National Drug Take Back Day: A Great Time to Dispose of Prescription Medications Cluttering Your Cabinets

By: Douglas C. Throckmorton, M.D

On Wednesday, April 27, FDA staff can bring in their unwanted, unused, or expired prescription drugs to the FDA campus for safe disposal as part of the Drug Enforcement Administration’s (DEA) National Prescription Drug Take Back Initiative. In past years, we’ve collected more than 200 pounds of unused medications that would have otherwise lingered in medicine chests and kitchen cabinets. FDA’s event is in advance of National Drug Take Back Day, marked on April 30.

Douglas C. Throckmorton, M.D.Medicines no longer being used may pose grave and unnecessary dangers to families and the people visiting their homes. For example, in the last two decades, FDA has received more than 30 reports of accidental exposure to the powerful pain medication in fentanyl patches – most of them in children under two years old. Tragically, 12 of these incidents required hospitalization and another 12 were deadly. Drug Take Back programs are the preferred method for fentanyl patch disposal and frequent drug take back programs run by local communities are a big step toward preventing unnecessary deaths due to accidental medication exposure.

Another important effect of National Take Back Day is that it helps to divert medicines from entering the environment. We share the public’s concerns regarding the potential environmental impact of disposing unused medicines in household trash, or by flushing. We are working with other agencies, including the U.S. Environmental Protection Agency (EPA), to better understand the human health and ecological risks from medicines in our water and have a shared overall goal of reducing medicine levels in our water.

FDA has strongly supported work to expand the availability of take back programs for several years. We will continue to work with manufacturers to develop new formulations with reduced risk for accidental harm and with our federal partners to develop alternative, safe disposal systems. We look forward to a time when effective disposal alternatives are more widely available.

The importance is underscored when you think about the epidemic this country is facing with opioid medications. Many people who misuse medications, such as opioids, get their first dose by using medications prescribed to other people. FDA is deeply concerned about the growing epidemic of abuse, misuse, dependence, and overdose of opioids in the United States. In response to this crisis, FDA has developed a comprehensive action plan to take concrete steps toward reducing the impact of opioid abuse on American families and communities.

So if your prescription medications have expired or you are no longer taking them, Drug Take Back Day is a way to make sure they are disposed of properly. April 30 marks the eleventh nationwide opportunity since 2010 for Americans across the country to do what we’re doing at FDA this week and get rid of all unused drugs in the home. It’s simple and easy. Gather them up and take them to a disposal site near you. The service is available from 10 a.m. to 2 p.m. It’s free and anonymous, no questions asked. Past drug take-back days have been highly successful. Cumulatively, previous events have collected well over 5 million pounds of unwanted, unused, or expired drugs.

Safe disposal of medicine is a year-round activity. FDA’s Disposal of Unused Medicine site offers valuable “do-it-yourself” safety information when there isn’t a take back site available.

Together, we can make difference.

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

Strengthening Partnerships: FDA’s China Office Engages in Key Outreach with Chinese Provincial FDA, Academia, and Industry

By: S. Leigh Verbois, Ph.D.

独木不成林,单弦不成音

Dú mù bù chéng lín, dān xián bù chéng yīn

‘A single tree makes no forest, one string makes no music.’

“A single tree makes no forest, one string makes no music.”This old Chinese proverb inspired FDA’s China Office, as members of our staff embarked on a five-day trip to meet with provincial FDA regulators, industry, and academia in China’s Yangtze River Delta region.

FDA Staff with Zhejiang FDA

FDA Staff Meets with Zhejiang FDA
Hangzhou, China
Front Row, Left to Right: Gang Wang (FDA China Office), Bo Ju (Zhejiang FDA), Yuanchang Shao (Zhejiang FDA), Leigh Verbois (FDA China Office), Jue Chen (Zhejiang FDA), Chiang Syin (FDA China Office), William Sutton (CDRH),
Back Row, Left to Right: Jinfeng Liang (Zhejiang FDA), Wenhua Zheng (Zhejiang FDA), Yini Ye (Zhejiang FDA), Lixin Shen (Zhejiang FDA), Nicole Taylor Smith (FDA China Office), Lixia Wang (FDA China Office)

The Yangtze River Delta region is an economic area that encompasses the Shanghai municipality, Zhejiang and Jiangsu provinces. The commercial epicenter, which accounts for 20 percent of China’s gross domestic product, is home to a significant number of FDA-regulated medical product manufacturers.

We traveled more than 3,300 kilometers (1,980 miles) to meet with key leaders and experts to strengthen partnerships, share information, and build the foundation for future cooperative engagement. Our first stop was Shanghai, where I had the great fortune to be able to address hundreds of students and faculty at East China University of Science and Technology’s School of Pharmacy and China Pharmaceutical University.

My message to the students was that they are the future leaders who will be in charge of the next generation of pharmaceutical innovation and data integrity.

In Shanghai, we also had the opportunity to sit down with U.S. Embassy Consul General Hanscom Smith to compare notes and to talk about current FDA priorities underway in the region.

China Pharmaceutical University (CPU)

China Pharmaceutical University (CPU)
Nanjing, China
CPU Faculty and Students attending Dr. Leigh Verbois’s Presentation on “CDER’s Novel Drug Approvals and Priorities”

The team then rode a high speed bullet train to Nanjing to meet with Jiangsu FDA, the regional regulator. This type of information sharing between the provincial FDA and the FDA China Office supports our shared mission of assuring that medical products produced in China meet U.S. safety standards.

On day three, we traveled again by bullet train to Suzhou where we partnered with China’s Association for Medical Device Industry to hold a two-hour, town hall meeting with almost 200 of China’s big device manufacturers that export products to the United States.

Working with FDA’s Center for Devices and Radiological Health (CDRH), our team provided information on Unique Device Identification (UDI) requirements. In the greater China region, it is estimated that there are nearly 4,000 medical device establishments affected by these requirements.

Hangzhou, China

Hangzhou, China
One of the many bridges in Hangzhou to symbolize “Building Bridges” between the FDA China Office and our Chinese stakeholders

The next morning, we headed for Hangzhou. After about two hours by train, we arrived in Hangzhou ready to meet with provincial FDA officials. Our meeting focused on specific ways we could collaborate on future medical device and drugs outreach, and more effectively share information.

The final day of our weeklong journey started with an industry roundtable focused on pharmaceuticals, held in partnership with Zhejiang FDA. As fellow regulators, we joined together to engage in substantive discussion with representatives from major manufacturers located in the Zhejiang, Jiangsu, and Shanghai regions, many of whom were interested in recent data integrity efforts in China. The FDA team then boarded our last train back to Shanghai for a final meeting with local officials that focused on our mutual priorities, as well as ways to expand and leverage efforts going forward.

The team flew back to Beijing feeling very satisfied that we accomplished much and clearer than ever that continued collaboration with Chinese regulators, industry and academia will help to ensure that medical products manufactured for the U.S. market are safe and effective. After all, one tree alone does not make a whole forest.

Leigh Verbois, Ph.D., is Director of FDA’s China Office in the Office of International Programs

What We Mean When We Talk About EvGen Part I: Laying the Foundation for a National System for Evidence Generation

By: Rachel E. Sherman, M.D., M.P.H., and Robert M. Califf, M.D.

Rachel Sherman

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

Across the clinical research enterprise, there is a growing awareness of serious shortfalls in the current paradigm of generating the scientific evidence that supports medical product evaluation and clinical care decisions and the need to modernize methods and expectations surrounding this evidence base.

We know, for instance, that most clinical practice guideline recommendations are not based on high-quality evidence, typically derived from appropriately designed randomized controlled trials. We also know that adherence to standards supported by such high-quality evidence results in better outcomes for patients.

There is reason to believe that we’ve arrived at a tipping point where previously separate, “siloed” efforts can be linked to create a national system for evidence generation (EvGen). In this first of a series of posts, we’ll take a look at the elements required to build such a national system, beginning with a pair of foundational concepts—interoperability and connectivity.

Interoperability

Robert Califf

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

Put simply, interoperability is the idea that different systems used by different groups of people can be used for a common purpose because those systems share standards and approaches. To take one example: modern train tracks employ agreed-upon standards in terms of track gauge and other specifications so that many different kinds of vehicles can safely use the rail system.

In similar fashion, a national system for evidence generation that applied common data standards and definitions could “lay the track” for significant improvements in the exchange of biomedical data. Patients, consumers, professional groups, payers, the medical products industry, and health systems all stand to benefit from potential gains in efficiency and reductions in cost that would accompany standardized approaches to data collection, curation, and sharing, once up-front investments are absorbed. Then, with these standards in place, effort could be devoted to generating actionable knowledge rather than simply managing data.

Connectivity

Establishing interoperable systems is a critical step in building a national system for evidence generation. An equally important step is to enable collaboration among the many groups that generate data, for example patients, clinicians, hospital systems, health insurance organizations. Evidence is derived from high-quality data that often originates from many different sources or settings. We can create an interconnected environment that leverages all the available data to provide answers to important public health questions. A defining characteristic of such a network is the ability to leverage all available data for different tasks as needed, allowing the network to integrate complex relationships between data input and output. Coupled with interoperable standards, a national system for evidence generation based on these principles will be capable of generating very large quantities of data and enabling those data to flow among system components.

The result? Researchers will be able to distill the data into actionable evidence that can ultimately guide clinical, regulatory, and personal decision-making about health and health care.

These two core constructs represent the essential scaffolding that must be developed and put in place to support a national system for evidence generation. In our next posting, we’ll examine ways we can begin building and continuously improving such a system for the benefit of all stakeholders.

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

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

Engagement and Collaborative Problem Solving: Two Ingredients for FSMA Success

By: Michael R. Taylor and Stephen Ostroff

As we’ve developed the rules needed to implement the FDA Food Safety Modernization Act, we’ve done a great deal of outreach to explain the new requirements and obtain feedback from stakeholders.

group touring Florida citrus grove

Tim Dooley (top of photo, center right), vice president of Blue Goose Growers in Fort Pierce, Florida, leads a tour of the company’s citrus groves.

We’ve got to continue doing this with the people working on the nation’s farms–since the produce safety rule issued in late 2015 primarily involves them.

This was a lesson learned in our recent trip to southern Florida, where we toured citrus farmlands and took part in a public meeting on the final FSMA rules at the University of Florida’s Institute of Food and Agricultural Sciences (UF/IFAS). We found that growers want to meet the new standards in the produce safety rule but need greater clarity and understanding about how the rule can be applied to their specific farm setting.

Florida farmers are under a lot of pressure that has nothing to do with the FSMA rules. The citrus groves there have been hard hit in recent years by a disease called citrus greening that results in stunted, bitter, green fruit and drastically reduced harvests. The stark backdrop to our conversations is that these growers are fighting for survival–and every cost counts.

That makes it especially important that they, and all farmers covered by the produce rule, understand what will be required. And, just as important, what won’t be required.

For example, we talked to growers who have dozens of wells on their farms and are worried about the rule’s water testing requirements and associated costs. But in many cases, only a fraction of those wells are used to apply water in a way that is intended or likely to contact crops during growing, or for other uses that are  subject to the microbial water quality criteria in the produce rule.

Some growers pull surface water out of extensive canal systems where the water from any one canal may deliver water to many farmers. Other growers use seep irrigation systems in which the water seeps from a surface water source through the soil. The growers told us that the soil filters the water, which comes in contact with root vegetables like carrots, beets and radishes.

Their questions were: How are we covered by the produce safety rule and how do we achieve compliance? One of the growers produces beets and our answer to him was that beets are not covered because the produce rule exempts specific crops that FDA identified as rarely consumed raw, such as garden beets and sugar beets. We explained that water used in seep irrigation that contacts root crops covered by the rule does have to meet the applicable microbial standard. But farms have the option of establishing and using alternatives for certain agricultural water requirements if they have scientific evidence to support them.

Each region of the country has its own complexities, and Florida has a dramatically diverse landscape of crops, settings, and soils. The soil around Lake Okeechobee transitions from sandy at one end to densely dark muck at the other. Within the citrus industry, agricultural water can come from completely different sources, surface and ground water that have different testing requirements. We at FDA are constantly learning about the complexities that are part of everyday life for our nation’s food producers.

This trip highlighted how important it will be for us to be continually engaged at the local, state and federal levels in collaborative problem solving with growers and others in the food industry as we implement the FSMA rules.

We value the leadership of Florida Commissioner of Agriculture Adam Putnam, Deputy Commissioner Lisa Conti and others on their team. We have long been partners with Martha Roberts of UF/IFAS, an authority on food safety issues. And Florida itself is a pioneer in food safety, in 2008 establishing the first mandatory state regulatory program for produce with provisions for inspections and audits for tomato handling, production and packing.

Susan Turcovski, the director of FDA’s Florida District, and her team accompanied us on this visit. They are also on the front lines of implementation and their role will be critical in the months and years ahead. We were joined by Leanne Skelton, the U.S. Department of Agriculture’s liaison to FDA on FSMA issues, and spent time at USDA’s Horticultural Research Lab in Fort Pierce.

Education is an important part of our FSMA efforts. Another member of our group was Dr. Michelle Danyluk, one of the leads for the Southern Training, Education, Extension, Outreach, and Technical Assistance Center at the University of Florida. The center is one of four regional centers funded by USDA and FDA that will coordinate and implement FSMA-related training.

We’ve got our work cut out for us but every conversation brings us closer to the food safety system envisioned by FSMA that systematically takes steps to prevent the causes of foodborne illness. Working together, we’ll get there.

Michael R. Taylor is FDA’s Deputy Commissioner for Foods and Veterinary Medicine; Stephen Ostroff, M.D., formerly FDA’s Acting Commissioner, will be succeeding Mr. Taylor as Deputy Commissioner on June 1, 2016.

2015: An Important Year for Advancing Generic Drugs at FDA

By: Kathleen “Cook” Uhl, M.D.

Generic drugs allow greater access to health care for all Americans.

At FDA’s Office of Generic Drugs (OGD) in the Center for Drug Evaluation and Research, 2015 was an important year. It was our first full year of operation after vastly expanding our office’s scope and structure. This change allowed for the office to have greater prominence and allowed for additional staff to handle a growing workload and enhance our ability to advance the safety and availability of generic drugs in the U.S.

Kathleen "Cook" UhlConsider this: In 2014, generics saved the U.S. health system an estimated $254 billion – and FDA continues to work hard to advance the use of generic drugs to help improve public health.

Our increased capacity and expansion came at a critical time. In 2012, a new law called the Generic Drug User Fee Act (GDUFA) authorized additional funds for FDA for the review of generic drug applications, inspection of facilities and other regulatory actions. But with those additional funds came an FDA commitment to reach a variety of goals. These goals were articulated in a document that accompanied the GDUFA legislation, which was negotiated between FDA and industry and enacted by Congress. The additional funds help FDA efficiently handle thousands of applications for new generic products and reduce the time needed to review generic medications for approval.

We’re on track for meeting all of those goals. Today, to help the public understand our progress, OGD released our first annual report. It’s filled with detailed accounts of our work, which seeks to improve the generic drug program with more efficient reviews of applications, and by developing the science needed to help the generic drug industry demonstrate that their products are as safe and effective as their brand-name counterparts.

Among the highlights, the report notes that 2015 marked the highest number of generic drug approvals and tentative approvals ever awarded by FDA – more than 700 in all. Last year, in December, we granted the highest number of approvals and tentative approvals in a single month (99) since the generic drug program began.

Another major commitment of GDUFA was to take a first action, by 2017, on 90 percent of the “backlog,” those applications pending prior to GDUFA as of October 1, 2012. We had 2,866 abbreviated new drug applications (ANDAs) and 1,873 prior approval supplements (PASs), but by the end of 2015, we completed first actions on 84% of ANDAs and 88% of PASs – already close to the 90% goals set for 2017! We also approved 90 “first generics,” meaning that in 2015 we added a new cost-saving generic alternative for 90 brand name drugs.

Despite our progress, we have a lot more work to do. But we don’t expect to do it entirely on our own. Achieving goals that work for the public requires input from the public, including industry, the research community, lawmakers and other stakeholders.

As part of our effort to align with stakeholders’ visions, we’re holding a public meeting on May 20 to solicit valuable feedback on our regulatory science initiatives and help us chart directions forward. We invite all to attend and to contribute by providing your thoughts and ideas to our public docket.

We encourage you to read our annual report and to participate in our annual meeting. With our ongoing efforts and strong public input, we are confident that 2016 and beyond will be as successful as 2015.

Kathleen “Cook” Uhl, M.D., is FDA’s Director, Office of Generic Drugs in the Center for Drug Evaluation and Research

Continuous Manufacturing Has a Strong Impact on Drug Quality

By: Lawrence Yu, Ph.D.

If we used a time machine to transport a pharmaceutical scientist from the 1960s into a current pharmaceutical production plant of today, it might be surprising to learn that they would already be very familiar with most of the processes and production techniques being used. That’s because not much has changed in pharmaceutical production over the last 50 or so years.

Lawrence YuFor decades, most drugs have been manufactured using what is known as “batch” technology — a process whereby the ultimate finished product has been made after many stops and starts in a series of steps. Unfortunately each break in the process causes inefficiency and delay, as well as the increased possibility of defects and error.

Today, a new and exciting technology — continuous manufacturing — enables much faster production and more reliable products through an uninterrupted process. How much faster is continuous manufacturing?  In some cases, manufacturing that takes a month by batch technology might only take a day using continuous manufacturing techniques.

Of course, speed alone would not matter if continuous manufacturing compromised quality. But by eliminating breaks between steps and reducing opportunities for human errors during the stops and starts in the batch process, continuous manufacturing is more reliable — and safer. That’s a powerful combination.

There’s the added benefit that more efficient production of quality products can drive down manufacturing costs, possibly resulting in lower drug prices for consumers. Continuous manufacturing also allows manufacturers to respond much quicker to changes in demand, potentially contributing to prevention of drug shortages.

We are seeing a growing number of manufacturers working towards building continuous manufacturing into their processes. One manufacturer, Vertex, the maker of a cystic fibrosis drug called Orkambi (lumacaftor/ivacaftor) has been using the continuous manufacturing process for this drug since its approval date in July 2015.

Last Friday marked another significant step towards integrating continuous manufacturing into pharmaceutical production. FDA approved, for the first time, a manufacturer’s change in their production method from “batch” to continuous manufacturing. This new approval is for manufacturing Janssen Products, LP’s, medication for the treatment of HIV-1 infection, Prezista (darunavir). The company’s efforts in manufacturing advancement were facilitated by the use of FDA’s recently-released draft guidance to industry titled, Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base, a product of the agency’s Emerging Technology Team (ETT) designed to help manufacturers implement a variety of technological advancements.

Although it is not easy for drug manufacturers to transition from batch to continuous manufacturing, there are significant rewards. FDA encourages others in the pharmaceutical industry to consider similar efforts.

Progress comes at an opportune time. The medications we use are changing. We are entering an era of precision medicine, when drugs must be made with unique features and provided more quickly to patients in need. FDA will continue our efforts to encourage the advancement of continuous manufacturing as one of a variety of ways to enhance the quality of the medications used by the American public.

Lawrence Yu, Ph.D., is FDA’s Deputy Director, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research

Developing a Consensus Voice: The Combination Products Policy Council

By: Nina L. Hunter, Ph.D., and Rachel E. Sherman, M.D., M.P.H.

We recently announced the launch of lean process mapping to build a better system for combination products review – one that is more cohesive, more collaborative, more systematic, and more predictable. We look forward to providing an update on this effort soon.

Nina Hunter

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

In the meantime, we’re delighted to announce the creation of FDA’s first Combination Products Policy Council. Building on successful cross-cutting efforts such as the Biosimilars Implementation Committee and the Medical Policy Counsel in the Center for Drug Evaluation and Research (CDER), the Council will be a senior-level, agency-wide forum for discussing, resolving, and implementing product and policy issues. Because of the multiple FDA organizations involved, this council will have decisional authority on issues relating to combination products, cross-labeled products, and medical product classification.

The different parts of a combination product and the different product types labeled for use together in premarket applications for combination products and cross-labeled products can create complexities for reviewers and require expertise from multiple centers.

Rachel Sherman

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

Currently, the lead center manages the review process using procedures associated with the center-specific application type and user fee goal dates. But differences in statutory and regulatory requirements for different application types, including evidentiary standards, data requirements, and review limitations, make it challenging to coordinate reviews and ensure alignment and consistency in addressing issues across centers.

In response to these complexities, we are creating a key component in the Office of the Commissioner that can convene parties across centers, foster understanding and consistent application of requirements, and develop a unified FDA position on issues that arise. Although this process will not replace the existing formal appeal process, we anticipate that many issues can be resolved before reaching that stage.

Council Mission

  • Modernize the inter-center consultation process and related aspects of combination product and cross-labeled product review;
  • Promote development of innovative, safe, and effective combination products and cross-labeled products; and
  • Promote alignment in addressing challenging medical product classification issues.

The Council will be composed of representatives from relevant centers and offices. In addition, experts from within centers and other FDA offices will provide expertise as needed for specific policy topics under consideration.

In addition to serving as a communications hub, the Council will be involved in the development of agency-wide and external communications such as draft guidances, publications, and blog posts on policy decisions. FDA envisions a variety of topics may be relevant for consideration by the Council, including such “front-burner” items as product jurisdiction and designation practices, application of evidentiary standards for clearance/approval to combination products and cross-labeled products, and regulation of novel products.

We’ve heard that many stakeholders desire a voice in modernizing the combination review program, and we’re listening! In addition to the topics listed above, one of the Council’s priorities will be to consider how best to seek input from external stakeholders on various issues. We would hope that such comments include policy issues recommended for discussion and recommendations on how the policy issue could be addressed or implemented.

We are confident that the Council’s efforts will ensure transparency and consistency in our approach to combination product policy development and implementation, ultimately helping to ensure that innovative combination products marketed to the American people are safe, effective, and appropriately labeled. We look forward to providing updates about the Council, as well as additional modernization efforts in this important area.

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

Rachel E. Sherman, M.D., M.P.H., is FDA’s Associate Deputy Commissioner in the Office of Medical Products and Tobacco and the Chairperson of the Council