This is not food related, but the issues seen at this facility that made the contaminated epidurals that led to the fungal meningitis outbreak provide lessons in product and environmental control.
· Firm shipped product before receiving sterility results (results were negative however).
· Firm didn't follow established standards for autoclaving and didn't keep products in the autoclave for the minimum 20 minutes needed to ensure sterility
· Firm didn't thoroughly clean powder hoods used to protect pharmacists while they prepare compounded substances. Investigators observed residual powder within the hood, which could lead to contamination of medications
· Mats designed to trap dirt and other contaminants were visibly soiled, and a leaking boiler next to the clean room caused water to pool around it and adjacent walls, creating conditions that could support contaminant growth, according to the findings.
In the report below, Massachusetts Governor Patrick states that over the years, some pharmacies have evolved from neighborhood drug stores to large-scale manufacturers that sell products across state lines, and that regulations in Massachusetts and at the federal level have not kept pace with the changes. He said that he had directed the pharmacy board to start making unannounced inspections of compounding pharmacies that make sterile injectable medications and strengthen penalties for pharmacies that don't comply with rules.
Not sure I want my local pharmacy making medicine, especially ones that can be injected in me. Dispensing medicine is one thing, but making it, no thanks.
We see this type of thing in food companies as well…the firm expands into a niche outside of their core competency and grow the business, but never become technically competent in that new business. They fail to spend the capital on the facility needed to meet the requirements of producing that product. Then, as more product is shipped, the inevitable production error occurs, impacting far too many.
Report airs problems at firm linked to fungal meningitis outbreak
Lisa Schnirring Staff Writer
Oct 24, 2012 (CIDRAP News) – Massachusetts officials yesterday said New England Compounding Center (NECC), the firm linked to a multistate fungal meningitis outbreak, sent shipments from two of the recalled lots before it received sterility testing results.
Investigators also found black particulate matter in several unopened vials of the recalled methylprednisolone acetate, which was used in epidural injections for back pain and injections for peripheral joint problems, according to a report of preliminary investigation findings.
Federal officials have said that as many as 14,000 patients could have been exposed to the recalled injections.
Nine more infections have been reported in the outbreak, raising the number of infections to 317, the US Centers for Disease Control and Prevention (CDC) said today in its latest update. One more death was reported, putting that total at 24, and the number of affected states held steady at 17.
The CDC reported one more joint infection linked to the contaminated steroids, raising that number to five, and it said 54 cases have now been confirmed with lab tests. So far all but two of the infections involve Exserohilum rostratum, a type of black mold that hadn't previously been known to cause meningitis.
In a press conference with reporters yesterday, Madeleine Biondolillo, MD, who directs the Massachusetts Department of Public Health's Bureau of Health Care Safety and Quality, said the investigation began on Sep 25 and involves collaboration with their colleagues at the US Food and Drug Administration (FDA) since Oct 1. She said the investigation is ongoing and that authorities have obtained evidence, reviewed NECC's standard operating procedures, probed the company's records, and interviewed its employees.
NECC didn't label the medications for specific patients, a violation of Massachusetts licensing regulations for compounding pharmacies, Biondolillo said.
According to the Massachusetts Department of Public Health (MDPH) investigation report, NECC's sterility tests on the shipments sent before results came in didn't show contamination. However, investigators said they were still exploring the adequacy of NECC's testing methods.
In addition, authorities found that the company didn't follow established standards for autoclaving and didn't keep products in the autoclave for the minimum 20 minutes needed to ensure sterility.
The report also says NECC didn't thoroughly clean powder hoods used to protect pharmacists while they prepare compounded substances. Investigators observed residual powder within the hood, which could lead to contamination of medications.
Mats designed to trap dirt and other contaminants were visibly soiled, and a leaking boiler next to the clean room caused water to pool around it and adjacent walls, creating conditions that could support contaminant growth, according to the findings.
At the media briefing, Massachusetts governor Deval Patrick said federal officials have launched a criminal investigation into NECC's actions and he announced more steps the state and its Board of Pharmacy have taken in response to the steroid contamination, including permanently revoking NECC's operating license and those of its three principal pharmacists.
"Those whose laboratory practices caused this outbreak should never practice pharmacy or manufacture in Massachusetts again," he said.
Patrick said that, over the years, some pharmacies have evolved from neighborhood drug stores to large-scale manufacturers that sell products across state lines, and that regulations in Massachusetts and at the federal level have not kept pace with the changes. He said that he had directed the pharmacy board to start making unannounced inspections of compounding pharmacies that make sterile injectable medications and strengthen penalties for pharmacies that don't comply with rules.
The state will now require compounding pharmacies in Massachusetts to submit annual production, volume, and distribution reports to make it easier for authorities to flag operations that are acting more like manufacturers, which require federal licensing and extra scrutiny, Patrick said. He added that the state will require compounding pharmacies to report interactions with federal regulators and will form a special commission to examine best practices in other states and what changes may be needed at the federal level.
In a related development, two members of Congress yesterday asked the Government Accountability Office (GAO) to investigate compounding pharmacies and their oversight by state and federal agencies. The members are Rep John Tierney, D-Mass., ranking member of the House Subcommittee on National Security, Homeland Defense, and Foreign Operations, and Rep Elijah Cummings. D-Md., ranking member on the House Committee on Oversight and Government Reform.
In a statement outlining their letter to the GAO, Tierney said, "In light of these tragic deaths, we need to know how many other companies are engaged in similar activity and whether they may be falling through the cracks between state and federal regulating agencies."
Meanwhile, the CDC yesterday issued a new health alert network advisory to clinicians that contained its latest advice on how to manage asymptomatic patients who received epidural or paraspinal injections with the contaminated steroids.
The agency still advises against prophylactic antifungal treatment for people exposed to the recalled medication in the absence of diagnostic tests that suggest meningitis. The antifungal drugs used to treat the condition require powerful doses that can cause serious adverse side effect.
Based on new data, however, the CDC said the period of greatest risk for developing fungal meningitis is during the first 6 weeks (42 days) after injection, so clinicians should consider additional monitoring.
The FDA has reposted new lists of customers who received the recalled steroids from NECC, after taking them down upon finding technical problems with them. The agency first posted the lists on Oct 22, with the caveat that the information was from NECC and it couldn't guarantee their accuracy or completeness.
Oct 23 MDPH NECC preliminary investigation report
Oct 24 CDC fungal meningitis outbreak update
Oct 23 Biondolillo comments
Oct 23 Patrick comments
Oct 23 Rep Tierney statement
Oct 23 CDC HAN health advisory
Oct 22 FDA statement and lists
Inside the New England Compounding Center
NEW YORK A former employee of the New England Compounding Center, under scrutiny as a result of the nationwide meningitis outbreak which has claimed 15 lives to date, said questions about whether NECC was engaging in specialty compounding or was crossing over into manufacturing were actively discussed by company management as far back as 2009.
The former employee, who spoke only on the condition of anonymity, told CBS News that New England Compounding Center's insurance contract in 2009 "had a very clear manufacturing exclusion in their policy, " meaning the company was not covered for manufacturing, only smaller specialty compounding.
Under government regulations, if the company was a manufacturer, it would be subjected to more regulatory oversight.
CBS News tracked down five former NECC employees who provided new details about the pharmacy's operation.
An employee who left in 2008 told CBS News that she did not recall any orders that did not have a prescription attached to them.
But another employee, who also spoke on the condition of anonymity because of a non-disclosure agreement, said by 2009 NECC was regularly filling large orders.
"It was usually more bulk than individual shipments," the employee said. "It was very rare that it was one bottle for one person."
While he was employed at NECC, the pharmacy produced vials in the low thousands each day depending on the drug, he said.
FDA officials have said the three potentially contaminated lots had over 17,000 vials in them.
Fourteen thousand patients may have been exposed to the contaminated injections, federal officials say. As of Monday there were 214 cases of meningitis and 15 deaths tied to the injections from NECC, according to the Centers for Disease Control.
On Monday, the FDA announced another case of possible meningitis from another possible NECC drug, noting in a statement: "At this point in FDA's investigation, the sterility of any injectable drugs, including ophthalmic drugs that are injectable or used in conjunction with eye surgery, and cardioplegic solutions produced by NECC are of significant concern..."
"Our intent has always been to comply with all regulations, and cooperate with all regulatory agencies,'' said Cosmo Macero, a NECC spokesman in an email. He did not respond to other inquiries.
The New England Compounding Center is a family-owned and operated pharmacy based in Framingham, Mass. It is owned by Barry J. Cadden, his wife, Lisa Cadden and her brother Gregory Conigliaro, according to public records from the Secretary of Commonwealth.
Massachusetts Department of Public Health officials announced that two other companies: Ameridose and Alaunus Pharmaceutical, also owned by Cadden and his wife's family, would shut down temporarily. In addition to NECC, the FDA is also investigating Ameridose.
Dr. Madeleine Biondolillo, the Director of the Bureau of Healthcare Safety and Quality at the Massachusetts Department of Public Health, was asked about the family ownership at a recent press conference. She said: "The corporate governance structure [of NECC] is very much at the center of the investigation."
Former employees of NECC told CBS News the main manager, Barry Cadden, was good to his employees and careful about compliance.
"NECC was like a small close-knit community," said one employee who started working at New England Compounding Center when he was 19 years old. He started in shipping, then data entry and worked his way up to sales and management.
A former quality assurance specialist at NECC's sister company Ameridose, who requested that she not be identified, said the two companies were completely separate and did not share clean rooms or raw material. The former employee who left in 2011 said the only thing the two companies shared was the same management. But she said NECC did not have the same high level of quality assurance as the much larger Ameridose.
Officials at the Massachusetts Department of Public Health said NECC was in violation of its license and noted that the company's shipments to other states "bears looking at at a federal level."
Yet the company did not conceal the fact that it was shipping nationwide. The company's website claimed the business was licensed in all 50 states.
Susan Maynard, a former sales representative who worked at NECC as a regional sales manager from 2008 to 2011 described NECC's scale and aggressive national marketing in her online resume noting that she had "168 existing hospital accounts and 300 prospect accounts" throughout six states. She notes that she opened 240 new accounts between 2009 and 2011 and reached $100,000 in monthly sales in 2009.
Inside the "clean room"
Tom DiAdamo, who worked as a sales representative for NECC in 2009, told CBS News that he was "really surprised when this happened" and said that Barry Cadden, "is a dynamite guy who is meticulous about safety."
Former employees say NECC's offices were small. with 8 to 10 rooms for about 50 employees.
Despite a 2006 warning letter from the FDA that mentioned the agency was concerned about "potential microbial contamination," former employees said the "clean room" where the vials would have been filled was a controlled space. Workers in the clean room wore blue scrubs, masks and gloves, former employees said. There were usually no more than 6 people in the clean room and one employee said workers handled vials through gloves that were attached to boxed hoods. In order to get into the clean room a worker would have to enter a middle room that was air tight, change clothes and spray their gloves with sterilizer, according to a former employee.
A current employee posted on his online resume that NECC adhered to "USP 797" which is the safety and sterilization standard set by the United States Pharmacopeia that sets standards for pharmacies. Massachusetts is one of 18 states that mandates the 797 standard, according to an expert who advises US Pharmacopeia..
One former employee who worked in the pharmaceutical industry for over a dozen years and left NECC in 2008 told CBS News: "I hate the fact that it's being painted as some kind of back alley operation," she said, "Cause it certainly wasn't."