When you have "leaking boiler" and "clean room" in the same sentence in a report about making medicine, it's usually problematic.
The Massachusetts Department of Public Health issued a preliminary report Tuesday evening about its investigation of the New England Compounding Center, a now-closed compounding pharmacy near Boston thought to have been the source of a fungal meningitis outbreak that has spread to 17 states. As of Wednesday afternoon, the Centers for Disease Control and Prevention web site said 24 people have died.
Compounding pharmacies are only supposed to make new potions based on a prescription from a doctor. NECC was making medicine in big batches and shipped 17,676 vials around the country, including to facilities in Pennsylvania, New Jersey and Delaware.
Later on Tuesday, the FDA released a list of facilities receiving shipments from NECC. The link to the FDA announcement with the full list is here.
The NECC customer list, sorted alphabetically by customer, with product information is here.
The NECC customer list, sorted by state, with no product information is here.
The Philadelphia area facilities receiving NECC shipments, according to the list, ranged from individual doctors to big hospitals. The hospitals include Thomas Jefferson University Hospital, Pennsylvania Hospital, Methodist Hospital, Hahnemann University Hospital, Cooper University Hospital and Our Lady of Lourdes Medical Center.
The FDA earlier warned health-care facilities about using NECC products and asked them to hold the products for further investigation.
Many of the patients involved in the 308 problem cases received injections of a steroid (methylprednisolone acetate) to treat pain, but the supposedly sterile vials were apparently not so sterile.
Perhaps the passage in the report with the greatest yuck factor was this one:
"A leaking boiler adjacent to the requisite clean room created an environment susceptible to contaminant growth: A pool of water was visually observed around the boiler and adjacent walls, creating an unsanitary condition; the culture results of this potential contaminant are still pending."
Also concerning to investigators was that NECC's parent company ran a recycling center nearby.
''Medication compounding involves the practice of taking commercially available products and modifying them to meet the needs of an individual patient pursuant to a prescription from a licensed provider," the Massachusetts report said. "Nearly all retail pharmacies in Massachusetts perform compounding, however only 25 compounding pharmacies meet the standards necessary to produce sterile injectable products."
The FDA has said it feels constrained in supervising compounding pharmacies by a 2002 Supreme Court decision, giving the pharmacies greater freedom than mass manufacturers. But once the outbreak occurred, FDA investigators joined Massachusetts personnel.
The report said that during the facility inspections, investigators documented "serious health and safety deficiencies" related to the practice of pharmacy.
Besides the leaking boiler, the report also said:
NECC distributed large batches of compounded sterile products directly to facilities apparently for general use rather than requiring a prescription for an individual patient. Records show that NECC had lists of potential patient names but did not have patient-specific prescriptions from an authorized practitioner when compounding and dispensing medication, as required by state law. Manufacturing and distributing sterile products in bulk was not allowed under the terms of its state pharmacy license. If NECC was appropriately licensed as a manufacturer with the FDA the company would have been subject to additional levels of scrutiny. NECC did not conduct patient-specific medication history and drug utilization reviews as required by regulations.
NECC distributed two of the recalled lots of methylprednisolone acetate (PF) 80 MG/ML prior to receiving results of sterility testing:
- Lot 06292012@26 was prepared on June 29, 2012. Final sterility testing was completed on July 17, 2012. Two shipments of product were made prior to the final sterility tests results being received.
- Lot 08102012@51 was prepared on August 10, 2012. Final sterility testing was completed on August 28, 2012. Eleven shipments of product were made prior to the final sterility tests results being received.
- While NECC’s records show the sterility tests found no contamination, the adequacy of NECC’s sterility testing methods are currently under examination.
Final sterilization of product did not follow proper standards for autoclaving (sterilization through high pressure steam) pursuant to United States Pharmacopeia Standard 797 (USP 797) and NECC’s own Standard Operating Procedures:
- Examination of NECC records indicated a systemic failure to keep products in the autoclave for the required minimum 20-minute sterilization period necessary to ensure product sterility.
- Visible black particulate matter was seen in several recalled sealed vials of methylprednisolone acetate from Lot 08102012@51.
Powder hoods, intended to protect pharmacists from inhaling substances during medication preparation, within the sterile compounding area were not thoroughly cleaned pursuant to USP 797. Residual powder was visually observed within the hood during inspection. This contamination may subsequently lead to contamination of compounded medications.
Condition of “Tacky” mats, which are used to trap dirt, dust, and other potential contaminants from shoes prior to clean room entry, violated the USP 797. Mats were visibly soiled with assorted debris."
The preliminary report's conclusion suggested greater federal oversight is needed of compounding pharmacies.
"The Department’s collaborative investigation with the FDA is comprehensive and will continue until investigators have all information needed to determine what, if any, further action should be taken against NECC and its leadership," the report said.
"This investigation also extends to NECC’s business practices and environmental conditions surrounding the business, including the presence of a nearby recycling center that shares ownership with NECC. Investigators are also looking into NECC’s corporate entity, including, but not limited to, corporate ownership and governance structures at both NECC and sister companies, Ameridose and Alaunus. DPH will analyze and incorporate all evidence and information gathered by the FDA and the Board of Registration in Pharmacy into a final, comprehensive report. This report will be presented to the Board of Registration in Pharmacy, which will determine appropriate regulatory sanctions under administrative law. DPH will also assist with any investigation, federal or state, that explores the actions of NECC and its principals.
"DPH will continue to support and cooperate with federal policymakers in addressing gaps in oversight of compounding pharmacies, including leaders on the U.S. Senate Health, Education, Labor, and Pensions Committee, and the U.S. House of Representatives Energy and Commerce Committee, and members of the Massachusetts Congressional delegation, including Congressman Ed Markey. DPH will also work closely with the Massachusetts General Court to explore state-specific policy solutions. Findings of these investigations will be used to inform these state and federal actions to address regulatory gaps within the quickly evolving compounding industry."
A link to the preliminary report is here.