KV Pharma & Compounding: We Told You So

After getting beaten up for creating sticker shock over the price of its Makena treatment for premature births, KV Pharmaceutical is now

Thanks to the meningitis outbreak, the New England Compounding Center has now recalled all of its compounded medications, including hydroxyprogesterone caproate, or 17P, which is a compounded version of Makena and shows up on page 38 of the list of recalled products (see this and this). The FDA calls this a voluntary recall and a precautionary measure.

Nonetheless, a KV Pharma spokesman was quick to point out that the drugmaker was raising safety issues about compounding alternatives for nearly two years. "This is the point that KV has been working to make. Women deserve to know whether a sterile injectable they are being given while in a high risk pregnancy has been produced under conditions that lead to the highest level of safety and efficacy," he wrote us.

KV Pharma, you may recall, initially threatened to sue any compounders that made a version of Makena. Although the drugmaker does not have a patent, the FDA approval under the Orphan Drug Act, effectively, eliminated competition, because KV Pharma was granted seven years of market exclusivity (see this). As a result, KV began sending cease-and-desist letters to compounders before the FDA issued an unusual decision not to take any enforcement action except under the circumstances noted.

The agency move came after physicians and patients, among others, expressed outrage over the initial $1,500 price tag for Makena compared with a small fraction for compounded versions that had been used for years. And the FDA action reflected concern by the White House that the approval created a monopoly situation, but also sent KV Pharma stock into a freefall. In response, the drugmaker asked the FDA to test samples of rival products and ingredients.

Last June, however, the FDA disclosed that samples – some of which were provided by KV and others gathered by the FDA from compounding pharmacies, doctor’s offices, API distributors, and APIs offered for importation – did not reveal any safety problems. As we reported previously, of 16 samples collected by the agency, none yielded any issues with potency or purity standards using methods set by the United States Pharmacopeia (back story).

The agency also tested 13 samples prepared by eight compounding pharmacies and found that one was subpotent and in the range of 80 percent of declared potency; the FDA noted that the standard for potency is between 90 percent and 110 percent. All 13 samples met the standard in the Makena New Drug Application for total purity, although two of the samples failed to meet the standard for unidentified impurities in the Makena NDA (read here).

But did one of those samples comes from the New England Compounding Center? The KV Pharma spokesman isn't saying, despite being quick to use the meningitis outbreak to bolster the case being argued by his company, which has since filed bankruptcy due to depressed Makena sales and filed lawsuits against three states for failing to cover the drug in their Medicaid programs (see here and here).

"We have not made public the list of compounding pharmacies from whom our researchers acquired finished product samples. Nor do we know from which compounding pharmacies FDA acquired samples for its own testing," he writes us. "What we do know is that the same facility that produced the compounded drug formulation which apparently led to the cases of meningitis makes and now is recalling 17p – a sterile injectable being used in women who are at high risk." We asked the FDA if the agency tested samples from the New England Compounding Center and will update you accordingly with any response. [UPDATE: An FDA spokeswoman says the agency investigation is ongoing, so there are no specifics available.] KV Pharma, by the way, also unsuccessfully sued the FDA for allegedly abdicating its responsibility to prevent some compounding pharmacies from offering lower-cost versions of Makena. A federal judge ruled that the agency appropriately exercised its discretion in whether to pursue enforcement actions against compounders (read here). Thanks to the meningitis outbreak, though, there are growing calls for the FDA to more aggressively pursue compounders.

Among them is US Senator Richard Blumenthal of Connecticut, who yesterday wrote FDA commish Margaret Hamburg that "clear guidelines have been drawn by both FDA and Congress, first in 1992 and later under section 503A as added by the FDA Modernization Act of 1997, and still again in FDA’s own compliance guidance in 2002 that require certain conditions be met in order to compound prescription drugs" (here is the letter).

[UPDATE: As a reader noted, Kevin Outterson, an associate professor of law at Boston University, told The New York Times that the FDA "has more regulatory authority over a drug factory in China than over a compounding pharmacy in Massachusetts." Why? He added that the FDA developed rules for compounding, but the US Supreme Court struck them down a decade ago Congress never re-established clear authority. We showed the Blumenthal letter to Outterson and he had this to say: "His discussion of the 5th Circuit & 9th Circuit cases doesn't clearly discuss the SCOTUS decision on appeal from the 9th, or the lack of Congressional action following that decision."]

shock pic thx to ogimogi on flickr