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The use of drug compounding facilities to produce over-priced generic drugs raises quality and regulatory questions.
The continuing campaign to ratchet down prescription drug prices has generated considerable talk about how compounders could provide less costly, alternative therapies. Express Scripts ignited the discussion by announcing Dec. 1, 2015 that it would offer a cheaper version of Turing Pharmaceuticals’ Daraprim (pyrimethamine) from pharmacy compounder Imprimis Pharmaceuticals.
The role of compounders in supplying needed medicines was aired at a recent hearing held by the Senate Special Committee on Aging on exorbitant price hikes on older off-patent drugs. Senators on all sides blasted the jump in treatment cost from $1200 to $69,000 in recent months for Turing’s toxoplasmosis therapy Daraprim. Several witnesses blamed such steep and sudden price hikes on increased consolidation in the generic drug industry and the resulting drop in competition. Proposed remedies are to accelerate FDA approval of new generics, increase transparency in how prices are set for brands and generics, provide more leeway to import certain medicines from Canada, and for FDA to encourage compounding of over-priced therapies.
But proposals to tap compounders for alternative treatments raises a lot of concern at FDA and among drug industry experts, who recall only too well the fungal meningitis outbreak linked to the distribution of contaminated sterile drugs by a New England compounder. Allan Coukell, senior director of The Pew Charitable Trusts, sent a letter to members of the Senate aging panel noting that compounded drugs do not meet the same approval standards for manufacturing quality and safety and efficacy as do new and generic drugs approved by FDA. Coukell advised that compounding, consequently, “cannot become an alternative to the protections of FDA-approved manufacturing.”
A related issue is whether Turing is preventing compounding pharmacies from obtaining pyrimethamine tablets needed to produce liquid formulations of this critical anti-parasitic for infants. At the Senate hearing, David Kimberlin, a pediatric infectious disease specialist at the University of Alabama, said that Turing’s use of a specialty pharmacy for Daraprim distribution blocked his compounding pharmacy, and other hospitals, from obtaining the drug.
FDA continues to raise concerns about the quality of therapies from compounders and is ramping up inspections and recalls of products that fail to meet standards. At the recent Enforcement Conference sponsored by the Food and Drug Law Institute (FDLI), Cynthia Schnedar, director of the Office of Compliance in the Center for Drug Evaluation and Research, noted that FDA has conducted some 200 inspections of compounders since late 2013 and has issued approximately 60 warning letters citing serious violations. The agency also has sent 20 letters to state boards of pharmacy, referring findings from inspections of compounding pharmacies under state jurisdiction.
Increased FDA oversight of compounders was authorized by the Drug Quality and Security Act enacted in November 2013, which established under section 503B of the Act a new category of “outsourcing facilities” for compounders that produce sterile drugs. These operations must register with FDA, comply with GMPs, submit to FDA inspections and pay an annual fee to the agency. “Traditional” pharmacy compounders that provide conventional drugs to fill prescriptions from specific doctors, patients and hospitals may continue to operate as before under section 503A. FDA has issued a dozen draft guidances and held numerous public meetings to implement this complex program.
Legal experts at the FDLI conference raised questions about the legality and feasibility of insurers and pharmacy benefit managers turning to compounders such as Imprimis for supplies of less costly drugs. Express Scripts’ announcement of its arrangement with Imprimis says that the compounder will offer an oral formulation of pyrimethamine and leucovorin for $1 a capsule (as opposed to $750 per Turing pill) in response to patient-specific prescriptions from physicians, as is required for traditional compounders. But attorneys suggested that the proposed collaboration with Imprimis might turn the compounder into an outsourcing operation that has to register with FDA.
That’s what Imprimis indicates it plans to do, but so far it is operating as a traditional pharmacy compounder, even though it produces and dispenses broadly many sterile products for ophthalmology, sinus, and urology conditions. This San Diego-based firm has grown in the last three years by buying up compounding pharmacies across the country for the stated purpose of providing “cost-effective compounded medication options where sole-source generics have increased prices,” including its pyrimethamine product, which was offered as an alternative to Daraprim in October 2015.
Imprimis describes its current sites as “outsourcing facilities” and compounders of sterile and non-sterile products. The company says it plans to register its Texas and New Jersey operations as 503B outsourcing facilities, and reports that it is building a “state-of-the-art” outsourcing facility in New Jersey, which should open early next year and will comply with GMPs and FDA 503B standards. For now, Imprimis says it is meeting internal quality assurance standards to comply with state laws and USP standards. Whether it will transition successfully to meet FDA compounding regulations for more high-profile and large-scale operations remains to be seen.