FDA’s Clinical Investigator Training Helps Support the Drug Development Process

By: Leonard Sacks, M.D., and Mili Duggal, Ph.D., M.P.H.

Though many people do not know it, FDA does much more to facilitate drug approval than evaluate new drug applications. We are also actively involved in drug development well before the application stage. One important way we do this is by training scientists who conduct the clinical trials for drugs in development. This helps ensure that the drug studies conducted by investigators meet the applicable regulatory requirements and that the applications submitted meet regulatory standards.

Leonard Sacks

Leonard Sacks, M.D., is Associate Director for Clinical Methodologies, Office of Medical Policy, at FDA’s Center for Drug Evaluation and Research

We are excited to announce our seventh annual Clinical Investigator Training Course, which will be held in collaboration with the University of Maryland’s Center of Excellence in Regulatory Science and Innovation (M-CERSI) from November 7-9, 2016, at the Civic Center, Silver Spring, Maryland. The course is designed for physicians, nurses, pharmacists, and other healthcare professionals who are involved in the design, conduct, and evaluation of clinical trials. Participants receive training by senior FDA experts and guest speakers from industry and academia, which enables them to learn the scientific, regulatory, and ethical aspects of clinical trials.

FDA has successfully conducted the Clinical Investigator Training Course since 2009, training more than 1,000 attendees from the U.S. and other parts of the world, including Germany, Spain, Zimbabwe, and China. Over the years, participants have included healthcare professionals from government organizations, regulatory bodies, academia, industry, and the healthcare sector.

Mili Duggal

Mili Duggal, Ph.D., M.P.H., is an ORISE Fellow, Office of Medical Policy, at FDA’s Center for Drug Evaluation and Research

FDA developed this course so that investigators could learn directly from our staff and interact with them. Clinical trial investigators play a critical role in the development of medical products. They are responsible for protecting the safety and welfare of study subjects and for acquiring adequate and reliable data to support regulatory decisions. FDA recognizes that investigators should be comprehensively trained to conduct trials efficiently. The course’s goal is to develop competence and expertise among clinical investigators, improve the quality of clinical trials, and support patient safety.

As we continue to build our program, FDA will work to integrate the latest scientific information and good clinical practices into our course. We anticipate a new round of exciting discussions with our attendees this year and we invite all who are interested and wish to attend to take a look at the course website for more details. We look forward to helping many more talented researchers hone their clinical investigator skills to advance new drug development for the American public.

Leonard Sacks, M.D., is Associate Director for Clinical Methodologies, Office of Medical Policy, at FDA’s Center for Drug Evaluation and Research

Mili Duggal, Ph.D., M.P.H., is an ORISE Fellow, Office of Medical Policy, at FDA’s Center for Drug Evaluation and Research

Evaluating FDA’s Approach to Cancer Clinical Trials

By: Richard Pazdur, M.D.

Since the announcement of the FDA Oncology Center of Excellence (OCE) two months ago (June 29, 2016) as part of the White House’s Cancer Moonshot, we’ve been working to further FDA’s efforts to get new oncology products into the hands of patients. We are committed to meet the needs of patients and health care communities by driving progress in the prevention, diagnosis, and treatment of cancer.

Dr. Richard PazdurAt the core of the OCE’s work – and of the Cancer Moonshot – is taking a new look at what we have been doing in the past so we can operate more efficiently in the future. The OCE will leverage the combined skills of oncologists and scientists with expertise in drugs, biologics, and devices to employ the best and most innovative approaches to bring forth safe new oncology products.

The vision set forth by the Vice President underscores our commitment to optimally designed clinical trials that efficiently provide answers to important questions. Given the recent advances in our understanding of cancer and our improved technological capabilities, we are now placing an emphasis on evaluating how we design clinical trials to make the system more efficient to more rapidly deliver safe and effective products for patients.

We are working with stakeholders across government and industry to revisit the criteria used for determining whether a patient is eligible to participate in a trial. Modifying the eligibility criteria could expand the number of people who qualify and therefore open new opportunities for participation and enhance the generalizability of what we learn. Of course, regardless of adjustments, patient safety will remain paramount.

We recently published our perspective on shifting away from the conventional phase one, phase two, and phase three drug development paradigm to a more seamless approach that could expedite the regulatory pathway, providing earlier access to highly effective therapeutic drugs. Adopting this approach could complement FDA’s expedited regulatory programs such as breakthrough designation and accelerated approval to get products to patients in the most efficient manner possible.

Another initiative is the use of common control trials. These trials, sharing a common control arm, involve multiple different drugs for the same indication and may involve different companies. When a common control arm is used, it decreases the overall number of patients that need to be recruited and enrolled, optimizing clinical trial resources and potentially decreasing the time it takes to get a new study off the ground.

Encouraging the use of large simple trials is another way to make more efficient use of clinical trial resources. These trials generally use easily-measured endpoints that are well understood, optimizing the collection of data for safety or secondary efficacy endpoints and thus reducing the amount of data needed compared to conventional randomized trials.

As befits the Center of Excellence, one of our top goals is striving for excellence both in drug and device regulation and in emerging oncology science. To achieve that goal we must also collaborate with academia, industry, patient groups, professional societies, and other international regulators. We have already begun this work by scheduling several public meetings that will provide a forum to interact with patients and other stakeholders.

These initiatives will allow us to expedite drug development and approval of truly novel agents that will have a major impact on our patients, while allowing us to make thoughtful decisions regarding the risk-benefit of oncology drugs.

Richard Pazdur, M.D., is FDA’s Acting Director, Oncology Center of Excellence

FDA and Access to Medications

By: Janet Woodcock, M.D.

A severe allergic reaction called anaphylaxis is a medical emergency that affects the whole body and, in some cases, leads to death. If you have had an anaphylaxis episode, you always face the risk of another one. To mitigate the risk you or your caregiver should carry an emergency treatment called epinephrine at all times, because every second counts.

Janet WoodcockAt the FDA, we understand how important it is for this treatment to be safe, effective, and work correctly every time. And in the case of a very severe reaction such as anaphylaxis, when there may be no second chance, the device that delivers the medication is just as critical. EpiPen, a popular form of emergency epinephrine that auto-injects the dose, is one of these treatments.

But sometimes, when medications become prohibitively expensive, some people lose access to a potentially life-saving treatment. When that happens, people often look to the FDA. Recent news about the price spike of EpiPen has caused concern. In addition, the EpiPen product has patents listed through 2025 that could delay generic competition. And so we are asked, what role does the FDA play?

The FDA doesn’t regulate drug prices – prices are set by the drug makers or distributors. It’s our job to ensure medications, including emergency medications, are safe and effective. We also recognize when we approve new drugs, including generic versions of a drug, it may improve competition in the marketplace. The good news is that the FDA has already approved four epinephrine auto-injectors to treat anaphylaxis in an emergency, and two are currently marketed. The EpiPen does not have any FDA-rated therapeutic equivalents. But like EpiPen, these alternative products are approved by the FDA as safe and effective for treating anaphylaxis. As always, patients should check with their doctor on whether a particular treatment is appropriate and available.

We stand ready to quickly review additional applications that come to us from manufacturers, especially applications for generic versions. To speed along the process, our Office of Generic Drugs prioritizes and expedites our review of applications for first generics, making sure that the first applicants to make a generic are moved to the head of the queue and given priority review.

We at the FDA are also doing all we can to encourage manufacturers to develop innovative new auto-injectors that ensure a life-saving drug can be administered easily and safely by anyone. To help development, we built a roadmap that will get these products on the market faster. In June 2013, the agency provided technical information for industry about designing and testing auto-injectors. In February, the FDA provided industry with draft guidance on how to determine if patients can effectively use the new devices. We do not want substandard quality products to come to market, because a patient suffering a life-or-death event has to be able to pick up and use a device without a moment’s hesitation.

The FDA is committed to ensuring that consumers can trust the products that are available. Anaphylaxis is a condition some people can’t avoid, but cost should not be the reason someone cannot access care.

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

Making Continuous Improvements in the Combination Products Program: The Pre-RFD Process

By: Thinh Nguyen and Rachel E. Sherman, M.D., M.P.H.

One question that sponsors often ask FDA is whether their medical product will be regulated as a drug, a device, a biologic, or as a combination product, and in the case of the latter, which FDA component will regulate it.

Thinh Nguyen

Thinh Nguyen, FDA’s Director, Office of Combination Products

One way sponsors may determine how their product will be classified is to submit a Request for Designation (RFD) to the Office of Combination Products (OCP). This request requires FDA to provide a written determination of product classification and/or which agency component will regulate the product if it is a combination product. Sponsors have also been able to obtain less formal feedback regarding product classification through communications with OCP.

We are pleased to announce that the Agency is making some changes to our internal procedures for responding to communications from sponsors regarding preliminary product classification assessments from OCP. The Pre-Request for Designation (Pre-RFD) process is the result of cooperative efforts by OCP, the Office of Medical Products and Tobacco, and CDER Lean, including a formal internal evaluation that incorporates current state process mapping and identifies and integrates process improvements.

Rachel Sherman

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

The Pre-RFD process shares some similarities with the RFD process. In both cases, FDA’s assessment depends on sponsors providing a complete, clear, and detailed product description, which includes the product’s indication for use, its composition/ingredients, and an explanation of how it works. In most instances, both processes also require input from the product jurisdiction officers in the relevant Centers and, if necessary, legal perspectives from the Office of Chief Counsel.

Once OCP has received the necessary input, the Office makes its assessment of the classification and/or Center assignment for the product. OCP’s goal for Pre-RFDs is to respond to sponsors within 60 days following receipt of all information needed to initiate the review—the same timeline for responding to RFDs. During this review period the office will communicate with the sponsors as needed.

When may this Pre-RFD process be useful?

The Pre-RFD process can be used at any point during medical product development. It may be preferable to the more formal RFD process when a sponsor would like to engage FDA using a more interactive approach—a course that may be especially helpful when a medical product is at an early stage in its development, or when a sponsor is contemplating whether to develop a specific product, or what configuration of that product to pursue. In such cases, sponsors may find the Pre-RFD process beneficial for the following reasons:

(1) Sponsors are not required to provide a recommendation for classification and assignment of their product along with a corresponding rationale (e.g., bench studies; clinical studies) for that recommendation;

(2) Sponsors are not required to discuss the classification of currently marketed products that they believe to be similar to their product; and,

(3) Sponsors can receive preliminary feedback and information from the Agency that is derived from a structured and efficient process. The feedback will ultimately help lead to better decision-making and development of products for the sponsors.

Pre-RFD flow chart

FDA’s Pre-RFD Process Flow: To view, click on the image.

Because our feedback will be based on the information submitted, sponsors should bear in mind that the speed and quality of any review, whether Pre-RFD or formal RFD, is highly dependent on the quality of the submitted data.

The Agency is developing a draft guidance about the Pre-RFD process, which provides details about information sponsors should include in a Pre-RFD and describes the procedure for FDA’s review. In addition, the Agency plans to publish a list of product classifications for various types of products. We believe this list will offer additional transparency and clarity to sponsors that will ultimately foster innovation and promote better health for patients. We welcome your feedback regarding the Pre-RFD and RFD Programs, as well any other thoughts regarding the jurisdictional assessment of products.

A sponsor who wishes to submit a Pre-RFD or an RFD for a product can find detailed information at the OCP website or contact OCP at combination@fda.gov for further assistance.

Thinh Nguyen is FDA’s Director, Office of Combination Products

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

FDA Supports Greater Access to Naloxone to Help Reduce Opioid Overdose Deaths

By: Karen Mahoney, M.D.

Overdose deaths involving prescription opioids such as oxycodone, hydrocodone and morphine and illicit opioids such as heroin and illegally produced fentanyl have more than tripled since 1999 – with about 28,000 people dying in 2014 alone.

Many of these tragedies could have been avoided if the people experiencing the overdose had immediately received the prescription drug naloxone, a life-saving medication that can stop or reverse the effects of an opioid overdose.

Naloxone is still a prescription in all 50 states and the District of Columbia, though many have or are taking steps to make naloxone more accessible. Consistent with our opioid action plan announced earlier this year, the FDA is exploring options to make naloxone more available to treat opioid overdose. One option to do this is identifying ways to assist manufacturers in submitting an application to the FDA for an over-the-counter (OTC) version of a naloxone product.

That’s why the FDA is working on innovative ways to help facilitate the process of helping manufacturers pursue approval of an OTC naloxone product, including helping to develop the package label that would be required for such a product. This is an important step to help increase access to and the use of this life-saving drug.

Although the two currently available prescription naloxone products intended for use in the community — an auto-injector product for self-injection, and a nasal spray formulation – have instructions for use, they do not have the consumer-friendly Drug Facts Label (DFL), which is required for OTC drug products. Before submitting a new drug application or supplement for an OTC drug product, companies develop this DFL and conduct the required studies to show that consumers can follow the DFL to understand how to use the product without the help of a healthcare professional.

To help facilitate the development of OTC naloxone, the FDA has created a model DFL and an accompanying simple pictogram that could be placed next to the DFL to visually correspond to the label directions. This model DFL and pictogram are intended to provide consumers with the information they would need to understand how to safely use naloxone, including when it is appropriate to purchase naloxone and how to use it in an emergency opioid overdose situation. Since it is a model label, information that is highly specific to a particular product would not be included.

The FDA has also arranged for label comprehension testing of the model DFL. This testing is now being conducted and we expect that the results will yield important information about consumer understanding of the model naloxone DFL. Using this information, naloxone manufacturers may then be able to focus their final label comprehension testing on how well consumers understand product-specific information, such as instructions for the device that delivers naloxone that has not been already tested on the model DFL.

Creating a model DFL and arranging for label comprehension testing are among the ways that the FDA is working to fulfill our commitment to enhanced naloxone access, where possible, in our opioids action plan. We will continue to work with interested manufacturers and developers to further explore the best uses of naloxone for the emergency treatment of known or suspected opioid overdoses until emergency medical help arrives.

FDA’s opioid action plan is part of the comprehensive Opioid Initiative launched by the U.S. Department of Health and Human Services (HHS) in March 2015. The Initiative focuses on high-impact strategies to 1) improve opioid prescribing, 2) expand access to medication-assisted treatment for opioid use disorders, and 3) increase the use of naloxone to reverse opioid overdoses.

Karen Mahoney, M.D., is FDA’s Deputy Director, Division of Nonprescription Drug Products, at the Center for Drug Evaluation and Research

Piloting an Improved Intercenter Consult Process

By: Michael Rappel, Ph.D., and Rachel E. Sherman, M.D., M.P.H.

Over the last few months, we’ve shared what FDA is doing to improve the review of combination products, including establishing the Combination Product Council and identifying necessary process improvements through lean mapping of the combination product review process. We are pleased to update you on the proposed intercenter consult request (ICCR) process that will be piloted across the Agency today.

Michael Rappel

Michael Rappel, Ph.D., Senior Science Advisor in FDA’s Center for Drug Evaluation and Research and member of the Lean Management Team.

Combination products—those that combine drugs, devices, and/or biological products—present both policy and review challenges in large part because they include constituent parts that fall into more than one regulatory category (e.g., drug and device; drug and biologic) covered by more than one FDA product center. As such, close intercenter collaboration and communication are important to facilitate timely, appropriately-tailored and well-informed submission review. A combination product will generally have a lead center which may seek consults from the other centers that oversee one of the product’s constituent parts. Timely and consistent consults are critical, yet achieving this has been challenging due to different policies, practices, and timelines for consults across centers and insufficient communications between centers and sponsors.

Our new process addresses these issues with four important improvements:

  • Establishing timelines, specific to center and submission type, for identifying products as combination products and issuing and completing consults needed to support the review;
  • Developing  a tiered consult approach that streamlines interactions across centers and identifies a clear process for identifying the right experts for a consult;
  • Defining clear roles and responsibilities for the Lead Center, the Consulted Center(s), the Office of Combination Products (OCP), and the Combination Product Council for review of a combination product submission; and,
  • Creating a standard, semi-automated, user-friendly ICCR form that is managed electronically to ensure 1) users always have the most updated version and 2) all forms, and thus all intercenter combination product consults, are tracked through a single system.
Rachel Sherman

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

FDA will begin piloting this new ICCR process today in select offices within our three medical product centers, focusing on those offices or divisions that routinely receive combination product submissions that require cross center consults. The pilot will be comprised of three phases, with phase 1 planned to last for two months. Additional offices in each center will be rolled into the pilot in subsequent phases with the goal of achieving implementation across all Offices by the end of 2Q 2017 (targeted).

During each phase of implementation, we will collect quantitative and qualitative data to evaluate success. What we learn at each stage will allow us to refine processes, procedures, and training for subsequent phases. In particular, data from phases 1 and 2 will be used largely to refine the initial steps of the ICCR process (e.g., consult request, ICCR form, reviewer assignment) though some limited consult completion data (e.g., consult quality and timeliness) available for Investigational Device Exemptions/Investigational New Drugs may provide initial insights on consult closeout. Consult completion data for other submission types will also be collected but may not be available for several months due to the longer submission review timelines.

This iterative approach will ensure implementation of a robust ICCR process that enables efficient, effective collaboration on the review of combination products. Further, auditing regarding combination product designation and consult tier assignment completed by each center will verify effective knowledge transfer or highlight gaps to focus on in subsequent improvement efforts.

This current effort has been driven by a cross-Agency ICCR working group and builds on the important work of many others across the Agency.

We hope this overarching approach to cross-center activity will, if successful, serve as a flagship model for other cross-Agency initiatives requiring close collaboration. We believe that this kind of nimble, adaptive cooperation reflects the future of medical product development and review in an increasingly complex and nuanced arena. Stay tuned—we plan to keep you updated on our progress along the way. Meanwhile, if you have any feedback or input, please feel free to contact us at: combinationproductICCRpilot@fda.hhs.gov.

Michael Rappel, Ph.D., is Senior Science Advisor in FDA’s Center for Drug Evaluation and Research and is a member of the Lean Management Team

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

The Unique Voices of Our Patient Representatives

By: Robert M. Califf, M.D., and Heidi C. Marchand, Pharm.D.

We recently met with 21 inspirational patients and patient caregivers who have made the extraordinary commitment to become FDA patient representatives. These volunteers were in Washington to participate in our two-day Patient Representative Workshop so they can receive training that will allow them to help FDA meet its critical responsibility of guiding the development and evaluation of safe and effective medical products.

Robert Califf

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

The patient representative program has existed since 1999 and is integral to fulfilling FDA’s strong commitment to ensure that the needs and choices of patients – as well as their families, caregivers, and advocates – are incorporated in ever greater ways in the work we do.

Patients add context and content to the cutting-edge science and other empirical evidence that is so important in our regulatory decision-making.  Including their perspectives and voices in our work along the entire medical product continuum, from development to review and evaluation to post-market surveillance, offers opportunities to enhance our knowledge of the benefits and risks of medical products. It’s not only smart science; it just makes good sense. We know, for instance, that patients who live with a chronic disease are experts in the tangible effects of that disease and its treatments.

The training that patient representatives receive helps prepare them to serve on FDA advisory committees, meetings and workshops, where they are knowledgeable about what it is like to cope with their disease – including such topics as side effects from treatments and important lifestyle issues. They also provide valuable contributions as consultants to our review staff.

Heidi Marchand

Heidi C. Marchand, Pharm.D., Assistant Commissioner in FDA’s Office of Health and Constituent Affairs

To give you an idea of the unique set of skills and experiences patient representatives bring to their work, consider the stories and experiences we heard at the workshop.

One was an elite world class athlete, who initially thought her pain was muscular in nature before it was diagnosed as a serious blood clot. She has been on a series of different products since then and is now intimately familiar with what it is like to be on anticoagulants – reflecting on both the benefits and risks of taking these medications.

Two of our patient representatives are caregivers who have a personal experience with a rare disease, Batten’s Disease, a fatal, inherited disorder of the nervous system. Sadly, each lost a young son to the disease. But in the face of this tragedy, these two mothers have advocated tirelessly to find a cure for this disease and worked to educate other parents.

Another mother related the story of her daughter who, at age 16, survived two craniotomies to remove a lemon-sized brain tumor. The daughter went on to receive of 48 weeks of chemotherapy and 8 weeks of brain and spine radiation. The daughter is now 33 years old and doing well. And the mother told us how critical it was for her daughter to take an opioid to relieve her pain. This kind of input, from those who have experienced it first hand, is critical to our future decisions.

2016 FDA Patient Representative Group photo

FDA Patient Representatives at the 12th Annual FDA Patient Representative Workshop, hosted by FDA’s Office of Health and Constituent Affairs

The stories that these patient representatives tell are moving. But even more moving – and indeed inspirational – is their commitment to the future. That’s why they were selected – because of their individual involvement with their respective patient communities, their analytical skills, and their ability to maintain an open mind and consider options.

While we will help train them about the nuts and bolts of FDA – such as the various pathways that products take to get to market – it is their personal experience and their ability to understand and to articulate the perspectives, concerns, and experiences of patients – that makes them truly special.

As we continue to evaluate potential treatments and cures for different diseases, we must make sure that patients are more than simply statistics in this equation. They are real people, with names, faces, and, thanks to these patient representatives, important voices who represent an essential piece of the puzzle to be solved.

FDA is committed to looking for new and better ways to integrate the patient voice. Our patient representatives are an important piece of this commitment. They have an extraordinary impact. We thank them for their service and commitment, and look forward to working with them.

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

Heidi C. Marchand, Pharm.D., is Assistant Commissioner in FDA’s Office of Health and Constituent Affairs

Addressing Global Challenges through Transatlantic Cooperation

By: Howard Sklamberg, J.D., Lou Valdez, and Donald Prater

Howard Sklamberg

Howard Sklamberg, J.D., FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

On a recent trip to Brussels, our FDA delegation met with many of our European Union (EU) regulatory counterparts and stakeholders to discuss ways to strengthen our shared commitment to product safety and public health.  

Reflecting the broad scope of our transatlantic dialogue, we engaged on an array of issues, including supply chain safety, quality metrics, risk-based surveillance, data integrity, mutual reliance, and food safety systems.

Building on previous exchanges between FDA and the European Parliament (EP), we first met with Members of the Environment, Public Health and Food Safety Committee, known as ENVI.  ENVI Committee members visited FDA in 2013 and 2015 to share their perspective on how certain health-related topics are being addressed in the European Union. In addition, our FDA delegation exchanged views on recent trilateral cooperation with India and China on Good Clinical Practices and food safety and other approaches to cooperation on the international stage.

Lou Valdez

Mary Lou Valdez, FDA’s Associate Commissioner for International Programs

We then met with the head of the European Commission’s Directorate General for Health and Food Safety (DG SANTE), Director General Xavier Prats-Monné, and his colleagues.

We shared our observations on several topics, including:

  • How drug development has changed, including globalization of suppliers and distributors;
  • The challenges among regulatory bodies in keeping pace with risk-based allocation of inspection resources;
  • The complexity of the global supply chain and the need to collaborate on enforcement;
  • The significant progress being made on the Mutual Reliance Initiative (MRI);
  • Pharmaceutical GMP inspections; and
  • The interaction among FDA’s Europe, China, and India offices and regulatory counterparts in the EU and Governments of China and India.
Donald Prater

Donald Prater, D.V.M., Director of the Europe Office in FDA’s Office of International Programs.

We then turned to food safety. Currently, the U.S. and the European Commission are working on a Food Safety Systems Recognition arrangement, a program that FDA has developed to increase regulatory cooperation and build toward reliance on the work of regulatory counterparts.

Such cooperation is facilitated through the reciprocal assessment of one another’s food safety systems to ensure the safety of foods produced under one another’s oversight. The United States already has an arrangement in place with New Zealand and recently signed one with Canada.

We also reviewed the Food Safety Modernization Act (FSMA) and discussed ways FDA and the European Commission can assist suppliers in the EU to better understand the FSMA requirements. Acknowledging that food safety standards are quite high in the United States and the EU, we discussed ways we can leverage the systems on both sides of the Atlantic to further protect consumers and more efficiently use our oversight resources globally.

FDA and EU Delegations in Brussels

A U.S. Food and Drug Administration (FDA) delegation met with many of their European Union (EU) regulatory counterparts in Brussels to discuss ways to strengthen the shared commitment to product safety and public health. Pictured from left to right are: Karin Kadenbach, Member European Parliament (MEP); Sandy Kweder, Deputy Director, FDA’s European Office; Lou Valdez, FDA’s Associate Commissioner for International Programs; Matthias Groote, MEP; Howard Sklamberg, FDA’s Deputy Commissioner for Global Regulatory Operations and Policy; and, Susanne Melior, MEP.

Next up were meetings on medical devices and cosmetics with the Directorate General for Internal Market, Industry, Entrepreneurship, and SMEs, also known as DG GROWTH.

We were welcomed by Carlo Pettinelli, Head of the Directorate for Consumer, Environmental and Health Technologies, and we discussed the key objectives of the Medical Device Single Audit Program (MDSAP) of the International Medical Device Regulators Forum (IMDRF). Mr. Pettinelli acknowledged the importance of MDSAP, and indicated that the European Commission would continue to provide coordination and communication to support the engagement of EU Member States in the program.

We also set aside time for discussion with key industry stakeholders representing medical products – primarily drugs and devices, including, the American Chamber of Commerce Healthcare Committee to the EU and the European Federation of Pharmaceutical Industry Association (EFPIA). There we reviewed FDA’s Pharmaceutical Quality and MRI initiatives.

Our trip concluded with a media roundtable and a briefing to the Deputy Chief of Mission and staff at the U.S. Mission to the European Union. Our FDA Europe Office is based at the USEU and provides critical support to U.S. Ambassador Anthony Gardner.

Throughout all our meetings, one theme was crystal clear: Transatlantic cooperation is vitally important to address the challenges and opportunities of a globalized marketplace.  By carefully evaluating and understanding each other’s regulatory systems, there is tremendous potential to better allocate our resources based on risk, and improve the safety of food, medical products, cosmetics, and other products around the world.

Howard Sklamberg, J.D., is the Deputy Commissioner for Global Regulatory Operations and Policy

Mary Lou Valdez is the Associate Commissioner for International Programs

Donald Prater is Director of FDA’s Europe Office

The Rise in Orphan Drug Designations: Meeting the Growing Demand

By: Gayatri Rao, M.D., J.D.

Developing drugs for rare diseases, once considered a rare phenomenon itself, has fast become a mainstay for many companies’ drug development pipelines. This is exciting news for the 30 million Americans with rare diseases and their families.

Dr. Gayatri RaoCongress played no small role in making this a reality when it passed the Orphan Drug Act in 1983.  One of the key features of this Act was the creation of the Orphan Drug Designation Program, which provides important financial incentives to encourage companies to develop drugs and biologics for rare diseases. This legislation includes major tax credits to defray the cost of conducting clinical trials, as well as eligibility for seven years of market exclusivity. As a result of later amendments to the Act, no user fee is required for orphan drug product submissions, except when an application includes an indication for a non-rare disease or condition.

The number of requests for orphan drug designation received by FDA’s Office of Orphan Products Development (OOPD) has grown dramatically in recent years and is prompting FDA to adjust its timeframes for reviewing orphan drug designations in order to meet the demand. In 2014, we saw a 30% increase over the prior year’s record number. Yet, that record was broken the very next year when we received close to 470 requests. And the pace does not seem to be slowing. In fact, comparing the number of new requests received so far in 2016 with the corresponding date in 2015, there appears to be yet another 30% increase.

We strive to review these requests in an efficient and timely manner because we understand how critical designation can be for companies to move forward with their drug development plans. At the same time, we endeavor to safeguard the intent of the Orphan Drug Act by conducting a thorough review to ensure that the drugs we designate fully satisfy the criteria for designation and the financial incentives associated with designation.

While there is no statutory or regulatory review deadline, it has been our internal goal to review 75% of designation requests within 90 days of receipt. By streamlining our programs, modifying work priorities, and restructuring workloads, we have generally been able to meet or exceed that internal goal. However, the sustained increase in designation requests over the last three years, coupled with the increasing number of incentive programs and competing workload priorities, have forced us to reconsider our internal review target. Reviewing these applications in an efficient and timely manner continues to be a top priority, but to ensure we continue to conduct these reviews with the appropriate level of care and consideration, our current goal is to review on average 75% of designation requests within 120 days of receipt.

We will continue to evaluate workload in relation to resources, and may need to further adjust review timelines in the future.

Companies can play a critical role in ensuring that the new review timeframe does not translate into a delay in obtaining orphan drug designation by doing their part to reduce the number of review cycles needed (i.e., when OOPD needs additional information from the sponsor prior to determining the outcome of an orphan drug designation request).

On average, a request for designation today goes through two such review cycles. Sponsors can shorten this process by ensuring that designation requests are complete and fully address all requirements. We recommend sponsors review the information at www.fda.gov/orphan for helpful hints and FAQs when developing their requests.

The rise in the number of requests for orphan drug designation holds promise for the future of rare disease drug development. We remain committed to the timely and effective administration of the Orphan Drug Designation Program with the shared hope of bringing safe and effective products quickly to the patients who need them most.

Gayatri Rao, M.D., J.D., is FDA’s Director for The Office of Orphan Products Development

The United Nations Sustainable Development Goals: Efficient and effective regulatory systems are the tide that raises all boats

By: Mary Lou Valdez, M.S.M., and Kristin Wedding

Lou Valdez

Mary Lou Valdez, FDA’s Associate Commissioner for International Programs

Do you think it’s possible to ensure healthy lives and promote well-being for all people of all ages by 2030? That’s just one of the United Nations 17 Sustainable Development Goals (SDGs), which the world’s leaders agreed to in September 2015. And, FDA has an important role in supporting these goals.

On June 23-24, 2016, we had the opportunity to participate in the National Academies of Science, Engineering, and Medicine’s Forum on Public-Private Partnerships for Global Health and Safety (PPP Forum). The two-day workshop focused on engaging the private sector and developing partnerships to advance health and the SDGs.

Good health and well-being are linked to many of the SDGs, including zero hunger, ending poverty, economic growth, industry, innovation and infrastructure, and reduced inequalities. But what, you might ask, are FDA’s potential contributions as a regulatory agency in achieving the SDGs?

Regulatory Systems and the SDGs: the Challenges

Kristin Wedding

Kristin Wedding is International Policy Analyst in FDA’s Office of International Programs

Strong functioning regulatory systems for food and medical products are at the nexus of public health, economic development, trade, and investment. Within our public health mission, effective regulatory systems often are a necessary precursor for economic development and growth, including private sector investment. Conversely, the absence of effective regulatory systems is an underlying threat to achieving many of the SDGs. For example:

  • unsafe food contributes to malnutrition and jeopardizes food security (Goal 2);
  • lack of access to safe and effective medical treatments exacerbates chronic diseases (Goal 3), and impedes people from getting and keeping a job (Goal 8).
  • illness hampers children’s learning and school attendance (Goal 4), and often disproportionately impacts girls (Goal 5); and,
  • insufficient access to clean water and sanitation (Goal 6) results in the death of more than 1,000 children each day from preventable diarrheal diseases.

Regulatory Systems and the SDGs: the Opportunities

At the workshop, FDA chaired an expert panel on the critical role of regulatory systems and PPPs in promoting global public health, economic development, and sustainable investments to achieve the SDGs. We were joined by Dr. Juergen Voegele of the World Bank, Dr. Rajeev Venkayya of Takeda Pharmaceuticals, and Dr. Dan Hartman of the Bill & Melinda Gates Foundation.

Despite our diversity, we sent a unified message that regulatory systems are essential drivers for the success and sustainability of global health investments to meet the SDGs. It is the responsibility of all of us – as stakeholders, donors, and partners – to make our investments matter.

UN Panel Discussion

Panel discussion at National Academies of Science, Engineering, and Medicine’s Forum on Public-Private Partnerships (PPPs) for Global Health and Safety: A Workshop on Engaging the Private Sector and Developing Partnerships to Advance Health and the Sustainable Development Goals (SDGs).
Mary Lou Valdez, M.S.M, Associate Commissioner for International Programs, FDA, and Juergen Voegele, Ph.D., Senior Director, Agriculture Global Practice, The World Bank.

FDA participates in a number of global partnerships aimed at strengthening regulatory systems, including the World Bank-led Global Food Safety Partnership (GFSP) the PPP Forum, as well as our work with multilateral institutions such as the World Health Organization.

We look forward to continuing the discussion about future pathways for collaboration and action in demonstrating the critical roles regulatory systems play in the attainment of the SDGs. The public health of U.S. citizens – and others around the globe – can benefit from our efforts now and in the future.

As Dr. Hartman so aptly noted during the panel session, in this time of globalization “efficient and effective regulatory systems are the tide that raises all boats.”

Mary Lou Valdez, M.S.M., is FDA’s Associate Commissioner for International Programs

Kristin Wedding is International Policy Analyst in FDA’s Office of International Programs