Compounded Drug Crisis Spotlights Regulatory Confusion

The call for stiffer FDA regulation of compounded drugs has been reignited by a national fungal meningitis outbreak. Last week, the Centers for Disease Control and Prevention (CDC) reported 7 deaths linked to contaminated vials of steroid injectables from a Massachusetts compounding operation. 91 people have been taken ill, with the numbers rising daily. Thousands of individuals have been exposed to some 17,000 vials of methylprednisolone acetate produced by the New England Compounding Center (NECC) and shipped to 23 states in recent months. Such a large volume of drug compounding and marketing to such a broad geographic area runs counter to FDA policy, especially for a drug that is available from regulated manufacturers.

Compounded sterile injectables have been associated with serious adverse events, and NECC has been cited by FDA and state regulators for a range of violations in recent years. In April 2012, FDA and the CDC warned against use of a contaminated product used in eye surgery from Franck’s Pharmacy in Florida. FDA inspectors found fungus in several NECC lots last week; the firm instituted a broad recall and shut down operations.

Pharmaceutical manufacturers have pressed for stricter control of compounding pharmacies, which now number over 7000 according to the International Academy of Compounding Pharmacists. About 3000 produce sterile products, and a growing number are large enough to compete with drug companies. Compounding pharmacies traditionally provide a valuable service in preparing special doses or formulations that are not available commercially but needed by individual patients, particularly children and the elderly. But only 162 compounders have applied for voluntary industry accreditation.

The current meningitis outbreak reflects a rise in the treatment of back pain with spinal injections of steroids, as an alternative to surgery. Sales of the NECC injectable treatment have risen, apparently due to supply shortages of generic versions of methylprednisolone; a brand product from Pfizer (Depo-Medrol) is expensive.  Commercial versions of this product are not approved for injection into spinal joints, but evidently have been used off-label for such treatment.

Compounding pharmacies fall into a gray area between FDA enforcement of drug manufacturing and state regulation of pharmacists. FDA has long tried to impose standards on large-scale compounders that move beyond local operations and compete unfairly with pharmaceutical manufacturers. An agency report in 2007 cites 200 adverse events involving 71 compounded products since 1990. Legislation approved in 1997 authorized FDA to clarify its policies governing pharmacy compounding.

But the resulting regulations were invalidated by the courts on the grounds of unfairly restricting commercial speech. After that ruling was upheld by the Supreme Court in 2002, FDA issued a compliance guide spelling out its enforcement policy, but its powers have been limited. And in some cases the Agency has supported compounders over manufacturers, as when KV Pharmaceuticals jacked up the price on the premature birth preventive, Makena, in anticipation of FDA action against compounders.

Nevertheless, regarding recent comments by Sen. Richard Blumenthal (D-Conn),  the lethal consequences of this latest compounding disaster may generate further legislative changes.