Compounding Expensive FDA-Approved Drugs to Reduce Price: Potential Challenge to the 505(b)(2) or Generic Pathway
[Posted on: Thursday, October 29, 2015]

If your prescription drug is too expensive, can you simply buy a compounded drug to get a cheaper version? And if this goes forward, does it not create a challenge for all developers of 505(b)(2) or even generic drugs? What about expanding this logic to the very expensive biological drugs? Would FDA allow that? The news could have very disturbing undertones. The excessive price hike for a life-saving drug, Daraprim, by Turing Pharma recently brought the drug price debate to national headlines. The CEO of Turing Pharma, Martin Shkreli, has been skewered by the media, industry and politicians since the news came out. It did not help that Shkreli promised to lower the price of the drug but then backtracked on that promise. Now we have a new player in this discussion. A San Diego-based compounding pharmacy, Imprimis Pharmaceuticals, announced that it will sell a compounded version of Daraprim at $1 per pill compared to Turing’s $750 per pill. This news was widely praised by media and Imprimis was hailed as the savior of patients who desperately need the drug. But there is a cloud behind this silver lining. Daraprim is an FDA-approved tablet and the only formulation of the active ingredient, pyrimethamine, approved by FDA. Under the laws governing compounded pharmacies only listed bulk drugs can be compounded. The only exception is if an approved drug is listed by FDA as a drug on shortage with an established clinical need. Daraprim is not listed as an allowed compounded drug or on shortage so it does not meet the exception from the law. Per FDA’s orange book, Daraprim is eligible for generic versions. If there is a formulation change of the active ingredient of Daraprim, pyrimethamine, it must be approved by FDA under the 505(b)(2) pathway. Imprimis intends to create a capsule formulation to Daraprim’s tablet form which could have different bioavailability than the tablet and hence requires at least bioavailability-bioequivalence studies as a generic version. The decision by Imprimis breaks pretty much all the laws for new drug approval. The company plans to compound an illegal copy of an FDA-approved drug without seeking FDA’s approval to do that. Also, Imprimis is not registered as a compounding pharmacy with the FDA, which is required per the Compounding Quality Act of 2013 for all compounding pharmacies intending to bulk manufacture drugs for inter-state distribution. Compounding pharmacies are rarely audited by FDA for compliance with GMP regulations, and many of them were found to be non-compliant with GMP recently. Since Imprimis was never audited by FDA, there is likelihood that they do not meet the GMP regulations for pharmaceutical manufacturing as well, raising additional concerns about the safety of the pyrimethamine capsules compounded at its facilities. While the gesture by Imprimis is a laudable effort to combat high drug prices but it raises so many questions that FDA will need to intervene. This decision will be politically hard for FDA as it may give the perception that FDA is siding with Turing Pharma but FDA needs to enforce the laws and cannot (or should not) cherry pick based on public opinion. More likely, Turing Pharma has the right to demand FDA’s action against Imprimis and also take Imprimis to court for selling an illegal version of its drug. This could create a precedence for all cases of 505(b)(2) drugs where the drug approved by FDA is perceived to be too expensive formulation-changes. Imprimis has already announced that it plans to create other similar compounded drugs for expensive formulations. This could even open the door to getting around seeking approval for a generic drug. Why should one get approval for a generic drug or a new formulation, if one can simply compound it and sell!

Expert Opinion: Mukesh Kumar
VP, RA, Amarex Clinical Research