Trade group told compounding pharmacies how to skirt the FDA
The trade group representing compounding pharmacists, like the one that made a drug linked to the recent outbreak of meningitis, tutored pharmacists on how to sidestep requests by the Food and Drug Administration worried that compounders across the country might be selling a substandard drug, possibly made with Chinese ingredients.
The New York Times
A year before people began dying of meningitis caused by a tainted drug from a compounding pharmacy in Massachusetts, the Food and Drug Administration worried that compounders across the country might be selling another substandard drug, this one possibly made with Chinese ingredients.
But when the FDA began seeking samples to test, the trade group representing compounding pharmacists went on the offensive. Instead of encouraging members to help the agency determine if the injectable drug, used to reduce the risk of premature birth, was substandard, the group tutored pharmacists on how to sidestep requests.
In an email to members, the International Academy of Compounding Pharmacists suggested they respond to any request for samples by saying: "We do not compound or distribute 'samples' of any of our prescription medications to anyone." And if a compounded drug were on the premises, the trade group added, a pharmacist should say it was awaiting pickup by a patient.
A spokesman for the trade group said the instructions were intended to guard against unauthorized release of samples to corporate competitors and not to hinder the FDA investigation. But the memo is emblematic of the industry's frequent and often successful attempts to fend off regulators at a time when concerns are growing about the quality of compounded drugs and the uncertain provenance of their ingredients, some of which originate in China and flow through various repackagers and middlemen with little extra scrutiny, according to interviews with health experts and government records.
Drugs made by compounders — who mix or alter ingredients to create customized medicine for a specific patient — are rarely tested, unless someone is harmed or a complaint is filed. In Texas, a hub of compounding pharmacies and one of only two states that randomly test compounded drugs, random tests by the state's pharmacy board over the last several years found that as many as one in four compounded drugs was either too weak or too strong. The testing results are just slightly better in Missouri, the other state that randomly tests. Potency varied by as much as 300 percent in the Missouri tests.
And records of FDA drug seizures at U.S. borders, as well as several criminal cases, point to a link between drug compounders and Chinese manufacturers, some not registered with the FDA. Records analyzed by The New York Times show that in 62 cases over the last decade, the FDA blocked the importation of drugs for use in compounding; nearly half were from China, one of the largest producers of raw pharmaceutical ingredients, where many manufacturers operate outside the regulatory net.
The FDA said Friday that investigators did not believe the original ingredients used by the Massachusetts pharmacy, the New England Compounding Center in Framingham, were the source of the crisis unfolding in 16 states, where at least 297 people have contracted meningitis and 23 have died. (Authorities have yet to disclose the name or location of the compounder's supplier or suppliers.) Those affected had been treated for back and neck pain with contaminated steroid injections produced at the compounding center.
Modern supply chains are a maze of importers, repackagers and dealers. But while large drug companies, bound by FDA rules, must keep meticulous track of who has handled their raw materials, compounding pharmacies are not bound by those guidelines, even though some have grown so large that they resemble commercial manufacturers.
Michael Chappell, a former high-ranking FDA official who helped to oversee the agency's regulatory policies, said federal officials have had difficulty at times getting answers to questions about where compounders bought their ingredients.
"Is it being repackaged in the back of a '57 Buick in a parking lot somewhere?" Chappell asked. "The answer was always, 'We get them from our suppliers.' But what do you know about that supplier? Who makes the original chemical?"
Some compounding pharmacies have taken advantage of the legal no man's land in regulation. The FDA can inspect them and issue warnings, but the agency says states have ultimate jurisdiction.
The FDA has authority if it decides a compounding pharmacy is manufacturing, and not simply mixing drugs for individual patients. But to make that determination, the agency has to look at a pharmacy's records to see its volume, and pharmacies argue the law does not require them to produce those records.
Some consumer advocates say the FDA has the authority to investigate compounding pharmacies but often chooses not to.
Unlike commercial drug manufacturers, compounding pharmacies are not bound by the agency's so-called good-manufacturing practices, which require companies to report incidents when their medicine might have harmed patients. Usually the FDA learns about such cases only through the media or voluntary reporting.
In 2001, the agency looked at samples of compounded products from 12 different pharmacies, including antibiotics, steroids, and drugs to treat glaucoma and asthma, and found a third of the products failed one or more standard quality tests, mostly having to do with potency. A similar FDA survey in 2006 found the failure rate about the same.
KV Pharmaceuticals, a large drug company in St. Louis, did not rely on the government to assess the quality of compounded drugs that competed with its FDA-approved product, Makena, used to reduce the risk of premature birth. KV hired a corporate intelligence firm to obtain and test samples of the compounded version, 17P, for potency and purity.
In January, the company's researchers published their findings, alleging that 80 percent of the drug did not meet purity specifications. Michael J. Jozwiakowski, a co-author of the study, said the only companies they could find that manufactured the active pharmaceutical ingredient, available to compounders, were Chinese companies not registered with the FDA. One sample contained nothing but glucose.
When the FDA was given the data last fall, the agency decided to take its own samples of the compounded version, prompting the International Academy of Compounding Pharmacists, the trade organization, to offer its members advice on how to respond to FDA requests, in an emailed member alert titled, "F.D.A. Calling Compounders about 17-P."
The trade-group spokesman, David Miller, said the alert, despite its title, was intended to defend against data collectors from KV Pharmaceuticals, which member pharmacies said had been calling asking for samples.
"There was no evidence that any of the calls pharmacies received were coming from a genuine governmental official," Miller said. "Regulators do not 'call around' asking for information. They come to a pharmacy with an official inspection form."
He denied that the alert contained language instructing members not to cooperate with federal regulators.
"There is not one word in that document that says do not comply with a regulator," he said.
Dr. Michael Carome, deputy director of Public Citizens' Health Research Group, a nonprofit consumer organization, said the group's advice to members should have been to cooperate fully and answer all their questions. Instead, Carome said, the group suggested answers "for which the implicit, if not explicit message was to stonewall and obstruct" the FDA's attempt to assess the compounded drug.
The FDA said in June that after obtaining and testing 13 samples of the compounded drug, it had found no significant quality problems. KV Pharmaceuticals filed for bankruptcy this year, and it is suing the FDA.