Protecting the Public from Unsafe Compounded Drug Products

Margaret A. Hamburg M.D.

In 2012, a devastating outbreak of fungal meningitis linked to a contaminated compounded drug product tragically resulted in the loss of 64 lives and caused more than 751 illnesses, many of which were very serious. These events were a powerful reminder of the potential harm that could be caused by unsafe compounding products.

Margaret Hamburg, M.D.FDA is moving aggressively on many fronts to protect the public from such threats.

For example, we have conducted more than 175 inspections of compounding facilities in the past two years. Some of these inspections were for cause and were performed after we received reports of serious adverse events related to drugs made by compounding pharmacies or when states requested our assistance. Other inspections were proactive, targeted at facilities identified through a risk-based model. Our proactive inspections were conducted in coordination with state officials from around the country and focused on each firm’s sterile drug production, because drugs labeled as sterile are used in ways that could greatly compromise patient care and safety if they aren’t actually sterile.

Our findings uncovered a variety of problems with sterile drug production practices at these facilities. As a result of these inspections, numerous firms stopped making sterile drugs and many recalled drug products that had been made under substandard conditions. In some cases, we worked with state officials to revoke or suspend pharmacy licenses. We also issued warning letters to firms that were producing drugs under inadequate conditions, notifying them of violations of the law and the need to take steps to correct the violations and prevent their recurrence.

We have also worked with the Department of Justice (DOJ) to hold facilities accountable if they harm patients or engage in serious violations of federal requirements that put patient safety at risk. Working with DOJ, FDA has initiated investigations and enforcement actions against compounding facilities that violate federal law – and we intend to continue this work with DOJ.

In addition to our inspection and enforcement efforts, FDA has taken many steps to implement the compounding provisions of the Drug Quality and Security Act (DQSA) — legislation enacted by Congress last year in response to the fungal meningitis outbreak.

To implement the compounding statutory provisions, FDA is establishing a policy framework to address compounding by state-licensed pharmacies as well as the new category of outsourcing facilities, which was created under the DQSA. Among other things, outsourcing facilities are facilities that compound sterile drugs and choose to register with FDA as outsourcing facilities, and they must comply with current good manufacturing practice requirements and are subject to FDA inspection on a risk-based schedule.

Two years after the fungal meningitis outbreak our hearts continue to go out to the victims of the tragedy and their families. Our work on behalf of all patients who want and deserve medicines that do not subject them to undue risk is far from being done. FDA will continue to work with the states, the Department of Justice and others to enable Americans to have greater confidence in their compounded drugs.

Margaret A. Hamburg, M.D., is Commissioner of the Food and Drug Administration

We’re Working to Offset Ameridose Impact

By Margaret A. Hamburg, M.D.

Drug shortages are two words that no one wants to hear—not patients, not health care professionals, and not me.

Margaret Hamburg, M.D.FDA has been working hard to prevent and mitigate drug shortages. In 2011, the number of medications in short supply hit 251. Addressing drug shortages must be a top priority for us at FDA because these are medications that people need to stay healthy, to treat their illnesses, and even, in some cases, to stay alive.

This year, we’ve taken significant steps to expand our efforts and to engage in new ways with industry. Between Jan. 1 and Sept. 30, 2012, FDA worked with drug manufacturers to help avert the shortage of 145 drugs. Many critical medicines used to treat cancer and conditions such as attention deficit hyperactivity disorder (ADHD) are no longer in short supply.

However, drug shortages are still a serious problem, one that may be temporarily impacted by Ameridose LLC’s voluntary recall of all of its unexpired products. Ameridose, located in Westborough, Mass., is managed by some of the same people as the New England Compounding Center—which produced the drug that is implicated in the deadly, multi-state outbreak of fungal meningitis. An inspection of Ameridose was initiated as part of FDA’s ongoing investigation of the outbreak.

FDA recommended that Ameridose recall its sterile drugs because we could not be assured of the sterility of those products. However, this recall may affect supplies of certain life-saving drugs for some health care systems. FDA has identified a number of Ameridose products—including drugs used during surgery and to treat medical conditions that include congestive heart failure—that were on the current drug shortages list before the recall.

We also know that the supply of other drugs may be affected by the Ameridose recall. That’s why FDA is taking proactive steps to minimize the impact this recall may have on current drug shortages, and to prevent other shortages from occurring.

For recalled medications on the current drug shortages list, FDA is taking the same actions it has used successfully to mitigate other shortages.

  • FDA is working with manufacturers of these drugs, requesting that they ramp up production if they are willing and able to do so.
  • For any manufacturers of these drugs that may be experiencing manufacturing or quality problems, FDA is offering assistance to enable them to produce shortage drug products that are safe and high quality.
  •  As with shortages of any critical products, FDA will expedite the reviews of any pending applications that could help with addressing the shortages.
  • FDA is identifying any additional manufacturers willing to initiate or increase production.
  • If manufacturers of critical drugs are not able to meet U.S. patient needs, FDA will explore overseas companies that are willing and able to import foreign drugs to address the shortage. In these instances, FDA evaluates the imported drug to ensure that it is of adequate quality and that the drug does not pose undue risks for U.S. patients.

Since the beginning of the year, the number of advance notifications to FDA of potential shortages has greatly increased. If we know that a problem is on the horizon, we’re able to proactively work with industry, organizations, patients and stakeholders to address it. We have doubled the number of staff members who work in drug shortage prevention and response.

We at FDA are committed to doing everything we can, using all available tools, to prevent or mitigate drug shortages and help keep critically needed products on the market.

Margaret A. Hamburg, M.D., is Commissioner of the U.S. Food and Drug Administration.

State and Local Partnerships Are Crucial

By Margaret A. Hamburg, M.D.

When there is a multi-state outbreak of illnesses, what federal agencies are doing in response is often the focus of attention. All too often, the dedicated efforts of countless other public servants at the state, county, and local levels aren’t acknowledged as much.

Margaret Hamburg, M.D.As we all strive to resolve the tragic outbreak of fungal meningitis tied to contaminated steroid injections, I want to recognize the invaluable role of our colleagues across the country. These frontline public health officials at all levels of government work alongside the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) every day, and even more closely in times of crises.   

State, county, and local health officials are often the first to hear about a problem and begin investigating. In this deadly outbreak of fungal meningitis, the alarm was first sounded by the Tennessee Department of Health. Tennessee has been one of the hardest hit in this outbreak. The Tennessee health department was told by a clinician on Sept. 18, 2012, about a patient with culture-confirmed Aspergillus meningitis

By Sept. 27, Tennessee public health officials, in collaboration with the CDC and the North Carolina Department of Health and Human Services, had identified eight additional patients with similar meningitis symptoms, but lab results were not showing a clear cause. With persistence, shoe-leather epidemiology and amazing laboratory efforts, state and federal public health officials worked quickly to narrow down the common exposure of these patients. They ultimately identified a steroid solution compounded at the New England Compounding Center (NECC) in Framingham, Mass., as the likely source of the outbreak. Conclusive evidence of fungal contamination was confirmed on Oct. 3, when FDA identified fungus in sealed NECC vials. CDC and state laboratories later pinpointed the fungus, Exserohilum rostratum, in both patients and also in unopened vials of the steroid solution. 

The FDA has been working closely with the CDC and public health officials in Massachusetts and other states to investigate the scope and cause of the outbreak. In fact, both agencies have been working hand-in-hand with our colleagues in every state affected by this outbreak.

The demanding task of tracking down the thousands of people who were potentially exposed to medications from one of three implicated lots of contaminated NECC medication has involved state, county and local health officials, the CDC and health care providers. So far almost all—97 percent—of the patients exposed to the original three implicated lots have been contacted. Now, FDA is urging healthcare providers to follow-up with patients who were administered any NECC injectable product that was shipped on or after May 21, 2012, including an ophthalmic drug that is injectable or used in conjunction with eye surgery, or a cardioplegic solution purchased from or produced by NECC.

More legwork is being performed by local, county and federal epidemiologists who are interviewing patients to collect key data about their experience while state public health officials are pitching in to help FDA ensure that the recall of NECC products is carried out in a timely and effective way, with no NECC products remaining in distribution.

Nearly every day our counterparts in the states play a role in helping the FDA fulfill its mission of keeping Americans safe and healthy. We work together, across state lines and  levels of government, whether the issue is foodborne illness, drug safety or other concerns. Frankly, we are immensely grateful for their expertise, professionalism and commitment to the people of their states and beyond.  

In the face of this current tragedy, we are all working hard—together—to fully contain the health risks associated with this outbreak as quickly as possible to protect patients and the nation’s medical drug supply.

Margaret A. Hamburg, M.D., is the commissioner of the Food and Drug Administration.