Last spring, the FDA took the unusual step of inserting itself into the controversy over the KV Pharmaceutical drug known as Makena, which the agency had just approved for premature births under the Orphan Drug Act. How so? The drugmaker and the FDA came under fire after KV disclosed plans to charge $1,500, compared with $10 to $20 a week for compounded versions of a med that has been used for decades. In response, the FDA decided not to prevent compounders from compounding.

At the time, the agency issued a statement saying it “does not intend to take enforcement action against pharmacies that compound hydroxyprogesterone caproate based on a valid prescription for an individually identified patient unless the compounded products are unsafe, of substandard quality, or are not being compounded in accordance with appropriate standards for compounding sterile products” (back story).

KV Pharma, in fact, had intitially 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 its unusual decision not to take any enforcement action except under the circumstances noted. The agency decision, by the way, helped send KV Pharma stock into a freefall.

Now, though, the FDA is now is heading back in the other direction and may well find reason to take action against some compounders. In response to data given last month to the agency by KV Pharma, the FDA is conducting an investigation into various samples that apparently raised concerns about the quality of the active pharmaceutical ingredients and compounded products.

In a statement, the FDA says that, “according to the analysis…there is variability in the purity and potency of both the bulk APIs and compounded hydroxyprogesterone caproate products that were tested. Although FDA has not validated or otherwise confirmed the analyses provided by KV, FDA has carefully reviewed the data and will conduct an on-site review of the laboratory analyses. FDA has begun its own sampling and analysis of compounded hydroxyprogesterone caproate products and the bulk APIs used to make them. That process is ongoing.”

Here is a summary of what KV Pharma provided to the FDA: Seven of 10 sampled active pharmaceutical ingredient suppliers were located in China and that are neither registered with, nor inspected by, the FDA, and finished product came from 30 different pharmacies in 15 states. Eight of 10 API samples and 16 of 30 finished product vials failed to meet FDA standards for unknown impurities. One of 10 API samples and five of 30 finished product vials failed FDA potency standards (read more here).

“This research demonstrates important differences in product quality between FDA-approved Makena and these compounded 17P formulations. Healthcare providers and patients have no practical way of ensuring that compounded 17P formulations meet FDA’s quality standards,” Greg Divis, KV Pharma ceo and president, says in a statement.

We asked an FDA spokeswoman how many different compounders and compounded versions of Makena were being probed, but have not received a reply. We will update you if and when we do. [UPDATE: On Wed. Nov. 9, an FDA spokeswoman writes us that samples for finished compounded products came from 24 pharmacies.] We have also asked David Miller, executive director of the International Academy of Compounding Pharmacists, for a response and will update you accordingly. [UPDATE: Here is an alert IACP sent to its members about the FDA probe (look here).]

We should note, by the way, that KV Pharma lowered its price on Makena in response to the controveresy by nearly 55 percent, to $690 per injection (look here), but that did not stop one US Senator from launching a probe into price gouging (read this).