A sharp-eyed nurse at Yale-New Haven Hospital in Connecticut is being credited with raising a warning last week about floating mold in vital intravenous drugs, prompting a mass recall -- and possibly averting serious infections in patients in at least four states.

The nurse spotted the debris in a bag of magnesium sulfate IV solution as part of a routine safety check, according to spokesman Rob Hutchison.

“This nurse pulled it and immediately called the pharmacy,” said Hutchison, who didn’t identify the employee.

The hospital quickly quarantined about 40 different types of drugs produced by Med Prep Consulting Inc., a Tinton Falls, N.J., compounding pharmacy that has recalled all lots of all drugs and temporarily ceased operations under a consent order imposed by the state pharmacy board.

Five bags with floating mold were found at Yale-New Haven Hospital; tests showed the debris was a still-unidentified fungus. Eighty-eight orders of the magnesium sulfate solution -- in shipments ranging from 10 to 20 bags up to 500 bags -- were sent to 13 hospitals including Yale-New Haven, according to Angelo J. Cifaldi, a lawyer for Med Prep.

Hospital officials are reaching out to doctors and patients who may have received the contaminated drugs, Hutchison said. Health officials in Connecticut, New Jersey, Pennsylvania and Delaware all said they are working with federal investigators to determine what steps to take next. The drugs were produced and delivered between Feb. 18 and March 13.

The worry is that patients may have been injected with tainted 50-millileter doses of magnesium sulfate 2 gram in dextrose 5 percent solution in water.

“Giving a patient a contaminated injectable drug could result in a life-threatening infection,” Dr. Janet Woodcock, director of the Center for Drug Evaluation and Research for the Food and Drug Administration, said in a statement.

So far, no infections or other problems have been reported, FDA officials said.

But it’s a worrisome -- and very real -- possibility six months after an outbreak of fungal meningitis tied to contaminated pain shots that have been tied to 722 illnesses and 50 deaths.  The now-bankrupt compounding pharmacy blamed in that outbreak, New England Compounding Center of Framingham, Mass., had serious problems with contamination and sterility, investigations showed.

In addition to the magnesium sulfate solution -- which is used to replace electrolytes in hospitalized patients -- Med Prep also makes a wide variety of sterile drugs, including antibiotics, anesthetics, cardiac, labor and delivery and pain management medications, according to the FDA.

The firm received FDA warnings about its sterility practices in 2001 and 2010, agency records showed.

The 1,541-bed Yale-New Haven hospital has used drugs from compounding pharmacies in order to meet the demand for the volume of vital medications, Hutchison said. Drug shortages in recent years -- particularly shortages of sterile injectables -- have sent many hospitals to compounding pharmacies, experts say.

Of the 86 drugs affected by the Med Prep recall, 53 are in short supply, according to Erin Fox, manager of the Drug Information Service at the University of Utah, which tracks drug shortages. 

After pulling the Med Prep products, the hospital is trying to find ways to replace the drugs -- and mixing many of the specialized products themselves.

“We’re working very hard to source products from other vendors,” Hutchison said.

Many of the drugs will be unavailable, however, Fox said. And it can be very hard for a hospital to ramp up its own sterile drug production quickly. 

"I think it's concerning anytime a hospital is completely starting from scratch in a day or two."

Related stories: 

• Visible mold forces recall of N.J. pharmacy injection drugs
• Six months after fungal meningitis outbreak, patients still getting infections

AP

Nearly six months after injectable steroids made by the New England Compounding Center were implicated in an outbreak of fungal meningitis and other infections, more people are turning up ill, including those who previously tested clear of infection.

Nearly six months after the start of a deadly fungal meningitis outbreak blamed on tainted pain shots, patients who originally tested clear are showing up sick, raising worries that the incubation period for illness may be longer than anyone thought.

Though the flood of patients has slowed dramatically, two or three people each week are still reporting infections caused by contaminated steroids in the outbreak that has killed 48 and sickened more than 700, officials with the Centers for Disease Control and Prevention said.

Among those new patients are people who received mold-tainted doses of the drug methylprednisolone, but who previously got MRIs or lumbar punctures that showed they were free of infection. These slow-growing infections aren't as severe as meningitis, but worrying nonetheless.

“If you had an MRI in October, I don’t know that you’re out of the woods,” said Dr. Anurag Malani, an infectious disease expert at St. Joseph Mercy Hospital in Ann Arbor, Mich., the state that has seen the most cases -- 253 -- in the outbreak.

CDC officials issued a health alert this week urging clinicians to remain vigilant for new infections, even in people who show subtle symptoms -- or none at all.

“We are seeing some patients with very long incubation periods,” said Dr. Tom Chiller, associate director for epidemiological science in the CDC’s division of foodborne, waterborne and environmental diseases. “We expect to see people getting infections months after their injections.”

Nearly 14,000 people in 23 states were exposed to the contaminated drugs produced by the now-shuttered New England Compounding Center of Framingham, Mass. An estimated 11,000 actually received shots for back or neck pain, the CDC says. So far, 720 people in 20 states have fallen ill.

Most of the seriously ill people – those with fungal meningitis infections that caused strokes, for instance – showed up within several weeks or one to two months starting in late September.

Back then, CDC officials told worried patients that the greatest risk for meningitis was likely in the first 42 days -- six weeks -- after the shots, suggesting that they could breathe easy after the first week in November.

But patients have continued to become ill, most often not with meningitis, but with infections at the injection site, with epidural abscesses or with a condition called arachnoiditis, an inflammation of the nerves near the spine.

Though doctors have little experience with such fungal infections, the incubation period appears to be stretching longer than a previous outbreak in 2002, when a patient became ill 152 days – five months – after getting a steroid shot.

“I don’t think at this time we know how long the incubation period is,” Malani said.

That’s worrisome for people like John Horrell, 54, of Nashville, Tenn., who received a steroid shot for back pain from one of three tainted lots in September. He says he’s feeling “remarkably well” these days, with no signs of infection. Health officials told him the biggest worry was after 90 days or so, but now he’s not so sure.

“There’s people still having problems,” said Horrell, who owns a sound system firm. “We just keep our fingers crossed. I try not to worry about it.”

CDC officials want health workers to continue to monitor patients who got shots, particularly those whose have pain that is worse or different from the initial symptoms. But even patients who previously tested negative for infections and those with no apparent symptoms are at risk.

“These infections may be unrecognized because some patients have not continued to receive close clinical follow-up or because they have not recognized symptoms suggestive of a localized infection,” the new alert says.

CDC recommends that health workers have a low threshold for considering MRIs, or magnetic resonance imaging, to detect unseen infections.

Even patients who initially resisted MRIs because they didn’t want them or didn’t think they needed them have turned up with infections, said Malani.

The danger of not detecting the infections is that they only will get worse, Chiller said.

“Any untreated infection can sit there and smolder and spread,” he said, noting it can move beyond soft tissue to bone and the central nervous system, with devastating, even deadly, effects.

That, however, raises the next question in the ongoing meningitis puzzle: How long should infected patients be treated? Some patients say they’ve been told three months, then nine months -- then a year.

The primary drugs used to treat the fungus -- voriconazole and amphotericin B -- are both expensive and toxic, with a host of side effects ranging from hair loss and hallucinations to liver problems. 

Margaret Snopkowski, 51, of Fowlerville, Mich., has been on the drugs since early October, when she developed meningitis -- and later, arachnoiditis -- after getting a contaminated shot.

She's back home, but life is hardly back to normal, especially with the high doses of antifungal drugs necessary to keep her infection in check.

“She walks around like a zombie,” said her husband, Tom Snopkowski. “It just knocks her on her butt.”

Family members had hoped she’d be better by now, or at least looking to wean herself from the drugs. But that’s not happening, her husband said. Another MRI is scheduled for next week to see whether the infection has gotten worse.

“Now, they don’t even have an end date for that treatment," he added.

Related: 

Pharmacy tied to fungal outbreak files for bankruptcy

Fungal meningitis risk greatest first six weeks after shots, CDC says

Fungal meningitis victim hopes Congress hears: 'It's torturous'

Courtesy Minnesota Department of Health via AP

Vials of injectable steroid drugs made by the New England Compounding Center in Framingham, Mass., have been blamed for fungal meningitis and other infections that have caused 45 deaths and nearly 700 illnesses. Now, a new survey says that 13 percent of pharmacists and others polled said they found contamination in their sterile drugs last year.

As deaths continue to climb in the ongoing outbreak of fungal meningitis infections caused by contaminated pain shots, a new survey of hospital pharmacists shows that they believe it could happen again.

About 13 percent of pharmacists, pharmacy technicians and others who responded to a poll from the Institute for Safe Medication Practices said that they believed contamination had occurred in the compounded sterile drugs made by their shops last year.

Those are the same types of drugs now blamed for 45 deaths and nearly 700 infections in people who received tainted injectable steroids made by the shuttered New England Compounding Center of Framingham, Mass., according to the Centers for Disease Control and Prevention.

Only about half of staff pharmacists in the ISMP poll were confident that contamination had not occurred at their site in the past year. And nearly three-quarters of the 412 health care practitioners who responded said that contamination certainly could occur in drugs from their sites that were supposed to be sterile.

“We’ve known that this is a risk and a hazard for a long, long time,” said Mike Cohen, president of the ISMP, which monitors medication safety. “Consumers are still at risk. And they need to know.”

The fungal meningitis outbreak, which has left hundreds of people facing months or years of treatment, is among the “worst public health disasters related to medication in my lifetime,” Cohen said.

ISMP officials wanted to understand if the problems of properly managing high-risk compounded sterile preparations -- known as CSPs -- were as widespread as they thought.

It appears that the answer is yes.

The poll, which included mostly pharmacists, but also pharmacy techs, doctors and nurses, was conducted last November and December, at the height of the meningitis investigation, which was first detected in September.

It focused on how hospitals are managing CSPs, which are either made on-site by trained staff, or purchased from external compounding pharmacies, which includes companies such as NECC.

Sterile injectable drugs are particularly difficult to produce because they require mixing non-sterile drugs and other ingredients, which must be then terminally sterilized to ensure that no contamination such as bacteria, mold or fungi get into the final products.

In the case of NECC, federal inspectors found significant contamination throughout the site, including in the company’s so-called clean room.

But the new poll shows that problems may be present in other places, too. Eleven percent of the pharmacists and 29 percent of pharmacy techs in the study reported they believed there had been contamination of CSPs on site in the previous year. It’s not clear from the poll whether the contamination was detected before distribution, or whether the drugs made it to patients. Nor is it clear whether they reported the problems to hospital authorities or others.

Those are important questions, said Bona Benjamin, director of medication use quality improvement at the American Society for Health-System Pharmacists. If techs responsible for enforcing sterilization requirements under the strict USP 797 guidelines detected contamination as a result of careful testing, then it's a good sign. If the drugs were dispensed, then it's not. 

"Contamination is a well-known risk of compounding sterile products," Benjamin said. "I think the results are very interesting and I think it would bear a little bit of a deeper dive."

The poll also showed that half of the pharmacists were confident that contamination had not occurred on their watch, but that dropped to 38 percent when the pharmacy techs were asked.

Of the quarter of respondents who said that contamination could not occur in their facility, most noted that it was because high-risk CSPs were not prepared in their hospital pharmacies.

Ryan Forrey, associate pharmacy director at The Ohio State University Medical Center, said the ISMP poll underscores that hospitals should use high-risk CSPs only when they're necessary -- and that they should follow strict guidelines. 

"It highlights the need for work practices that are followed consistently and that are effective for reducing contamination," said Forrey, who is affiliated with the James Cancer Hospital and the Solove Research Institute.

The recent poll is only one more indication of the potentially serious problems involving sterile drug contamination, Cohen said. Food and Drug Administration Commissioner Margaret Hamburg faced harsh questioning by Congress in November about the agency’s handling of the fungal outbreak. In December, FDA officials recommended changing the way compounding pharmacies are regulated, in part to keep a closer eye on high-output pharmacies like NECC.

In the meantime, consumers should understand that sterile injectable drugs -- including back pain shots -- may be riskier than even the doctor acknowledges, Cohen said.

“If they’re going to get an epidural injection -- or have concerns about any injection, they should ask,” he said.

Related stories: 

• Lucky phone call alerted CDC to meningitis outbreak
• Fungal meningitis victim hopes Congress hears: 'It's torturous'
• Fallout from fungal meningitis mess: more drug shortages

The four primary owners of the pharmacy linked to a deadly U.S. meningitis outbreak that has killed 44 people received at least $16 million in salaries and shareholder distributions in 2012, according to papers filed in U.S. Bankruptcy Court.

New England Compounding Center owner Carla Conigliaro, the largest shareholder in the privately held company, received nearly $9 million in 2012, according to court papers filed late on Friday.

NECC also paid about $18,000 on her American Express card for purchases from gas stations, restaurants, the Apple Store and other places.

Barry Cadden, NECC's chief pharmacist, received about $3.2 million in 2012, filings show. His wife, Lisa Cadden, received about $2.8 million. Greg Conigliaro, a recycling entrepreneur who is Lisa Cadden's brother, received about $1.6 million.

The filings also showed that Framingham, Massachusetts-based NECC had made lease payments for a 2012 BMW X5 and 2011 Mercedes Benz GL-550. NECC paid, for example, $1,251 a month for Carla Conigliaro's Mercedes Benz lease payment, court papers show.

Brown Rudnick LLP, which is representing the official committee of unsecured creditors in NECC's bankruptcy, said NECC had paid more than $21 million to the pharmacy's four primary owners and other insiders.

Medical Sales Management, which shares some common ownership with NECC, received more than $4 million from NECC in 2012, court papers show.

A spokesman for NECC did not return a telephone call seeking comment.

NECC filed for bankruptcy protection last month after U.S. authorities shut down its pharmacy operations amid a meningitis outbreak that has killed 44 people and sickened 678 others, according to the U.S. Centers for Disease Control.

NECC shipped thousands of vials of a fungus-tainted steroid to medical facilities throughout the United States, according to authorities.

Related stories:

• Pharmacy behind fungal meningitis outbreak pushed hard to expand
• The brothers-in-law at the heart of the fungal meningitis outbreak
• More drug shortages may follow meningitis outbreak

The compounding pharmacy at the center of an ongoing outbreak of fungal meningitis and other infections says the cleaning company it hired is also at fault for unsanitary conditions linked to more than 650 infections and 39 deaths in the U.S.

The New England Compounding Center sent a letter Dec. 31 to UniFirst Corp., asking UniFirst officials to indemnify NECC against claims stemming from the compounding and sale of tainted steroid injection drugs, according to a filing with the Securities and Exchange Commission.

“This demand relates to the limited, once-a-month cleaning services the Company provided to portions of NECC’s cleanroom facilities,” UniFirst, of Wilmington, Mass., explained in required filings.

“Based on its preliminary review of this matter, the Company believed that NECC’s claims are without merit.”

Federal health regulators found fungi in three lots of tainted steroids linked to infections and deaths and more fungi and bacteria in other drugs made by NECC.

In addition, Food and Drug Administration inspectors found evidence of contamination documented throughout the NECC facility and dating from January 2012 through September. In some cases, surfaces were overgrown with visible mold, inspectors said.

UniFirst provided services through its UniClean business as specified by NECC and using NECC’s own “defined cleansing solutions,” UniFirst spokesman Adam Soreff told NBC News in a statement. UniClean technicians cleaned approximately 1½ hours each month.

“UniClean was not in any way responsible for NECC’s day-to-day operations, its overall facility cleanliness, or the integrity of the products they produced,” Soreff said.

NECC filed for Chapter 11 bankruptcy protection on Dec. 21, with officials pledging to establish a fund for victims. NECC faces more than 400 lawsuits from patients who received epidural steroid injections later found to be contaminated with fungus linked to the serious and deadly infections. Some 14,000 people in 23 states received the injections before the problem was discovered in September.

Related stories: 

• Pharmacy tied to fungal meningitis outbreak files for bankruptcy 
• FDA ponders new pharmacy rules after deadly outbreak
• Fungal meningitis victim hopes Congress hears: 'It's torturous'

Many of the 13,000 or so people who haven’t been sickened by contaminated pain injections from the pharmacy at the center of the fungal meningitis outbreak may have infections they don’t know about, federal health officials warned on Thursday.

Patients who got steroid injections from one of three contaminated batches should check back with their doctors if they have any symptoms at all, officials with the Centers for Disease Control and Prevention said -- and doctors should consider running magnetic resonance imaging (MRI) scans to check for infections.

Researchers in three of the 19 affected states ran an experiment in which they did MRIs on 128 patients who had not been diagnosed with infections before. They all had new or worsening symptoms such as pain at the injection site. More than half of them -- 52 percent -- had MRI evidence of some type of infection, including abscesses, a type of nerve inflammation called arachnoiditis or even infections of the bone in the spine.

“These findings demonstrate that among patients with no previous evidence of infection, and with new or worsening symptoms at or near the site of their injection, more than 50 percent had findings suggestive of a localized spinal or paraspinal infection,” CDC wrote in a health alert sent to doctors.

The outbreak of fungal meningitis has made at least 620 people sick and killed 39 of them, and CDC says to expect more infections. It’s been traced to a single pharmacy, the New England Compounding Center (NECC) in Framingham, Mass. The pharmacy has been closed and all of its products recalled, but the crisis has prompted a Congressional investigation of how regulators allowed NECC to continue operating.

The Food and Drug Administration says its inspectors have found unsterile conditions and many contaminated products at NECC and has asked for wider regulatory powers for policing such pharmacies.

NECC distributed its products far more widely than it was licensed to, and officials say more than 75 clinics in 23 states got some of the contaminated steroids. Close to 14,000 people received contaminated injections.

Of the 620 who have been infected, 367 had meningitis, a dangerous and often deadly inflammation of the coating that protects the brain and spinal cord. Another 250 have local infections of the spine or the joints where they were injected, such as the ankles or shoulder. All will require weeks or months of treatment with strong antifungal drugs.

Because treatment is so harsh, CDC has held off on saying everyone who got an injection should be treated just to be safe. And CDC’s been conservative on recommending scans to see if there’s an infection that isn’t causing obvious symptoms, in part because MRIs are expensive and often difficult for patients to schedule.

But anyone who has pain or other symptoms should go back to the doctor, CDC now advises.

“CDC is recommending that clinicians should consider obtaining an MRI with contrast of the injection site in patients with persistent but baseline symptoms because the presentation of these spinal or paraspinal infections can be subtle,” the alert says.

“Some patients who received spinal or paraspinal injections with implicated MPA from NECC may currently have an unrecognized, localized spinal or paraspinal infection. CDC is therefore re-emphasizing the need for clinicians to remain vigilant for evidence of fungal infection in these patients.”

Related stories:

• Some fungal infections thwart treatment in outbreak
• FDA ponders new rules after fungal meningitis outbreak
• CDC says lucky phone call alerted agency to outbreak

Centers for Disease Control and Prevention

CDC officials meet at the beginning of the outbreak of fungal meningitis, which has now killed 39 people and made more than 600 ill.

A single phone call from a North Carolina clinic gave a Centers for Disease Control and Prevention investigator the heads up she needed to realize that an outbreak of fungal meningitis, which has now killed 39 people and made 620 sick, was likely going to be a national emergency.

The CDC published its first account on Wednesday of how state and federal investigators have handled the outbreak, and the agency warns the trouble is still not over. The report, published in the New England Journal of Medicine, describes how doctors, public health officials and clinic workers raced to track down patients at risk from lots of contaminated pain medication.

Dr. Rachel Smith had only been working at the CDC’s  fungal diseases branch for a year and a half when the reports came in last September about a patient at a Tennessee pain clinic who had a very unusual type of meningitis, apparently caused by a fungus. Dr. April Pettit, an infectious disease expert at Vanderbilt University who treated the patient,  had notified the Tennessee Department of Health, which in turn notified CDC.

There was a chance the contamination was a local problem, perhaps from dirty needles at the one clinic.

“We were certainly worried this could be a bigger issue but wanted to do due diligence,” Smith told NBC News in a telephone interview.

They’d already figured out that steroid injections might have been the source of the contamination and started calling pain clinics that may also have bought drugs from the same source: the New England Compounding Center in Framingham, Mass.

They asked the clinics to keep an eye out for patients with symptoms of fungal meningitis, such as headache, fever and pain where they got the injection. At some places, including the North Carolina clinic, Smith had to navigate layers of receptionists and she left multiple voicemails and messages.

“I still remember getting this call back from North Carolina,” Smith said. “They called me like three or four times, trying to get through because they no idea what this woman had, and when I called and said, ‘Hey do you have anyone with these symptoms?’ they said ‘Oh my god. That is what this woman has.'”

The next day, CDC officials started calling and emailing all 50 states. “It was really that one patient who turned the whole thinking about this outbreak,” Smith said.

And what made the CDC extra vigilant about the first few cases was the fact that NECC, the source of the steroids, was a compounding pharmacy. “Compounding pharmacies and compounded products had been the source of other outbreaks. When we saw this drug had been compounded we were a little more worried about it,” Smith said.

Since then, the Food and Drug Administration has found several batches of drugs made by NECC were contaminated with several species of fungus and bacteria. Inspections showed the pharmacy, which has since been closed, was filthy. Congress is investigating how FDA and state regulators allowed the pharmacy to operate far beyond its license, and the FDA is proposing new ways to regulate these companies.

The CDC’s report says it’s essential to make sure that drugs distributed by compounding pharmacies are clean.

“This outbreak shows that we need to make sure that drugs that are used for sterile injections are safe and uncontaminated,” Smith says. “The public has trust in us as public health officials and in the health system as a whole to deliver safe health care.”

Quick action by the public health system likely saved lives, said Smith. In other outbreaks of fungal infections the death rate has been around 40 percent. In this one, although as many as 14,000 people may have been injected with contaminated products, only 6 percent of those who were infected have died.

Without the alerts and publicity, many people may never have known why they were sick. For some patients, the first sign that something was seriously wrong was a stroke. Most had only vague symptoms -- headache, sometimes a fever, and sometimes pain where they were injected.

“Anecdotal data collected during the first week of the outbreak indicated that many of the initial patients had mild-to-moderate symptoms that ordinarily would not have prompted urgent medical evaluation,” the CDC report reads.

“We are still seeing cases and it’s not over yet,” Smith cautioned.

Now, more people are turning up with localized infections such as abscesses at the point of injection. But these can become very serious as the fungus works its way into tissue and even bone, where it is very hard to eradicate using antifungal drugs. Victims will have to take the drugs for weeks or months, and the antifungal medications themselves can damage the liver or kidneys.

Related stories:

• FDA to Congress: Fungal meningitis could happen again
• We didn't have the power to stop NECC, regulators say
• Compounding pharmacies - heroes or outlaws?

Cj Gunther / EPA

A Food and Drug Administration agent enters the offices of New England Compounding Center in Framingham, Mass. on Oct. 16. The FDA has proposed a new way to regulate pharmacies responsible for a deadly outbreak that has killed 39 people.

The Food and Drug Administration is recommending a new way to regulate so-called compounding pharmacies after an outbreak of fungal meningitis that has infected 620 people and killed 39 of them.

The FDA recommends dividing these pharmacies into two categories: typical compounding pharmacies, which make medicines to order based on individual prescriptions, and high-output pharmacies that would be regulated differently. A consumer group says this is a recipe for disaster.

The outbreak, first confirmed in September, has been traced to the New England Compounding Center in Framingham, Mass. It was licensed as a compounding pharmacy, which means it was supposed to mix and distribute drugs only on an individual, prescription-by-prescription basis.

However, investigations have shown NECC worked on a much, much larger scale, and somehow wiggled out of several run-ins with both the FDA and state regulators over the scale of its operation and also previous cases of contamination.

FDA investigators have found vials of steroids used for back and joint pain injections were contaminated with at least two species of fungus, as well as bacteria. Patients being treated for back pain had these contaminated drugs injected right into their spines, where the fungus grew slowly, eventually spreading into spinal fluid and causing vague symptoms such as headache and fever.

So far, 33 of the victims have had strokes, and patients all face weeks and months of therapy with strong antifungal drugs that themselves can have severe side effects, the Centers for Disease Control and Prevention says.

FDA officials are holding a meeting later on Wednesday with representative of states to discuss how to better regulate pharmacies, especially since more and more super-compounders like NECC are operating.

“A category of ‘nontraditional’compounding has evolved in the last decade that FDA believes requires additional oversight. The Agency is working with Congress to consider new authorities regarding ‘non-traditional’ compounding pharmacies,” the  FDA said in a statement issued ahead of the meeting.

“Historically, regulation of pharmacy compounding has focused on drawing a line between traditional pharmacy compounding and other manufacturing.” States have regulated the small compounding pharmacies, while FDA has regulated the big manufacturers.

“Going forward, FDA believes the focus should be shifted from attempting to draw a bright line between traditional pharmacy compounding and other manufacturing to clearly defining traditional pharmacy compounding that should be primarily overseen by the states and higher risk non-traditional pharmacy compounding that would require compliance with federal standards,” the FDA says.

The consumer group Public Citizen says the FDA is trying to give up some of its responsibility for regulating pharmacies.

“The FDA’s proposal for oversight of ‘non-traditional’ compounding, if implemented, would decriminalize what is now illegal drug manufacturing conducted under the guise of pharmacy compounding, and ensure the continuing occurrence of serious disease outbreaks caused by tainted drugs in the future,” said Dr. Michael Carome, deputy director of Public Citizen’s Health Research Group. “The proposal would legitimize current abuses to the system and put the public at risk.”

Carome suspects Hamburg wants to pass much of its responsibility for regulating even the big compounders to the states. And, he says, many of the drugs that would be made by the new class of compounding pharmacies would be sterile drugs meant to be injected. “This is a high-risk class of drugs, no matter how many doses you make” Carome said in a telephone interview.

Carome’s group wrote a letter to Health and Human Services Secretary Kathleen Sebelius urging her to reject any such proposal.

“We have expressed concern all along, since the fungal meningitis outbreak became known, that this represents a significant regulatory failure on the part of the FDA, that at the highest levels the agency sought to dodge criticism,” Carome said in a telephone interview.

“There needs to be an independent investigation of this.” Carome suggests the Office of Inspector General could undertake such an investigation.

Neither the FDA nor officials with the department of Health and Human Services have responded to questions about Public Citizen's concerns. 

Carome’s not alone in accusing the FDA of of dodging questions. Several senators and representatives, even some Democrats friendly to the administration, accused FDA Commissioner Dr. Margaret Hamburg of avoiding giving straight answers to their questions at hearings in November.

"This is a complete and utter failure on the part of your agency," Rep. Cliff Stearns, the Florida Republican who chairs the House Energy and Commerce oversight subcommittee, told Hamburg at a Nov. 14 hearing.

Hamburg told Congress the FDA needs stronger authority to regulate the pharmacies. Congress passed a bill in 1999 that would do that, but part of it was thrown out by the Supreme Court and Congress and the FDA never decided how to proceed.

“Under current law, FDA can act and needs to act. They can’t wait for new legislation,” Carome contends. But he also supports a bill offered by Connecticut Democratic Rep. Rosa DeLauro that would strengthen FDA’s authority.

Republicans who control the House say they aren’t sure the FDA needs any more powers, and it’s not clear if or when Congress could come up with a bill.

And FDA has noted that compounding pharmacies play an important role in filling needs during drug shortages.

Related stories:

• FDA to Congress: Fungal meningitis could happen again
• We didn't have the power to stop NECC, regulators say
• Compounding pharmacies - heroes or outlaws?

Regulators repeatedly passed up opportunities to crack down on a Massachusetts pharmacy blamed for an outbreak of fungal meningitis that has killed 36 people and made 541 sick, the Boston Globe reported Monday.

Barry Cadden, the pharmacist who started up the New England Compounding Center, boasted about taking the pharmacy national even as he promised state regulators that he wanted to supply only locally, the newspaper reported. And the Food and Drug Administration handed over responsibility for monitoring NECC to the state pharmacy board even as Cadden made good his promise to expand beyond his license.

Compounding pharmacies like NECC are supposed to supply drugs on an individual, prescription-by-prescription basis. But NECC was mass-producing and mass-distributing drugs, state and federal regulators have found.

“By 2002, the year the FDA started investigating the firm, it was clear that New England Compounding’s strategy went far beyond the local focus Cadden had promised. Yet state and federal regulators did next to nothing to slow its growth,” the Globe reports.

Cadden set up an exhibit at a 2003 meeting of eye doctors, aggressively marketed NECC’s products and co-sponsored the Eastern Pain Association meeting in New York in 2005.

NECC is now closed and both the FDA and state regulators are trying to figure out how things went so badly wrong.

Related links:

• More bacteria, fungi found in NECC's drugs
• FDA says another fungal meningitis outbreak could happen
• Cadden refuses to testify about outbreak

By Tim McLaughlin, Reuters

BOSTON - The U.S. Food and Drug Administration took 684 days to issue a warning letter after uncovering serious issues at the pharmacy at the center of the deadly U.S. meningitis outbreak, newly released documents showed.

The New England Compounding Center (NECC) chastised the FDA for taking so long, telling the agency its response time was nearly 18 months longer than the FDA's average response, according to letters released by a Freedom of Information Act request from Reuters.

Since the FDA's December 2006 warning letter to NECC, both sides have come under intense scrutiny. State and federal regulators, including the FDA, are being asked why they didn't move sooner against NECC, given a long history of concerns about the family-owned pharmacy's operations.

The Centers for Disease Control and Prevention said 34 people have died and 490 have been injured after Framingham, Massachusetts-based NECC shipped thousands of fungus-tainted vials of methylprednisolone acetate to medical facilities throughout the United States. The steroid was typically used to ease back pain.

On Tuesday, defense lawyers for NECC's owners told a U.S. District Judge in Boston there was nothing to show they had a direct hand in the cause of the meningitis outbreak.

But the newly released documents reveal a combative side to NECC chief pharmacist, Barry Cadden, and his brother-in-law, Greg Conigliaro, the recycling entrepreneur who helped him launch the specialty pharmacy.

Inspectors said Conigliaro became indignant during a September 2004 inspection by the FDA and Massachusetts regulators, documents showed. At one point, Cadden told his brother-in-law, "Don't answer any more questions!" according to a 2005 FDA memorandum.

The inspectors had concerns about how NECC was compounding and dispensing Trypan Blue, a dye sometimes used in eye surgery. Inspectors also expressed concern about how NECC was repackaging Avastin, highlighting the threat of contamination when the pharmacy opened sterile containers of the cancer drug.

The FDA's eventual warning letter to NECC in December 2006 was based on an inspection that began in September 2004 and ended on January 19, 2005, according to the documents.

"This prolonged gap between inspection and warning letters does not comply with FDA's procedures," Cadden, NECC's chief pharmacist, wrote in a January 5, 2007 letter to FDA compliance officer Ann Simoneau.

In follow-up correspondence, FDA officials apologized for the "significant delay" in correspondence time between the inspection and the warning letter. While the FDA conceded the gap was unusual, it in no way diminished the regulator's "serious concerns" about NECC's pharmacy operations, documents showed.

Related stories: 

Pharmacy owner refuses to testify about fungal outbreak

Fungal meningitis victim: "It's tortuous"

State pharmacy board chief fired

Bacteria, fungi found in pharmacy's drugs

Susan Walsh / AP

Food and Drug Administration (FDA) Commissioner Dr. Margaret Hamburg testifies Wednesday, Nov. 14, 2012, before the House Energy subcommittee on Oversight and Investigations hearing on the fungal meningitis outbreak. Without better legislation, Hamburg says, more such outbreaks could happen.

Food and Drug Administration officials know little about compounding pharmacies in the U.S., including who all is making drugs and medical supplies, how much they are making and where they are sending it, the agency's commissioner said Thursday. 

And, says FDA's Dr. Margaret Hamburg, it’s entirely likely there could be another outbreak of infections like the spread of fungal meningitis caused by contaminated pain injections that has killed 32 people and sickened more than 460.

Even while repeated inspections showed the pharmacy blamed for making and distributing the contaminated drugs was operating with dirty conditions and wasn’t following the rules, regulators at FDA were arguing about how much they could actually do to shut them down, Hamburg told a Senate hearing.

Hamburg and Dr. Lauren Smith, interim commissioner of the Massachusetts Department of Public Health, faced a second day of questioning in Congress about the outbreak. Reports by the House and Senate subcommittees holding the hearings paint a picture of a mixed record, with some states, such as Tennessee and Colorado, acting promptly and others, such as Massachusetts, doing little. And they also point a finger at the FDA.

“While the quick work of the public health community has led to early identification and treatment of many cases of meningitis, and reduced the fatalities resulting from the administration of the contaminated methylprednisolone, the committee’s investigation demonstrates that this crisis should have, and could have, been avoided entirely,” the Senate Health, Education, Labor and Pensions (HELP) committee report reads.

At issue is how the New England Compounding Center could have continued to make and distribute contaminated drugs that were given to at least 14,000 unsuspecting patients, even while regulators had their eyes on the company.

"It was obvious they were acting illegally," said said David Miller, chief executive of the International Academy of Compounding Pharmacy in Missouri City, Tex. "The Massachusetts Board of Pharmacy knew this was going on, FDA knew they were doing this 10 years ago and still did nothing to stop it."

Hamburg said it could happen again.

“For more than a decade there have been problems in this area and there will be more problems unless we really work together,” she told the subcommittee’s hearing. “I just think we can do better.”

Hamburg has been pressing for federal legislation to make clear what the FDA can do to regulate pharmacies. Some members of Congress have said at two days of hearings that they are not sure FDA needs more power but rather needs to use the powers it already has.

Sen. Pat Roberts, R-Kan., read out a list of state and federal actions against the New England Compounding Center dating back to 2002, none of which closed it down. Regulators say NECC was acting as a large-scale manufacturer, distributing tens of thousands of medical products to 45 states, while it was licensed to be a compounding pharmacy. Compounding pharmacies are supposed to mix products to order on the basis of individual prescriptions.

“In March 2002, a prescribing doctor reported to the FDA that as many as five patients became ill following an epidural injection of NECC-produced betamethasone repositories,” the Senate HELP committee report reads. Betamethasone is a steroid that can be used to treat pain like methylprednisolone, the main drug involved in the current outbreak.

“He reported the illnesses to the FDA, alerted NECC about the issue, and returned unused doses to NECC without taking samples. However, when the FDA arrived to inspect NECC on April 9, 2002, there were no records for the drugs in question.” No disciplinary action followed.

Two more patients got sick in August with meningitis-like symptoms, linked to methylprednisolone made by NECC, again reported to FDA.

The strongest action FDA ever took against NECC, before it raided the facility in October of this year, was a warning letter in 2006 over a different issue. “Finally, in 2006, a warning letter!” Roberts shouted. “Finally, we get something done!”

But FDA never acted on that warning, either. “Holy mackerel,” Roberts said. “What am I missing here?”

“I wasn’t at the agency at the time,” Hamburg said. “I know there was a lot of internal debate about whether and how to proceed. That’s why it was slow, because there was ambiguity in the law. I think that we all wish we had done more.”

Hamburg said she is trying to find out how many companies like NECC there are, making products in mass quantities.

“We do not know the universe of compounding pharmacies,” she told the hearing. “I do think that we should know,” she added. “We are beginning to reach out to our colleagues on the state level.”

Currently, the FDA regulates drug manufacturers, while state boards regulate pharmacies, including compounding pharmacies. FDA has mixed authority in different parts of the country, and another problem is the changing nature of the industry, Hamburg said.

“The problem is that it is not a clear distinction between what is a compounder and what is a manufacturer, either in law or in practice, and the industry is evolving,” she said. “We have tried to use the authority that we have, but it’s reactive.”

And FDA doesn’t even know where to begin looking harder. “We think there are about 7,500 pharmacies doing so-called advanced compounding, then about 3,000 doing sterile processing,” Hamburg said.

Hamburg said there is a need for federal regulations that set a framework for states to follow. “Some states are very strong in terms of their boards of pharmacy, others are weaker,” she said. “We have authority but it is limited and unclear and contested.”

Miller disputed this. “The difference between NECC and a compounding pharmacy is they weren’t filling prescriptions. They were bulk manufacturing and selling,” Miller told the committee. “By all current indications, the operations of NECC were clearly outside the scope of the state’s licensure requirements and their license should have been pulled long ago.”

Sen. Tom Harkin, D-Iowa, who chairs the panel, said the committee was sending a letter to every state board of pharmacy asking them to detail companies acting as compounding pharmacies.

“This committee will forge ahead in developing legislation,” Harkin said. He said he hoped a draft could be ready by early next year.

Harkin also said agencies like FDA and the Centers for Disease Control and Prevention need to be funded and staffed well so they can protect public health.  “This comes down to resources,” Harkin added. “We continually ask the Food and Drug Administration to do more and more and more.”

One person who could have answered questions wasn't there. Barry Cadden, president of NECC, did not accept the committee's invitation to appear. On Wednesday he refused to testify to a House panel, involking his Fifth Amendment right not to speak.

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