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

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

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

FDA Takes Action against Zika Virus

By: Robert M. Califf, M.D., and Luciana Borio, M.D.

Zika virus was first identified in 1947 in Uganda and for decades only sporadic cases and a few outbreaks were recognized in a number of locations, including parts of Africa, Asia, and the Pacific. Since 2015, the situation has changed dramatically, with 48 countries and territories reporting a first outbreak of Zika virus as of July 2016. In the United States, cases of Zika virus disease acquired by the bite of an infected mosquito have only been reported in U.S. territories; to date, cases of Zika virus infection reported in the continental United States have involved travelers and in some instances their sexual contacts. However, given the number of Zika cases among travelers visiting or returning to the United States and the increased mosquito activity in the summer months, we expect that imported cases could result in local spread of the virus in some areas of the United States.

Robert Califf

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

The FDA is taking important steps to rapidly respond to the Zika virus outbreak. We are engaged with our partners across the U.S. Government, the private sector, and the international community—including the World Health Organization and ANVISA (the Brazilian Health Regulatory Agency)—to help minimize the impact of this outbreak.

Protecting Tissues and the Blood Supply

One of the FDA’s first actions was to take important steps to help protect the safety of the blood supply. The FDA issued guidance in February 2016 recommending the deferral of individuals from donating blood if they have been to areas with active Zika virus transmission, were potentially exposed to the virus, or have had a confirmed infection. The guidance also recommends that areas with active Zika virus transmission, like Puerto Rico, obtain whole blood and blood components from areas of the United States without active virus transmission unless a blood donor screening test for Zika virus is used. Because there were no blood donor screening tests available for Zika virus at the time, HHS arranged for and funded shipments of blood products from the continental U.S. to Puerto Rico to ensure an adequate supply of safe blood for residents until a blood donor screening test became available. The FDA worked closely with developers in a highly accelerated time frame to make available an investigational test for blood screening in March 2016. The availability of this investigational test, which has been in use in Puerto Rico since early April, has allowed blood establishments to safely collect blood in areas with active Zika virus transmission. A second investigational blood screening test was made available in June 2016. Together, these tests have also enabled blood donor screening to be put in place in areas of the United States where local virus transmission is anticipated, but not yet detected, helping to maintain the safety of the blood supply.

Dr. Lu Borio

Luciana Borio, M.D., is FDA’s Acting Chief Scientist

Zika virus also poses a risk for transmission by human cells, tissues, and cellular and tissue-based products (HCT/Ps) such as corneas, bone, skin, heart valves, and semen used for medical, surgical, or reproductive procedures. Because of this risk, the FDA issued guidance recommending that donors of HCT/Ps be considered ineligible if they were diagnosed with Zika virus infection, were in an area with active Zika virus transmission, or had sex with a male with either of those risk factors, within the past six months.

Supporting Diagnostic Development

The ability to accurately detect and diagnose Zika virus infection is critical for a robust response to this public health threat. The FDA is actively working with manufacturers to support their diagnostic development programs, helping to ensure that their tests are properly validated before they are used to inform patient care. This collaboration has been very successful, and since the beginning of the year, we have authorized the use of five diagnostic tests for Zika virus under FDA’s Emergency Use Authorization authority—four tests to diagnose active infection and one test to assess whether individuals who may have recently been exposed to Zika were actually infected. This test is especially important for women given the link between Zika virus infection and microcephaly and other poor pregnancy outcomes in babies of mothers who were infected with Zika virus during their pregnancy.

Strategies to Suppress Mosquito Population

FDA—as well as our colleagues at EPA— are reviewing the use of innovative strategies to help suppress the population of virus-carrying mosquitoes to help mitigate the threat of vector-borne epidemics, such as Zika virus, which is thought to spread to people primarily through the bite of an infected Aedes aegypti mosquito.

Recently, the FDA released for public comment a draft environmental assessment (EA) submitted by Oxitec, Ltd. (Oxitec). The EA assesses the potential environmental impacts of a proposed field trial of the company’s genetically engineered (GE) Ae. aegypti mosquitoes. The FDA also released for public comment a preliminary Finding of No Significant Impact (FONSI) agreeing with the conclusion in Oxitec’s draft EA that the proposed field trial of the company’s GE mosquitoes would not result in significant impacts on the environment.

The goal of the proposed field trial is to determine whether released Oxitec GE mosquitoes will mate with local wild-type Ae. aegypti and suppress their population at the release site. The FDA is reviewing the thousands of comments received during the public comment period before determining whether to finalize the EA and FONSI or prepare an environmental impact statement (EIS). Oxitec will not proceed with the field trial of the GE mosquitoes until FDA issues its final EA and FONSI or EIS. Oxitec’s GE mosquitoes are one possible approach that could be incorporated into an integrated vector control program to help mitigate the threat of vector-borne epidemics; however, it is too early to say with any certainty whether such an approach would be successful.

Facilitating Medical Product Development

There are currently no vaccines or treatments for Zika virus that have been shown to be safe and effective. Facilitating the development and availability of vaccines is one of the highest priorities for the FDA and the international community. The FDA continues to actively engage with commercial and government developers, including the NIAID and BARDA, to advance the development of investigational vaccines for Zika virus as soon as possible. We are also working with ANVISA to assist in their efforts to expedite the development of vaccines for Zika virus. As was recently reported, a commercial company announced plans to begin evaluating the first investigational Zika virus vaccine in a Phase I clinical study.

Unfortunately, during outbreak situations, fraudulent products claiming to prevent, treat or cure a disease almost always appear. FDA is monitoring for fraudulent products and false product claims related to Zika virus and will take appropriate action to protect consumers when necessary.

More than 120 FDA staff from across the Agency are  responding to the Zika virus outbreak, working together to address the complex range of issues that this evolving epidemic continues to present in order to protect and promote the public health, both domestically and abroad. This type of teamwork exemplifies the capacity of people at FDA to rally together to solve problems, often with little explicit credit other than the satisfaction of meeting the mission of promoting and protecting the public health. There are many fundamental scientific questions that need to be addressed with respect to Zika virus, and our scientists are working to help answer some of these questions in our own laboratories. We stand ready to use our expertise and authorities to the fullest extent to help facilitate the development and availability of products that may help mitigate the Zika virus outbreak.

Visit our Zika response web page for more information, including the latest Zika virus response updates from FDA.

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

Luciana Borio, M.D., is FDA’s Acting Chief Scientist

FDA Advisory Committee Members and ‘Appearance Issues’

By: Michael Ortwerth, Ph.D.

FDA relies on its advisory committees as a source of independent scientific and technical expertise and advice on challenging public health issues. Most advisory committee members are appointed as “special government employees” (SGEs). Like regular government employees, these committee members are subject to Federal conflict of interest laws and regulations.

Michael OrtwerthA lack of understanding about our selection and evaluation process has, at times, resulted in confusion and misunderstandings by the public.  We’ve been working to bring greater transparency to how the financial interests of committee members are evaluated.

In 2008, we published “Guidance for the Public, FDA Advisory Committee Members, and FDA Staff on Procedures for Determining Conflict of Interest and Eligibility for Participation in FDA Advisory Committees.” That guidance describes how we apply financial conflict of interest requirements.

What has not been previously addressed in guidance is something called “appearance issues.” Sometimes FDA advisory committee members who do not have interests and relationships that are financial conflicts of interest nevertheless have interests and relationships that may create the appearance that they lack impartiality. Appearance issues are addressed in a government-wide regulation regarding standards of ethical conduct for government employees at 5 CFR 2635.502 (informally known as “Section 502”).

Some examples include:

  • When a member of the household works or is seeking to work for the sponsor with a product before the committee;
  • When a member has had past financial interests with the sponsor with a product before the committee; and,
  • When a member has a current consulting contract with a sponsor but the contract is not related to the product or issue before the committee.

We have recently published new draft guidance describing FDA’s procedures for evaluating appearance issues and how we determine whether to grant an authorization for a member with an appearance issue to participate in an FDA advisory committee.

Section 502 implements the ethical principle that a government employee should be impartial in performing their official duties, meaning that they must not give preferential treatment to any private organization or individual or use public office for private gain. To the extent that an advisory committee member’s performance of official duties might appear to benefit themselves or certain other individuals who are close to them, they must take appropriate steps to avoid an appearance of violating these ethical principles.

We also explain in the draft guidance the circumstances that FDA considers when determining whether an appearance issue may exist. We evaluate the circumstances and assess whether the interests, relationships, or circumstances would cause a reasonable person with knowledge of the relevant facts to question the advisory committee member’s impartiality in the matter before the committee. For example, if an advisory committee member serves on the board of directors of a nonprofit organization and that organization receives donations from the sponsor that is presenting before the committee, we review the details of the donation to determine whether the member should be cleared for service on the advisory committee.

FDA has flexibility and discretion in deciding whether an advisory committee member with an appearance issue should be authorized to participate in the advisory committee meeting. We evaluate whether the government’s interest in the advisory committee member’s participation outweighs the concern that a reasonable person may question the integrity of the agency’s programs and operations. If so, FDA may authorize the member to participate in the meeting.

Although FDA advisory committees provide advice and input to the Agency, FDA makes the final decisions.

The draft guidance is being issued for public comment before we issue a final guidance. Under Federal law, FDA is not permitted to disclose confidential information provided by advisory committee members related to appearance issues. But we are specifically requesting comments on whether the agency should request that advisory committee members voluntarily disclose if they have been granted an appearance authorization.

FDA is committed to ensuring that appropriate expertise and experience is brought to bear on the critical public health issues facing the agency. Often, we convene advisory committee meetings to obtain independent expert advice and perspective. At the same time, it is important that the process we use to screen advisory committee members for participation in meetings be as transparent as possible, and that we protect the credibility and integrity of advisory committee advice. We welcome your comments on how the agency can continue to meet these important goals.

Michael Ortwerth, Ph.D,. is FDA’s Director of the Advisory Committee Oversight and Management Staff

Leveraging the Power of Collaboration – FDA’s New Oncology Center of Excellence

By: Richard Pazdur, M.D.

I am honored to be selected by Commissioner Califf today as the acting director of FDA’s new Oncology Center of Excellence (OCE) in support of the Vice President’s National Cancer Moonshot Initiative.

Dr. Richard PazdurThis new center will be a place where the combined skills of regulatory scientists and reviewers with oncology clinical expertise in drugs, biologics, and devices will come together to support an integrated approach to the advancement of cancer treatment.

The OCE emulates both academia and cancer care centers, which are increasingly organized in multidisciplinary models to enhance collaboration, which is so essential when confronting a complex disease like cancer.

Such a collaborative approach – the sharing of ideas, information and best practices – closely fits my own vision for oncology at the FDA.

When I first joined FDA from the MD Anderson Cancer Center in Houston Texas in 1999, oncology products were reviewed in different divisions within the Center for Drug Evaluation and Research (CDER), in addition to those reviewed by other centers. My current Office of Hematology and Oncology Products (OHOP) was created in 2005 in an attempt to consolidate the review of oncology products within CDER. Additional reorganization into disease-specific teams followed in 2011. This reorganization greatly enhanced both our retention and recruitment of professional staff from leading academic centers. Disease-specific expertise expedited review processes and fostered multiple outreach activities to patient and professional groups. Between 2010 to the present, OHOP approved 61 new molecular entities to treat a variety of cancers – and most approvals were well before their deadlines.

The OCE will build on FDA’s integrative approach to medical product development and the collaborative work that has been a hallmark of the broader FDA oncology community for nearly a decade such as our cross-center monthly meetings to discuss key oncology issues, collaborative workshops and programs and the work we’ve done together on research and scientific publications.

This new center will also continue to facilitate the incorporation of the patient view in our regulatory decision-making, which has become a personal mission for me since my wife Mary, an oncology nurse, died of ovarian cancer last November.

And by bridging the various medical product centers, the OCE will be ideally suited to support innovation and to address the recognition that multiple treatment and diagnostic options are in the best interest of patients.

Certainly the key to OCE’s future success will be leveraging the talents of the staff at FDA. The very first thing I plan to do as acting director is to meet  with those involved in oncology medical product development and review across centers to hear their ideas for the OCE and how we can work together to enhance our efforts across the agency.

Developing the structure of the OCE is an ongoing process. Working closely with the center directors we will develop a staged approach for establishing the new center while ensuring the work across centers continues without disruption.

I look forward to guiding the agency through this initial phase, building our cross-disciplinary review staff, providing external outreach to diverse stakeholders and streamlining administrative processes to ensure rapid review of important cancer products to the American public.

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

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

CBER Laboratories in the Life Sciences-Biodefense Complex

By: Carolyn A. Wilson, Ph.D.

Wise management of research programs means more than selecting projects that will yield the most scientific information but also making sure that we are making wise use of the dollars we allot for research.

Carolyn A. WilsonThat’s why FDA’s Center for Biologics Evaluation and Research (CBER) thinks strategically when it plans research programs by the more than 70 principal investigators who work in our two-year-old laboratories in the Life Sciences-Biodefense Complex at FDA’s White Oak campus.

We ask ourselves how we can most efficiently – and cost-effectively – obtain the answers to our scientific questions that our regulators will need to achieve their mission of ensuring the safety, purity, and potency of biological products.  Products regulated by CBER include vaccines, allergenics (allergy diagnostics and treatments), cellular, tissue, and gene therapy products, and blood and blood products.

To sharpen our research planning we recently undertook a major evaluation of our center’s scientific and administrative strategies and programs with the assistance of an outside consulting firm.

The findings have enabled us to refine  our strategies for wringing the most new knowledge from every dollar we spend on regulatory science – the science of developing new tools, standards and approaches to assess the safety, efficacy, quality and performance of FDA-regulated products. These refinements to CBER’s research strategy include:

  • A Resource Committee that manages CBER’s annual budget, as well as a Regulatory Science Council that develops center-wide goals, guides office-level objectives, and oversees all research activities. These two councils will increase overall transparency of decision-making, make sure that research is prioritized, and aim to make budget planning more timely and responsive to our mission.
  • More direct control of funds by individual CBER offices and earlier allocation of that funding, and annual peer review of 25 percent of existing and new projects to ensure accountability for how they are run.
  • Systems to increase the transparency of CBER research and research funding, enhance management decisions, and facilitate tracking of funding allocated to activities and projects.
  • Elevating the culture of science through monthly presentations highlighting the public health impact and mission relevance of CBER research; biannual CBER-wide Science Symposium, providing opportunities for communication and potentially improved collaboration across all CBER research projects; and, enhanced prominence of CBER research fellows in the research enterprise.
jars of vegetables

Faulty home food preservation is one potential source of botulism. FDA scientists are developing methods that will help manufacturers to make a vaccine that will prevent this bacterial illness.

These research and administration refinements are helping us better identify and prepare for tomorrow’s needs.  And when you consider the approximately 70-80 research programs we have underway, we’re doing a lot. A few examples include:

  • Studying botulism toxoids (inactivated illness-causing chemicals released by bacteria) to support development of the first vaccine to prevent this potentially fatal infection. CBER scientists are designing new tests to predict what vaccine approaches may be protective. These tests may also help screen vaccines that protect against other toxins such as those from anthrax, as well as the plant-derived toxin ricin.
  • Determining the critical immune events that provide protective immunity to intracellular microbes (bacteria and parasites that live inside human cells). Based on this, FDA scientists will develop new measurements to predict protection that may help evaluate new vaccines for these microbes.

    Girl sneezing in a field of flowers.

    Allergies can turn nature walks into annoying sneezing fits. FDA scientists are developing new tools to help manufacturers produce more potent allergy shots and enhance their safety.

  • Developing new tools and data to help manufacturers produce more potent allergy shots and enhance their safety.
  • Helping to develop a test for cow intestine to ensure heparin harvested from this tissue is not contaminated with the agent causing the bovine transmissible spongiform encephalopathy (TSE, also known as “mad cow disease”), a known risk to humans. This would help to ensure a safe, reliable, domestic source of heparin, which is now obtained mostly from China.
  • Developing new methods and technologies for rapid-testing detection and characterization of emerging infectious pathogens that threaten the safety of tissue and tissue-based products. In the course of developing these technologies, the lab has found previously unidentified microbial contaminants in archived tissues used for these studies. These findings provide preliminary evidence to support the potential for application of rapid test technologies in evaluation of emerging infectious disease transmission risks associated with the implantation, transplantation, infusion, or transfer of human tissue.

As CBER continues to advance regulatory science in its Life Sciences-BioDefense Complex, our projects will adapt to new challenges that the science of biologics will inevitably pose to FDA. And CBER will address those challenges, keeping in mind both the public health and our fiduciary responsibility to make every research dollar count.

Carolyn A. Wilson, Ph.D., is Associate Director for Research at FDA’s Center for Biologics 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