Oct 12 2012

Meningitis Tragedy Leads to Calls for Increased FDA Oversight

Image via ABC News

On 25 September 2012, three lots of steroid injections intended to treat pain were recalled by the pharmaceutical compounding company New England Compounding Center (NECC) in Framingham, MA, because of fungal contamination.  By Thursday, 11 October 2012, 12 people had died and there were 137 confirmed cases of fungal meningitis due to contaminated injections.  The vials of contaminated steroid were distributed to over 76 medical centers in 23 states, and over 13,000 people may have been exposed to the drug.

Compounding pharmacies are regulated by individual State Boards of Pharmacy (such as the Massachusetts State Board of Registration in Pharmacy) and by voluntary groups, such as the Pharmacy Compounding Accreditation Board.  Until November 1997, when the Food and Drug Administration Modernization Act (FDAMA) was passed, there was actually no federal regulatory control of compounding pharmacies.  Section 127 of FDAMA added section 503A to the FD&C Act and provided the first regulatory oversight of compounding pharmacies.  Section 503A deemed that, assuming compounding pharmacies met certain requirements concerning the promotion and advertising of compounded products, the compounded products made in these pharmacies would not be considered “new drugs.”  The exemptions included:

  1. 501(a)(2)(B) – Exemption from the adulteration provision of cGMPs
  2. 502(f)(1) – Exemption from the misbranding provision of labeling drugs with adequate directions for use
  3.  505 – Exemption from submitting NDA or ANDA approval applications

Because of the restrictions on promotions and advertising, Section 503A was subsequently challenged by multiple compounding pharmacies and was declared invalid in 2001 by the U.S. Ninth Circuit Court of Appeals.  That ruling was upheld by the Supreme Court in 2002.  However, the FDA states in its Guidance for Pharmacy Compounding that it will consider enforcement action “when the scope and nature of a pharmacy’s activities raise the kinds of concerns…and result in significant violations.”  Subsequently, the FDA has issued multiple warning letters to compounding pharmacies, including prior letters to NECC.

The solution seems relatively simple: increase regulatory oversight and enforcement of compounding pharmacies and ensure they adhere to strict cGMPs along with other standards applied to drugs.  However, there is another side to the coin, as has been brought to light by the recent MakenaTM scandal.

MakenaTM is a drug that reduces the risk of preterm birth.  KV Pharmaceuticals won approval from the FDA for the drug in 2011 under the Orphan Drug Act.  However, when KV brought MakenaTM to market, they charged $1,500 for the drug.  Prior to KV Pharmaceuticals’ approval, the same drug had been compounded for the same indication for years at a cost of around $20.  Under intense pressure to allow greater access to prescription drugs and to prevent drug monopolies, the FDA allowed compounding pharmacies to continue making the drug even though KV Pharmaceuticals was granted marketing exclusivity via their approval under the Orphan Drug Act.  This resulted in a lawsuit against the FDA by KV Pharmaceuticals in which KV Pharmaceuticals claimed that MakenaTM was the only drug available for prevention of preterm birth that had been proven to be safe and effective by the FDA, and thus the compounding of the drug should be stopped.  KV Pharmaceuticals lost that lawsuit and filed for bankruptcy last month.

There are already calls by elected officials to increase regulatory oversight of compounding pharmacies.  Sen. Richard Blumenthal (D-CT),  Sen. Edward Markey (D-MA), and a bipartisan group of Representatives and Senators have all voiced concern over the outbreak and are supporting the initiation of change in the oversight of compounding pharmacies.  Hopefully, in response to these tragic and preventable events, lawmakers, in conjunction with the FDA, the CDC, and other applicable groups, will find a solution to the complexities that are involved in regulation of compounding pharmacies.