FDA: A Great Place for Science…and for Scientists on the New Frontier of Regulatory Science

By: Robert M. Califf, M.D.

Robert CaliffAs FDA Commissioner, I’m proud of our agency’s extraordinary commitment to using the best available science to support our mission to protect and promote the health of the American public. This is especially critical today, as rapid scientific and technological advances are helping to expand our understanding of human biology and underlying disease mechanisms and to identify the molecular profile of a food contaminant.

These breakthroughs offer unprecedented opportunities for us to develop new treatments and cures and to protect our food supply with a robust system that meets the challenges of globalization.

But there’s another benefit that derives from our application of cutting-edge science to the challenges we face, which has become increasingly evident to me through my conversations with some of FDA’s more than 10,000 scientists. And that’s the deep personal and professional satisfaction gained from working in FDA’s state-of-the-art laboratories on front-line issues that make a real difference in the lives of all Americans. As one FDA scientist commented, “At FDA, your work is really at the crossroads of cutting-edge technology, patient care, tough scientific questions, and regulatory science.”

Being Part of a Vibrant Collaborative Scientific Environment

Whether you’re a biologist, chemist, epidemiologist, pharmacist, statistician, veterinarian, nurse, physician, or an engineer and whether you’re a recent graduate or a seasoned scientist, FDA offers an unmatched opportunity to be a part of a vibrant, collaborative culture of regulatory science.

FDA scientists gain a bird’s eye view of the pharmaceutical and food industries, and develop a thorough familiarity and understanding of the regulatory structure that guides these industries. As one young FDA scientist recently commented, “We see a tremendous breadth of different products here, which helps us learn quickly and makes our jobs interesting and challenging.” Another newly trained FDA scientist shared, “We have the chance to work with highly trained colleagues, within and across disciplines, to build and keep our scientific training cutting-edge.”

While the work of FDA scientists helps to advance scientific understanding, it goes much further than that. That’s because our work is directly tied to regulatory decisions. As such it has a powerful and immediate effect on the health of millions of Americans. As another FDA scientist explained, “We get to see how these basic science and clinical advances get applied to producing medical treatments and devices and how these can make differences in people’s lives.”

FDA offers a number of fellowship, internship, graduate, and faculty programs through which newly-minted scientists can join FDA and continue to apply and develop their skills. Many of these individuals remain on as full-time FDA scientists. One former FDA Fellow said they appreciate how “FDA makes room for and respects voices of young, qualified scientists.”

Tackling the Most Challenging Scientific Issues

So, although I may frequently boast about FDA’s responsibility and ability to do rigorous scientific research and its importance for the American public, I’m speaking as much about our scientists as our science. And I hope that when other young talented scientists consider these testimonies from our multifaceted scientific workforce they will be encouraged to join us.

I want to see more professionals take advantage of the opportunities FDA offers to collaborate on some of the most transformative scientific issues of our times – both for their benefit and for the nation’s. We need the best scientific minds to tackle the challenges of food safety, medical product development, and to evaluate how emerging technologies are affecting FDA-regulated products so that our reviewers can make science-based decisions about a product’s benefits and risks.

That’s why we’ve successfully added thousands of qualified new employees over the last several years and worked hard to fill mission-critical positions. It’s also why we continue to seek more hiring flexibilities and other ways that enable us to be more competitive with private-sector salaries for these positions.

The career opportunities at FDA are enormous, and I look forward to welcoming the next generation of scientists of every stripe to help us fulfill our mission. It’s not only good for science and essential to FDA’s ability to protect and promote public health; it’s a unique opportunity for these talented scientists and their careers.

FDA Scientists Discuss Their Cutting-Edge Research in FDA Grand Rounds Webcasts

Robert M. Califf, M.D., is Commissioner of the U.S. Food and Drug Administration

Important steps toward streamlining access to investigational drugs for patients in need

By: Richard A. Moscicki, M.D.

FDA is only too aware that there are many patients who have a serious or life-threatening medical condition for which there is no available FDA-approved therapy. For such patients, one option may be to obtain access to an investigational drug that has not yet been approved by FDA. To do this, a physician submits an application to the FDA requesting authorization to use the investigational drug in the treatment of their patient. This is called expanded access to investigational drugs.

Dr. Richard MoscickiWhile FDA has been helping physicians navigate the system for many years, we are aware there have been physician and patient concerns about this process, which can be time consuming and difficult to understand. Consequently, FDA has recently made significant changes to streamline and simplify the process for single patient expanded access requests.

To make the expanded access process more efficient, we’ve just introduced a much simpler application form called the Form FDA 3926, which will be the form doctors now will typically fill out when they want to provide an investigational drug for a patient through expanded access. While the Form 1571 had 26 information fields and seven attachments, the new Form 3926 has fewer fields (11) and only one attachment. With this streamlined format, we estimate that physicians will be able to complete the form in just 45 minutes, as compared to the more difficult and time consuming effort required previously.

Also, as part of our commitment to streamlining the expanded access process, on May 16, 2016, the FDA and the Reagan-Udall Foundation held a meeting with interested stakeholders to explore additional options that might help patients and their physicians understand the process to request access to unapproved drugs. A common theme of the meeting was that navigating the expanded access process really does take a village. The physician, the drug company, FDA, and the institutional review board (IRB) all have important roles and must work together for the expanded access process to succeed.

The FDA and Reagan-Udall Foundation convened this forum to listen to the public express their needs about expanded access and to discuss ideas with stakeholders on ways that the complex process can be made more efficient and effective. Much work on the details remains, but in general there was agreement on the need for a central repository or clearinghouse where useful and relevant information could be stored in one place — a sort of “one-stop-shop” for physicians and patients to seek information about the expanded access process. As our thinking about this resource develops, we’ll keep the public informed.

For physicians seeking more information about expanded access to an investigational drug, we have developed an educational webinar to help them become familiar with the new application form. This live webinar will occur on July 12 at 1:00 PM EDT and will offer one hour of Continuing Education (CE) credit. The webinar will be recorded for viewing without CE credit. We also have released a guidance regarding Form FDA 3926, a guidance with Questions and Answers on expanded access, as well as a guidance directed at industry addressing questions regarding charging for investigational drugs.

Expanded access is designed for seriously ill patients who have exhausted other options.  The last thing a patient suffering from a serious or life-threatening condition needs is red tape. For many years, FDA has dedicated staff to assist physicians and patients in navigating our system. We expect these important steps will help us continue our efforts to serve patients in need and to advance public health.

Richard A. Moscicki, M.D., is FDA’s Deputy Center Director for Science Operations, Center for Drug Evaluation and Research

Be A Champion for Clinical Trial Diversity

By: Jonca Bull, M.D.

The FDA is launching a campaign to encourage minorities to participate in clinical trials for all medical conditions.

Jonca Bull, M.D., is Director of FDA’s Office of Minority HealthThe first part of the campaign will be launched on June 19, 2016, World Sickle Cell Day, observed annually to help increase public knowledge and raise awareness of Sickle Cell Disease, which primarily affects people of African and Hispanic descent. We want to encourage diverse communities to learn more about how they can become a part of the research process to bring new therapies to the market.

Clinical trials are a critical step in making new medical products available. Medical products—from vaccines to drugs for blood pressure or diabetes management — are tested in clinical trials.

Although FDA generally does not conduct clinical trials, we do the critical work in reviewing the data to assess the safety and efficacy of medical products before they can be used in medical practice. None of this is possible without clinical trials and the patients who go the extra mile by being research participants.

In order to help ensure that medical products are safe for everyone, we need a diverse pool of research participants—racial and ethnic minorities, women, even the elderly.

We know that certain diseases impact some populations differently. For example, diabetes occurs  more frequently in blacks and Hispanics, high blood pressure and heart failure occurs more frequently and severely in blacks; and, Asian American communities experience more hepatitis B.

Clinical trials participants need to more closely mirror the patients who will ultimately use the medicine. This is especially important when considering health disparities — diseases that occur more frequently or appear differently in non-white populations. But most clinical trials participants are white and male. That means we may miss vital data that could be used to be make better evidence-based, regulatory decisions. If we do not develop a more diverse pool of research participants, health disparities may persist because we will not know if a medical product is safe and effective in the actual population that will ultimately use it.

And that’s why we’re launching our campaign, which includes a series of educational aids such as videos, a blog, and an infographic. In these videos Shirley Miller, who lives with sickle cell disease, talks about her experience participating in clinical trials and encourages her peers to learn more about research studies.

In another video Dr. Luciana Borio, FDA’s Acting Chief Scientist, discusses why clinical trial diversity matters from FDA’s perspective.

This campaign is taking us one step closer to a world where health equity is a reality for all. It supports FDA’s initiative: “The Year of Clinical Trial Diversity.”

It is a part of our larger effort to improve clinical trials diversity — we also work with stakeholder groups, support research, develop multi-lingual resources, and use social media to promote a community of “Clinical Trials Champions.”

You can be a “Champion” by watching and sharing the videos and related resources.

Everyone has a stake in the game —health care providers, researchers, and patients. Share these videos and other materials. Start a conversation today.

Videos:

More information about this campaign and FDA’s OMH can be found here: www.fda.gov/minorityhealth

Follow us on Twitter @FDAOMH

Dr. Jonca Bull is FDA’s Assistant Commissioner for Minority Health, Office of Minority Health

Globalization and FDA’s New Partnerships to Ensure Product Safety

By: Howard Sklamberg

Globalization is posing challenges for public health. For FDA, part of that challenge is the ever-increasing volume and complexity of FDA-regulated products coming to America’s shores.

Howard SklambergIn fiscal year 2015, there were more than 34 million shipments of FDA-regulated products into the United States, up from just 15 million shipments a decade ago. These products are handled by 130,000 importers, and are manufactured, processed, or packaged at more than 300,000 foreign facilities.

We know this global trade expansion has ramifications for our nation’s public health. We also know we cannot be the inspectors for the world. Hence, we need to effectively direct our resources in a risk-based manner as we grapple with this tremendous volume of imported goods.

How? One way is to identify foreign regulators whom we can rely upon to partner with in verifying that safety standards are being met and then construct an approach that will meet the requirements of multiple regulatory jurisdictions. We are currently engaged in three innovative programs that meet this challenge.

The Medical Device Single Audit Program

The Medical Device Single Audit Program, or MDSAP, is an international approach to the auditing and monitoring of the manufacture of medical devices to ensure their safety and efficacy. This audit program will allow a single regulatory audit of a medical device manufacturer’s quality management system that satisfies the requirements of multiple regulatory jurisdictions.

Currently, five nations – Australia, Brazil, Canada, Japan, and the U. S. – are participating in the MDSAP Pilot. It began 18 months ago and will run through the end of 2016. The program’s goals include:

  • Enabling regulatory oversight of medical device manufacturers’ quality management systems;  and,
  •  Promoting more efficient use of regulatory resources through work-sharing and mutual acceptance among regulators.

Mutual Recognition Agreements

In 2014, FDA launched the Mutual Reliance Initiative (MRI), a strategic collaboration between the FDA and the EU Member States. The goal of the program is to determine if the FDA and EU can agree to recognize each other’s drug Good Manufacturing Practice (GMP) inspections, a potentially time-saving approach.

If successful, we could rely upon EU experts to inspect facilities within their own borders, a more practical way of overseeing the large number of drug manufacturing sites outside of the United States. And it would be similarly more practical if the EU relied on FDA experts to inspect facilities within the United States.

Both the EU and the FDA are in the process of evaluating each other’s processes. The EU has visited several of FDA’s district offices in the United States and one drug laboratory and evaluated the work they do. The FDA has a different challenge since each country in the EU has at least one inspectorate, and in Germany, each state has their own inspectorate. To date, FDA has observed eight audits – in Sweden, Greece, Croatia, Germany, Hungary, Italy, the Czech Republic, and the United Kingdom – and will continue to observe audits of other Member States this year and in 2017.

Food Safety Systems Recognition

Preventing problems at relevant points along the global food supply chain can be a daunting job. FDA is soliciting help by leveraging foreign food safety systems that are similar to our own.

The agency’s Systems Recognition program determines whether another country has comparable regulatory programs and public health outcomes to what we have in place in the U.S.

A major advantage of Systems Recognition is that it allows FDA to be more risk-based in its oversight of imported food and we can more wisely plan our overall inspection activities, including foreign facility inspections, import field exams, and import sampling.

Thus far, we’ve completed: New Zealand and the U.S. signed a Systems Recognition Agreement (in 2012) and recently another agreement was signed with the Canadian Food Inspection Agency.

What’s Next? 

The three initiatives I’ve briefly outlined represent the best of FDA innovation and expertise in grappling with the increasing amount of imported FDA-regulated products. Our work will focus on a continued careful reliance on trusted foreign partners; a move away from duplicative work; more risk-based inspections; better data; and the minimization of public health risks globally.

Howard Sklamberg is FDA’s Deputy Commissioner for Global Regulatory
Operations and Policy

What We Mean When We Talk About EvGen Part II: Building Out a National System for Evidence Generation

By: Rachel E. Sherman, M.D., M.P.H., and Robert M. Califf, M.D.

In an earlier FDA Voice blog post, we discussed a pair of concepts – interoperability and connectivity – that are essential prerequisites for the creation of a successful national system for evidence generation (or “EvGen”). In this post, we take a look at how we would apply these constructs as we go about building such a system.

Building EvGen

Rachel Sherman

Rachel E. Sherman, M.D., MPH, is FDA’s Associate Deputy Commissioner for Medical Products and Tobacco

Creating knowledge requires the application of proven analytical methods and techniques to biomedical data in order to produce reliable conclusions. Until recently, such analysis was done by experts operating in centers that typically restricted access to data. This “walled garden” approach evolved for several reasons: the imperative to protect the privacy and confidentiality of sensitive medical data; concern about the negative consequences that could arise from inappropriate, biased, or incompetent analysis; and, the tendency to see data as a competitive asset. Regardless of the specific reason, the result has been the same: widespread and systemic barriers to data sharing.

If we are to reverse these tendencies and foster a new approach to creating evidence of the kind envisioned for EvGen, we must bear in mind several critical principles:

  1. There must be a common approach to how data is presented, reported and analyzed and strict methods for ensuring patient privacy and data security.
  2. Rules of engagement must be transparent and developed through a process that builds consensus across the relevant ecosystem and its stakeholders.
  3. To ensure support across a diverse ecosystem that often includes competing priorities and incentives, the system’s output must be intended for the public good and be readily accessible to all stakeholders.

What Would EvGen Look Like in Practice?

Robert Califf

Robert M. Califf, M.D., is Commissioner of the U.S. Food and Drug Administration

What would a robust national platform for evidence generation look like? It may be helpful to envision EvGen as an umbrella for all activities that help inform all stakeholders about making treatment decisions.

The task of evaluating drugs, biologics, or devices encompasses different data needs and methods. However, all share a common attribute: the characterization of individuals and populations and their associated clinical outcomes after they have undergone diagnostic or prognostic testing or been exposed to a therapeutic intervention.

Moreover, when medical practice itself is part of the evaluation, characterization of the organization and function of delivery systems is critical. In other words, the kinds of evidence needed to evaluate medical products for safety and effectiveness and the kinds of evidence needed to guide medical practice overlap substantially.

Over the last decade, there has been enormous progress in the area of “secondary use,” in which data collected for one purpose (for instance, as part of routine clinical care) can be reused for another (such as research, safety monitoring, or quality improvement).

The Sentinel Initiative, launched in response to a Congressional mandate to develop an active postmarket risk identification and analysis system, is one example. Modeled after successful programs such as the Centers for Disease Control and Prevention’s Vaccine Safety Datalink, Sentinel allows FDA to conduct safety surveillance by actively querying diverse data sources, primarily administrative and insurance claims databases but also data from electronic health record (EHR) systems, to evaluate possible medical product safety issues quickly and securely.

Another example, the National Patient-Centered Clinical Research Network (PCORnet), is a national system that includes many of the attributes needed for EvGen. PCORnet includes participation from government, industry, academia, and patients and their advocates. Whereas FDA’s Sentinel system is built primarily on claims data repurposed for safety surveillance, PCORnet is designed to leverage EHR data in support of pragmatic clinical research.

The NIH’s Health Care Systems Research Collaboratory has demonstrated through its Distributed Research Network that the concept of secondary data use can be extended into the realm of prospective pragmatic interventional trials. The NIH Collaboratory program, which includes many of the same health care systems involved in Sentinel and PCORnet, has 10 active trials underway.

In addition, the Reagan-Udall Foundation Innovation in Medical Evidence Development and Surveillance (IMEDS) Evaluation Program is exploring governance mechanisms to ensure that private-sector entities, notably regulated industry, can collaborate with Sentinel data partners to sponsor safety queries about marketed medical products. Such measures have the potential to expand the involvement of private-sector partners beyond the arena of methodology, further helping to ensure that Sentinel continues its expansion into a national resource.

Similarly, efforts are underway to establish a National Device Evaluation System (NDES). As currently envisioned, the NDES would be established through strategic alliances and shared governance. The system would build upon and leverage information from electronic real-world data sources, such as data gathered through routine clinical practice in device registries, claims data, and EHRs, with linkages activated among specific data sources as appropriate to address specific questions.

As substantial work already is being done in all of these areas, valuable experience is being gained. The next step is to ensure that these pioneering efforts coalesce into a true national resource. More on that in future postings.

Rachel E. Sherman, M.D., M.P.H., is FDA’s Associate Deputy Commissioner for Medical Products and Tobacco

Robert M. Califf, M.D., is Commissioner of the U.S. Food and Drug Administration

National Drug Take Back Day: A Great Time to Dispose of Prescription Medications Cluttering Your Cabinets

By: Douglas C. Throckmorton, M.D

On Wednesday, April 27, FDA staff can bring in their unwanted, unused, or expired prescription drugs to the FDA campus for safe disposal as part of the Drug Enforcement Administration’s (DEA) National Prescription Drug Take Back Initiative. In past years, we’ve collected more than 200 pounds of unused medications that would have otherwise lingered in medicine chests and kitchen cabinets. FDA’s event is in advance of National Drug Take Back Day, marked on April 30.

Douglas C. Throckmorton, M.D.Medicines no longer being used may pose grave and unnecessary dangers to families and the people visiting their homes. For example, in the last two decades, FDA has received more than 30 reports of accidental exposure to the powerful pain medication in fentanyl patches – most of them in children under two years old. Tragically, 12 of these incidents required hospitalization and another 12 were deadly. Drug Take Back programs are the preferred method for fentanyl patch disposal and frequent drug take back programs run by local communities are a big step toward preventing unnecessary deaths due to accidental medication exposure.

Another important effect of National Take Back Day is that it helps to divert medicines from entering the environment. We share the public’s concerns regarding the potential environmental impact of disposing unused medicines in household trash, or by flushing. We are working with other agencies, including the U.S. Environmental Protection Agency (EPA), to better understand the human health and ecological risks from medicines in our water and have a shared overall goal of reducing medicine levels in our water.

FDA has strongly supported work to expand the availability of take back programs for several years. We will continue to work with manufacturers to develop new formulations with reduced risk for accidental harm and with our federal partners to develop alternative, safe disposal systems. We look forward to a time when effective disposal alternatives are more widely available.

The importance is underscored when you think about the epidemic this country is facing with opioid medications. Many people who misuse medications, such as opioids, get their first dose by using medications prescribed to other people. FDA is deeply concerned about the growing epidemic of abuse, misuse, dependence, and overdose of opioids in the United States. In response to this crisis, FDA has developed a comprehensive action plan to take concrete steps toward reducing the impact of opioid abuse on American families and communities.

So if your prescription medications have expired or you are no longer taking them, Drug Take Back Day is a way to make sure they are disposed of properly. April 30 marks the eleventh nationwide opportunity since 2010 for Americans across the country to do what we’re doing at FDA this week and get rid of all unused drugs in the home. It’s simple and easy. Gather them up and take them to a disposal site near you. The service is available from 10 a.m. to 2 p.m. It’s free and anonymous, no questions asked. Past drug take-back days have been highly successful. Cumulatively, previous events have collected well over 5 million pounds of unwanted, unused, or expired drugs.

Safe disposal of medicine is a year-round activity. FDA’s Disposal of Unused Medicine site offers valuable “do-it-yourself” safety information when there isn’t a take back site available.

Together, we can make difference.

Douglas C. Throckmorton, M.D., is Deputy Center Director for Regulatory Programs in FDA’s Center for Drug Evaluation and Research

Strengthening Partnerships: FDA’s China Office Engages in Key Outreach with Chinese Provincial FDA, Academia, and Industry

By: S. Leigh Verbois, Ph.D.

独木不成林,单弦不成音

Dú mù bù chéng lín, dān xián bù chéng yīn

‘A single tree makes no forest, one string makes no music.’

“A single tree makes no forest, one string makes no music.”This old Chinese proverb inspired FDA’s China Office, as members of our staff embarked on a five-day trip to meet with provincial FDA regulators, industry, and academia in China’s Yangtze River Delta region.

FDA Staff with Zhejiang FDA

FDA Staff Meets with Zhejiang FDA
Hangzhou, China
Front Row, Left to Right: Gang Wang (FDA China Office), Bo Ju (Zhejiang FDA), Yuanchang Shao (Zhejiang FDA), Leigh Verbois (FDA China Office), Jue Chen (Zhejiang FDA), Chiang Syin (FDA China Office), William Sutton (CDRH),
Back Row, Left to Right: Jinfeng Liang (Zhejiang FDA), Wenhua Zheng (Zhejiang FDA), Yini Ye (Zhejiang FDA), Lixin Shen (Zhejiang FDA), Nicole Taylor Smith (FDA China Office), Lixia Wang (FDA China Office)

The Yangtze River Delta region is an economic area that encompasses the Shanghai municipality, Zhejiang and Jiangsu provinces. The commercial epicenter, which accounts for 20 percent of China’s gross domestic product, is home to a significant number of FDA-regulated medical product manufacturers.

We traveled more than 3,300 kilometers (1,980 miles) to meet with key leaders and experts to strengthen partnerships, share information, and build the foundation for future cooperative engagement. Our first stop was Shanghai, where I had the great fortune to be able to address hundreds of students and faculty at East China University of Science and Technology’s School of Pharmacy and China Pharmaceutical University.

My message to the students was that they are the future leaders who will be in charge of the next generation of pharmaceutical innovation and data integrity.

In Shanghai, we also had the opportunity to sit down with U.S. Embassy Consul General Hanscom Smith to compare notes and to talk about current FDA priorities underway in the region.

China Pharmaceutical University (CPU)

China Pharmaceutical University (CPU)
Nanjing, China
CPU Faculty and Students attending Dr. Leigh Verbois’s Presentation on “CDER’s Novel Drug Approvals and Priorities”

The team then rode a high speed bullet train to Nanjing to meet with Jiangsu FDA, the regional regulator. This type of information sharing between the provincial FDA and the FDA China Office supports our shared mission of assuring that medical products produced in China meet U.S. safety standards.

On day three, we traveled again by bullet train to Suzhou where we partnered with China’s Association for Medical Device Industry to hold a two-hour, town hall meeting with almost 200 of China’s big device manufacturers that export products to the United States.

Working with FDA’s Center for Devices and Radiological Health (CDRH), our team provided information on Unique Device Identification (UDI) requirements. In the greater China region, it is estimated that there are nearly 4,000 medical device establishments affected by these requirements.

Hangzhou, China

Hangzhou, China
One of the many bridges in Hangzhou to symbolize “Building Bridges” between the FDA China Office and our Chinese stakeholders

The next morning, we headed for Hangzhou. After about two hours by train, we arrived in Hangzhou ready to meet with provincial FDA officials. Our meeting focused on specific ways we could collaborate on future medical device and drugs outreach, and more effectively share information.

The final day of our weeklong journey started with an industry roundtable focused on pharmaceuticals, held in partnership with Zhejiang FDA. As fellow regulators, we joined together to engage in substantive discussion with representatives from major manufacturers located in the Zhejiang, Jiangsu, and Shanghai regions, many of whom were interested in recent data integrity efforts in China. The FDA team then boarded our last train back to Shanghai for a final meeting with local officials that focused on our mutual priorities, as well as ways to expand and leverage efforts going forward.

The team flew back to Beijing feeling very satisfied that we accomplished much and clearer than ever that continued collaboration with Chinese regulators, industry and academia will help to ensure that medical products manufactured for the U.S. market are safe and effective. After all, one tree alone does not make a whole forest.

Leigh Verbois, Ph.D., is Director of FDA’s China Office in the Office of International Programs

What We Mean When We Talk About EvGen Part I: Laying the Foundation for a National System for Evidence Generation

By: Rachel E. Sherman, M.D., M.P.H., and Robert M. Califf, M.D.

Rachel Sherman

Rachel E. Sherman, M.D., M.P.H., is FDA’s Associate Deputy Commissioner for Medical Products and Tobacco

Across the clinical research enterprise, there is a growing awareness of serious shortfalls in the current paradigm of generating the scientific evidence that supports medical product evaluation and clinical care decisions and the need to modernize methods and expectations surrounding this evidence base.

We know, for instance, that most clinical practice guideline recommendations are not based on high-quality evidence, typically derived from appropriately designed randomized controlled trials. We also know that adherence to standards supported by such high-quality evidence results in better outcomes for patients.

There is reason to believe that we’ve arrived at a tipping point where previously separate, “siloed” efforts can be linked to create a national system for evidence generation (EvGen). In this first of a series of posts, we’ll take a look at the elements required to build such a national system, beginning with a pair of foundational concepts—interoperability and connectivity.

Interoperability

Robert Califf

Robert M. Califf, M.D., is Commissioner of the U.S. Food and Drug Administration

Put simply, interoperability is the idea that different systems used by different groups of people can be used for a common purpose because those systems share standards and approaches. To take one example: modern train tracks employ agreed-upon standards in terms of track gauge and other specifications so that many different kinds of vehicles can safely use the rail system.

In similar fashion, a national system for evidence generation that applied common data standards and definitions could “lay the track” for significant improvements in the exchange of biomedical data. Patients, consumers, professional groups, payers, the medical products industry, and health systems all stand to benefit from potential gains in efficiency and reductions in cost that would accompany standardized approaches to data collection, curation, and sharing, once up-front investments are absorbed. Then, with these standards in place, effort could be devoted to generating actionable knowledge rather than simply managing data.

Connectivity

Establishing interoperable systems is a critical step in building a national system for evidence generation. An equally important step is to enable collaboration among the many groups that generate data, for example patients, clinicians, hospital systems, health insurance organizations. Evidence is derived from high-quality data that often originates from many different sources or settings. We can create an interconnected environment that leverages all the available data to provide answers to important public health questions. A defining characteristic of such a network is the ability to leverage all available data for different tasks as needed, allowing the network to integrate complex relationships between data input and output. Coupled with interoperable standards, a national system for evidence generation based on these principles will be capable of generating very large quantities of data and enabling those data to flow among system components.

The result? Researchers will be able to distill the data into actionable evidence that can ultimately guide clinical, regulatory, and personal decision-making about health and health care.

These two core constructs represent the essential scaffolding that must be developed and put in place to support a national system for evidence generation. In our next posting, we’ll examine ways we can begin building and continuously improving such a system for the benefit of all stakeholders.

Rachel E. Sherman, M.D., M.P.H., is FDA’s Associate Deputy Commissioner for Medical Products and Tobacco

Robert M. Califf, M.D., is Commissioner of the U.S. Food and Drug Administration

2015: An Important Year for Advancing Generic Drugs at FDA

By: Kathleen “Cook” Uhl, M.D.

Generic drugs allow greater access to health care for all Americans.

At FDA’s Office of Generic Drugs (OGD) in the Center for Drug Evaluation and Research, 2015 was an important year. It was our first full year of operation after vastly expanding our office’s scope and structure. This change allowed for the office to have greater prominence and allowed for additional staff to handle a growing workload and enhance our ability to advance the safety and availability of generic drugs in the U.S.

Kathleen "Cook" UhlConsider this: In 2014, generics saved the U.S. health system an estimated $254 billion – and FDA continues to work hard to advance the use of generic drugs to help improve public health.

Our increased capacity and expansion came at a critical time. In 2012, a new law called the Generic Drug User Fee Act (GDUFA) authorized additional funds for FDA for the review of generic drug applications, inspection of facilities and other regulatory actions. But with those additional funds came an FDA commitment to reach a variety of goals. These goals were articulated in a document that accompanied the GDUFA legislation, which was negotiated between FDA and industry and enacted by Congress. The additional funds help FDA efficiently handle thousands of applications for new generic products and reduce the time needed to review generic medications for approval.

We’re on track for meeting all of those goals. Today, to help the public understand our progress, OGD released our first annual report. It’s filled with detailed accounts of our work, which seeks to improve the generic drug program with more efficient reviews of applications, and by developing the science needed to help the generic drug industry demonstrate that their products are as safe and effective as their brand-name counterparts.

Among the highlights, the report notes that 2015 marked the highest number of generic drug approvals and tentative approvals ever awarded by FDA – more than 700 in all. Last year, in December, we granted the highest number of approvals and tentative approvals in a single month (99) since the generic drug program began.

Another major commitment of GDUFA was to take a first action, by 2017, on 90 percent of the “backlog,” those applications pending prior to GDUFA as of October 1, 2012. We had 2,866 abbreviated new drug applications (ANDAs) and 1,873 prior approval supplements (PASs), but by the end of 2015, we completed first actions on 84% of ANDAs and 88% of PASs – already close to the 90% goals set for 2017! We also approved 90 “first generics,” meaning that in 2015 we added a new cost-saving generic alternative for 90 brand name drugs.

Despite our progress, we have a lot more work to do. But we don’t expect to do it entirely on our own. Achieving goals that work for the public requires input from the public, including industry, the research community, lawmakers and other stakeholders.

As part of our effort to align with stakeholders’ visions, we’re holding a public meeting on May 20 to solicit valuable feedback on our regulatory science initiatives and help us chart directions forward. We invite all to attend and to contribute by providing your thoughts and ideas to our public docket.

We encourage you to read our annual report and to participate in our annual meeting. With our ongoing efforts and strong public input, we are confident that 2016 and beyond will be as successful as 2015.

Kathleen “Cook” Uhl, M.D., is FDA’s Director, Office of Generic Drugs in the Center for Drug Evaluation and Research

Continuous Manufacturing Has a Strong Impact on Drug Quality

By: Lawrence Yu, Ph.D.

If we used a time machine to transport a pharmaceutical scientist from the 1960s into a current pharmaceutical production plant of today, it might be surprising to learn that they would already be very familiar with most of the processes and production techniques being used. That’s because not much has changed in pharmaceutical production over the last 50 or so years.

Lawrence YuFor decades, most drugs have been manufactured using what is known as “batch” technology — a process whereby the ultimate finished product has been made after many stops and starts in a series of steps. Unfortunately each break in the process causes inefficiency and delay, as well as the increased possibility of defects and error.

Today, a new and exciting technology — continuous manufacturing — enables much faster production and more reliable products through an uninterrupted process. How much faster is continuous manufacturing?  In some cases, manufacturing that takes a month by batch technology might only take a day using continuous manufacturing techniques.

Of course, speed alone would not matter if continuous manufacturing compromised quality. But by eliminating breaks between steps and reducing opportunities for human errors during the stops and starts in the batch process, continuous manufacturing is more reliable — and safer. That’s a powerful combination.

There’s the added benefit that more efficient production of quality products can drive down manufacturing costs, possibly resulting in lower drug prices for consumers. Continuous manufacturing also allows manufacturers to respond much quicker to changes in demand, potentially contributing to prevention of drug shortages.

We are seeing a growing number of manufacturers working towards building continuous manufacturing into their processes. One manufacturer, Vertex, the maker of a cystic fibrosis drug called Orkambi (lumacaftor/ivacaftor) has been using the continuous manufacturing process for this drug since its approval date in July 2015.

Last Friday marked another significant step towards integrating continuous manufacturing into pharmaceutical production. FDA approved, for the first time, a manufacturer’s change in their production method from “batch” to continuous manufacturing. This new approval is for manufacturing Janssen Products, LP’s, medication for the treatment of HIV-1 infection, Prezista (darunavir). The company’s efforts in manufacturing advancement were facilitated by the use of FDA’s recently-released draft guidance to industry titled, Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base, a product of the agency’s Emerging Technology Team (ETT) designed to help manufacturers implement a variety of technological advancements.

Although it is not easy for drug manufacturers to transition from batch to continuous manufacturing, there are significant rewards. FDA encourages others in the pharmaceutical industry to consider similar efforts.

Progress comes at an opportune time. The medications we use are changing. We are entering an era of precision medicine, when drugs must be made with unique features and provided more quickly to patients in need. FDA will continue our efforts to encourage the advancement of continuous manufacturing as one of a variety of ways to enhance the quality of the medications used by the American public.

Lawrence Yu, Ph.D., is FDA’s Deputy Director, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research