This past Friday, October 26, 2012, the U.S. Food and Drug Administration released a copy of the FDA Form 483 issued to the New England Compounding Center (NECC) that produced contaminated steroid injections and triggered an FDA investigation of a multistate fungal meningitis outbreak among patients who received the injections. The FDA observed and has since confirmed contaminated products and listed a number of observations regarding conditions at NECC’s Framingham, Massachusetts facility.
The investigators observed problems with NECC’s ability to maintain its clean room, which is the enclosed space that is designed and maintained to have a controlled environment with low levels of airborne particles and surface contamination. Production of sterile drug products in a properly functioning and maintained clean room reduces the risk of the introduction of microbial contamination into the drug during processing, including filling into its final container.
The FDA found some vials of the purportedly sterile injectable drug contained a greenish black foreign matter and others a white filamentous material. NECC’s Pharmacy Director stated that the firm uses non-sterile active pharmaceutical ingredients and raw materials even though the formula worksheets state the raw materials are sterile.
The FDA observed condensation and tarnished discoloration on the interior surfaces of an autoclave used in the final sterilization step in the process of methylprednisolone and triamcinolone, which are intended for injection.
Rooftop units serving NECC’s HVAC system are approximately 100 feet from a recycling facility that handles such materials as mattresses and plastics and uses large equipment (e.g. excavators and freight trucks) that produced airborne particulates such as dust, and dark particulate and white filamentous substances were found covering the louvers of an HVAC return located in NECC’s plant.
Other conditions the FDA found were described as “yellow residue”, “greenish residue”, a “brown and soiled” mat inside NECC’s plant, and “reddish-brown and cloudy substances in a “Clean Room” used to formulate and fill sterile preparations, including methylprednisolone.
The FDA issues a 483 at the end of an inspection when the investigators believe that they observed conditions or practices that, in their judgment, may indicate violations of the Federal Food, Drug, and Cosmetic Act, or related regulations. The 483 issued to NECC was 8 pages long.
The 483 does not constitute a final FDA determination that any observation listed on the 483 is a violation of the Federal Food, Drug, and Cosmetic Act or any related regulations.
The FDA continues to work closely with the U.S. Centers for Disease Control and Prevention and state partners, including the Massachusetts Board of Registration in Pharmacy, to investigate the outbreak of fungal meningitis among patients who received NECC’s compounded preservative-free methylprednisolone acetate (80mg/ml), an injectable steroid.
The FDA recommends that follow-up with patients be done when the following three conditions are met: the medication was an injectable product purchased from or produced by NECC, including an ophthalmic drug that is injectable or used in conjunction with eye surgery, or a cardioplegic solution.