of the drug in the paste, Levine’s counsel argued, but Ergogenic shouldn’t have been marketing a paste containing a prescription drug to lay horsemen. (Sildenafil is the active ingredient in the erectile dysfunction drug Viagra, buthas previously been connected to anti-bleeder supplements.)

That civil case was settled out of court in June 2015 and did not appear to impact the pharmacy’s license status.

Histories of either civil action or state reprimand against a compounding pharmacy while it remains in operation are not uncommon and too often reveal the unsettling lack of an iron fist in the world of compounding pharmacy regulation. Many consumers assume that if a pharmacy is in business with a valid license, then its products are trustworthy and someone is looking over the pharmacists’ shoulders. But compounders exist in a gray area between the state and the U.S. Food and Drug Administration. States deal with licensing and day-to-day activities, while the federal government can deal with cases of mislabeling, adulterated product, or compounders making copies of mass-manufactured drugs. Experts inside the pharmacy world say many perceive their state authorities as slow to act and federal authorities as relatively toothless.

In Florida, compounders creating sterile preparations must have a special permit and are inspected annually by the state. If a consumer experiences a problem with a compound, they may file a complaint with the board. That complaint must travel through several approvals before an investigation may even begin, let alone sanctions handed down for any violations.

State pharmacy boards license pharmacies and individuals, and most conduct annual inspections of compounding facilities (though one Kentucky pharmacy worker told the Paulick Report that pharmacists are given advance warning when the state will show up for a routine inspection). Although state pharmacy boards have the option to strip a facility or individual of a license, they cannot forcibly close the pharmacy’s doors. More commonly, boards prefer a stair-step approach to discipline in cases where complaints are upheld, the theory being that not all violations are cases of willful neglect.

“Discipline is determined from the facts, and not the mere number of cases,” said Steve Hart, executive director of the Kentucky Board of Pharmacy. “Revocations are reserved for the most egregious of facts, and KRS 315.121(6) authorizes a petition for reinstatement after five years. It would be rare to revoke a licensee after one disciplinary case, but not impossible. For the most part, discipline is progressive.”

The most classic equine example of ‘progressive’ discipline that didn’t work is certainly Paul Franck, the Florida pharmacist who used to own Franck’s Pharmacy in Ocala. Franck’s was the producer of a supplement blamed for the selenium poisoning of 21 polo ponies in 2009. His name cropped up again in 2012 when Franck’s was found to have made a surgical dye that allegedly blinded or otherwise damaged the eyes of 47 human patients.

The polo ponies in Florida dropped dead in April 2009 and Franck’s admitted its error publicly days later, but stiff punishment was not forthcoming. The Florida Department of Health filed a complaint against Franck’s in July, citing several administrative code violations. The punishment: a fine, a reprimand, probation of Franck’s operating permit, and a requirement for continuing education on “medication error prevention.” In December, the Florida Board of Pharmacy reduced the suggested fine and deleted the probation. It took the pharmacy until May 2012, three years after the horses’ deaths, to pay just under $15,000 in fines for the mistake. The pharmacy closed its doors to the public a few months later, and Paul Franck took a new job three miles away.

What about the feds?

The Food and Drug Administration has some authority over compounding pharmacies, but the agency’s enforcement has been spotty and leaves loose ends. Compounders do not have to register with the FDA, but the agency can step in to investigate cases of unauthorized bulk compounding, adulterated compounds, compounds being marketed as copies of existing mass-marketed drugs, and cases of mismatch between a compound’s label and its contents. The safety of the bulk ingredients used by compounders, and the consistency or quality of the final product are unobserved by either the state or the FDA.

The FDA can work together with state pharmacy boards to investigate or initiate action against a pharmacy, but a Government Accountability Office report published in 2015 noted the two don’t always work hand-in-hand. Some states are unable to share results of their routine inspections of compounding pharmacies with the FDA due to their own privacy laws.

The FDA also struggles to gain a sense of how many adverse drug reactions are due to a compound rather than a manufactured drug – the GAO report noted that the FDA form for consumer complaints doesn’t ask whether a compounded drug was involved. Further confusing the issue, the FDA is in the process of overhauling its guidelines on how it will deal with consumer concerns about compounded products (a procedure which has so far spanned many months). In the meantime, it has repealed the old guidelines altogether, leaving employees unsure of what to do.

“Prior to its withdrawal, compliance staff relied primarily on the guide when determining whether the agency would take action,” read the GAO report. “Under federal standards of internal control, agencies are to clearly document internal controls, and the documentation is to appear in … operating manuals.”

Even if an FDA agent appears on a pharmacy’s doorstep, there is no guarantee the agency will learn what’s actually going on inside.  In testimony before a House of Representatives subcommittee, Sally Howard, FDA deputy commissioner for policy, planning, and legislation, cited some 42 compounding pharmacies between 2002 and 2012 that refused to let FDA inspectors inside or provide requested records. That number represented a total of 25 percent of the pharmacies inspected during that time period. The Paulick Report found this spring that 28 of those pharmacies are still in operation today, and 16 of them advertise veterinary compounding on their websites.

If a complaint to the FDA results in discovery of violations, the agency has a handful of responses available, ranging from warning letters to actual legal action against an individual. The GAO report states that the agency doesn’t use any of these options consistently. Since 2003, the GAO report read, the FDA carried out 39 inspections related to complaints about animal compounds, sent out 15 warning letters, requested three voluntary recalls, and taken four legal actions against pharmacies.

A warning letter, industry experts told the Paulick Report, doesn’t pack much of a punch. In the 2014 case of the FDA’s warning letters to marketers of generic omeprazole, FDA representatives indicated that as of late 2015 they had no response from multiple companies receiving those warning letters, and 10 of the 14 products targeted are still available online today. The one company that issued a voluntary recall of its omeprazole compound was Tri-Star Equine Marketing, located a stone’s throw from Ergogenic and owned by Jerry Glantz. Ergogenic’s Scott Mangini was carbon-copied on the FDA warning letter to Tri-Star.

The FDA has made an effort to expand its authority as of late. In the case of Franck’s, the FDA tried to get a preliminary injunction against the pharmacy to stop it from engaging in further animal compounding. A U.S. District Court judge ruled the agency did not have the authority to do so.

“We still find the decision to be extremely helpful for compounding pharmacies in the abstract because it called FDA’s enforcement policy into question,” said attorney Kara Palmer, director at Hyman, Phelps, & McNamara, a Washington, D.C. law firm which specializes in representing food and drug companies. “The FDA had advocated a very broad enforcement authority on animal drug compounders based not on anything specific but on the application itself and the court struck that down. I think the FDA is still in a quandary about what to do about animal drug compounding and does not have an appropriate enforcement mechanism in place.”

The FDA is taking another run at Paul Franck, who was working at Trinity Care Solutions by 2014. That institution recalled all its sterile drugs and ceased compounding after an FDA inspection uncovered dead insects in ceiling panels above the sterile compounding room, along with a host of other violations of cleanliness and safety. On April 29 of this year, the FDA announced that a district court judge had entered an order of permanent injunction against Franck based on his history, preventing him from manufacturing, holding, or distributing sterile drugs until he complies with federal regulation.

What can consumers do?

In the face of the slow churn of government tides, horsemen may want to consider themselves their own best protection against using using dangerous compounds on horses. Fortunately, experts say there are a few things consumers can do to determine whether the pharmacy they’re buying from is operating according to acceptable standards.

Many horsemen purchase drugs from compounders in an effort to save money, but Dr. Dionne Benson, executive director of the Racing Medication and Testing Consortium, said price should be a big “tell”—particularly if the drug you’re buying claims to combine two commonly-used remedies for the same problem, like omeprazole and ranitidine, which both treat gastric ulcers.

“True compounded medications

[that are combinations] should cost more than either medication [on its own] because you should be using two FDA-approved medications,” said Benson. “It’s not so concerning with omeprazole and ranitidine, but with some drugs we don’t know how they play together. They could turn into battery acid, they could make one much stronger, they could make one much weaker, they could cancel each other out and you could be doing nothing.”

The reason FDA-approved versions of drugs are more expensive isn’t price gouging; it’s because the testing process for a new animal drug takes years and tens of thousands of dollars. It also requires regular testing for the sterility of the ingredients and the consistency of the resulting product. Without that, Benson said, trainers and horsemen are running the risk of incurring a drug overage or even worse, poisoning their horse with an incorrectly-formulated compound. A study from the Minnesota Racing Commission found compounded triamcinolone acetate (used for osteoarthritis) that was labeled at a strength of 6 mg/ml but contained only .00828 mg/ml. A study from the University of California-Davis compared compounded formulations of the bronchodilator clenbuterol and found one as high as ten times its labeled concentration, which could be enough to kill a horse.

A close look at the label of a compounded product could also tell a lay person whether the drug has been put together thoughtfully. Authorized medication (including compounds) will have a national identification number (some drugs have NADA numbers, others ADA, NBC, or ANADA) that should correspond to the ingredients inside the drug’s packaging. The FDA also maintains an online “green book” that contains authorized producers of prescription drugs such as phenylbutazone (including generics).

“When you don’t see those, that’s when you should get a little concerned,” said Benson, noting that the most cunning compounders have gotten better at dressing their labels up to look more like mass manufacturers, but are typically missing those indexing numbers.

Insiders suggest that seals of approval from many private organizations professing to certify a pharmacy’s quality are less meaningful than they were a few years ago. The possible exception to this is Verified Internet Pharmacy Practice Sites (VIPPS), which is an arm of the National Association of Boards of Pharmacy. That seal should give consumers confidence about the safety of ordering drugs online.

In the meantime, sources tell the Paulick Report that Ergogenic is still out there, selling a compounded form of omeprazole paste. The pharmacist currently at its helm is a Robert Carl Schwartzman, who was licensed around the time the Florida Department of Health placed an emergency restriction on Mangini’s license (although Mangini is still a “pharmacy affiliate,” according to the DOH website). Schwartzman comes along with his own regulatory history, having been handed a six-month probation in 2001 for failing to report lost or stolen controlled substances from the K-Mart Pharmacy in Ft. Lauderdale where he worked, expired medications, and additional violations.

Erogenic’s website is still active and advertises a lengthy list of sterile animal drugs available for purchase.