A ‘Roadmap’ for Navigating Patient Advocacy

By: John J. Whyte, M.D., M.P.H.

So, you and your organization have a passion for helping people and you want to work with FDA to advance your advocacy work. Are you unsure of the most effective way to enable patients to gain greater access to safe and effective drug therapies?

John WhyteWe know government agencies can be big and confusing. That’s why we’re working on a roadmap to help make your navigation easier.

And you can get involved.

FDA’s Center for Drug Evaluation and Research (CDER) is sponsoring a daylong public workshop on March 31, 2016, titled Navigating CDER: What You Should Know for Effective Engagement. Our presentations will help patient advocates gain a better understanding of FDA and provide specific resources to help you and your colleagues learn ways to effectively advocate and engage with the Agency on behalf of the patients you serve.

We’ll provide a broad overview of patient engagement with various offices within CDER, and drill down into key specifics such as:

  • Who and when to call;
  • How to set up a meeting at FDA;
  • Provide tips on making the most out of your meeting; and,
  • How to prepare an effective presentation for FDA staff.

We’ll also discuss topics such as understanding labeling, generic drugs, and how patients can effectively interact and provide input to FDA. And, we’ll look at some programs including different drug approval processes, expanded access, and FDA’s role in patient focused drug development (PFDD). These are only a few of the many important areas we’ll tackle.

For several years, FDA has been working to focus on the needs and goals of the patient as the Agency makes decisions about drug therapies for the advancement and protection of public health. These efforts can only be as effective as our ability to connect with the patients and their representatives we seek to engage.

Join us if you can. If you can’t, we’ll be making information about the meeting available on our website. We look forward to a productive and informative day!

John J. Whyte, M.D., M.P.H., is Director of Professional Affairs and Stakeholder Engagement at FDA’s Center for Drug Evaluation and Research

‘Leaning in’ on Combination Products

By: Nina L. Hunter, Ph.D., and Rachel E. Sherman, M.D., M.P.H.

Medical products that combine drugs, devices, and/or biological products are known as combination products. These products present a number of regulatory, policy, and review management challenges because they include components from multiple regulatory categories (e.g., drug and device, drug and biologic, biologic and device, drug, device, and biologic) with distinct regulatory requirements, and review of a combination product generally requires involvement of more than one FDA Center.

Nina Hunter

Nina L. Hunter, Ph.D., FDA’s Associate Director for Science Policy in the Office of Medical Products and Tobacco

However, as FDA continues to adapt to the rapidly evolving ecosystem of therapeutic development, it’s more important than ever to find ways to encourage innovation and support the development of these needed technologies.

To that end, FDA has been working on ways to improve the overall efficiency, consistency, and predictability of combination product review. We’ve already shared some of our progress with you in a recent blog post.

An important next step is launching the lean management process mapping approach to build a better system for combination products review – one that’s more cohesive, more collaborative, and more systematic.

What is lean management process mapping, you might ask? It begins with an analysis of what’s being done now, then designs a future state that eliminates waste and maximizes value.

We expect two significant outputs from this mapping:

  • A “current state” map that shows how we’re doing now. Importantly, this initial look will highlight existing sources of delay or redundancy. Creating this baseline map also will allow us to identify metrics for success and to assess the impact of improvements as they are put in place.
  • A “future state” map showing a streamlined, efficient process that will eliminate previously identified delays and redundancies.
Rachel Sherman

Rachel E. Sherman, M.D., M.P.H., FDA’s Associate Deputy Commissioner in the Office of Medical Products and Tobacco

Has lean management already been successfully applied at the FDA? Yes!

Under the leadership of Kyle Hair, the Lean Management Team in the human drugs program in the Office of Strategic Programs has executed strategic work and communication plans for initiatives across the Agency.

For example, when the “Lean Team” consulted with the Office of Clinical Pharmacology within the Center for Drug Evaluation and Research, it helped establish project management staff functions, roles, and responsibilities for the Office’s core processes. The team also has applied its expertise to stand up the new Office of Pharmaceutical Quality, as well as apply its expertise to such topics as drug safety communications and risk evaluation mitigation strategy.

Lean management works. And we’re confident that applying lean management principles to combination product review will allow us to enhance communication and coordination among the groups that oversee the development, review, and approval of combination products.

Of course, we realize that success in this area depends upon meaningful interactions among all FDA Offices and Centers involved with combination products review. The active participation emphasized by lean management principles will ensure that the needed collaboration is present from the start.

Lean methods also encourage critical thinking and problem-solving, with a focus on reliable, efficient, timely, and reproducible evaluation and decision-making. In this case, our efforts will be focused on the ultimate goal of a combination product review system that is transparent, clear, and consistent.

But lean process mapping is only one piece of the puzzle. Stay tuned for more information about other key priorities and initiatives aimed at modernizing the review of combination products!

Nina L. Hunter, Ph.D., is FDA’s Associate Director for Science Policy in the Office of Medical Products and Tobacco

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

Launching a New Natural History Grants Program: Building a Solid Foundation for Rare Disease Treatments

By: Katherine Needleman, Ph.D. and Gumei Liu, M.D., Ph.D.

Today, on Rare Disease Day 2016, FDA’s Office of Special Medical Programs/Office of Orphan Products Development (OOPD) is proud to announce the launch of a new grants program to fund natural history studies with the hope of bringing new and important diagnostics and therapeutics to patients with rare diseases.

Kathy Needleman

Katherine Needleman, Ph.D., is the Director of the Orphan Products Grants Program of FDA’s Office of Orphan Products Development

A rare disease, by definition, affects fewer than 200,000 individuals in the United States. Its impact, however, is far from rare. Altogether, about 7,000 known rare diseases affect about 30 million Americans. Yet the vast majority of rare diseases do not have adequate diagnostic tools or treatments.

Developing such diagnostics or treatments — whether it’s a drug, biologic, or medical device — has been compared by many to building a house. Both require a solid, sound foundation. For any rare disease treatment development program, that foundation consists of having a thorough understanding of the natural history of a disease.

How do you define the natural history of a disease? Think about it as the course a disease takes – from the time of its onset, progressing through its pre-symptomatic phase and clinical stages, to the end of the disease. Insight into a disease’s natural history can help lead to better, more well-designed trials that can accelerate the development of life-saving diagnostics and therapeutics.

Gumei Liu

Gumei Liu, M.D., Ph.D. is a reviewer and grant project officer in FDA’s Office of Orphan Products Development

A lack of understanding of the natural history is often a major obstacle to developing life-saving products for patients with rare diseases. Without it, it becomes very difficult to decide what to study, know what to look for within a study, and capture the data necessary for approval of a treatment or even a cure.

OOPD’s new Natural History Grant Program is intended to provide much needed support and complement ongoing efforts to help change the trajectory of rare disease product development. The funded studies should help characterize the natural history of a rare disease or condition, identify genotypic and phenotypic subpopulations, and develop and/or validate clinical outcome measures, biomarkers, and companion diagnostics.

There are several ways to conduct natural history studies. They can look back in time (retrospective), look ahead (prospective), or be a survey study (collection of data through questionnaires). Each has its pros and cons and the method will to a great extent depend on what we know about a specific rare disease and the currently available treatment options.

Patient advocacy groups can and do play a critical role in collecting natural history data as is highlighted in FDA’s video discussion (watch video below) on natural history studies featuring perspectives from patient advocates. Often what prevents organizations, like patient advocacy groups, from conducting natural history studies is funding. And that’s where the grants program can make a difference.

The Orphan Products Natural History Grants Program is open to funding all types of natural history studies that are appropriate for the rare disease being studied and can aid in development of diagnostics and treatments. There are two funding levels and durations that will be offered:

  • A maximum of $400,000 in total costs per year for up to five years for prospective natural history studies involving clinical examination of affected individuals; and
  • A maximum of $150,000 in total costs per year for up to two years for retrospective natural history studies or survey studies.

The Orphan Products Natural History Grants Program is built upon OOPD’s Orphan Products Grants program that was established by the Orphan Drug Act more than 30 years ago and which has typically funded clinical trials. OOPD has successfully utilized its budget to help bring over 50 products to market with that clinical trial grant program.

We hope that this new Orphan Products Natural History Grants Program will help build the important foundation necessary to accelerate the development of life-saving diagnostic and treatments for the many rare disease patients who need them.

Katherine Needleman, Ph.D., is the Director of the Orphan Products Grants Program of FDA’s Office of Orphan Products Development

Gumei Liu, M.D., Ph.D. is a reviewer and grant project officer in FDA’s Office of Orphan Products Development

Strengthening our Regulatory Relationships in India

By: Mathew T. Thomas and Dean Rugnetta

India’s economic expansion is in part due to the tremendous growth in the pharmaceutical industry. The United States is a large consumer of medical products, and India is one of the largest suppliers of its drug products. And our important work together remains an FDA priority.

Investigator Daniel Roberts

Investigator Daniel Roberts (FDA India Office) and an Indian Regulator sharing inspectional approaches for current good manufacturing practices for pharmaceuticals during the workshop in Ahmedabad

We are working with our counterparts in the Indian government to ensure the medical products manufactured there, especially those for export to the U.S., meet FDA’s safety and quality requirements. FDA established an office in India in 2008, in part to promote government-to-government interactions like these and to keep pace with rapid developments and innovations in the pharmaceutical sector.

In November 2015, representatives from FDA’s India Office, our Center for Drug Evaluation and Research (CDER), Office of Regulatory Affairs (ORA), and Office of International Programs (OIP), partnered with the India Government’s Central Drug Standards Control Organization (CDSCO), to share inspectional techniques and guidance for conducting current good manufacturing practices of pharmaceutical facilities.

Carmelo Rosa and Denise DeGiulio

Carmelo Rosa (CDER), Denise DiGiulio (CDER), and an Indian Regulator discuss Quality By Design guidance with the workshop participants in Ahmedabad

Training sessions were provided in two cities (Ahmedabad and Bengaluru) for about 200 Indian regulators representing CDSCO and some of the State drug control agencies. The training was an example of the cooperation by both agencies to increase knowledge and skills, thereby contributing to the health and welfare of citizens in both countries.

The collaboration resulted in representatives from both agencies learning more about the regulatory perspectives of the other – and doing so first-hand. It was clear from the interactions that the Indian inspectors had extensive knowledge of FDA and of the international techniques for conducting inspections. The FDA representatives at the sessions benefited from input regarding the differences between FDA and Indian legislation and regulations. And as new inspectors comprised the majority of attendees, there was the opportunity for learning on both sides.

FDA Workshop Team in India

FDA Workshop Team in Bangaluru. Front Row – Denise DiGiulio (CDER), Carmelo Rosa (CDER), Leslie Ball (Office of International Programs), Mathew Thomas (India Office), Thomas Cosgrove (CDER), Thomas Arista (ORA). Back Row: Shiva Prasad (India Office), Daniel Roberts (India Office), Solomon Yimam (India Office)

Senior officials from the Government of India attended both events and affirmed their goals of ensuring patient safety and of collaborating with FDA to make sure that products from India are safe and meet appropriate quality standards.

FDA and Government of India regulators will continue leveraging knowledge and strengths to ensure patient safety in India and product quality of FDA-regulated pharmaceuticals.

Mathew T. Thomas is the Director of FDA’s India Office in New Delhi, India

Dean Rugnetta is the Deputy Director in FDA’s India Office in New Delhi, India

FDA Offers Free, Continuing Education Course to Help Health Care Providers Understand ‘Biosimilars’

By: Leah Christl, Ph.D.

You may have heard about a new category of products called “biosimilars.” What are biosimilars and how do they relate to biological products already widely in use?

Leah ChristlBiological products derived from living organisms can treat patients with cancer, chronic kidney disease, rheumatoid arthritis, inflammatory bowel disease, and other serious conditions. Biological products that are “biosimilar” to, or “interchangeable” with, an already-approved FDA biological product (an FDA-licensed reference product) are one way to improve access and increase treatment options at potentially lower cost for our nation’s health care system.

These products are licensed through a new pathway created in the United States in 2009. FDA is well aware that health care professionals–including prescribers, the nurses who will administer them, and the pharmacists who will dispense them–need to understand how these drugs work and how they are intended to be used.

To that end, FDA has developed a free, Continuing Education Course for health care professionals – titled, FDA Overview of Biosimilar Products – to help them strengthen their knowledge and understanding of biosimilars and interchangeable products. Biosimilars and interchangeable products, for instance, are not generic products, and this education course will help health care professionals fully appreciate the distinction.

There’s a growing interest in biosimilars and interchangeable products in the pharmaceutical industry. The first biosimilar in the U.S. was approved in 2015. It boosts the production of white blood cells and helps to ward off infection in patients receiving strong chemotherapy for some tumors. FDA is reviewing several other marketing applications for proposed biosimilar products.

This course also will help health care professionals understand how a biosimilar can be prescribed and dispensed, and how and when an interchangeable product can be substituted for another biological product.

The program will inform healthcare professionals about the development process and approval pathway for biosimilars and interchangeable products. It also includes information about FDA’s general review process for these products that will help attendees gain a better understanding of the relationships between biosimilars and interchangeable products.

The course is available to health professionals on FDA’s CDERLearn Website, and can be completed on a tablet for those on the go and not at their desktop computer.

Leah Christl, Ph.D., is the Associate Director for Therapeutic Biologics in the Office of New Drugs, at the Center for Drug Evaluation and Research at FDA

What is FDA Doing to Improve the Health of African-Americans?

By: Jovonni Spinner, M.P.H., C.H.E.S.

Every February, we celebrate Black History Month – a time to reflect, celebrate, and honor the contributions of African-Americans to our society. We know that achieving and maintaining good health is a long-standing issue for this group, many of whom may experience worse health outcomes in critical areas like heart disease and diabetes. But, we want to focus on the positive and provide consumers with health education materials to support healthy behavior changes!

Jovonni SpinnerIt’s true that the health equity gap has narrowed over time, but there is still significant room for improvement. Here are few things that the FDA and the Office of Minority Health (OMH) have done over the past year to reduce health disparities.

Public Engagement: More than 29.2 million blacks/African-Americans are on social media — and we want to meet consumers where they are. So we’re using Facebook, Twitter, and other social media platforms and electronic communications (e.g. our newsletter and e-blasts) to educate African- Americans on issues such as heart disease, diabetes, and sickle cell disease among others, and also provide tangible solutions to help manage these chronic conditions.

For example, to mark American Heart Month in February, we developed a social media toolkit to help our stakeholders engage with their members and partnered with the Association of Black Cardiologists to spearhead an #ILoveMyHeart social media campaign.

Stakeholder Engagement: We have cultivated relationships with a core set of partners to better understand their health needs, aligned our priorities to meet those needs, and worked together to leverage each other’s resources for the common good. By doing so, we’ve increased our stakeholder’s capacity to communicate with the agency on regulatory issues. For example, multicultural stakeholders are now better able to make their voice heard in FDA-sponsored public meetings and on open dockets.

Minority Health Research: We worked with academia to fund African-American-based research projects (e.g. HIV/AIDs and triple negative breast cancer) and research fellows working on topics like genomics and digital communications. This allows us to increase the knowledge base on these issues and ensure a diverse workforce is in place to solve these complex health problems.

Resources: We have taken care to tailor our health education resources, such as infographics and fact sheets, to African Americans. Our website has valuable information on sickle cell disease and lupus, both of which affect African Americans more than any other racial/ethnic group.

Clinical Trial Diversity: Did you know that sometimes minority populations may respond differently to medical products? One example is an FDA-approved heart failure medication that reduces the risk of death and hospitalization in people with certain types of long-lasting/chronic heart failure.

During clinical trials, it was found there was an increased risk of an allergic reaction called angioedema in blacks. In this trial, only 5% of the participants were black, even though blacks represent 13% of the U.S. population and experience heart failure at rates higher than the rest of the population. This is why we continue to work toward increasing clinical trial diversity, to ensure that medical products are safe and effective for everyone!

President Obama has said, “If you’re walking down the right path and you’re willing to keep walking, eventually you’ll make progress.” OMH will continue walking down the path to improving health equity and we want you to join us, because this work cannot be done alone.

Visit FDA’s OMH at: www.fda.gov/minorityhealth

Follow us on Twitter @FDAOMH

Jovonni R. Spinner, M.P.H., C.H.E.S., is a Public Health Advisor in FDA’s Office of Minority Health

Clarifying What We Mean When We Talk About Biomarkers: An NIH/FDA Joint Leadership Council Success

By: Melissa A. Robb, B.S.N., M.S. (RegSci), and Robert M. Califf, M.D.

What if there was a more uniform way to convey key technical terms to help advance scientific progress? Thanks to the Biomarkers, Endpoints, and other Tools (BEST) Resource, we’re one step closer to that goal.

Melissa Robb

Melissa A. Robb, B.S.N., M.S. (RegSci), FDA’s Associate Director for Regulatory Affairs, Office of Medical Policy, Center for Drug Evaluation and Research

Now available on the National Center for Biotechnology Information’s Bookshelf, the BEST Resource was developed through a collaboration of the Food and Drug Administration (FDA) and the National Institutes of Health (NIH). It includes a glossary of terms and definitions that will ensure the consistency and clarity needed to drive progress in biomedical research and clinical care.

Why is this textbook so important? In the spring of 2015, the FDA-NIH Joint Leadership Council identified a problem: Confusion about the definitions and inconsistent use of key terms–including biomarkers, surrogates, and clinical outcome assessments. This can deter progress in developing medical products and thereby potentially compromise efficiency in achieving public health benefits.

Accordingly, the council identified a high priority: harmonizing terms—or making sure that everyone is “speaking the same language”–that describe and categorize types of endpoints.

Members from multiple FDA Centers and NIH institutes formed a working group to focus on creating a glossary. This was the first step to a publicly available and open access textbook that could be continuously updated and expanded.

Robert M. Califf, MD, MACC; Commissioner, U.S. Food and Drug Administration

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

As the basis of their work, the group considered existing terminology and definitions. Those include FDA guidance documents and other literature, especially a seminal FDA-sponsored Institute of Medicine study.

The use of biomarkers has recently expanded widely to include fields such as mechanistic biomedical research, clinical trials, drug discovery, medical product development, clinical care, and regulatory science. Recognizing this broad influence and the accepted vernacular of these varied fields, the group sought to first reach consensus around biomarker taxonomy.

For example, there’s misunderstanding about the various types of biomarkers and the distinction between biomarkers and surrogate endpoints. One challenge was to settle upon definitions that were broad enough to be used by diverse communities, including biomedical scientists, translational researchers, clinical researchers, medical product developers, and clinicians, and also across diverse types of products.

Where possible, to provide more context and insight into important terms, examples are given alongside many definitions in the BEST Resource. NIH and FDA intend to use the definitions included in this glossary when communicating on topics related to its contents (e.g., biomarkers) to ensure a consistent use of the terms and therefore, a common understanding of the issues. FDA’s Biomarker Working Group, with representation from all of our Centers, contributed to developing these definitions.

Now we need your help. We need your feedback and comments on the glossary. You can provide them at the BEST (Biomarkers, EndpointS, and other Tools) Resource.

In the meantime, we’ll continue to work on adding context to terms related to regulatory science, clinical trials, and laboratory science.

Effective, unambiguous communication is essential for efficient translation of promising scientific discoveries into approved medical products. Once we are all speaking the same language, we can tackle other challenges to bring the promises of biomedical research and clinical care to fruition.

The FDA-NIH Biomarker Working Group members include: from FDA – Shashi Amur, Robert L. Becker, Robert Califf, Aloka G. Chakravarty, David S. Cho, Nina L. Hunter, Ilan Irony, Christopher Leptak, Kathryn M. O’Callaghan, Michael A. Pacanowski, Elektra J. Papadopoulos, Vasum Peiris, Melissa Robb, Hobart L. Rogers, Rachel E. Sherman, Robert J. Temple, Ann Marie Trentacosti, and Sue Jane Wang; and from the NIH – Holli Hamilton, Pamela McInnes, Lisa M. McShane, and Monica R. Shah.

Melissa A. Robb, B.S.N., M.S. (RegSci), is FDA’s Associate Director for Regulatory Affairs, Office of Medical Policy, Center for Drug Evaluation and Research

Robert M. Califf, M.D., previously FDA’s Deputy Commissioner for Medical Products and Tobacco, became FDA’s Commissioner of Food and Drugs on Feb. 25, 2016

Changing course: A new approach to opioid pain medication at FDA

By: Robert M. Califf, M.D.

As a doctor, I have a first-hand understanding of the important and legitimate need for powerful medication to help people deal with chronic or severe pain. If you have had a family member or loved one touched by a serious illness or injury, you understand it too. You know how tough it can be to see them try to endure pain that can’t be touched by anything you can get over the counter.

Robert M. Califf, M.D., MACC, FDA's Commissioner of Food and Drugs

But as all of you know, more Americans now die every year from drug overdoses than they do in motor vehicle crashes. Opioids were involved in 28,648 deaths in 2014, according to the CDC.

The FDA is deeply concerned about this growing epidemic, and I am personally disturbed by the toll it has taken in communities across the country. It’s an issue I’ve been involved with for years as an academic, having overseen the NIH’s National Institute on Drug Abuse Clinical Trial Network, which was involved in some of the early medication assisted treatment studies.

After seeing the dependence and mortality numbers continue to rise and hearing from voices who care about this issue, I asked our folks to take a hard look at whether we’re doing everything we can to ensure that we’re appropriately taking into account the public health crisis that confronts us in the context of the role we play in ensuring the safety and efficacy of drugs.

The conclusion of that comprehensive assessment was that we can do more.

So we are announcing a change in course in how our agency approaches opioids – their approval, their labeling and their prescribing. We are going to fundamentally re-examine the risk-benefit paradigm for opioids and ensure that we consider their wider public health effects.

To that end, we have developed a comprehensive action plan to take concrete steps toward reducing the impact of opioid abuse on American families and communities.

There are four main pillars to the plan.

First, we’re going to be more transparent and open in the approval process for this category of drugs. Starting today, the FDA will convene an expert advisory committee before approving any new drug application for an opioid that is not in an abuse-deterrent formulation (ADF).

Additionally, we’re going to engage the Pediatric Advisory Committee to make recommendations on pediatric opioid labeling before any new labeling is approved.

Importantly, the advisory committee process is going to provide opportunity for public input, which is going to help us better understand and answer the concerns people have about these drugs.

We have also engaged the National Academies of Sciences, Engineering, and Medicine on how to take into account our evolving understanding of the risks of opioids, not only to the patient but also the risks of misuse by other persons who obtain them. The goal is to formally incorporate the broader public health impact of opioid abuse in approval decisions. And in March, we will seek advice from the Agency’s Science Board to reassess the risk-benefit approval framework for opioid use. The results of these efforts will be made public.

Second, we’re going to improve our communication with the medical community about these drugs. That starts with enhancing safety labeling. Our goal is to provide better information to doctors about the risks of these drugs and how to safely prescribe them. We’re developing changes to immediate release opioid labeling that will bring it more in line with the extended-release/long-acting labeling that occurred in 2013.

After reviewing the existing requirements and hearing recommendations from an advisory committee, we’re also going to update our Risk Evaluation and Mitigation Strategy (REMS) program requirements for opioids. We need to increase the number of prescribers who receive training on pain management and improve the safe prescribing of opioids to decrease inappropriate prescribing.

That effort will complement work being done at the Department level and at the CDC to help ensure that opioids are prescribed appropriately. We believe that this is a key component of ending this public health crisis. The more than 250 million prescriptions for these types of pain killers in 2012 – enough for every adult in the U.S. to have a bottle of pills – is clear evidence of the work ahead of us.

Third, we’re going to work to improve the information that’s available about opioid use. We’re going to require drugmakers to strengthen post-market analysis of these drugs. Today, that information, especially about long-term use, is lacking. We need more and better evidence on the risks of misuse and abuse associated with long-term opioid use and to better understand predictors of addiction, among other issues.

Finally, we’re going to focus efforts on approving drugs that have the potential to help mitigate the crisis. That means spurring the development of promising generics with abuse deterrent formulations. The FDA will issue draft guidance with its recommendations for the approval standards for generic abuse-deterrent formulations. We believe the availability of less costly generic products should accelerate prescribers’ update of abuse deterrent formulations.

And we’re going to work to improve access to naloxone, which is effective at treating overdoses. The FDA is reviewing options, including over-the-counter availability, to make naloxone more accessible. That work builds on FDA’s recent approval of intranasal naloxone.

What I’ve just described is a change in course – a framework for how FDA can better do its part to confront the opioids epidemic. In the coming weeks and months, we’re going to further develop these plans and continue to fill in the details for each initiative I’ve described.

But it’s time for us to act – to take the first steps toward changing how we do business and addressing this problem.

Robert M. Califf, M.D., previously FDA’s Deputy Commissioner for Medical Products and Tobacco, became FDA’s Commissioner of Food and Drugs on Feb. 25, 2016

Building a Modern Generic Drug Review Process

By: Stephen Ostroff, M.D.

Recent hearings on Capitol Hill highlighted an issue of growing importance for patients and for public health: access to quality, affordable medicines, in particular generic drugs. FDA’s generic drug program promotes access to quality affordable medicines by reviewing Abbreviated New Drug Applications (ANDAs), the pathway that allows generic drugs to come to market.

Acting FDA Commissioner, Stephen Ostroff, M.D.The generic drug sector has been enormously successful, growing from about 40 percent of drugs dispensed about 20 years ago to 88 percent today. And the cost savings have been enormous – approximately $1.68 trillion from 2005 to 2014 alone.

As my colleague Dr. Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research (CDER) at FDA, said in Congressional testimony, FDA is currently working to efficiently process and approve generic drug applications, at record or near-record levels, so when drug patents expire, less expensive generic options are available.

What’s helping FDA keep up that pace of approvals is the added resources that FDA and industry agreed to several years ago in the Generic Drug User Fee Amendments (GDUFA), part of the law passed by Congress known as the Food and Drug Administration Safety and Innovation Act of 2012. With this funding, we were able to hire and train over 1,000 new employees, develop an updated informatics platform to support our review program, and reorganize our generic drug office. Now, after several years of building a modern generic drug review process, FDA is on track to achieve the kind of success this legislation envisioned.

Today FDA is achieving – and in some instances surpassing – important GDUFA goals, including our approval of the ‘first generic” versions of an innovator drug.

generic drug chart

Generic Substitutions & Annual Savings

Although potential first generics constitute only a small percentage of our overall workload, they are very important for the market. Over the past three years, we have approved hundreds of first generics for over 200 new drug products. How? We made substantial program improvements. We solicited nationwide technical input from outside experts and organizations; issued a public-facing, transparent prioritization policy; formed a team to expedite the review of first generics; trained review staff; and enhanced our computer systems to streamline the process.

We’ve also eliminated our filing backlog of ANDAs. In August 2014, there were more than 1,100 applications that had not been reviewed for an initial filing decision. Today there is no backlog.

The cumulative result of our efforts is a huge increase in the productivity of the generics program. We ended 2015 at a new monthly high of 99 generic drug approvals and tentative approvals in December.

Finally, FDA is undertaking major changes in quality regulation so the public can be confident that we’re holding generic drugs to the same standards as brand drugs, no matter where in the world they are manufactured or tested.

All of us at FDA are extremely proud of what we’ve accomplished in implementing GDUFA. In the first two years of the program, we substantially enhanced our ANDA review program. Now we’re cranking it up. There will be up months and down months, but the overall trend will be one of continuing increases in output. More approved generics, if marketed, can further expand patient access to quality, affordable medicines.

We are currently engaged in discussions with industry and the public regarding the development of the second generation of GDUFA, which we call GDUFA II. GDUFA II is scheduled to begin in 2017. We welcome the opportunity which GDUFA II offers to build on our success, and make significant program improvements. Our goal is to bring safe, effective, high quality, affordable generics onto the market. This will benefit the health of every American.

Stephen Ostroff, M.D., is Acting Commissioner of Food and Drugs

Modernizing Pharmaceutical Manufacturing to Improve Drug Quality: Ensuring a Safe and Adequate Supply of Drugs

By: Michael Kopcha, Ph.D., R.Ph.

FDA is working with drug makers in a new way to help the industry adopt scientifically sound, novel technologies to produce quality medicines that are consistently safe and effective — with an eye toward avoiding drug shortages.

Michael KopchaWhen manufacturing problems arise in drug manufacturing facilities, drug shortages may follow. In fact, 65 percent of all drug shortages are caused by manufacturing and quality issues. This underscores the need for a safe and reliable drug supply chain.

In recent years, hundreds of drug shortages have been reported to FDA. We’ve done much to minimize their impact and prevent future drug shortages. For example, we’ve expedited the review of new applications for generic drugs when potential shortage issues arise with approved drugs.

Unfortunately, a significant number of these shortages have affected patients with serious conditions, including cancer, life-threatening infections, and severe malnutrition. These shortages can delay or prevent care to patients and can lead practitioners with no other option but to prescribe less effective therapies.

Other industries (such as electronics, chemicals, and automobile) have embraced the use of advanced manufacturing technologies and demonstrated improved quality, increased efficiency, and a reduced number of product failures. These lessons learned could be replicated. Working to modernize pharmaceutical manufacturing technology is key to our new approach to help the industry reduce and prevent drug quality and shortage problems.

By adopting similar technological advances as other industries, the pharmaceutical industry can create a more robust drug manufacturing process with fewer interruptions. This will minimize product failures and provide greater assurance that the product will consistently deliver the expected clinical performance.

FDA strives to support the modernization of pharmaceutical manufacturing by providing guidance to drug companies that are pursuing new technologies. One example is the recent approval of the first ever 3D printed pill which was for Spritam (levetiracetam), a medication to treat epilepsy. In this case, FDA worked closely with the manufacturer to make 3D printing technology a reality.

By adopting this novel technology, the drug maker is able to produce pills that can disintegrate more rapidly in a patient’s mouth, greatly aiding those who have trouble swallowing. This approval is a strong example to FDA’s efforts to put emerging technology to work for the health of Americans.

FDA is taking further measures to improve drug quality. To further help advancements in pharmaceutical manufacturing, FDA established the Emerging Technology Team (ETT). This specialized group—which includes representation from the Agency’s Office of Pharmaceutical Quality and the Office of Regulatory Affairs—works directly with industry to help identify and resolve scientific issues for new technologies. What makes this approach novel is that this dialogue can occur during early technology development prior to the submission of a drug application to the FDA. Such early engagement enables the FDA to proactively identify and address potential roadblocks and helps eliminate potential delay in the adoption of promising new technologies.

To clarify the mission and scope of the ETT, we’ve recently issued a draft guidance titled, Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base. It provides recommendations to pharmaceutical companies on effective ways to work with the ETT. The document explains the ETT and provides specific recommendations to drug manufacturers for obtaining important early feedback from the FDA regarding their efforts to develop novel manufacturing technologies.

We’ve received much positive feedback and look forward to continuing productive interactions with industry. Expanding this program will not only help to prevent drug shortages, it will help reinvigorate our country’s pharmaceutical manufacturing sector while fulfilling a critical part of FDA’s mission: ensuring that safe and effective drugs are consistently available to the American public.

Michael Kopcha, Ph.D., R.Ph., is FDA’s Director, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research