SCORE at Six Months: Meeting the Challenge of Complex Recalls

By: Stephen Ostroff, M.D., and Howard Sklamberg, J.D.

When a potentially contaminated food is on the market, time is of the essence to keep people from becoming ill. Yet there are times when it is difficult to determine what actions should be taken. This can happen when we do not have enough information to reach a clear decision.

Stephen Ostroff, M.D.

Stephen Ostroff, M.D., is FDA’s Deputy Commissioner for Foods and Veterinary Medicine

To better address these situations, in April FDA established a team of senior leaders that is brought in to make decisions in the most challenging cases. The team is called SCORE, which originally stood for Strategic Coordinated Outbreak Response and Evaluation, but it soon became clear that the scope of its work is broader than outbreaks. The team looks at cases in which recalls and other actions may be needed, even when there are no reports that people have fallen ill. So SCORE now stands for Strategic Coordinated Oversight of Recall Execution.

And we’re happy to report that SCORE is already making a difference, helping to overcome obstacles and streamlining processes to get potentially harmful foods off the market as soon as possible to reduce further consumer exposure.

In the last six months, SCORE has reviewed and directed operations in cases that include flour contaminated with peanut protein, (a major food allergen), facilities contaminated with Listeria monocytogenes, pistachios in which Salmonella was detected, and baby food that was not manufactured in compliance with infant formula regulations. All of these cases resulted in recalls and announcements issued by the firms and FDA.

Howard Sklamberg

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

SCORE was launched, in part, in response to concerns raised by the Department of Health and Human Services’ Office of the Inspector General about FDA’s ability to ensure that companies initiate voluntary recalls in a prompt and effective manner. While FDA staff were already helping to facilitate thousands of prompt and successful voluntary recalls, we recognized the need for an enhanced response in certain, more complex cases.

In the cases brought to the team, we believe that SCORE has helped determine the right course of action and shorten recall timeframes, getting the products off the market faster. SCORE has helped improve tactical planning, leading to additional inspections and sampling assignments, and to getting the word out to more consumers about potentially dangerous products. In one case, FDA suspended a food facility’s registration after a reinspection and additional sampling requested by SCORE showed continued contamination. Suspension of registration effectively shuts a facility down until FDA determines that there is no longer a reasonable probability that foods produced there will cause serious illnesses or death.

We set individual deadlines and got prompt results in these, and other, instances. FDA staff are seeing these actions as a model for their efforts going forward.

FDA has been evolving over the past few years into an agency that speaks with one voice in its oversight of food safety. SCORE’s membership includes leaders from within the directorates of Foods and Veterinary Medicine and Global Regulatory Operations and Policy, in addition to the Office of the Chief Counsel. The spectrum of expertise covers inspections and investigations, compliance and enforcement, policy, legal, communications, outbreak response and, most important, science.

This team is in its infancy but the results it has achieved thus far signal an integrated approach to food recalls that will help ensure a swift response no matter what obstacles arise. The arrival of the compliance dates for the FDA Food Safety Modernization Act rules overseeing the safety of domestic and imported foods are putting additional food safety controls in place to help reduce food contamination. And the work of SCORE and its colleagues will continue.

SCORE’s goals for the next year include identifying and closing gaps that slow the process of determining whether a food is a threat to public health or interfere with identifying the right actions to take in response to potential contamination. Our ultimate goal is to continue to improve our ability to protect consumers from contaminated food.

Stephen Ostroff, M.D., is FDA’s Deputy Commissioner for Foods and Veterinary Medicine, and Howard Sklamberg, J.D., is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy.

Where We Are/What We Have Done – Two Years After Releasing Our FDASIA 907 Action Plan

By: Janice Soreth, M.D.

Since it’s been more than two years since FDA unveiled its Action Plan to advance the inclusion of diverse populations in clinical trials, we’d like to update you on how much we have accomplished, and acknowledge that continued commitment is critical in order to build on this foundation.

Janice SorethThe Congressional mandate under Section 907 of the FDA Safety and Innovation Act of 2012 required FDA to develop a report examining the extent to which various demographic groups were included in clinical trials and their outcomes reported in labeling for medical products for which applications were submitted to FDA. The legislation also required FDA to develop an Action Plan based on the report findings and input from stakeholders, issued in August 2014. The Action Plan identified 27 discrete actions for FDA to take within the three priority areas: improving data quality, encouraging greater clinical trial participation, and ensuring more data transparency.

As we discussed at our public meeting on February 29th, we have made progress on nearly every one of our action items and we continue to make strides.

In June 2016, FDA issued the draft guidance, “Evaluation and Reporting of Race and Ethnicity Data in Medical Device Clinical Studies.” We are also updating the 2005 “Guidance for Industry Collection of Race and Ethnicity Data in Clinical Trials.”

Our popular Drug Trials Snapshots, providing information about who participated in clinical trials supporting FDA-approved drugs and biologics, have now been posted on some 75 products. This innovative program developed by our Center for Drugs Evaluation and Research also highlights whether there were any differences in the benefits and side effects among sex, race, and age groups

We have significantly advanced efforts to raise clinical trials awareness. FDA’s Office of Women’s Health instituted a new initiative on “Diverse Women in Clinical Trials” that is disseminating consumer resources in English and Spanish and tools for clinical researchers in partnership with NIH’s Office of Research on Women’s Health. Our Office of Minority Health developed a tool kit and posted several public service announcements on FDA’s YouTube channel aimed at engaging patient participation. And we are currently reviewing the public comments from a range of organizations that we received to the public docket that was opened at the time of the public meeting.

Finally, I want to announce that I recently took over the chairmanship of the steering committee charged with implementing this plan. I am currently the Acting Associate Commissioner for Special Medical Programs, which has oversight of our advisory committee programs, combination products, and pediatric and orphan products programs among other responsibilities. Since joining FDA as a primary medical reviewer 25 years ago, I have served as CDER’s director of the division of Anti-Infectives and Ophthalmology and most recently spent five years in London as Deputy Director of the FDA Europe Office and Liaison to European Medicines Agency.

As we look back at our accomplishments, we believe that transparency in reporting about clinical trial inclusion will make a difference in encouraging broader demographic diversity and want to thank the former chair, Barbara Buch, M.D., of CBER, for her accomplishments. Going forward, I encourage you and all of our key stakeholders – patient and disease advocates, health professionals, and industry to continue partnering with us to advance this important work in ensuring demographic diversity and representation.

Janice Soreth, M.D., is Chair of the FDA Safety and Innovation Act Section 907 Steering Committee and the Acting Associate Commissioner for Special Medical Programs

Our 20th Patient-Focused Drug Development meeting: Enhancing the patient’s voice in FDA’s approach to drug review and development

By: Theresa M. Mullin, Ph.D.

Since the launch of the Patient Focused Drug Development program as part of the fifth authorization of the Prescription Drug User Fee Act (PDUFA V), we have worked intensively to explore ways to enhance the patient’s voice in drug development. Recently we reached a particularly gratifying milestone in this important work — our 20th Patient-Focused Drug Development (PFDD) public meeting.

Theresa MullinThe PDUFA program provides much needed funding from the pharmaceutical industry to support FDA’s premarket review activities and the agency’s work to encourage drug development. Under PDUFA V, FDA committed to obtain patients’ views in at least 20 disease areas over the course of the program’s five year period, which ends in September, 2017. That means conducting a public meeting for each disease area to obtain patient perspectives on the impact of the condition on daily life and current treatment approaches. Our 20th PFDD meeting, with patients who have received organ transplants, took place on September 27th. With that meeting completed, we fulfilled our commitment — one year ahead of schedule.

The PFDD meetings have given us the opportunity to strengthen our understanding of the targeted disease areas and hear directly from patients, their families, and caregivers about the symptoms that matter most to them; the impact of the disease on daily life, and their experiences with currently available treatments. Having this kind of input is extremely valuable for us because hearing what patients care about can help us determine how best to facilitate drug development for a particular disease area. Hearing the patients’ perspectives also helps us understand how patients view the benefits, risks, and burdens of treatments for their condition.

While FDA plays a critical role in drug development, we are only one of the players in the process; other stakeholders, including healthcare providers and industry sponsors, who have attended the PFDD meetings to hear from patients, are also gaining valuable information. The  PFDD meetings have also helped  identify areas of unmet need within the patient population (e.g., the psoriasis meeting highlighted the need for treatments for the pediatric population living with psoriasis) and helped raise awareness and focus engagement within the patient community itself (e.g., in preparation for the narcolepsy meeting patient groups collaborated to form a coalition called Unite Narcolepsy). We’ve chronicled this and more in our Voice of the Patient reports, which provide a detailed account of the valuable input we’ve heard at each meeting.

The Voice of the Patient reports are intended to be useful to both our FDA colleagues conducting reviews and the broader community. These reports summarize what FDA heard through patient speaker panels, audience participation, the webcast, and submissions to the public docket. Each report faithfully captures this information as a valuable resource for the FDA review divisions and is distributed internally to the relevant review divisions for reference when advising sponsors on their drug development programs and when assessing products under review in that disease area.

As drug development advances in the 21st Century, sponsors are using increasingly sophisticated and vital forms of technology to generate the medicines of the future. But there is a critical part of drug development — gaining ever increasing importance in the process — that has little to do with advanced technology. Instead, it has to do with listening to patients and their personal experiences living with their disease and its treatment, and determining the best ways to reliably capture this perspective so that it can be better integrated into decision making.

We believe that the long-term impact of PFDD will be better, more informed FDA decisions and oversight both during drug development and during our review of a marketing application. We are extremely grateful to all of the hundreds of patients and their loved ones who have so generously and, in some cases, courageously, participated in our meetings and have shared their personal stories, experiences, and perspectives.

We may have met the letter of our PDUFA commitment, but we are not finished. Patient-Focused Drug Development is a priority for FDA. Beyond the 20 meetings we have already held, we plan to hold four more PFDD meetings by the end of FY2017. Additionally, we recognize that there are many more disease areas to address. To help expand the benefits of FDA’s PFDD initiative, FDA welcomes similar patient-focused meetings organized by the patient groups themselves. For this parallel effort to FDA’s PFDD initiative, interested patient groups can submit a letter of intent. More information is outlined on FDA’s website.

One of the most valuable things we can do as regulators at FDA is simply to listen. I’m reminded of that each time we hold a PFDD public meeting. FDA will continue to listen — and learn — and we look forward to continuing to gain the additional insights that only patients, their families, and caregivers can provide.

Theresa M. Mullin, Ph.D., is Director of FDA’s Office of Strategic Programs in the Center for Drug Evaluation and Research

First Major FSMA Compliance Dates: Landmarks and Learning Experiences

By: Stephen Ostroff, M.D., and Howard Sklamberg, J.D.

The phrase “where the rubber meets the road” is one that comes up in conversations about different subjects, from athletics to academics, when carefully laid plans are put to a crucial test. That’s where we are today with the arrival of the first major compliance dates under the regulations developed by FDA to implement the FDA Food Safety Modernization Act (FSMA).

Stephen Ostroff, M.D.

Stephen Ostroff, M.D., is FDA’s Deputy Commissioner for Foods and Veterinary Medicine

This is the day when larger businesses must comply with certain new standards under the preventive controls rules for human and animal food, two of the main rules developed to drive down the incidence of foodborne illnesses in our country. Larger human food facilities must meet preventive controls and modernized Current Good Manufacturing Practice requirements (CGMPs); larger animal food facilities must meet CGMPs. (The human and animal food rules have staggered compliance dates; animal food businesses have additional time to meet the preventive controls standards, as do smaller producers of human foods.)

The preventive controls rules were the first two of seven foundational FSMA rules to become final starting in September 2015. Human food facilities are required to have a food safety system in place that includes an analysis of hazards and risk-based preventive controls to minimize or prevent those hazards. The standards that animal food facilities must meet mark the first time that CGMPs have been broadly required for the safe production of animal food.

FSMA was signed into law in 2011 in the wake of mounting concerns by consumers and lawmakers about outbreaks of foodborne illness that kill thousands of people and animals every year. What followed was an unprecedented effort by FDA to involve the diverse landscape of food safety stakeholders, including growers, manufacturers, importers, distributors, consumer groups, and academic institutions, in the formulation of rules that are practical, flexible and effective for the food industry at home and abroad while protecting the public from contaminated food.

Howard Sklamberg

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

Since FSMA was enacted in 2011, we have literally traveled the world to get input on the rules we proposed in 2013 and early 2014 to implement the law. FDA teams have been involved in approximately 600 engagements, including public meetings, webinars, listening sessions, farm tours, visits to manufacturing plants and extensive presentations and meetings with various stakeholder groups.

As a result of these conversations, we made significant changes in September 2014 to four of the FSMA proposed rules, including the preventive controls rules, to make them more feasible and, ultimately, more effective.

So what happens now? This is a new chapter for all of us. FDA is focusing on providing the support that companies need to comply with the new requirements with education, training and technical assistance. We will be looking at how facilities are working to comply with the new food-safety standards and protect consumers from unsafe food. Of course, our mandate is to protect public health and, when necessary, the agency will act swiftly to do so.

The conversations we had with stakeholders in creating the rules will continue as we move further into the implementation phase with the preventive controls and other rules. We will be sharing our thinking on how requirements should be met in guidance documents and asking for the public to continue to provide feedback. If necessary, changes will be made; aspects of the rules will be fine-tuned. This first wave of compliance dates is important to the entire spectrum of FSMA implementation; the lessons learned will be invaluable in the years ahead when smaller food facilities are held to the new standards.

So today, the rubber meets the road. But these compliance dates aren’t the beginning of the end of our work to make FSMA a reality. They’re the end of the beginning. The partnership that FDA has forged with food producers of all kinds, and with its state, local, tribal and international regulatory partners, will ultimately protect consumers for generations to come.

Stephen Ostroff, M.D., is FDA’s Deputy Commissioner for Foods and Veterinary Medicine; Howard Sklamberg, J.D., is FDA’s Deputy Commissioner for Global Regulatory Operations and Policy

Evaluating FDA’s Approach to Cancer Clinical Trials

By: Richard Pazdur, M.D.

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

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

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

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

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

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

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

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

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

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

FDA and Access to Medications

By: Janet Woodcock, M.D.

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

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

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

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

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

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

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

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

FDA Is Preparing Guidances that Will Help Food Companies Prevent Foodborne Illness

By: Susan Mayne, Ph.D., and Tracey Forfa, J.D.

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When we were drafting and seeking public comment on the rules that will implement the FDA Food Safety Modernization Act (FSMA), we promised that we would do whatever we could to help the regulated industry understand and meet the new requirements.

Susan Mayne

Susan Mayne, Ph.D., is Director of FDA’s Center for Food Safety and Applied Nutrition

We meant what we said about “educating before and while we regulate,” since these new standards will ultimately transform the nation’s food safety system.

This month, we have taken important steps in fulfilling that promise with the release of three draft guidances that when finalized will help domestic and foreign food facilities meet the requirements of the preventive controls rules that became final in September 2015.

Those rules require hazard prevention practices in human and animal food processing, packing, and storage facilities. FSMA created the framework that holds manufacturers accountable for having a food safety plan, implementing it, verifying that it is working, and taking corrective action when it isn’t. Compliance dates are fast approaching for large food facilities. The human food facilities must meet preventive controls and Current Good Manufacturing Practice requirements (CGMPs) and the animal food facilities must meet CGMPs by September 19, 2016. (The preventive controls rules have staggered compliance dates; smaller facilities have a year or more additional time to comply.)

One of the draft guidance documents covers ways to comply with the preventive controls requirements of the human food rule. Given the scope of that rule, we are prepared to issue only five draft chapters now, covering specific sections of the rule, but we will ultimately issue 14 chapters in all.

Tracey Forfa

Tracey Forfa, J.D., is Acting Director of FDA’s Center for Veterinary Medicine

These initial chapters cover basic information about establishing preventive controls in a human food facility. The first chapter is about the food safety plan in which a human food facility outlines how it has identified and evaluated its food safety hazards and how it will control hazards requiring preventive controls. The subsequent chapters provide direction on conducting a hazard analysis; understanding the biological, chemical and physical hazards that are commonly of concern; identifying and implementing the preventive controls that will significantly minimize or prevent hazards; and managing the preventive controls through such actions as monitoring, corrective actions and verification activities.

The other two draft guidances when finalized will help domestic and foreign facilities comply with key requirements in the Preventive Controls for Animal Food rule, which covers all animal food, including animal feed and pet food. One of those documents provides direction on ways to comply with the rule’s CGMP requirements, which are baseline food safety and sanitation standards for animal food facilities. This draft guidance also provides information on provisions related to the CGMP requirements, such as qualifications and training of personnel.

While CGMPs have long existed for the production of human food, this is the first time that most animal food producers will be subject to CGMPs. Concerns about incidents of food contamination that were sickening and killing pets were among the driving forces behind the enactment of FSMA.

The third draft guidance when finalized will help domestic and foreign food facilities whose by-products of human food production are used as animal food. Such by-products include grain products and vegetable pulp. They also include foods like potato chips, baked goods and pasta that are safe to eat but considered the wrong size, shape, color or texture.

Food producers required to meet food safety requirements for human foods had been concerned that they would have to meet a whole new set of requirements for such by-products. The draft guidance makes clear that the by-product will only be subject to limited CGMPs to protect it from contamination during holding and distribution, if the human food facility is subject to and in compliance with FDA’s human food CGMPs and all applicable human food safety requirements of the Federal Food, Drug, and Cosmetic Act and implementing regulations and is not further processing the by-products for use as animal food.

If the human food facility is further processing the by-products, the facility has a choice of complying with the requirements of either the human or animal food rule, as long as the food safety plan addresses how the facility will prevent or significantly minimize the hazards for the animal food that require a preventive control.

These draft guidances, and the others that we’re working on for the FSMA rules, will be further refined based on input we receive from the public. The comments we received on the proposed FSMA rules were important in helping us shape the final rules so we look forward to working with stakeholders in the same way on these documents.

Meeting the FSMA mandate involves cooperation between the FDA and the food industry. From the smallest food operation to the largest company, we want to be sure that we’re all on the same page and these draft guidances will help get us there.

Susan Mayne, Ph.D., is Director of FDA’s Center for Food Safety and Applied Nutrition

Tracey Forfa, J.D., is Acting Director of FDA’s Center for Veterinary Medicine

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 for further assistance.

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

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

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

By: Karen Mahoney, M.D.

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

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

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

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

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

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

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

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

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

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

Protecting the Public and Especially Kids from the Dangers of Tobacco Products, Including E-Cigarettes, Cigars and Hookah Tobacco

By: Mitch Zeller, J.D.

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This month, for the first time, FDA will be able to help protect the public, and especially kids, from the dangers of all tobacco products.

For years, it has been illegal under federal law to sell cigarettes and smokeless tobacco to minors. Under a rule finalized in May, federal law now prohibits retailers from selling e-cigarettes, hookah tobacco or cigars to people under age 18.

Mitch Zeller, J.D., Director of FDA's Center for Tobacco ProductsBeginning today:

  • It will become illegal nationwide to sell cigars, hookah tobacco, and e-cigarettes to anyone under age 18 and retailers will need to check photo ID of anyone under age 27.
  • Retailers will not be allowed to give away free samples of newly deemed tobacco products.
  • Retailers will not be allowed to sell cigars, hookah tobacco, and e-cigarettes in a vending machine where anyone under age 18 has access at any time.

In 2009, the President signed the Family Smoking Prevention and Tobacco Control Act into law, giving FDA the authority to regulate cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco. But cigar, hookah tobacco and e-cigarette markets remained unregulated, creating a market environment I have equated in the past to the Wild, Wild West.

While there has been a significant decline in the use of traditional cigarettes among youth over the past decade, their use of other tobacco products continues to climb – putting a new generation of kids at risk of addiction. E-cigarette use, for example, skyrocketed from 1.5 percent in 2011 to 16 percent in 2015 (an over 900 percent increase) among high school students; and hookah use also increased significantly. And every day, more teenage boys try a cigar than try a cigarette.

That’s why this historic rule is so important. It enables FDA to regulate all tobacco products except accessories – improving public health and protecting future generations from the dangers of tobacco.

In addition to restricting youth access to tobacco products, FDA will now be able to review new tobacco products not yet on the market, prevent misleading claims and help better provide consumers with information to make informed decisions about their tobacco use. This means tobacco product manufacturers will be required to register and list their products with FDA.  And all newly regulated products will need to get a marketing order from FDA, unless they are grandfathered (were sold in the U.S. as of February 15, 2007.) Manufacturers will also be required to report ingredients and harmful and potentially harmful constituents in their products.



Under these public-health based regulations, tobacco product manufacturers seeking a marketing order from FDA must now demonstrate what is actually in these products, and how these products impact the health of those who use them – important rules to be expected for products that expose consumers to known or potential health risks.

To assist companies in making the transition to an FDA-regulated marketplace, we have published several guidance documents to help businesses, big and small, meet these new requirements. We also continue to offer webinars for retailers and manufacturers and support from our Office of Small Business Assistance.

This historic final deeming rule is a major public health step forward. We believe by restricting youth access to additional tobacco products such as cigars, hookah, and e-cigarettes and by scientifically reviewing these products, we will reduce the public health toll of tobacco use, which remains the leading cause of preventable disease and death in the country and the world – and keep our kids tobacco-free.

Mitch Zeller, J.D., is the Director of FDA’s Center for Tobacco Products