Lack of regulatory oversight of compounding pharmacies continues to be a problem
The meningitis outbreak caused by a contaminated steroid formulation used as a pain-control agent for spinal injuries shows little sign of abating. As of Oct. 7, the Centers for Disease Control counted 91 cases in nine states, and seven deaths. All products (not just the preservative-free methylprednisolone acetate formulation that is believed to be the source of the outbreak) of the New England Compounding Center (Framingham, MA) are being recalled—but nearly 18,000 doses, in three lots, had been distributed from July to September. The first case of fungal meningitis—a rare condition that usually gets immediate attention—was noted in Tennessee on Sept. 21; when a second case showed up a few days later, CDC knew it had a growing problem. Tests of unopened vials from NECC showed fungal contamination (as well as other foreign matter), according to CDC, and on Sept. 25, NECC began a voluntary recall and essentially ceased operations.
The methylprednisolone injection is used to reduce inflammation in patients with spinal injuries; it is a “intrathecal” injection—directly into the spine. There is a branded version of the injection—Pfizer’s Depo-Medrol (however, that drug’s label states that spinal joints are “anatomically inaccessible” are not suited for this treatment; moreover, according to some press reports, the value of the steroid injection for back pain is questionable). Although FDA and CDC are not, as yet, definitively confirming that the contaminated drug is the source of the meningitis, much of the evidence points in that direction. Fungal meningitis can cause stroke and other serious conditions, and is essentially a brain infection.
This outbreak highlights the long-standing gray area in which compounding pharmacies operate. Technically, FDA has very limited oversight over pharmacies of any sort. Compounded drugs “are not approved by FDA and they don't undergo that same premarket approval for safety effectiveness that FDA approved drugs do,” stated Kathy Anderson, an acting FDA director, during an Oct. 4 teleconference. Pharmacies are licensed by states, and most of the regulatory authority resides with state boards of pharmacy. Thousands of pharmacists compound drugs for individual patients or specialized treatments (such as for pediatric care); the regulatory system is geared toward individual pharmacists handling a local patient population.
But, for years, some compounding pharmacies are essentially factories making large quantities of drugs and shipping them nationally. FDA has tried to regulate such pharmacies as manufacturers, but states and compounding pharmacies have fought off that oversight. The practice cuts both ways; compounding pharmacies have been producing “botanical” hormone replacement therapy, in competition with an FDA-approved drug. On the other hand, when KV Pharmaceuticals began to market Makena (progesterone) as an FDA-approved teatment for premature brith (and at a price massively higher than the compounded progesterone that has been available for decades), FDA siad it would take no enforcement action against compounding pharmacies. Subsequently, KV filed for bankruptcy.
State boards of pharmacy have limited resources to regulate their licensees, let alone those in other states; and FDA has been restricted by court rulings from overseeing them too rigorously. Meanwhile, the International Academy of Compounding Pharmacists (Houston) notes that there is a Pharmacy Compounding Accreditation Board—and that NECC was not an accredited member (IACP’s latest campaign is to reduce restrictions by the Drug Enforcement Agency on distribution of controlled substances, which makes the entire situation even more dicey). Unlike outbreaks of counterfeit drugs, where FDA compliance officers swoop into action and shut down bad actors, there is likely to be little change that comes out of this meningitis outbreak, no matter how bad it gets.