A Year of Significant Progress in Public Health

By: Margaret A. Hamburg, M.D.

Margaret Hamburg, M.D.A new year offers both an opportunity to look forward and an opportunity to reflect on the achievements of the previous year. And, in 2014, FDA’s accomplishments were substantial, touching on many of the agency’s broad responsibilities to protect and promote the public health.

Whether our achievements involved medical product safety and innovation, food safety and nutrition, tobacco control, or other areas of our important work, all were accomplished thanks in large part to our ability to respond to evolving needs and opportunities including the embrace of new approvals, technologies and cutting-edge science.

Consider these highlights:

Drug Approvals: This past calendar year, FDA approved 51 novel drugs and biologics (41 by CDER and 10 by CBER), the most in almost 20 years. Among CDER’s 2014 approvals are treatments for cancer, hepatitis C and type-2 diabetes, as well as the most new drugs for “orphan” diseases since Congress enacted the Orphan Drug Act over 30 years ago. Seventeen of these new approvals are “first in class” therapies, which represent new approaches in the treatment of disease. In addition, CBER approved many important biological products in 2014, including a number of groundbreaking vaccines for meningitis B, the flu, and certain types of Human Papillomavirus, the latter of which is expected to prevent approximately 90 percent of the cervical, vulvar, vaginal and anal cancers caused by HPV.

These developments are a testament not just to our expanding understanding of human biology, the biology of disease and the molecular mechanisms that drive the disease process, but also to FDA’s innovative approaches to help expedite development and review of medical products that target unmet medical needs, while adhering to the established standards for safety and efficacy. These include enhanced guidance to shape the research and development agenda, early input on clinical study needs and design, expedited review programs, targeted regulatory advice and other tools and incentives that spur investment and innovation in new medical products to address unmet medical needs.

Opioids: This past year FDA took several actions to address the abuse of opioid drugs. First, we approved abuse deterrent labeling for three opioid products that are designed to deter prescription drug abuse. These drugs used different technologies to combat the abuse problem in different ways, such as by making the product resistant to crushing or dissolving or using “aversive technology” to discourage users from taking more than the approved dosage of the drug. To help encourage the development of more drugs in abuse-deterrent forms, we are also working to provide additional advice to manufacturers. Although abuse-deterrent opioid drugs are not a silver bullet to prevent opioid abuse, we believe that our work in this area will give physicians effective new treatment options with less risk of abuse.

FDA also worked to improve the treatment of patients who overdose on opioids. We approved a new dosage form of naloxone, with an autoinjector to enable a caregiver to administer the drug in the emergency treatment of opioid overdose (as it rapidly reverses the effects of an overdose). While we continue to support development in this area, this approval offers a new valuable tool to help prevent the tragedy of opioid drug overdose.

Antibiotic Resistance: We made important strides in confronting the growing resistance of some bacteria to antimicrobial drugs. Our efforts, which are a critical part of the recently unveiled National Strategy on Combating Antibiotic Resistant Bacteria, offer a multi-pronged approach that recognizes that to effectively address this challenge means simultaneously addressing the many different causes for increasing antibiotic resistance. One important response has been efforts to expand the pipeline of new medical products, including therapeutics to treat and cure infection, diagnostics to aid in the identification of the cause of infection and of resistant infections, and vaccines to help prevent infection with bacteria in the first place.

These efforts are already having an impact. In 2014, FDA approved four novel systemic antibiotics. In contrast, only five new antibiotics had been approved in the previous ten year period.

In addition to working on the human medical product side, we also developed and, over the next two years will be implementing, an important complementary strategy to eliminate the use of medically important antibiotics for growth promotion in food-producing animals. This strategy, once fully implemented, also will bring the remaining uses of such drugs to treat, control or prevent disease in these animals under the oversight of veterinarians. All 26 animal health companies who produce those drugs have committed to participate, and 31 products already have been withdrawn from the market.

Pharmacy Compounding: We continued to respond effectively to the 2012 outbreak of fungal meningitis that was linked to contaminated compounded drugs. This included conducting more than 90 inspections of compounding facilities across the nation in the past year. As a result, numerous firms that engaged in poor sterile practices stopped making sterile drugs, and many firms recalled drugs that have been made under substandard conditions. Where appropriate, we have worked with the Department of Justice to pursue enforcement action against some of these facilities.

We also have continued to implement the compounding provisions of the Drug Quality and Security Act (DQSA), and to develop and implement policies to address compounding by state-licensed pharmacies and the new category of registered outsourcing facilities.

Food Safety: Over the past year, the Agency has made great strides in implementing the landmark FDA Food Safety Modernization Act (FSMA). Through our proposed rules for preventive controls requirements for both human and animal food, standards for produce safety, foreign supplier verification programs, third party auditor accreditation, focused mitigation strategies to prevent intentional adulteration of food aimed at causing large-scale public health harm, and requirements for sanitary transportation practices to ensure the safe transport of food, we are working to ensure the safety of American consumers related to the foods they eat.

Nutrition: Good health depends not just on food safety, but also on what we choose to eat. FDA plays an important role in promoting good nutrition and healthy food choices by helping consumers understand the importance and benefits of good nutrition – and of being able to make informed choices about what we eat.

New rules in 2014 to finalize requiring calorie information on restaurant menus and vending machines give our citizens information they need to make healthy food choices and hopefully help reduce the epidemic of obesity in the United States. We also proposed changes to the familiar “Nutrition Facts” label on packaged foods which, when finalized, will give our citizens updated nutrition information, reflecting the most current nutrition science, to help them make healthy choices when purchasing packaged foods.

Tobacco Control: There are few areas that have as profound an impact on public health as tobacco products, which is why, five years ago, Congress gave FDA the responsibility to oversee the manufacture, marketing, distribution, and sale of tobacco products.

Over the past year, we worked with state authorities to conduct more than 124,000 inspections of retailers to enforce the ban on the sale of tobacco products to children. We unveiled the first of its kind national public education campaign—The Real Cost—to reduce youth smoking. And we took the first steps towards extending the agency’s tobacco product authority over additional products such as electronic cigarettes (e-cigarettes), cigars, pipe tobacco, nicotine gels, waterpipe (hookah) tobacco, and dissolvables not already subject to such authority through our proposed “Deeming Rule.” In addition, as part of ongoing work on product review decisions, eleven tobacco products that were allowed to enter the market during a provisional period established by the Tobacco Control Act were found “not substantially equivalent” to a predicate tobacco product. As a result of this finding, these products can no longer be sold or distributed in interstate commerce or imported into the United States.

Ebola: The tragic Ebola epidemic in West Africa demonstrates that we do not have the luxury of closing our eyes – or our borders – to the public health problems that exist in the rest of the world. I’m proud that FDA has played an important role in the response to this disease, working closely with colleagues in our government as well as the scientific community, industry and a range of other organizations and nations. We have helped facilitate the development, testing, manufacture, and availability of investigational products for use in diagnosing, treating and preventing Ebola, and worked with sponsors and health care providers to facilitate access to these products as clinical circumstances warrant. In August 2014, FDA designated the drug Z-Mapp as an orphan drug for Ebola, with the hope that this would incentivize further development and study.

And I’m very pleased to report that FDA is represented on the ground in West Africa by dedicated officers of the Commissioned Corps of the Public Health Service who continue to staff and operate the Monrovia Medical Unit in Liberia that was built to treat the health workers who became ill responding to the outbreak. Like everything FDA does, both at home and abroad, our actions on Ebola represent our agency’s continuing commitment to health and safety, and the use of science to advance these important goals.

I am extremely proud of our accomplishments in 2014, and I am confident that FDA will have a successful 2015, as we continue our work to protect and promote the public health.

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

New Law Enhances Safety of Compounded Drugs and Protection of the Drug Supply Chain

By: Margaret A. Hamburg, M.D.

Since last year’s tragic meningitis outbreak and subsequent events involving compounded drugs, Congress has been hard at work to pass new legislation to provide FDA with the appropriate authorities for regulating compounded drugs to help make these products safe for the American public.

Margaret Hamburg, M.D.Over a much longer period of time, efforts have been made in Congress to enhance the security of the drug supply chain and protect consumers from exposure to counterfeit, stolen, contaminated or otherwise harmful drugs.

I am pleased that the Drug Quality and Security Act can help FDA protect public health in both of these critical areas.

One part of the new law offers a step forward in FDA’s oversight of certain entities that prepare compounded drugs. The new law will enable these compounders to register with the FDA to become “outsourcing facilities,” making them subject to certain other requirements including Federal quality standards, known as current good manufacturing practice. These facilities will also be subject to inspection by FDA on a risk-based schedule. If compounders register with FDA as outsourcers, hospitals and other health care providers will be able to provide their patients with drugs that were compounded in facilities that are subject to FDA oversight and federal requirements for current good manufacturing practice, among others. To that end, we will be encouraging healthcare providers and health networks to consider purchasing compounded products from facilities that are registered with FDA and subject to risk based inspections.

Drugs produced by compounders that are not registered as outsourcing facilities must meet certain other conditions described in the law, or they will be regulated by FDA as conventional drug manufacturers.

Generally, the state boards of pharmacy will continue to have primary responsibility for the day-to-day oversight of state licensed pharmacies, including traditional pharmacy compounding. And FDA will continue to cooperate with state authorities to address pharmacy compounding activities that may be in violation of the Federal Food Drug and Cosmetic Act.

Another part of the new law enables certain prescription drugs to be traced as they move through the U.S. drug supply chain. The goal is to protect the public from exposure to counterfeit, stolen, or otherwise harmful drugs. This will require manufacturers, repackagers, wholesale drug distributors, and dispensers (other than most licensed health care practitioners) to provide product and transaction information with each sale and notify the FDA and other stakeholders of illegitimate products, which will result in improved detection and removal of potentially dangerous drugs from the supply chain.

Starting four years after enactment of the law, manufacturers, followed by repackagers, will be required to affix a unique product identifier to each drug package that contains the drug’s national drug code (NDC), serial number, lot number, and expiration date. Starting six years after enactment of the law, wholesale drug distributors, followed by dispensers, may only trade products that  are encoded with product identifiers and will be able to verify the product identifier if they determine that they have  suspect product. Ten years after enactment, supply chain stakeholders and FDA will benefit from an electronic, interoperable system which will facilitate the efficient exchange of product and transaction information for prescription drugs at the individual package level. The system, when fully implemented, will enable verification of the legitimacy of the drug product identifier down to the package level, enhanced detection and notification of illegitimate product, and improved efficiency of recalls.

The Drug Quality and Security Act is a significant step toward having new and stronger drug quality and safety laws. While the law does not provide FDA with all the additional authorities sought, these provisions are a sign of progress.

We are committed and prepared to implement the new law that will help us to further protect public health.

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

Proactive Inspections Further Highlight Need for New Authorities for Pharmacy Compounding

By: Margaret A. Hamburg, M.D.

Ever since the recent fungal meningitis outbreak tragically took so many lives and injured so many others, we have been very clear that we all must act aggressively to help make sure nothing like this ever happens again. Last month I wrote in FDAVoice about the legislation and resources we believe are urgently needed to effectively oversee the evolving compounding pharmacy industry.

Margaret Hamburg, M.D.Above all, patient safety is our greatest priority. In addition to working with Congress and other stakeholders on legislation, we also have been very focused on evaluating our current surveillance and enforcement approach to compounding pharmacies and are using our existing, yet limited, authorities more effectively to protect consumers.

FDA has continued to conduct for-cause inspections upon receiving reports or complaints about serious adverse events related to drugs made by compounding pharmacies, or when states have requested our assistance.

And in coordination with state officials from around the country, we have just recently completed proactive inspections of 31 firms that are known to have produced sterile drugs in the past. We identified these firms using a risk-based model that included factors such as serious adverse event reports, historical inspection data, and reports of product quality problems. The inspections specifically focused on each firm’s processing of sterile drugs to identify firms that may pose a higher risk of producing contaminated sterile products. A summary of these inspections can be found on our website.

During the course of both our proactive and reactive inspections over the past few months, we observed concerning sterility practices, inappropriate conditions for sterile processing and other practices that create risk of contamination. As of this week, we have issued to all but one pharmacy that we inspected an inspection observation report (called an FDA Form 483, or just a “483”) that lists objectionable conditions observed at the facilities. The one firm not receiving a FDA Form 483 was not producing sterile drugs.  

As noted on some of these 483s, select FDA observations during the inspections include:  unidentified black particles floating in vials of supposedly sterile medicine; rust and mold in “clean rooms” where sterile injectable medications were produced; technicians handling supposedly sterile products with bare hands; and employees wearing non-sterile lab coats.

In part, due to FDA’s inspectional observations noted during the inspections, several firms have voluntarily recalled their products, and others temporarily suspended production of their products intended to be sterile while they correct deficiencies found by the investigators.

It may surprise some people to know that, even in light of the recent tragic events, some of the firms we inspect still challenge our authority to conduct full inspections of their facilities. Our inspections have been delayed or the inspectors were denied full access to records at some of these facilities. At least four of our recent inspections were delayed by such resistance; and in two other instances, we had to get administrative warrants from the courts, resulting in U.S. marshals accompanying FDA inspectors back to the firms so FDA could complete the inspection. These challenges and others highlight the need for clearer authorities for FDA to efficiently protect public health.

Additionally, these inspectional observations reveal that there continues to be reason for concern about sterility deficiencies and other problems in some compounding pharmacies across the country – problems that could potentially affect the health of patients. To carry out this proactive inspection effort, FDA had to shift resources from other areas, and this is not a sustainable approach for the longer term. 

We are committed to working with the states, industry and Congress to put the necessary protections in place, but we need to act quickly. And we will continue to work tirelessly on this issue. Patients deserve nothing less.

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

FDA Must Have New Authorities to Regulate Pharmacy Compounding

By: Margaret A. Hamburg, M.D.

The deadly outbreak of fungal meningitis associated with a compounded medication was a horrible tragedy, and I’ve asked myself many times if and how it could have been prevented. I speak for everyone at FDA when I say that our hearts go out to the many victims, including those still struggling with this devastating infection, and their loved ones.

Margaret Hamburg, M.D.While our investigation of this deadly outbreak has been a top priority, our responsibility at FDA is also to help make sure this doesn’t happen again. We are currently deploying resources to work with states to inspect certain state-licensed pharmacies that produce sterile drug products that we believe may present the highest risk. Over the past two months, we have inspected over 30 facilities and will continue to work to protect public health. 

But our authorities are limited and not the right fit for FDA to provide appropriate and efficient oversight of this growing industry. There should be legislation that establishes appropriate, minimum federal standards for firms that compound sterile drug products in advance of or without a prescription and ship them interstate.  FDA must have clear authority to proactively inspect pharmacies to determine the scope and nature of their operations.  Even during this time of heightened awareness, our inspectors are being delayed in their work or denied full access to records at some of the facilities we are inspecting.

And serious problems at compounding pharmacies continue to occur. Just this week there have been two recalls of sterile compounded and repackaged drug products. In one recall, the presence of floating particles, later identified to be a fungus, were reported in five bags of magnesium sulfate intravenous solution, resulting in a nationwide recall of all sterile drug products produced by the pharmacy. In the other recall, all sterile drug products from a second pharmacy were recalled as a result of reports that five patients were diagnosed with serious eye infections associated with the use of repackaged Avastin. 

There is a legitimate role for traditional pharmacy compounding. Every day, thousands of pharmacists practice traditional pharmacy compounding—mixing a drug in response to a valid prescription for an individual patient’s need. For example, these drug products could be liquids for patients who can’t swallow pills, or they could be made without certain allergens. These operations are licensed and primarily regulated by the states.

However, a new breed of specialty pharmacy compounding has evolved that has outgrown the law, and can pose a threat to the health of the public.  New legislation is needed that specifically addresses such compounding and the now-established safety concerns.

These pharmacies produce medications in advance of or without obtaining a prescription and distribute them across the country. They make drug products that are intended to be sterile and must be made to exacting standards to prevent dangerous contamination. The magnitude and complexity of these operations have outpaced the current patchwork of state laws that differ in prescription requirements and quality control rules.

I firmly believe that new legislation is necessary to help FDA effectively oversee firms engaged in widespread distribution of sterile compounded drug products in advance of or without receiving a prescription. To that end, FDA is working with Congress, states, industry, and all interested stakeholders to develop a basic framework to protect public health. The Senate committee with jurisdiction over this issue has been working hard on a bipartisan basis to craft such a framework, and we are hopeful that their efforts will yield strong legislation for patients across the nation.

In the new framework, FDA believes that certain high-risk sterile compounding facilities should be subject to federal oversight to ensure that the compounding of sterile drug products at those facilities can be done without putting patients at undue risk, including: 

  • requiring compliance with federal quality standards that are appropriate for the compounding of riskier products and exposure of larger numbers of patients,
  • requiring federal registration of the compounding facilities that will be subject to federal quality standards so FDA knows where they are and what drug products they are making, and
  • requiring these higher-risk compounding pharmacies to report to FDA serious adverse reactions to their drugs of which they become aware so that we can act before potential problems get out of hand. 

And for all pharmacy compounding, FDA believes certain basic protections should be in place. These include: 

  • clear authority to examine a pharmacy’s records to more quickly locate the cause of an outbreak or other violations of the law, and
  • prohibiting compounding of the most complex and highest risk products—drugs and biologics that should only be made for patients by an FDA-registered drug manufacturer under an approved new drug application. The manufacturer will have demonstrated in this application that the product is safe and effective and can be safely made according to the highest quality standards.  

FDA supports and would like to explore with Congress several other ideas, such as requiring compounded drug products to have clear label statements identifying the nature and source of the product. The labeling statements would provide prescribers and consumers with valuable information about the products they are using or taking so that they can make informed judgments about their use. Of course, funding will be necessary to support the inspections and other oversight activities outlined in this framework.  We look forward to working with Congress to explore funding mechanisms, which could include registration or other fees, as Congress has authorized and FDA has successfully implemented in other settings. 

Protecting Americans from unsafe and contaminated drugs is not just an important responsibility for FDA—it is part of our core mission. We must be able to identify dangerous practices before they result in actual harm and, when necessary, intervene to minimize the damage and prevent such tragedies in the future.

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.