We Moved Forward on Many Fronts This Year

By: Margaret A. Hamburg, M.D.

At the FDA, the agency that I’ve had the privilege to lead for the past five years, I am gratified to report that we have a lot to be proud of this year. In fact, this past year’s accomplishments on behalf of public health have been as substantial as any in FDA’s recent history.

Margaret Hamburg, M.D.We moved significantly forward, for example, in creating a system that will reduce foodborne illness, approving novel medical products in cutting-edge areas of science, and continuing to develop our new tobacco control program. We worked successfully with Congress and with regulated industry to reach agreement on a number of difficult issues, while continuing to use the law to the full extent possible to protect consumers and advance public health.

While there were many significant actions and events to recognize, below are some of the highlights of 2013.

In the foods area, there were many new actions this year that will have a long-standing impact on improving our food supply for consumers. Throughout the year we have been proposing new rules to reach the goals set forth by the FDA Food Safety Modernization Act (FSMA). These science-based standards will help ensure the safety of all foods produced for our market, whether they come from the U.S. or from other countries.

We also took important steps towards reducing artery-clogging trans fat in processed foods, and understanding the health impact of arsenic in rice. With a final rule that defines when baked goods, pastas and other foods can be considered free of gluten, people with celiac disease can have confidence in foods labeled “gluten free.” And we are studying whether adding caffeine to foods may have an effect on the health of young people and others.

There have likewise been many accomplishments in advancing the safety and effectiveness of medical products. We worked closely with Congress on the recently enacted Drug Quality and Security Act, which contains important provisions relating to the oversight of human drug compounding. The law also has provisions to help secure the drug supply chain so that we can better help protect consumers from the dangers of counterfeit, stolen, contaminated, or otherwise harmful drugs.

Using tools provided by last year’s landmark Food and Drug Administration Safety and Innovation Act (FDASIA), we are continuing to improve the speed and efficiency of medical product reviews, including those involving low-cost, high quality generic drugs and innovative new medical devices. The average number of days it takes for pre-market review of a new medical device has been reduced by about one-third since 2010. The percentage of pre-market approval applications that we approve has increased since then, after steadily decreasing each year since 2004.

We launched a powerful new tool to accelerate the development and review of “breakthrough therapies,” allowing FDA to expedite development of a drug or biologic (such as a vaccine) if preliminary clinical evidence indicates that it may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases. This offers real opportunities to get promising drugs more quickly to patients who need them. In fact, using this new approach, FDA recently approved two advanced treatments for rare types of cancer and one for hepatitis C. We have also strengthened efforts to ensure product quality, increased protection of the drug supply chain, and reduced drug shortages.

We confronted the growing misuse of powerful opioid pain relievers by advising manufacturers on how to make these drugs harder to abuse with formulations that are more difficult to crush for inhalation or dissolve for injection. And we recommended that hydrocodone combination products be subject to stricter controls to help prevent abuse. 

We took an important step towards fighting the development of antibiotic-resistant bacteria by implementing a voluntary plan to phase out the use of antibiotics to enhance the growth of food-producing animals, and to move any remaining therapeutic uses of these drugs under the oversight of a licensed veterinarian. So-called “production” use is considered a contributing factor in the development of bacteria that are resistant to the antibiotics used in human medical treatment.

In many areas of our work we are supporting the emerging field of personalized medicine. Advances in sequencing the human genome and greater understanding of the underlying mechanisms of disease, combined with increasingly powerful computers and other technologies, are making it possible to tailor medical treatments to the specific characteristics, needs, and preferences of individual patients.

Many cancer drugs today are increasingly used with companion diagnostic tests that can help determine whether a patient will respond to the drug based on the genetic characteristics of the patient’s tumor. In May, FDA approved two drugs and companion diagnostic testing for the treatment of certain melanoma patients with particular genetic mutations.

Advances in science and technology are also seen in the creation of new medical devices. For example, 3-D printing - the making of a three-dimensional solid object from a digital model – was once considered the wave of the future. But in February, FDA cleared for marketing a device created by 3-D printing – a plate used in a surgical repair of the skull that is built specifically for the individual patient.

While we have worked hard to get therapies to patients, we are at the same time using the tools available to us to remove unsafe and dangerous products from the market. In November, we used new enforcement tools provided by the food-safety law to act quickly in the face of a potential danger to public health presented by certain OxyElite Pro products. These supplements had been linked to dozens of cases of acute liver failure and hepatitis. After FDA took action, the manufacturer agreed to recall and destroy the supplements.

Finally, we made significant progress in implementing the letter and spirit of the Family Smoking Prevention and Tobacco Control Act. We have signed contracts with numerous state and local authorities to enforce the ban on the sale of tobacco to children and teens; conducted close to 240,000 inspections; and written more than 12,100 warning letters to retailers. And, in the first quarter of 2014 we will launch a public education campaign aimed at reducing the number of young people who use tobacco products.

All of us take great pride in the skill and vigor with which we overcame the year’s challenges and new demands. And so, as the year draws to a close, I extend my gratitude to the employees at the FDA who work tirelessly on behalf of the American public year in and year out. To all of our stakeholders, my heartfelt wishes for a joyous holiday season and a safe and healthy 2014.

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

The path toward a risk-based regulatory framework for health IT

By: Jodi Daniel, Bakul Patel and Matthew Quinn 

Yesterday, the Health IT Policy Committee (HITPC) accepted and approved recommendations from the Food and Drug Administration Safety and Innovation Act (FDASIA) working group for a risk-based regulatory framework for health information technology. The working group’s recommendations suggest a scope for an IT framework, risk and innovation criteria, and approaches for avoiding regulatory duplication. 

Only six short months ago, the Food and Drug Administration (FDA), the Office of the National Coordinator for Health IT (ONC), and Federal Communications Commission (FCC) kicked off the FDASIA workgroup of the HITPC to provide stakeholder input into a report on a risk-based regulatory framework that promotes safety and innovation and reduces regulatory duplication, consistent with section 618 of FDASIA. This provision permitted the Secretary of Health and Human Services (HHS) to form a workgroup in order to obtain broad stakeholder input from across the health care, IT, patients and innovation spectrum. The FDA, ONC, and FCC actively participated in these discussions with stakeholders from across the health care, IT, patients and innovation spectrum. The working group met more than 28 times, and yesterday FDASIA workgroup chair, David Bates, presented the final recommendations to the HITPC. 

In recognition of this important milestone, and on behalf of the three agencies, we want to express our deep appreciation to the members of the workgroup (and a special thanks to David Bates) for committing themselves to this aggressive timeline and delivering a suite of thoughtful recommendations.

Next Steps

As the FDASIA workgroup’s efforts conclude, the agencies’ efforts now intensify. Over the next few months the FDA, ONC, and FCC will review the HIT Policy Committee’s recommendations and the public comments submitted through the docket we opened on regulations.gov. Using these thoughtful inputs, ONC, FDA, and FCC will work closely together to develop a report (by the January 2014 statutory deadline) that proposes an overarching health IT regulatory strategy and provides recommendations on ways to appropriately promote innovation, protect patient safety, and avoid regulatory duplication. 

We recognize the complex nature of health IT and its importance to our nation’s health.  Therefore, we intend to provide an opportunity for public comment and additional stakeholder input on the draft report following its publication in January 2014. We look forward to continued collaboration with all stakeholders as we advance our thinking on this important topic. 

Jodi Daniel is Director, Office of Policy and Planning, Office of the National Coordinator for Health IT

Bakul Patel is Senior Policy Advisor, FDA’s Center for Devices and Radiological Health

Matthew Quinn is Director of Healthcare Initiatives, Federal Communications Commission (FCC)

FDA, Small Businesses, and the Common Goal of Advancing Public Health

By: Margaret A. Hamburg, M.D.

When federal agencies celebrated “Small Business Week” last month, FDA had special reason to pay tribute. It is well known that the U.S. biomedical industry plays an essential role not only in advancing the health of individuals, but also the health of the overall economy. Less well appreciated is that small businesses account for much of this activity.  A new FDA report issued to Congress this week describes the multitude of ways we work with small businesses to support their innovative ability to craft new treatments, medicines, and devices that improve the health of all Americans. 

Margaret Hamburg, M.D.The outreach efforts described in this report are vital, because small businesses not only have a unique role but also unique needs in their involvement with a regulatory body like the FDA. That’s why we’re working on a number of fronts to strengthen the ability of small businesses to engage and to help ensure that they are not disadvantaged by their size.

One way we do this is by reducing or even waiving user fees for small businesses that meet certain criteria. Sometimes a startup company might have a groundbreaking product, but lacks the financial resources to cover the full cost of user fees, which are paid to the FDA to help cover the cost of product reviews. Encouraging this kind of small business innovation is the reason FDA participates in the Small Business Innovation Research (SBIR) Program, which funds research and development projects that have potential for commercialization and public benefit. Since 2008, FDA has awarded 36 SBIR grants with the average grant being just over $170,000. Small businesses are also eligible to apply for more broadly available FDA grants, such as Orphan Product Grants, which address rare diseases and disorders, and are tailored to meet the focus and needs of small firms.

Perhaps even more important to small businesses than funding is information. FDA works hard to maintain a variety of communications with small businesses. Seminars, webinars, and workshops open to, and often specifically designed for, small businesses are offered throughout the year free of charge. Links to these event listings can be found in Appendix D of the report. FDA’s product centers also have dedicated small business offices that give companies direct points of contact, which are identified in our new report. These offices provide technical support and education to small companies, hold meetings to hear the views and perspectives of small businesses, develop informational materials, and provide an accessible channel through which small businesses can acquire information from FDA. I hope small businesses will take advantage of these resources and reach out to FDA’s small business contacts.

Small businesses also benefit from early communication with FDA during the product review process. This early communication is especially valuable in FDA’s Rare Disease Program in which most product sponsors are small firms and the product evaluations can be particularly complex for companies with limited resources. Our centers have found that early communication between FDA and product sponsors gets safe and effective products to consumers faster. 

I encourage you to read the report for more information on how FDA promotes innovative research by small businesses, protects small businesses from unreasonable regulatory barriers, and thereby allows American ingenuity to thrive.

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

Looking Back and Looking Ahead: FDASIA’s One Year Anniversary

By: Margaret A. Hamburg, M.D. 

One year ago today President Obama signed into law the Food and Drug Administration Safety and Innovation Act, bipartisan legislation reauthorizing user fee programs for innovator drugs and medical devices and establishing two new user fee programs for generic drugs and biosimilar biological products. 

Margaret Hamburg, M.D.Coming at a time of continuing budget restraints, this steady and reliable source of funding is essential to support and maintain FDA’s staff of experts who review the thousands of product submissions we receive every year, and do so in a timely and thoughtful manner. Over the years, our user fee programs have ensured a predictable, consistent, and streamlined premarket program for industry and helped speed patient access to new safe and effective products. 

One of our major undertakings since last July has been putting in place the infrastructure for a new generic drug user fee program that will expedite the availability of low-cost, high quality generic drugs. The program has already achieved several significant milestones, including reducing the backlog of generic drug applications, enhancing review efficiencies, and streamlining hiring. Likewise, reauthorization of the medical device user fee program has helped to expedite the availability of innovative new products to market, and the program has already seen a decrease in the application backlog for device submissions. 

But user fees are by no means the only focus of the 140-page law. Additionally, FDASIA includes provisions to strengthen the drug supply chain, enhance engagement with FDA stakeholders, address the problem of drug shortages, and promote innovation. 

Since last July, FDA continues to meet its FDASIA milestones, and is on track to implement more provisions very soon. Consider some of our more significant accomplishments. In the area of innovation, we launched the new breakthrough therapy designation for drugs that may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases and published guidance on the use of this and all of our expedited programs. In the area of engagement, we initiated the Patient-Focused Drug Development Program. The objective of this five-year effort is to more systematically obtain the patient’s perspective on a disease and its impact on patients’ daily lives, the types of treatment benefit that matter most to patients, and the adequacy of the available therapies for the disease. We have already held patient meetings on three major diseases and another is scheduled in September. 

Also, FDASIA is helping FDA take important steps to address the challenges posed by an increasingly global drug supply chain in which nearly 40 percent of finished drugs are imported and nearly 80 percent of active ingredients come from overseas sources. FDA has been able to halt food and devices from distribution if an inspector believes they are adulterated or misbranded, but the agency lacked this authority for drugs. FDASIA has extended the agency’s administrative detention authority to include drugs as well, and the agency is taking steps to implement this authority. In addition, earlier this year the agency pushed for higher penalties for counterfeiting and intentionally adulterating drugs before the federal sentencing commission – and succeeded. These are the first of several provisions that we must implement under Title VII, the section of FDASIA that strengthens FDA’s authorities over the drug supply chain. Later this week I hope many of you will join me at a public meeting to discuss how we might implement some of the other portions of this important section. 

To help the public keep track of our progress on these and other provisions, we’ve established a FDASIA web portal that includes a link to our three year implementation plan, which we intend to update on a monthly basis. 

Implementing FDASIA is a massive undertaking, requiring detailed planning to integrate these tasks with the rest of our workload. FDA is committed to implementing the requirements of FDASIA in a way that provides lasting improvements to public health, and we will meet these objectives as quickly as resources allow. 

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

“Breakthrough” Designation … Another Powerful Tool in FDA’s Toolbox for Expediting the Development and Review of Promising New Drugs for Serious Conditions

By: Janet Woodcock, M.D.

Janet Woodcock, M.D. is the Director of FDA’s Center for Drug Evaluation and Research

In fiscal year 2012, FDA approved 35 novel new drugs, also known as “new molecular entities.” Among these new products were drugs to treat patients with unmet medical needs, such as a groundbreaking treatment for a form of cystic fibrosis, the first FDA-approved human cord blood product for hematopoietic reconstitution, used to help patients with blood forming disorders, and the first drug to treat advanced basal cell carcinoma (a form of the most common skin cancer).

To enable our ongoing efforts to bring innovative drug products to the public as efficiently as possible, FDA relies heavily on several expedited development and review tools such as fast track designation, the accelerated approval pathway and priority review designation. For instance, 56 percent of the novel drugs approved by the Center for Drug Evaluation and Research in calendar year 2012 used some combination of these tools to speed promising therapies to patients with serious conditions. And any given drug may have received multiple expedited program designations. (See a brief summary of how each of these tools helps FDA shorten the development and review of promising new therapies.)

In July 2012, a provision in the new law called the Food and Drug Administration Safety and Innovation Act, or FDASIA for short, gave FDA another powerful expedited development tool, known as the “breakthrough therapy” designation. This new designation is now helping FDA assist drug developers expedite the development of new drugs with preliminary clinical evidence that indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases. Although the designation is not yet even a year old, FDA has received 62 requests to grant this new designation to products under development. We have been very active on this subject, meeting with companies and discussing ways to expedite the drug development process for drugs that show striking early results. We have already granted the breakthrough designation to 20 potential innovative new drugs that have shown encouraging early clinical results.

Drug developers should have a clear understanding of all of FDA’s expedited development and review tools. To help industry better understand each tool, including when the tools can be used and the features of each, we have just published an industry draft guidance titled Expedited Programs for Serious Conditions — Drugs and BiologicsAmong other important information, the draft guidance describes FDA’s policies and the threshold criteria for each expedited program, defines and discusses important concepts, including serious condition, unmet medical need, and available therapy, and provides some general considerations for products utilizing an expedited program, such as manufacturing and product quality, nonclinical considerations, and clinical inspection considerations.

The breakthrough therapy designation gives us another tool in our “toolbox” to help expedite the development and review of new drugs to treat patients with serious medical conditions and little or no treatment options. We’ll continue to use the new breakthrough therapy designation and our existing tools to help make our expedited programs even more effective.

We’ve said it before — and I believe it’s worth repeating — our decision-making on whether to approve a drug always involves an evaluation of many factors, such as the seriousness of the disease.  However, ultimately any drug approved must show that its benefits outweigh its risks and regardless of which expedited development or review program or programs are used, FDA does not compromise its safety or efficacy standards in exchange for rapid approval. Like all drugs we approve, those approved after having been designated as breakthrough therapies will meet our usual rigorous standards for safety and effectiveness.

Janet Woodcock, M.D. is the Director of FDA’s Center for Drug Evaluation and Research

The Road Ahead for Ensuring Access to Quality Drugs for All Americans … New Laws Under “FDASIA” Will Help Pave the Way

By: Howard Sklamberg

In January, I became director of FDA’s Center for Drug Evaluation and Research’s (CDER) Office of Compliance, giving me the responsibility – and great privilege — of playing a lead role in FDA’s work to help protect the American public from unsafe and ineffective drugs. It’s a big job, filled with many challenges.

Fortunately, after three years of service with FDA, most recently as the agency’s deputy associate commissioner for regulatory affairs (our field operation), and 12 years before that as a prosecutor with the Justice Department, I feel prepared to help the agency meet these challenges head on.

I’d like to take an opportunity to share my priorities, as well as my views and perspectives on the goals and challenges ahead for FDA, as we continue to work to ensure access to quality drugs in the United States.

Tragically, last October’s outbreak of fungal meningitis from contaminated methylprednisolone injections that killed over 50 Americans and sickened hundreds more directed FDA’s attention to the immediate public health priority of evaluating the quality of sterile compounded drugs and preventing further incidents. Our efforts have included proposing a new legislative framework for federal oversight, inspecting high-risk compounding facilities that produce sterile drugs, and working more closely with our state partners.

As important as our efforts are in the compounding arena, our compliance challenges extend to many other critical areas, many of which are related to the new and growing global marketplace for pharmaceutical products.

Today, nearly 40 percent of the drugs Americans take are imported and nearly 80 percent of the active ingredients come from overseas sources. A growing number of clinical trials that test the safety and effectiveness of potential new drugs are also moving overseas, making FDA oversight more challenging. Counterfeit drugs are proliferating around the world and sometimes even entering the U.S.supply chain. The ever burgeoning worldwide use of the Internet continues to spawn avenues for illegal online sales of medicines of unknown safety and quality. Also, poor manufacturing practices that lead to facility shut-downs often contribute to shortages of important drugs. We must ensure that wherever drugs are made, wherever their ingredients are from, or wherever and however they are tested and sold, that they meet FDA’s strict standards of quality and that they remain in adequate supply.

Despite these challenges, there’s good news. The Food and Drug Administration Innovation and Safety Act of 2012 (FDASIA) gave FDA powerful new tools to enhance our compliance and enforcement activities including stronger authorities and funding to support the inspection of foreign manufacturing facilities. For example, FDASIA facilitates our ability to partner with and work more effectively with foreign regulatory agencies. FDASIA also gave FDA more authorities to control the drug supply chain.

However, laws on the books do not automatically translate into effective change without effective implementation and enforcement of these laws. So, in addition to continuing our critical work with Congress on appropriate and effective oversight of compounding that exceeds the bounds of traditional pharmacy compounding, my other key priority is to work to implement FDASIA’s provisions, keeping CDER focused globally and armed with the best set of tools possible to do the job. Although we have much more work to do, a vision of enhanced capabilities of ensuring quality drug products for the American public is well in sight.

I have the distinct privilege and responsibility of being part of a fantastic team of dedicated FDA staff that’s really making a difference, and I look forward to continuing to serve the American public in working to ensure access to quality drugs.

Howard Sklamberg is Director of FDA’s Center for Drug Evaluation and Research’s Office of Compliance

Track Our Success as We Implement New Law

By: Leslie Kux and Malcolm Bertoni

As we continue to implement the exciting new tools provided by the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA), we are inviting interested members of the public to use the Internet to track our progress.

Leslie Kux

FDASIA gave FDA new authorities to help FDA establish improved systems for combating drug shortages, protect the drug supply chain in an increasingly global market, and get generic medicines on pharmacy shelves and available to consumers more quickly. It is also encouraging companies to invest in discovering and developing new antibiotics, accelerate patient access to new medical treatments and breakthrough therapies, and promote the development of more treatments for children.

To track FDASIA’s progress, we leveraged an existing FDA web page that publishes pertinent information about a wide variety of FDA initiatives, and we added what we think are even better web tools for searching for specific details about a particular action.

The site currently shows that more than 30 of the tasks aimed at improving public health are completed. The site also lists numerous other steps involved in implementing the law and in each case provides a targeted completion date for the task and links to more information. Each task listed also includes a contact for more information or how to get answers to questions—either the e-mail address of an individual FDA employee or of an office specifically designated to handle that task.

Weaving the new authorities from the 140-page law into existing programs is a Herculean task, and doing it right takes time. We are committed to get the job done as quickly as possible while still making the best decisions that will serve the nation now and in the future.

Malcolm Bertoni

We established this web page to make that process transparent, and to encourage the input of those involved. Our immediate focus is on those provisions of the law that will have the greatest public health impact for which resources are in place, allowing us to act quickly.

We appreciate that some may be interested in viewing the nitty-gritty detailed listing of the many, complex actions involved in implementing FDASIA, and some may not. But we know the actions themselves will prove important to consumers and patients, who will ultimately benefit from the provisions of this new law.

Consumers and industry can find in-depth information, including fact sheets, news releases and technical information, at the FDASIA web page. FDASIA represents the potential for major improvements, and we are using everything at our disposal, to pursue the important goals it presents.

Leslie Kux is FDA’s Assistant Commissioner for Policy

Malcolm J. Bertoni is FDA’s Assistant Commissioner for Planning

Help Shape the Future of Health IT

By: Bakul Patel, MS, MBA

Calling all movers and shakers in health care information technology!

We’re on a mission to help pave the way for innovative advances in safe and effective health information technology (HIT).

Who are “we”?

Under recent legislation, Congress charged FDA—in consultation with the Office of the National Coordinator for Health Information Technology (ONC) and the Federal Communications Commission—to develop a report with a strategy and recommendations relating to a risk-based regulatory framework for HIT that would promote innovation, protect patient safety, and avoid regulatory duplication.

Congress also provided that the agency could assemble a working group that is geographically diverse and consists of experts and interested persons from all stakeholders in the HIT community to help develop the required strategy and recommendations. We put out a call for nominations with a deadline of March 8 on the ONC’s website, so the deadline is fast approaching.

Please take a look at the list of areas of expertise we’re seeking for the working group’s membership.  

The response so far has been gratifying, but our mission is large and if you haven’t already submitted a nomination—for yourself or someone you admire in your field—we urge you to do so now.  We’ll be looking in particular for people who represent a large segment of our stakeholder community.

I’m a technology guy, so I get fired up when it comes to thinking about the possibilities in this rapidly evolving field. But if your eyes glaze over when you hear the phrase “health information technology,” here’s why you should be interested, too:

We live in exciting times. Electronic health records, patient-to-doctor Skyping, smart phones, efficient workflow systems, and ingenious mobile apps provide us with vast reservoirs of health-related information—literally at our fingertips—in seconds.

For example, the National Institutes of Health’s LactMed app gives nursing mothers information about the effects of medicines on breast milk and nursing infants, and there are other apps aimed at helping health care providers improve and facilitate patient care.

But ready access also offers safety challenges. How can we best protect patient privacy? How do we make sure the information is accurate? How can we foster efficiency and curtail costs in the way this information is disseminated in, say, the interpretation and transmittal of radiological images from a medical imaging center to an electronic tablet in a pediatrician’s office to a hospital overseas?

Our working group will be tackling these issues and a host of others. And we want the group to be as varied, wide-reaching, and forward-thinking as possible.

Whether you’re a venture capitalist looking to fund innovative projects; a health care professional who works in a hospital or in private practice; an expert in another area of information technology; or a consumer who wants to ensure the privacy of your own data, we seek and value your participation.

Please, put your name in the hat. It’s a rare opportunity to help shape the future of how health care is provided for generations to come.

Bakul Patel, MS, MBA, is a Policy Advisor in the Office of the Center Director in FDA’s Center for Devices and Radiological Health

FDA is asking the public to send in ideas for combating drug shortages

By: Valerie Jensen

FDA has made progress over the last year or so in preventing and resolving shortages of important drugs — including chemotherapies, anesthetics and antibiotics. Nevertheless, the agency believes that even more can be done and is therefore turning to the American public for advice, as explained in a Federal Register notice published this week. What the public tells FDA will help inform the agency’s development of a strategic plan that will ultimately enhance FDA’s response to preventing and mitigating drug shortages.

FDA has long been tackling the problem of drug shortages, and since October 2011, has stepped up its efforts to encourage drug and biological product manufacturers to report if they know of any circumstances that could lead to a drug shortage, including temporary interruptions in manufacturing. Such early notification is the agency’s most powerful tool to address drug shortages—we can’t work to prevent, mitigate, or resolve a shortage if we don’t know about it. Along these lines, FDA supported efforts to expand the FD&C Act’s early notification requirements as part of the Food and Drug Administration Safety and Innovation Act (FDASIA), enacted on July 9, 2012.  Happily, these efforts have been paying off.  For example:

  • The number of shortages is now less than half of what it used to be. There were 117 in 2012, down from 251 in 2011.
  • Many more shortages are now being averted. We prevented 195 in 2011. Last year, we prevented 282.

We expect the requirements in FDASIA to further enhance FDA’s efforts to work with manufacturers and other stakeholders to prevent or alleviate shortages. When notified of a potential or actual shortage, FDA can take a number of actions, as appropriate, including: expediting inspections and reviews of regulatory submissions, working with the manufacturer to solve the underlying problem contributing to the shortage, identifying alternative manufacturing sources, exercising enforcement discretion for the shipment of a critically needed drug with special instructions to healthcare providers, and using enforcement discretion for the temporary importation of non-U.S. product.

One shortage of a drug that improves or saves the life of even one patient is one shortage too many. More can be done to prevent shortages.

As required by FDASIA, FDA has also formed an internal Drug Shortages Task Force to develop a strategic plan to enhance the agency’s efforts to address and prevent drug shortages. Among other things, the strategic plan will include blueprints for enhanced coordination, communication, and decision making within FDA and with other federal agencies; and plans for effective communication in the event of a shortage, including who should be alerted about potential or actual drug shortages and what information should be shared.

FDA wants to hear from all interested stakeholders on the strategic plan. The agency published a Federal Register notice, posted Feb. 11, which provides additional information and seeks input on six targeted questions related to the Strategic Plan and to preventing and mitigating drug and biological product shortages. Comments will be accepted through Thursday, March 14, 2013.

Valerie Jensen, a pharmacist and expert on drug shortages, is associate director at FDA’s Center for Drug Evaluation and Research  

Early communication: A key to reduced drug development and approval times

By: Anne Pariser, M.D.

From “test tube” to market typically takes a new drug more than 10 years.  FDA has been working hard at many points along a drug’s developmental path to reduce this time and bring safe and effective new therapies to Americans as efficiently as possible. 

Much has been said about FDA’s success in using its “expedited approval” tools, specifically Priority Review and Accelerated Approval, to support innovative new drugs. These are important tools that FDA can use once a marketing application is submitted. For instance, last year, FDA’s Center for Drug Evaluation and Research (CDER) approved 39 novel medications, almost half of which benefited from one (or both) of these expedited approval tools. According to a recent FDA report, this is a 63% increase over the average number of annual approvals since 2002. 

But less has been said about FDA’s “expedited development” tools, which help foster new drug innovation during the investigational phases of drug research and development, well before a marketing application for a new drug is even submitted to FDA. Among these tools are more frequent and earlier opportunities for communication between FDA and drug developers. FDA’s Fast Track designation for drugs with the potential to address unmet medical needs is an example. For many years, Fast Track has helped speed new drug development by encouraging more communication early in the development process. In 2012, about 40% of CDER’s novel new drug approvals were drugs that were given this Fast Track designation.     

Just this past year, the Food and Drug Administration Safety and Innovation Act (FDASIA) authorized FDA to use a new Breakthrough designation for investigational new drugs when preliminary clinical data suggest that the drug may provide a substantial improvement over existing therapies for patients with serious or life-threatening diseases. The concept behind Breakthrough is that, with increased communication, FDA will work with new drug developers to help design efficient ways to study the safety and effectiveness of their drug. This early assistance can help ensure that the results of clinical trials provide the evidence that FDA must have to determine whether or not a drug is safe and effective for approval. A growing number of drug developers are already taking advantage of Breakthrough.

But even before Breakthrough had been authorized by FDASIA, FDA was working to encourage communication opportunities for drug developers to meet with FDA to help make sure their clinical trial designs and development plans offered the best chances of efficient, safe, and timely development and approval. These opportunities are available at the start of a drug’s clinical development cycle: right before the earliest phases of human testing known as the “pre-investigational new drug (IND) phase” (fittingly called pre-IND meetings) and continue throughout drug development.

Early communication in action

Recently, FDA has taken a look at the development times of new drugs that were approved with the benefit of pre-IND meetings and compared them to the development times for drugs that were approved without such meetings. The findings underscore the value of early communication. For those new drugs for which a pre-IND meeting between the drug developer and FDA was held, average clinical development times were substantially shorter than when a meeting was not held. For instance, for all new drugs approved between 2010 and 2012, the average clinical development time was more than 3 years faster when a pre-IND meeting was held than it was for drugs approved without a pre-IND meeting.

For orphan drugs used to treat rare diseases, the development time for products with a pre-IND meeting was 6 years shorter on average or about half of what it was for those orphan drugs that did not have such a meeting. Early communication is especially important for orphan drugs because these products require special attention and thus early talks can be especially beneficial.

Many factors can influence the speed and efficiency of a drug development program. Nevertheless, FDA strongly believes in the value of effective communication during the drug development and approval process, especially for novel development programs when established regulatory pathways do not exist. FDA is committed to working with drug developers to ensure efficient and effective drug development programs whenever possible.

Thirty-nine novel new drug approvals last year is encouraging – one third of which are indicated to treat rare diseases – and many of these new drugs are now making valuable contributions to public health inAmerica. FDA will continue to do its part to help bring safe and effective new drugs to market as soon as possible. We will continue efforts to enhance communication as a critical part of the drug research, development, and regulatory process – especially since it is so clear that communications can make a big difference.

Anne Pariser, M.D., is Associate Director for Rare Diseases, Office of New Drugs, Rare Diseases Program at FDA’s Center for Drug Evaluation and Research