The Merging of Medical Products: Enhancing review of therapeutic and diagnostic combination products

By: Robert M. Califf, M.D. and Jill Hartzler Warner, J.D.

Combination products – medical products that do not fit into the traditional categories of drugs, devices, or biological products – are a growing and important category of therapeutic and diagnostic products under FDA’s regulatory authority.

Robert Califf

Robert M. Califf, M.D., FDA’s Deputy Commissioner for Medical Products and Tobacco.

These products, that combine drugs, devices, and/or biological product (“constituent parts”) with one another, come in three configurations. The constituent parts may be physically or chemically combined, co-packaged, or separately distributed with specific labeling for their combined use.

Products in this category range from familiar products such as prefilled syringes and surgical kits to novel and innovative products, which target and enhance therapies. Examples of groundbreaking combination products include antibodies combined with drugs for targeted cancer therapy and products that mimic or replace organs, such as an artificial pancreas.

Combination products pose unique challenges – both because they may involve new, complex technologies – and because their review at FDA often involves the expertise of more than one Center.

While review of such products falls to a cross-center team of experts, it is led by the medical product Center responsible for the constituent part that provides the product’s primary mode of action, which, in the case of a syringe prefilled with a drug, for example, would be FDA’s Center for Drug Evaluation and Research.

Effective coordination among FDA staff, and between FDA and the company, is essential – and depends on identifying the proper experts across Centers, supporting processes for communication, and implementing systems for efficient data access and sharing.

Jill Warner

Jill Hartzler Warner, J.D., FDA’s Associate Commissioner for Special Medical Programs.

FDA’s Office of Combination Products (OCP), within the Office of Special Medical Programs, oversees and coordinates FDA’s regulation of combination products. This includes helping to resolve differences of opinion between Centers or with sponsors, developing guidance and regulations, and working with the medical product Centers to develop processes and policies..

Congress has expressed interest in FDA’s regulation of combination products as part of the 21st Century Cures legislative initiative, with one major theme being the assurance that the premarket review process runs smoothly.

While we already have policies and processes in place to address such issues, we know we can do more. To that end, we’ve recently conducted a focus group study with reviewers from the different Centers based on input from industry to assess how we’re doing. The report confirmed that differences in communication, policies, practices, systems and application types can be challenging when the Centers work together on a review of a combination product. The report also recommended actions to take, confirming the value of efforts already underway. Consistent with these findings, we’re taking a number of steps to clarify regulatory requirements and improve our internal processes and IT systems. It may sound a bit mundane, but doing this work could help us work more efficiently and avoid unnecessary surprises for sponsors. These steps include:

  • Issuing more guidance for review of combination products (e.g., our pending draft guidance document on human factors);
  • Enhancing and simplifying data access and sharing for internal staff;
  • Making it easier for staff to request and monitor inter-center consults;
  • Updating and maintaining our internal contact directory for experts to review a combination product; and
  • Improving our internal standard operating procedures for premarket reviews and compliance activities.

Some improvements are already in place and others will be coming this year and next. We continue to want to hear your ideas for enhancing how we work with you on combination products. We are listening — and excited to do our part by evaluating innovative combination products and helping to improve the well-being of patients by approving new safe and effective therapies.

Robert M. Califf, M.D., is FDA’s Deputy Commissioner for Medical Products and Tobacco.

Jill Hartzler Warner, J.D., is FDA’s Associate Commissioner for Special Medical Programs.

FDA Invests in Innovative Ways to Communicate to Hispanics

By: Gloria Sánchez-Contreras, M.A.

En Español

National Hispanic Heritage Month–celebrated annually from September 15 to October 15—gives Americans a great opportunity to celebrate the histories, cultures, and contributions of Hispanic Americans whose roots are in Spain, Mexico, the Caribbean, and Central and South America.

Gloria Sanchez-ContrerasAt FDA, we join in this celebration as we continue to use innovative ways to reach Hispanics as part of our mission to protect the public health. To achieve this goal, FDA uses media strategies that are culturally and linguistically tailored to Hispanics, who, according to research, are avid users of online and social media.

There are 54 million people of Hispanic origin in the United States, making them the nation’s largest ethnic or racial minority group, with 17 percent of the nation’s total population, according to the U.S. Census Bureau. The United States has the second-largest population of Spanish-speaking residents in the world, ahead of Colombia and Spain, and second to Mexico, a recent study by the Instituto Cervantes shows.

These statistics cannot go unnoticed. FDA recognizes the importance of connecting with this growing and diverse segment of our population. Consequently, we have increased our online consumer information in Spanish and developed a variety of bilingual communications strategies to reach and engage all Hispanics.

One of the most important strategies we use is to make sure that messages created for Hispanics speak to them effectively. We consider Hispanics’ informational needs, lifestyles, and cultural health beliefs both when creating new messaging and when translating messaging from English to Spanish.

For example, we know Hispanics respond better when communications are in their primary language – which can be English or Spanish – and when communications use images that relate to them. We do this by employing a bilingual and bicultural team that reviews messaging for cultural competence and adapts translations to ensure they are culturally sensitive and in plain language.

In addition to our English-language communications, we have developed strategies to reach out to Spanish-speaking Hispanics online. Our Consumer Updates and drug safety communications are regularly translated into Spanish. We share Spanish-language information through our social media channels, including Twitter, Facebook, Pinterest, and YouTube.

In addition, we also have a complete Web section in Spanish for consumers (, a press room (“Comunicados de Prensa”), and a central page ( that links to a variety of Spanish-language content developed across the Agency’s product centers and offices.

These are exciting times, and it is a privilege to lead some of these efforts for our agency. The Office of External Affairs works diligently across FDA to share important and timely public health news with Latino consumers, stakeholders, media, and community organizations. And during Hispanic Heritage Month—and all the months of the year–we want Hispanics to know that FDA is a trusted source of consumer information.

Gloria Sanchez-Contreras, M.A., is a Bilingual Public Affairs Specialist and the Spanish-Language Communications Lead in FDA’s Office of Media Affairs.

A Quarter Century of Groundbreaking Science: The Forensic Chemistry Center

By: Stephen M. Ostroff, M.D.

This month marks the 25th anniversary of our Forensic Chemistry Center (FCC) in Cincinnati, Ohio. I recently joined former and current administrators and staff of this lab—one of FDA’s many incredible field laboratories—at an event celebrating this milestone.

Acting FDA Commissioner, Stephen Ostroff, M.D.One thing is clear: The last quarter-century has been a period of tremendous success at the FCC. FCC scientists use their scientific analysis and original research to investigate the physical and chemical characteristics and effects of adulterants on products regulated by the Agency, including chemical fingerprinting of poisons, glass, pharmaceuticals, food products and product packaging materials. By analyzing physical samples they can identify counterfeits, trace the origin of a pathogen or solve a crime.

In short, they are the CSI of FDA.

The commitment, expertise, and curiosity of FCC scientists have helped FDA overcome many scientific challenges, and made an extraordinary difference in the lives and safety of millions of Americans. Time and again the sophisticated analyses of puzzling substances by our scientists—often using innovative, esoteric methods, and groundbreaking research, along with the development of new processes and procedures—have made a critical difference in FDA’s ability to investigate and enforce–and protect the American public.

FCC Anniversary group photo

Former and current administrators and staff of the Forensic Chemistry Center (FCC) in Cincinnati, Ohio, at an event celebrating the 25th Anniversary. From left to right: Paul Norris, Director, Office of Regulatory Science; Steve Solomon, Deputy Associate Commissioner for Regulatory Affairs; Dr. Ostroff, Acting Commissioner of Food and Drugs; Phil Walsky, Deputy Director, Office of Criminal Investigations; Fred Fricke, former Director of FCC; and, Duane Satzger, Director of FCC.

FCC’s work has paved the way for passage of important laws, legal prosecutions, and consumer protection activities like recalls. And it has helped strengthen international relationships and advance international cooperation to ensure product quality and consumer safety.

Just a few highlights of FCC’s important efforts include:

  • In the 1990s, the lab supported some of FDA’s early work evaluating nicotine, which was recently cited in the proposed rule to deem additional tobacco products subject to the agency’s tobacco product authorities;
  • In 2001, after 22 people died in the Croatian Republic after receiving dialysis using certain devices, FCC’s analysis identified the presence of a toxic performance fluid in those devices that resulted in their recall by the manufacturers;
  • FCC investigated numerous illnesses and deaths of cats and dogs during 2007-8, which led to the determination that the pet food was adulterated with melamine and related compounds;
  • FCC’s investigation and analysis following the death of cattle in Washington State helped the FBI rule out the possibility that it was caused by terrorism;
  • Following the deaths of a number of infants in India who had been given the measles vaccine, FCC investigated the vaccine’s manufacturing process and discovered that the cause was not, as initially feared, a vaccine of poor quality. Instead the children had received pancuronium bromide, a muscle relaxant, which had been packaged in vials with similar size and shape to the vaccine, rather than the vaccine itself. This discovery was communicated to the Indian government, leading to a critical change in their immunization practices; and,
  • FCC developed a method for examining the sea animals impacted by the Deepwater Horizon oil spill, which helped determine when the seafood would be safe to consume.

It is an extraordinary record. And it’s meant so much to FDA—and the nation—over the past 25 years. But the anniversary and success of this one lab also underscores the remarkable work done by all of FDA’s laboratories across the country. These labs and the districts in which they are located are the critical front line eyes and ears of FDA. And they are the springboard for excellent science.

Good science is fundamental to the mission of FDA. We need it to make good regulatory decisions. It’s what the public expects and deserves. By being able to handle and apply the science of today and anticipate the science of tomorrow we can be more flexible and adaptive, and support innovation.

Having seen the impressive and important work our labs are doing, I’m more committed than ever of the need to invest in better facilities and the best support. We must maintain state-of-the-art laboratories and research facilities, and attract, hire, and retain the best scientists to work in them. First-rate regulatory science requires first-rate scientists working in first-rate facilities.

It’s why I’ve made this a priority for FDA. And why we will put it high on our list of subjects for discussion with Congress as they shape future budgets for the Agency.

The scientists in FDA’s field laboratories are among the unsung heroes of FDA’s work to protect the public health. So let me congratulate and thank those at the FCC and across FDA on the milestone occasion of the 25th anniversary of the Forensic Chemistry Center.

Stephen M. Ostroff, M.D., is Acting Commissioner of the U.S. Food and Drug Administration

Why Partnerships are Key to the Science of Patient Input

By: Nina L. Hunter and Robert M. Califf, M.D.

We recently announced the first FDA Patient Engagement Advisory Committee (PEAC), supported by the Center of Devices and Radiological Health (CDRH). The Committee will provide advice to the FDA Commissioner on complex issues relating to medical devices, the regulation of devices, and their use by patients. The PEAC will bring patients, patient advocacy groups, and experts together for a broader discussion of important patient-related issues, to increase integration of patient perspectives into the regulatory process, and to help drive more patient-centric medical device innovation, development, evaluation, and access.

Nina Hunter

Nina L. Hunter, Ph.D., a Regulatory Scientist in FDA’s Center for Devices and Radiological Health, currently on detail as a Special Assistant for Medical Policy to the Office of Medical Products and Tobacco.

With the PEAC offering an important avenue for patient views to be incorporated in the assessment of new medical devices, complementary programs in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) are continuing to explore multiple approaches to patient involvement in development programs for drugs and biologic products, respectively. The Patient-Focused Drug Development (PFDD) Program, led by Dr. Theresa Mullin, provides a way for scientists from across the Agency to obtain patients’ input on specific disease areas, including their perspectives on their condition, its impact on daily life, and available therapies. As part of this program, FDA is holding a series of public meetings, each focused on a specific disease area. Outcomes of these meetings include detailed descriptions of patient perspectives on the most significant symptoms and treatments.

While FDA continues our work on patient engagement through our newly formed advisory committee and the PFDD Program, public-private partnerships (PPPs) are key to empowering patients across the spectrum of medical product development and evaluation. Here we will describe three such important partnerships.

FDA is a founding member of the Medical Device Innovation Consortium (MDIC), a PPP created with the objective of advancing medical device regulatory science. MDIC recently issued a catalog of available methods that can be used for collecting data on patient preferences, along with a framework for considering how to incorporate patient preferences across the total lifecycle of a device. The ultimate goal is to use these data to guide the development, assessment, and delivery of medical devices that better meet patients’ needs. As the scientific evidence and methodological approaches in this area mature, FDA will continue to collaborate with others on efforts to collect and use patient preference data for regulatory purposes.

Robert Califf

Robert M. Califf, M.D., FDA’s Deputy Commissioner for Medical Products and Tobacco.

Like the MDIC, the Kidney Health Initiative (KHI) is a PPP that includes representatives from the FDA, healthcare professional societies, patient groups, and the medical products industry. Recently, KHI convened a workshop under the leadership of Dr. Frank Hurst and Ms. Carolyn Neuland, with patients, care partners, scientists, doctors, nurses, technicians, companies, and FDA, to hear discussions about the issues that patients with kidney diseases consider most important. More than 80 patients attended this workshop; many of these were not members of an organized patient advocacy group, but instead individuals truly driven to improve the plight of all patients with kidney disease. CDRH and CDER are working with the KHI to advance scientific understanding of the implications for patient health and safety posed by new and existing medical products, as well as fostering development of new therapies for kidney diseases. This PPP creates a transparent infrastructure and processes that facilitate collaboration and communication among the greater Nephrology community and FDA.

FDA has also held several meetings with the National Institutes of Health (NIH) throughout the PROMIS initiative, including the Patient Reported Outcome Consortium. PROMIS aims to provide clinicians and researchers access to efficient, precise, valid, and responsive patient-reported measures of health and well-being. PROMIS measures can be used as primary or secondary endpoints in clinical studies of the effectiveness of treatment, and PROMIS tools can be used across a wide variety of chronic diseases and conditions and in the general population. These tools pertain to all medical products, and they can be used to understand the burden of their disease and impacts of treatment on how patients feel and function in their daily lives, so that appropriate patient-centered outcome assessments can be developed and integrated into clinical trials to produce meaningful data to guide treatment decisions. Specifically at CDRH, the use of patient-reported outcome measures (PROMs) in regulatory submissions has increased significantly, with approximately 20 submissions per year citing PROMs prior to FDA’s guidance on the topic, to over 120 last year alone. This jump indicates significant interest by industry and clinical researchers in generating patient-centered evidence from studies done for regulatory purposes.

FDA is ready to advance the science of patient input and work with a wider community of patients, clinicians, and social science researchers in a collaborative way. We expect the number of partnerships with patients and their caregivers to grow, and the effort to become more effective as the underlying science and cultural understanding continues to develop.

Nina L. Hunter, Ph.D., is a Regulatory Scientist in the Center of Devices and Radiological Health, currently on detail as a Special Assistant for Medical Policy to the Office of Medical Products and Tobacco.

Robert M. Califf, M.D., is FDA’s Deputy Commissioner for Medical Products and Tobacco.

National Preparedness Month: FDA and Access to Medical Countermeasures During Public Health Emergencies

By: Brooke Courtney, J.D., M.P.H.

Just weeks after witnessing the fall of the World Trade Center on Sept. 11, 2001, I was a student volunteer in a New York City hospital emergency department when several people arrived saying they had been exposed to anthrax.

Brooke CourtneyOne had even brought a small plastic bag holding white powder. Around this time, the media was reporting on letters mailed that were laced with white powder confirmed to be Bacillus anthracis, which causes anthrax.

At the hospital, we wondered whether we might become exposed to anthrax and how it could be prevented or treated. We quickly escorted the patients who had been exposed to white powder safely away from others to be examined by physicians.

Fortunately, our patients hadn’t been exposed to anthrax. But the letters contaminated with the agent tragically led to five deaths, and 17 more people became ill. Many others were treated with antibiotics as a precaution.

That year, 2001, was a turning point in our nation’s readiness for public health emergencies, including those that result from deliberate attacks or from natural causes like a disease outbreak. In particular, the U.S. government has invested substantially in medical products required for diagnosis, prevention or treatment of a wide range of threats, including anthrax. FDA is part of that national preparedness.

At FDA, we work to help ensure the availability of safe and effective medical countermeasures (MCMs). These are the medical products, including drugs, vaccines, and in vitro diagnostics (IVDs), to counter chemical, biological, radiological and nuclear (CBRN) threats, including emerging infectious diseases like Ebola.

In 2010, FDA launched an agency-wide effort, the Medical Countermeasures Initiative (MCMi), to advance and coordinate the challenging, ongoing MCM development and emergency use work that was occurring in FDA’s product centers and other offices and with other federal partners. Our most recent program update details many of FDA’s MCM achievements since that time, including important, exciting product approvals and regulatory science advances.

At the foundation of FDA’s MCM efforts is a legal and regulatory framework strengthened by Congress after 2001 with the enactment of several MCM-related laws. For example, FDA now has the authority:

  • When the Secretary of HHS declares that the circumstances justify such an authorization, to authorize the use of unapproved MCMs and unapproved uses of approved MCMs under Emergency Use Authorizations (EUAs) during or in preparation for an emergency, and,
  • For approved MCMs, to authorize emergency dispensing by stakeholders, waive certain manufacturing requirements, and extend the useful life of product held in state and local stockpiles.

As an example of our legal authorities in action, we’ve issued multiple EUAs to facilitate access to uncleared IVDs to support disease detection and diagnosis during the H1N1 influenza pandemic and for H7N9 influenza, Middle East Respiratory Syndrome coronavirus (MERS-CoV), and Ebola virus that emerged in West Africa in 2014.

Today, our nation is far more prepared than at the time of the anthrax attacks with flexible emergency legal authorities, critical MCMs stockpiled or under development, and enhanced knowledge about how to prevent or treat threats. But, as the recent Ebola epidemic and MERS outbreak show, threats both known and unknown continue to evolve or emerge and require our constant attention and vigilance.

September is National Preparedness Month. And while FDA and other agencies work hard every day to help prepare the nation for potential threats, everyone can be involved in disaster readiness. As we approach the end of Preparedness Month, here are a few things you can do now:

  • Become familiar with disasters that might occur where you live; plans for your community, workplace or school; and what HHS is doing. You can also download a variety of free disaster apps.
  • Make and test a family plan (e.g., communicating during an emergency).
  • Make an emergency kit of supplies, including medical products, you’ll need for at least three days.

Brooke Courtney, J.D., M.P.H., is Senior Regulatory Counsel in FDA’s Office of Counterterrorism and Emerging Threats.

Seeing is believing: Making clinical trial statistical data from medical product testing easy to understand

By: Richard A. Forshee, Ph.D.

If you heard that some FDA scientists were helping people pick out colors and designs, you might wonder if the agency had added interior decorating to its responsibilities.

Richard ForsheeWhat they’re really doing is helping scientists craft statistical graphs and plots of clinical trial safety data so that they tell clear, compelling stories. Key to success? Creating tables and graphs that aren’t so dense with numbers, boxes, lines, and words that extracting meaning from them is like excavating hard rock for minerals.

To do this, the Safety Graphics Working Group, a team from FDA, industry, and academia, created a web-based, publicly available database of graphical designs for reporting clinical trial safety data from tests of new medical products. Graphics expertise and funding provided by Vanderbilt University enabled the development of this web site, which was launched in 2013. More recently, the team published details of the concept of improving statistical graphics design in the journal Statistics in Medicine.

The collaborators developed a step-by-step process for creating statistical graphs and plots that quickly explain important findings by taking advantage of the way people naturally look for patterns in images, not just in pictures of nature, but also in representations of statistical data. They also provide computer codes for re-creating the models available on the website. The choices include some fanciful names, such as spaghetti and lasagna graphs, and violin and forest plots.

Clinical Trials Statistical Data Chart

Designing good graphs and plots for specific types of data requires thoughtful approaches to illustrating how that data can be most clearly displayed. This chart is a guide to choosing the most effective design for displaying data, depending on how much detail is to be displayed and what aspect of the data you want to emphasize. In this case, the chart provides options for displaying a type of data called a “continuous variable,” which could be, for example, how a specific drug has affected blood pressure as measured at the end of treatment.

The authors of the article also demonstrate how to use effective, self-explanatory symbols on graphs to explain the data instead of overwhelming a reader with it. Such data can include any of a wide variety of measurements, from liver enzymes to prolonged Q-T intervals (abnormal electrocardiogram results associated with heart beat abnormalities, fainting, and sudden death).

Of particular importance for FDA regulators, the designs make it easier to clearly illustrate statistical data representing a wide variety of potential adverse effects (AEs) observed during clinical trials of medical products or during post-licensure use (when products are on the market). For example, they might show which AEs are elevated in treatment versus control groups, which AEs are elevated in specific patient subgroups, and which might be a safety signal (potential link between a medical product and an adverse effect).

Creating those compelling graphs and plots is important to other scientists who read journal articles to keep up with the latest research in their field. And it’s also very important to a lot of people who make key decisions based on that data: editors of journals deciding whether a researcher’s paper is important enough to publish, and FDA regulatory officials reviewing clinical trial results of medical products submitted by industry.

Most scientists might think it’s impossible to turn statistical illustration into an art form. But the work of the Safety Graphics Working Group shows that “seeing is believing.”

Richard Forshee, Ph.D., is FDA’s Associate Director for Research at the Office of Biostatistics and Epidemiology in the Center for Biologics Evaluation and Research

FDA Announces First-ever Patient Engagement Advisory Committee

By: Nina L. Hunter, Ph.D., and Robert M. Califf, M.D.

Although it may seem odd in retrospect, the development of new technologies intended to improve patients’ lives has largely relied upon expert opinions rather than asking patients and families directly what they consider most important.

Nina Hunter

Nina L. Hunter, Ph.D., a Regulatory Scientist in FDA’s Center for Devices and Radiological Health, currently on detail as a Special Assistant for Medical Policy to the Office of Medical Products and Tobacco.

But that’s changing. We are entering an era of “patient-centered” medicine in which patients and their care partners participate actively in decision-making and priority-setting about all aspects of health care. Americans are becoming increasingly active consumers of health care, making choices about their doctors, diagnostics, treatments, and healthcare experiences rather than simply allowing health care providers to make the decisions for them. Moreover, FDA believes that patients can and should bring their own experiences to bear in helping the Agency define meaningful benefits or unreasonable risks for certain new devices.

Today we are excited to announce FDA’s first-ever Patient Engagement Advisory Committee (PEAC). This body will provide advice to the FDA Commissioner on a range of complex issues relating to medical devices, the regulation of devices, and their use by patients. It will give FDA the opportunity to obtain expertise on various patient-related topics, with the goal of improving communication of benefits and risks and increasing integration of patient perspectives into the regulatory process. Some questions that the PEAC may discuss include where and how best to engage patients across the device development and assessment lifecycle as well as how FDA and sponsors should communicate patient preference information to patients. The PEAC represents a new and exciting opportunity to foster patient partnerships with FDA, and it complements other efforts at FDA to bring the patient into the medical device regulatory process. This includes studies to evaluate patient preferences in medical devices and a recently published draft guidance on patient preference information for PMAs, HDE applications, de novo requests, and inclusion in device labeling that describes how patient tolerance for risk and perspective on benefit, in addition to clinical data and other information, may be considered in FDA’s assessment of the benefit-risk profile of certain devices. While it’s important to consider patient perspectives, we understand that patients still expect FDA to do our primary job — namely, ensuring the safety and effectiveness of FDA-regulated medical devices. This is primarily accomplished at FDA through regulation at the Center for Devices and Radiological Health and the Center for Biologics Evaluation and Research. When assessing whether valid scientific evidence shows that a device’s probable benefit outweighs its likely risks, FDA may consider rigorous, systematically gathered patient preference information as a part of the totality of the evidence from clinical and nonclinical testing. However, patient preference information will not be used to justify approval of unsafe or ineffective devices: if FDA determines the device would expose patients to an unreasonable or significant risk of illness or injury, or that the benefits do not outweigh the risks for a defined target population, FDA would not approve such a device.

Robert Califf

Robert M. Califf, M.D., FDA’s Deputy Commissioner for Medical Products and Tobacco.

When is patient preference information most useful? These data can be used in several major ways:

  • to help identify the most important benefits and risks of a technology from a patient’s perspective;
  • to assess the relative importance to patients of different attributes of benefit and risk, and clarify how patients think about the tradeoffs of these benefits and risks for a given technology; and
  • to help understand how patient preferences vary across a population.

As part of the Patient Preference Initiative and other activities to better integrate patient views into our decision-making, FDA is working with others to advance the science of patient input. We will discuss these extensive partnerships in an upcoming FDA Voice blog.

FDA’s sharpened focus on patient-centered technology development, evaluation, and use has already begun to positively affect the development of innovative therapies and clinical solutions. These efforts are helping to drive a more patient-centered medical product development and assessment process. We’re excited to invite the patient, industry, and academic communities to join in and help us accelerate this important work.

Nina L. Hunter, Ph.D., is a Regulatory Scientist in FDA’s Center for Devices and Radiological Health, currently on detail as a Special Assistant for Medical Policy to the Office of Medical Products and Tobacco.

Robert M. Califf, M.D., is FDA’s Deputy Commissioner for Medical Products and Tobacco.

Welcoming FDA’s New Overseas Leaders: FDA’s Foreign Posts Provide a Vital Resource for Consumer Protection

By: Howard Sklamberg and Mary Lou Valdez

Howard Sklamberg

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

It’s simple but true: relentless global commerce and interaction demand a globalized FDA. That’s why we’ve made determined efforts – sometimes with great difficulty – to place our professionals around the world in the key countries and regions that produce FDA-regulated food and medical products.

The Vital Role of FDA’s Overseas Offices

Our foreign offices add an unsung, yet vital, element to the Agency’s global work. FDA posts in China, Europe, India, and Latin America, in close cooperation with FDA Centers and the Office of Regulatory Affairs, help to strengthen our ability to protect public health. Our foreign posts assist by:

  • Increasing our knowledge and appreciation of the global regulatory landscape;
  • Facilitating collaboration with foreign regulators to strengthen evidenced-based approaches to product safety and quality; and
  • Helping manufacturers in other countries to understand FDA standards and regulations.

Equally important, placing investigators in a top-exporting nation allows us to get to a site more quickly in a public health emergency or investigate indications of violations that could imperil public health.

Recent Accomplishments

The Latin America Office has deepened FDA’s ties with the regulatory partners in the 44 nations and territories comprising that vast region. For example, Mexican regulators have followed up on FDA inspection results and have taken immediate actions against firms and products that violate U.S. and Mexican law. Through a 2014 bilateral Statement of Intent, our Latin America Office is helping to implement a Produce Safety Partnership with Mexico, which is vital inasmuch as nearly one-third of FDA-regulated food products we eat are either grown in or transported through Mexico.

Lou Valdez

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

Thanks to the work of our China Office, FDA signed two Implementing Arrangements in late 2014 with our Chinese food and drug regulatory counterparts: the China Food and Drug Administration and the Administration of Quality Supervision, Inspection and Quarantine. The arrangements expand the number of in-country investigators and significantly increase FDA’s ability to perform inspections of firms that manufacture FDA-regulated products. We also work closely with Chinese officials to help strengthen the Central/Provincial inspectional roles to ensure product quality and safety and better secure supply chains.

The India Office regularly engages with Indian regulators and industry. India is a major source of generic drugs imported to the United Sates and, as such, we work closely with them on pharmaceutical quality. India also is the 7th largest supplier of food to the United States – principally shrimp, spices, and rice. Recently the India Office played a key role in coordinating a Memorandum of Understanding on Food Safety that FDA signed with the Export Inspection Council of India. The India Office also hosts a number of workshops to increase understanding of U.S. requirements such as records management with industries interested in exporting their products to the U.S.

The Europe Office has continued to enhance FDA’s partnership with the European Medicines Agency (EMA), with whom we actively share data, information, and technical expertise. Since 2009, FDA and EMA have strengthened collaboration through the exchange of dedicated liaison officers and by engaging in mutual scientific interests in such areas as advanced medical therapies, biosimilar medicines, blood products, orphan products, and veterinary medicines. In addition, Europe Office professionals have briefed nearly a dozen European Union (EU) nations on the landmark Food Safety Modernization Act, and have also analyzed more than 150 audit reports from the EU’s Food and Veterinary Office to bring FDA expertise to food facility site selection.

The European Office plays a key role in the Mutual Reliance Initiative (MRI), an important FDA-EU endeavor to evaluate our comparable regulatory frameworks for inspections of manufacturers of human pharmaceuticals to determine if we can rely on each other’s inspectional information. The MRI has led to FDA accompanying EU officials on audits of three EU nations. The Europe Office also managed an EU audit of FDA’s oversight of the Active Pharmaceutical Ingredient (API) manufacturers within the U.S. That exchange led to the EU relying on our oversight, and allowing U.S.-made APIs into the European market.

New Leaders at Our Overseas Posts

We can look confidently toward the future and the roles our foreign posts can play in support of the FDA mission globally. It is with an eye on that future that we are marking “a changing of the guard” as we welcome new Office Directors and Deputy Directors to FDA foreign offices.

We extend a warm welcome to:

China Office

Leigh Verbois, Ph.D., Director 

Europe Office

Donald Prater, D.V.M., Director

India Office

Mathew Thomas, M.B., B.S., Director

Latin America Office

Edmundo Garcia, Director, Director

Capt. Philip Budashewitz, Deputy Director

We also share our deepest gratitude as we say good-bye to an outstanding group of foreign post directors who are moving on to new opportunities: Christopher Hickey, Ph.D., (former Director, China Office), Carl Sciacchitano (former Acting Director, India Office), Michael Rogers (former Director, Latin America Office), and Bruce Ross (former Deputy Director, Latin America Office).

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

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

Naming and Biological Products

By: Janet Woodcock, M.D. and Karen Midthun, M.D.

To create market competition among biological products and lower costs, the Affordable Care Act created a new approval pathway for products that are biosimilar to and interchangeable with FDA-licensed biological products. The FDA is committed to encouraging the development of these biosimilar and interchangeable products. Biological products derived from living organisms can treat patients with cancer, chronic kidney diseases and auto‐immune diseases, such as rheumatoid arthritis and inflammatory bowel disease.

Janet Woodcock

Janet Woodcock, M.D.

Earlier this year, the agency approved the first biosimilar, and other products are in development. But one key issue is how to name biological products to ensure safe use and foster acceptance of these new products.

So today we are releasing a draft guidance that details the FDA’s proposal on the nonproprietary naming of biological products.

Our draft guidance proposes that reference products and biosimilars have nonproprietary names (also called proper names) that share a core drug substance name and, in order to better identify each product, an FDA-designated suffix that is unique for each product. This suffix would be composed of four lowercase letters, and not carry any meaning. For example, the nonproprietary name of a reference product could be replicamab-cznm, and a biosimilar to that product could be replicamab-hixf.

For interchangeable biological products, our proposal requests feedback from the public about whether the nonproprietary name for such a product should include a distinct suffix, or should share the same suffix as its reference product (e.g., the nonproprietary name of both the reference product and the interchangeable product could be replicamab-cznm).

The proposed naming convention seeks to address two main issues:

  • To help prevent inadvertent substitution (which could lead to medication errors) of biological products that are not determined to be interchangeable by the FDA; and,
  • To support safety monitoring of all biological products after they are on the market, by making it easier to accurately track usage of biological products in all settings of care, such as outpatient, hospital, and pharmacy settings.
Dr. Karen Midthun

Karen Midthun, M.D.

FDA is also considering, and has requested public input on, the benefits and challenges of other naming approaches, such as a suffix derived from the name of the license holder.

In addition to thinking ahead, we must also consider what we need to do to address previously approved biological products that have nonproprietary names without a suffix. Applying the naming convention to these products would encourage routine use of designated suffixes in ordering, prescribing, dispensing, and recordkeeping practices and avoid inaccurate perceptions of the safety and effectiveness of biological products based on their licensure pathway.

Along those lines, FDA is seeking comment on the best approach to implement this naming convention for previously licensed products. FDA also is issuing a proposed rule to designate nonproprietary names that contain a suffix for six previously licensed biological products. Each of the six products is either a reference product for an approved or publicly disclosed biosimilar product application or a biological product that is either biosimilar to or related to one of these reference products.

We encourage the public to provide input on the FDA draft guidance and proposed rule by making comments to the appropriate dockets. We will consider all comments as we finalize the guidance and the rule. We also invite the public to respond to the questions posed by FDA in the notice announcing the availability of the draft guidance and will consider these responses in finalizing the guidance and the rule.

For more information:

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

Karen Midthun, M.D., is the Director of FDA’s Center for Biologics Evaluation and Research

Need a Guidance Document? We’ve Got You Covered

By: Chris Mulieri, PMP

We all understand the frustration of searching online for something and not finding it. The Food and Drug Administration recently helped end this problem by making it faster and easier to find our guidance documents – some of the most requested items on our website.

Chris MulieriGuidance documents represent FDA’s current thinking on a particular subject. Currently, there are about 3,100 of them – and the list is growing.

FDA’s Web & Digital Media team and the Office of Information Management and Technology have created a dynamic search list on one site so you can go to just one page and find the guidance documents you need, no matter where they are on This search tool is powerful and easy to use. Now you can go to just one search box to find what you need in moments, instead of the 10 different pages on FDA’s website where guidance documents are posted.

It doesn’t matter if it’s a guidance document on devices, drugs, biologics, tobacco, veterinary medicine, or foods – it’s all there.

We did this as part of FDA’s Transparency Initiative and in response to the feedback we got from our stakeholders via the American Customer Service Index (ACSI) online survey. They told us just how hard and time-consuming it was for them to find these important documents. So we decided to do something about it.

It’s not practical for us to put these documents all in one place. So, we assembled a working group with representatives from each of FDA’s Centers (which post the guidance documents on their own sites) and developed the search criteria.

In addition, we tagged the documents with metadata (search terms) needed to make search and filtering functions work as intended. Now, the list automatically populates as you enter search terms and filters. Each column is sortable.

You can narrow your search by filtering on different categories, including product, date issued, FDA organization, document type, and subject. Refine your search by draft guidance, final guidance, whether it’s open for comment, or by comment closing date.

How are we doing?

Since the launch of the guidance search in December 2014, page views have increased from about 22,000 to more than 136,000 for the first quarter of 2015. For the first time, the page is among the top visited on FDA’s website. And we’ve seen improved user satisfaction, reflected in the feedback in the ACSI responses.

We hope you’ll try the new guidance document search page soon and let us know what you think.

Chris Mulieri, PMP, is FDA’s Director, Web & Digital Media, Office of External Affairs.