Investigation Report of NECC Released, Details Noncompliance with Clean Room Protocols

The Executive Office of Health and Human Services of the Massachusetts Department of Public Health (MDPH) today issued a report on its preliminary findings in its investigation of New England Compounding Center (NECC). 

Since Sept. 24, 2012 a widespread outbreak of fungal meningitis has affected people in 17 states and caused 23 deaths. The outbreak originated from a medication compounded by NECC, a facility licensed by the Massachusetts Board of Registration in Pharmacy (Board). The MDPH has taken immediate action to protect public health and safety; in collaboration with investigators from the Food and Drug Administration (FDA), DPH investigators have worked to identify the root causes of these events.

While the complete scope and severity of this outbreak will not be fully understood for many weeks, public health officials say, to ensure the utmost transparency, MDPH released its preliminary findings from its ongoing investigation of NECC. This report constitutes early findings that may be subject to revision as the investigation unfolds, public health officials add.

According to the MDPH, 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. Nearly all retail pharmacies in Massachusetts perform compounding, however only 25 compounding pharmacies meet the standards necessary to produce sterile injectable products. By terms of their license with the Board, every Massachusetts pharmacy must comply with Massachusetts laws and regulations, including compliance with the United States Pharmacopeia Standards.

Compounding pharmacies may only perform compounding upon receipt of a patient-specific prescription. These requirements and restrictions are consistent with the rules in place in other states.

Upon beginning the joint onsite investigation of NECC early in this outbreak, MDPH and FDA investigators identified serious deficiencies and significant violations of pharmacy law and regulations that clearly placed the publics health and safety at risk.

The NECC onsite investigation process consisted of MDPH investigators obtaining documentary evidence (including photographs), reviewing and obtaining copies of Standard Operating Procedures, observational findings, reviewing and obtaining copies of all policies and procedures, reviewing batch records and interviewing NECC staff. The FDA conducted product testing and investigators took environmental samples of various areas of the facility to test for contaminants.

MDPH investigators principally communicated with three NECC staff members during the on-site investigation (Barry J. Cadden, Glenn A. Chin and Lisa Conigliaro-Cadden) along with FDA investigators. After Sept. 26, 2012, the majority of NECC employees were no longer on site. As has publicly been documented, NECC terminated many of their staff. The continuing investigation will include interviews of NECC employees, according to the MDPH report.

During the facility inspections, investigators documented serious health and safety deficiencies related to the practice of pharmacy. All pertain to violations of 247 CMR 9.01(3) or 247 CMR 6.01(5)(a):
- 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:
- One lot 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.
- One lot 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 NECCs records show the sterility tests found no contamination, the adequacy of NECCs 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 NECCs 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.

NECC did not conduct proper validation of autoclaves pursuant to USP 797:
- NECC failed to test their autoclaves to ensure proper function.
- Visible black particulate matter was seen in several recalled sealed vials of methylprednisolone acetate.
- 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.
- 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.

According to the report, the MDPHs 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. This investigation also extends to NECCs 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 NECCs corporate entity, including, but not limited to, corporate ownership and governance structures at both NECC and sister companies, Ameridose and Alaunus. MDPH 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. MDPH 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. MDPH 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.