Combination Products Review Program: Progress and Potential

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

Nina Hunter

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

About a year ago, we shared with you our Combination Product Review, Intercenter Consult Process Study Report, which was developed by FDA’s Office of Planning. The report’s findings were derived from focus group studies with reviewers from FDA’s different Centers and included input from industry. Since then, we have built on foundational policies and processes to address many of the issues identified in the report.

The team has made tremendous progress toward the goal of modernizing the combination products review program by improving coordination, ensuring consistency, enhancing clarity, and providing transparency within the Agency as well as with all stakeholders. We are excited to share our progress with you now. The table below summarizes some key achievements from the past year, including publication of draft guidances, a variety of new processes, and a look at future goals.

Robert Califf

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

As technologies advance across multiple fields, the distinctions that previously allowed combination products to be neatly categorized by FDA’s medical product centers are blurring or even vanishing.

Combination products account for a growing proportion of products submitted for review, and FDA will continue to pursue new approaches to collaboration that ensure safe, effective and innovative medical products are made available to patients as quickly as possible. Continued collaboration with you, our stakeholders, will be critical as together we continue to make progress in this important area.

We are still listening and have much more work to do!

Combination Products Review Table

This table summarizes key Combination Product Review Program achievements from the past year. Click on table for PDF version.

The PDF version of the table is also located here: combination-products-review-program

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

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

Consumer expenditure on FDA regulated products: 20 cents of every dollar

By: Sheri Walker, Ph.D., and Clark Nardinelli

Sheri Walker

Sheri Walker, Ph.D., is an FDA Senior Economist

One of the much-cited statistics about FDA is this: that FDA-regulated products account for about 20 cents of every dollar of annual spending by U.S. consumers. Add up 20 cents of every dollar and it amounts to more than $2.4 trillion in annual consumption that includes medical products, food and tobacco.

Our staff of 34 economists comes up with this estimate of FDA’s impact every year. We think it helps the public put in perspective the sheer scope of FDA’s responsibilities, especially when you recognize that FDA is only one of dozens of governmental agencies.

We largely rely on personal consumption expenditure data collected by the Bureau of Economic Analysis (BEA) every year to calculate total consumer spending in each of the major FDA product categories. These product categories include food (except alcohol and meat products regulated by USDA), drugs, medical devices, cosmetics, dietary supplements, and (since 2009) tobacco products.

Clark Nardinelli

Clark Nardinelli is FDA’s Chief Economist

Some BEA expenditure categories include more than one FDA product area. For example, biologics and dietary supplements are included in the expenditure for pharmaceutical and medical products (although, legally, dietary supplements are food). Cosmetic products are captured under the BEA expenditure category for personal care products. Pet food and animal drugs are estimated as a percentage of the pet-related products category. The estimate for medical device products is derived using data from the therapeutic equipment products category from the BEA and data from the Annual Survey of Manufacturers collected by the U.S. Census Bureau.

Food products represent the largest share of spending on FDA products, accounting for approximately 11 cents of every dollar of consumer spending. Without the addition of tobacco products, spending on FDA-regulated products would be slightly less than 20 cents per dollar.

20 cents pie chartWe know that some people say FDA oversees 25 cents of every consumer dollar. Maybe it’s an urban legend – or maybe it harkens back to decades ago. The 20 cents (or 20 percent of spending on consumer goods and services) has held steady over the past 5 years. Americans used to spend a much higher proportion of their income on food – with over 25 cents of every dollar going to food during World War II. But since then the share of food and tobacco in total consumer spending has been falling steadily while the share of consumer spending devoted to medical products has been steadily climbing. Whether those trends will continue, and whether FDA’s 20 cents will hold steady for the next 5 or 50 years, is impossible to predict.

Sheri Walker, Ph.D., is an FDA Senior Economist, and Clark Nardinelli is FDA’s Chief Economist

Key Facts about “Abuse-Deterrent” Opioids

By: Douglas C. Throckmorton, M.D.

Here at FDA, we work diligently to be part of our nation’s solution to the opioid abuse epidemic. While there is no single solution to this complex problem, we continue to encourage efforts to develop new opioid formulations with abuse-deterrent properties that make it harder to abuse these powerful medications.

Douglas C. Throckmorton, M.D.Knowing there are some 100 million Americans with significant pain each year, we need to help ensure that patients in need continue to have appropriate access to pain medications, including opioids. At the same time we must work to ensure that these powerful medications are used as safely as possible.

To date, FDA has approved seven opioid formulations with abuse-deterrent properties consistent with FDA guidance, and there are more in the development pipeline.

What does it mean to be abuse-deterrent? Opioids with abuse-deterrent properties are tablets or capsules that are designed to deter abusers from crushing them into a powder for swallowing, snorting or injecting to create a faster, more intense high.

Each manufacturer has its own proprietary technology for deterring abuse. Some abuse-deterrent formulations consist of tablets with a hardened surface that is difficult to crush and some turn the crushed medicine into a gooey substance that is difficult to inject.  Other current approaches combine the opioid with naloxone or naltrexone, drugs that block the effects of the opioid in the body that are activated when the opioid is crushed.  Additional approaches are currently under development.

The manufacturers of the seven FDA-approved opioids with abuse-deterrent properties to date have all submitted study data demonstrating that the products are expected to deter abuse. This work was guided by the 2015 final guidance for industry, Abuse-Deterrent Opioids — Evaluation and Labeling. As a result of FDA’s review, FDA-approved product “labeling” (prescribing information) for these medications clearly states the product’s abuse-deterrent properties. Other manufacturers have chosen to add what they may intend as abuse-deterrent properties to their product, but FDA has not seen sufficient evidence that these properties are effective and therefore the FDA-approved labeling for these products does not identify them as having abuse-deterrent properties. Prescribers and patients can look to our web site for the list of FDA-approved products with abuse-deterrent properties in their labeling.

It’s important to recognize that FDA refers to these drugs as “abuse-deterrent” not abuse-proof. There will always be some potential for abuse of these products. For instance, a patient can orally ingest a quantity beyond what is prescribed. It’s also true that people intent on abusing an opioid may find ways to overcome the abuse-deterrent properties of the drug that were not identified during premarketing research. With this in mind, FDA requires that any drug approved as having abuse-deterrent properties be further evaluated by its manufacturer after it is marketed. The manufacturer is required to conduct studies to evaluate the impact of the product on abuse in the community. If necessary, we may approve updated product labeling that describes the drug’s abuse deterrent features after approval.

Still, abuse deterrent technology certainly helps. That’s why FDA is looking at ways to encourage the development of abuse-deterrent generic versions of an opioid since none currently exist. We released draft guidance for industry in March and we’re looking forward to an interesting public discussion of the topic next Monday and Tuesday.

The FDA opioid action plan we issued in February involves a multi-faceted approach to reducing opioid misuse and abuse. And we continue to look for ways to make a difference. We recently announced we would help fund the development of assessment tools to evaluate packaging, storage, delivery, and disposal solutions, as well as product formulations, designed to prevent or deter misuse and abuse of opioid analgesics.

Support for abuse deterrent formulations is one important part of a strategy to help prescribers and patients make the best possible choices about how to use these powerful drugs. Our goal is to find the balance between appropriate access to opioids for patients in pain and the need to reduce abuse and misuse of these medications.

Douglas C. Throckmorton, M.D., is Deputy Center Director for Regulatory Programs in FDA’s Center for Drug Evaluation and Research

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