The American Chamber of Horrors

By: Vanessa Burrows, Ph.D., Suzanne Junod, Ph.D., and John Swann, Ph.D.

In the early 20th century, Americans were inundated with ineffective and dangerous drugs, as well as adulterated and deceptively packaged foods.

A cosmetic eyelash and eyebrow dye called Lash Lure, for example, which promised women that it would help them “radiate personality,” in fact contained a poison that caused ulceration of the corneas and degeneration of the eyeballs. An elixir called Banbar claimed to cure diabetes as an alternative to insulin, but actually provided no real treatment and caused harm to those patients who substituted this for effective insulin therapy. Food producers short-changed consumers by substituting cheaper ingredients. Some products labeled as peanut butter, for instance, were filled with lard and contained just a trace of peanuts, and some products marketed as “jellies” had no fruit in them at all.  Unscrupulous vendors even sold products to farmers, falsely promising they could treat sick animals – in at least one case, a product called Lee’s Gizzard Capsules killed an entire flock of turkeys instead of curing them.

Although the FDA sought to remove these unsafe and misleading products from commerce, it was severely limited in its efforts by the 1906 Pure Food and Drugs Act.  That law laid the cornerstone for the modern FDA and marked a monumental shift in the use of government powers to enhance consumer protection by requiring that foods and drugs bear truthful labeling statements and meet certain standards for purity and strength.

Over time, however, the shortcomings of the Pure Food and Drugs Act became apparent, as it failed to take into account the extraordinary changes in industries, products, markets, and advertising tactics. Dangerous drugs were a particular problem. As long as a drug met the law’s labeling requirements, the agency did not have the authority to remove even clearly dangerous products such as radium water and drugs with poisonous ingredients from the market because legal action against a drug product required a finding of fraud. If a drug’s maker could convince a court that he truly believed his own therapeutic claims, he won his case. In addition, the law provided no authority over cosmetics or medical devices, and did not specifically authorize standards for foods, which limited the agency’s ability to take action on behalf of consumers.

A popular book of the day, “100,000,000 Guinea Pigs: Dangers in Everyday Food, Drugs, and Cosmetics,” claimed that consumers were being used as guinea pigs in a giant experiment by food companies and makers of patent medicines, with the authors blaming the FDA for failing to act. But the critics failed to acknowledge the limits of the agency’s authority under the law at the time.

In an effort to inform the public about the 1906 law’s shortcomings, the FDA’s Chief Education Officer, Ruth deForest Lamb, and its Chief Inspector, George Larrick, led the creation of an influential traveling exhibit in 1933 to highlight about 100 dangerous, deceptive, or worthless products that the FDA lacked authority to remove from the market.

The exhibition was put on display at events like the 1933 World’s Fair in Chicago, at state fairs, and on Capitol Hill. It was so shocking that it was dubbed the “American Chamber of Horrors” by a reporter who accompanied First Lady Eleanor Roosevelt to view the exhibit. Lamb also adapted the exhibit into a 1936 book in which she explained, “All of these tragedies…have happened, not because Government officials are incompetent or callous, but because they have no real power to prevent them.”

The exhibit, which was viewed by millions, was an enormous success, helping promote greater awareness and understanding about the FDA’s role in protecting the public and the need for greater consumer protection and the limitations on its power to do so. To this end, it played an important role in moving Congress to enact a stronger food and drug law – the 1938 Food, Drug, and Cosmetic Act.

The 1938 law, which has been amended many times and remains the law of the land today, brought cosmetics and medical devices under the FDA’s authority, and required that drugs be labeled with adequate directions for safe use. It also mandated pre-market approval of all new drugs, such that a manufacturer would have to prove to the FDA that a drug was safe before it could be sold. And it prohibited false therapeutic claims for drugs. The Act also corrected abuses in food packaging and quality, and it mandated legally enforceable food standards. It formally authorized factory inspections, and added injunctions to the agency’s enforcement tools. In short, it gave the FDA many of the means it has today to protect the American public.

Many of the products from the original Chamber of Horrors exhibit are in the FDA’s permanent collection, and, to commemorate the 80th anniversary of the 1938 law, they are part of a special display currently on exhibit at the FDA. The objects provide a compelling visual record of how far science has brought us from the worthless and dangerous elixirs, foods, and other consumer products of the early 20th century, as well as underscoring the essential role the FDA today plays in protecting and promoting American health.

Vanessa Burrows, Ph.D., Suzanne Junod, Ph.D., and John Swann, Ph.D., are FDA Historians

FDA Budget Matters: Infrastructure to Support Robust Generic Drug Competition

By: Scott Gottlieb, M.D.

The FDA launched its Drug Competition Action Plan more than a year ago, with the aim of advancing policies that would promote robust generic drug entry as a way to foster competition and lower drug prices. Access to drugs is a matter of public health. And among the best ways to help consumers get broader access to medicines is through policies that help ensure branded drugs are subject to timely generic competition.

Dr. Scott GottliebOur work is far from finished. But the policies we’ve advanced are already showing benefits toward these goals. The benefits we’ve seen reinforce the fact that policy can be used as a vehicle to advance these purposes.

New resources have also helped advance our work. Owing in large measure to the FDA’s implementation of the Generic Drug User Fee Amendments of 2012 (GDUFA), which funded critical enhancements to FDA’s generic drugs program, our staff eliminated the backlog of generic drug applications. In 2017, we also approved the largest number of generic drugs in the FDA’s history.

As part of GDUFA, as well as through our own new efforts, the FDA also has put policies in place to promote generic drug development in areas where there’s inadequate competition. This includes a focus on developing new guidance aimed at promoting development of generic versions of complex drugs. These are drugs that are often harder to copy. By advancing clear, objective, science-based guidance for developing generic copies of complex drugs, we hope to foster more competition.

And the FDA also has improved the efficiency and predictability of the generic drug review process to help promote more robust generic drug competition. For example, we’re prioritizing the review of generic drug applications for which there are no blocking patents or exclusivities. The aim is to promote competition so that there are at least four approved applications for each product (including the brand drug). Our data shows that there are significant price decreases once there are at least three generic drugs on the market. Our new policy will help ensure that there is robust competition across the market that will drive down drug costs to consumers.

In addition, we’re taking other new steps to curtail various forms of “gaming” by brand companies, where some sponsors sometimes adopt tactics that seek to delay entry of generic competition.

But we know that we need to do even more to promote access and competition. And so we’ve put forward a broader plan, as part of the President’s Budget, to achieve these aims.

Toward these goals, the President’s fiscal year 2019 Budget Request included $37.6 million to fund two initiatives that will help modernize aspects of our generic drug review process.

The first initiative will create a new review platform — the Knowledge-aided Assessment & Structured Application (KASA) platform — to modernize generic drug review from a text-based to a data-based assessment. The KASA will enable a structured review that will make the application review process more efficient, and allow deficiencies to be spotted earlier. This will allow the FDA to provide earlier feedback to generic drug makers that will, in turn, help to reduce multiple cycles of application review, one of our key aims and a primary focus of our overall efforts to speed market access to new generic medicines. Going through multiple review cycles is one of the primary reasons why the approval of generic drug applications is sometimes delayed many years. The new KASA system will help sponsors submit high-quality and more complete applications on the first submission. It will decrease the risk that applications will be refused for receipt and reduce the number of review cycles that applications undergo.

We anticipate that the new platform will allow more generic applications to be approved after the first cycle. This will promote timely generic entry and increase overall competition.

The new platform will also enable more efficient and robust knowledge management across different aspects of the FDA’s review process, helping reviewers capture and manage all of the information about products allowing for more seamless and effective product surveillance based upon quality and risk. This system will benefit both the agency and generic drug sponsors by increasing overall speed and efficiency of the pre- and post-market processes.

Having a structured template that completely replaces the current largely narrative-based review will allow for more consistent and predictable entry and analysis of data. Current assessments require manual review of the entire application. KASA will enable automated analysis of some portions of the application, which will save time, and ensure consistency.

The second initiative is aimed at promoting the more widespread use of existing generic drugs by looking for ways to keep generic drug labeling up-to-date with the latest information about each medicine’s risks and benefits. Generic drugs are generally required to have the same labeling as the brand drug they reference. And the burden to update the labeling with new safety and effectiveness information is typically born by the brand company.

However, when brand reference drug companies voluntarily withdraw their marketing applications, they also stop updating their labeling. When this happens, the FDA loses a key mechanism that the agency relies on as a way to update generic labeling. This can stymie the ability to modernize generic labels. In turn, when labels become out-of-date, providers may not have complete information about the full range of benefits and risks of the product. This can serve to diminish the use of these lower cost alternatives.

Consistent with our current authorities, which allow for certain types of labeling changes to continue to be made for generic drugs after the brand drug is withdrawn, this budget request will provide the funding to allow the FDA to assume more responsibility to help bring these drug labels up to date. We intend to launch this initiative initially for oncology products.

Our goal is to help ensure that doctors and patients have up-to-date information for these products. This will better inform clinical decisions regarding these medicines, and help promote more widespread use of low-cost, generic alternatives. By ensuring generic product labels are up to date, we’ll promote wider and more clinically optimal use of these drugs, which can save patients money.

We appreciate that the appropriations committees of both chambers of Congress supported this budget request in their appropriations bills. Congress has long recognized the need for — and importance of – investments in our generic drug program and efforts to promote generic drug use. The benefits of these initiatives are significant to the FDA’s modernization and efficiency. They’ll help advance a robust generic drug market that drives product competition and lowers drug prices.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration 

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

Report Spotlights Achievements of FDA-Mexico Produce Safety Partnership

En Español

By: Stephen M. Ostroff, M.D.

The United States and Mexico are major trading partners in fresh produce. Each year, billions of dollars of fruits and vegetables move across the border. These include Mexican tomatoes, avocados, chilies, berries, cucumbers, lemons, and limes that reach U.S. consumers, as well as American apples, pears, grapes, onions, strawberries, potatoes, peaches and other produce that are sent to Mexico.

Stephen Ostroff, M.D.Both our countries benefit when we can help to ensure that these valuable commodities are safe for consumers on both sides of our borders. For that reason, the FDA-Mexico Produce Safety Partnership (PSP) was formed in July 2014, forging a stronger relationship between the FDA and Mexico’s National Agro-Alimentary Health, Safety, and Quality Service (SENASICA) and its Federal Commission for the Protection from Sanitary Risk (COFEPRIS).

We are pleased to share that our partnership is making real progress toward our goal of reducing the risk of foodborne illness associated with our produce trade. A new report, titled U.S. FDA-Mexico Produce Safety Partnership: A Dynamic Partnership in Action, provides some specific examples of this progress.

For example, the partnership recently worked to address the contamination of papayas grown in Mexico. In the fall of 2017, the FDA, SENASICA and COFEPRIS worked together to respond to four outbreaks of salmonellosis tied to Mexican-grown papayas. The Mexican agencies conducted inspections and sampled various farms and packing houses in several Mexican states, and shared their findings with the FDA. We were able to leverage their work and resources, along with the findings of our own outbreak investigation, to place four farms on import alert, thus providing information to the FDA inspectors who detained those products without having to physically examine them. SENASICA likewise implemented a regulatory response. In October 2017, Mexico strengthened its food safety oversight of papayas, which are subject to the Produce Safety Rule under the FDA Food Safety Modernization Act if they will be imported or offered for import in the U.S.

Chart - Mexico Exports of Fresh Produce to USAIn another example, in 2015, Listeria monocytogenes was detected in kiwi and apples grown in the U.S. and exported to Mexico. The exchange of information under the PSP, including the sharing of bacterial isolates and testing by both FDA and SENASICA laboratories, helped prevent more contaminated produce from entering Mexico. It also established a protocol for the future exchange of bacterial strains to improve detection and understanding of contamination.

These are just two of several instances in which the partnership has led to coordinated preventive activities in addition to enforcement activities that help to reduce the risk of foodborne illnesses and enable both countries to respond more rapidly to a potential or actual outbreak, better protecting both American and Mexican consumers.

Chart - U.S. Exports of Fresh Produce to MexicoBut the partnership has also provided benefits beyond individual outbreaks. Both countries have also been working collaboratively through working groups on institutionalizing approaches that reinforce preventive practices and rapid response to outbreaks. The groups have focused on information sharing, education and outreach, training, laboratory methods and processes, and how to respond effectively to outbreaks.

Looking to the future, the report outlines our five-year plan to increase engagement and the exchange of knowledge with key public and private partners. Through the partnership, we plan to also work on identifying common approaches for auditors and inspectors to better execute compliance and enforcement activities, and will create a strategy to conduct joint inspections and sampling. This will help both countries maximize their resources for the benefit of consumers on both sides of the border.

This is a long-term partnership. While there are differences in our systems, technologies, and environments, the U.S. and Mexico both want consumers to be confident in the safety of their food. By working together, we can achieve that goal.

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

FDA’s New Efforts to Advance Biotechnology Innovation

By: Scott Gottlieb, M.D., and Anna Abram

Scientific advances in biotechnology, such as genome editing and synthetic biology, hold enormous potential to improve human and animal health, animal welfare, and food security. And researchers and companies based in the United States helped pioneer these technologies. They position the U.S. as a global leader of this rapidly growing and highly promising field.

Dr. Scott Gottlieb

Scott Gottlieb, M.D., Commissioner of the U.S. Food and Drug Administration

To advance this progress, it’s key that the FDA adopt a regulatory approach to these technologies that’s as innovative and nimble as the opportunities that we’re tasked with evaluating.

FDA is committed to helping ensure the safety of biotechnology products, while also facilitating innovation by applying a risk-based regulatory approach that provides developers with regulatory clarity and predictability and maintains public confidence in our regulatory system.

And we’re taking some new steps to advance these goals. We know that products enabled by new techniques of biotechnology have the potential to significantly enhance public health.

For instance, these new methods can be used to alter animals to minimize or prevent their ability to spread human disease. Genome editing in animals and plants also can be used to produce human drugs, devices, or biologics, including tissues or organs for xenotransplantation. Scientists are also exploring editing the genomes of animals with the goal of improving the health and welfare of food producing animals and public health, for example by reducing their susceptibility to diseases like novel influenzas and resistance to zoonotic or foreign animal diseases.

Similar and equally beneficial applications of genome editing are currently being explored in food crops. These include our ability to develop disease-resistant plants and plants with increased resistance to environmental stress. Such advances can have many advantages to consumers, including better yields, more product variety, and healthier nutrient profiles.

Anna Abram

Anna Abram, FDA’s Deputy Commissioner for Policy, Planning, Legislation, and Analysis

We believe the FDA is uniquely positioned — with the expertise, experience, credibility and trusted scientific framework — to advance innovation and support the development of products with immense potential for public benefit. And we’re fully committed to these goals.

The breadth of FDA’s statutory authorities and regulatory framework allows us to comprehensively review the potential impacts of products on both human and animal health. For example, for genetically engineered animals, FDA evaluates not only the safety of food or drug products derived from that animal, but also the effect of the genetic alteration on the health of the animal. FDA has decades of experience successfully evaluating products of complex technologies, such as recombinant DNA-derived plant foods, medicines made with nanotechnology, and cellular and gene therapy products.

Moreover, because of the wide spectrum of products that we regulate, and the in-depth scientific and policy engagement that the agency has with innovators and counterpart regulatory agencies around the world, FDA can help facilitate the progression of research and development. For example, we’re focused on the timely transition of technologies from animal research models to products intended for use in humans. As our knowledge of genome editing applications increases over different product areas, we expect to build on those even greater synergies and increase our understanding to help with assessments of risks to human and animal health.

FDA will continue to apply a risk-based framework grounded in sound science to evaluate products of plant and animal biotechnology, and our framework will continue to evolve as science advances and experience with these technologies grows. We also look forward to working with stakeholders to help understand current scientific information and describe challenges and gaps in regulatory science that are important for our regulatory decision-making. We’re also going to take new steps to help developers understand their responsibility to ensure product safety and we’ll identify ways to help reduce unnecessary regulatory burden and undue barriers to bring potential beneficial products to commercialization while ensuring their safety.

Protecting and promoting public health is our mission and we’re taking steps to help ensure the safety (and as applicable, effectiveness) of products that can benefit patients and consumers, while supporting innovation and sustaining public confidence.

To help advance these goals, in early May, FDA formed a new Biotech Working Group. This Working Group is comprised of representatives from multiple FDA centers and offices. In the coming months, we’ll release an Action Plan that lays out the steps we intend to take to ensure that we have a flexible regulatory framework for evaluating the safety of products that also supports plant and animal biotechnology innovation.

Our actions will focus on three key areas:

First, advancing and protecting public and animal health by promoting innovation through an efficient and predictable science- and risk-based regulatory framework; second, strengthening public outreach and communication through strong, effective and transparent engagement with stakeholders; and third, increasing engagement with domestic and international partners through coordinated and collaborative actions to support regulatory alignment and efficiency.

The Working Group’s efforts are well underway and we’ll be providing more details soon.

Finally, we’ll continue the work we began to modernize the regulatory system for biotechnology, including the effort in 2015 with USDA and EPA to ensure preparedness of federal regulatory agencies for future products of biotechnology; as well as the implementation of the 2018 recommendations of the Interagency Task Force on Agriculture and Rural Prosperity. We’ll also continue to build on our Formal Agreement with the USDA, which commits the FDA and USDA to better align and enhance our efforts to develop regulatory approaches to biotechnology.

We’re committed to all of these goals, and we look forward to working with the Interagency Task Force and sharing more of our important work with our stakeholders going forward.

FDA is taking concrete and proactive steps to help ensure the safety of plant and animal biotechnology products, while promoting innovation and enhancing public and market confidence in FDA’s regulation of these products at home and abroad. We recognize the tremendous opportunities offered by this new technology. We’re committed to developing a framework that allows these innovations to safely advance, to fulfill the potential envisioned by those who are pioneering these approaches, and to inspire public confidence in these methods.

The advance of these technologies holds significant public health promise. Unlocking their full potential and competitiveness depends on the trust we build now and in the years to come.

Scott Gottlieb, M.D., is Commissioner of the U.S. Food and Drug Administration 

Anna Abram is FDA’s Deputy Commissioner for Policy, Planning, Legislation, and Analysis

Follow Commissioner Gottlieb on Twitter @SGottliebFDA

FDA Proposes Process Modernization to Support New Drug Development

By: Janet Woodcock, M.D.

The staff of the FDA’s Center for Drug Evaluation and Research (CDER) always tries to utilize cutting-edge science and up-to-date process management, befitting our stature as the global “gold standard” in drug regulation. Maintaining that standard requires us to keep up with evolving technology and the latest scientific, medical and regulatory advances. Current factors impacting drug development include the genomic revolution, the rise of targeted therapy, the availability of digital health data, the focus on patient involvement, complex drug-device combinations, globalization of drug development and harmonization of international standards. To be successful drug regulators, we reach well beyond the borders of the FDA. We collaborate with a wide variety of medical and scientific organizations such as those in biomedical research, the pharmaceutical industry, academia, global organizations and other regulatory agencies. Importantly, these collaborations also extend to patients and their caregivers and advocacy groups. All these interactions are critical to successful drug regulation.

Janet Woodcock

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

I have recently proposed changes to CDER’s new drug regulatory program. These changes are intended to free up resources so that our scientists and physicians have more time to focus on drug development, particularly for unmet medical needs, and on the multiple collaborations needed to make sure candidate drugs are developed and assessed properly, with appropriate input from external scientists, expert physicians and patient communities. The proposals include regulatory and review process changes, as well as organizational restructuring. We also intend to strengthen the support structures, including personnel and Information Technology (IT), that underpin the regulatory process.

As always, our goals are to expand access to safe and effective new drug therapies, conduct efficient and comprehensive safety surveillance, and ensure that accurate information about those drugs is available.

Here are some highlights of our proposal:

  • Recruiting the best and brightest individuals from many disciplines – Scientific leadership is vital for our ongoing success. After hiring talented scientists, we need to develop long-term career paths for them so they can become our next generation of seasoned leaders. Our recruitment efforts, strengthened by hiring incentives and other provisions in a new law called the 21st Century Cures Act, will help provide the staffing necessary for continued success in supporting the development and approval of innovative new therapies that meet previously unmet medical needs.
  • Enhancing our focus on multidisciplinary teams – Setting standards for approval and assessing innovative new drugs requires large and well-coordinated teams of highly trained professionals with many different types of expertise. CDER’s Office of New Drugs (OND) has a staff of more than 1,000 individuals who work together in many ways. New drug development and approval also requires coordination across many offices within CDER, including the Office of Translational Sciences (OTS), the Office of Surveillance and Epidemiology (OSE) and the Office of Pharmaceutical Quality (OPQ). A central component of our proposed changes involves stronger integration of our talented staff so they can better work together – within and across offices, a concept we refer to as “integrated assessment.” Previously, CDER reviewers would seek consults from specialists in other scientific disciplines (as issues were identified in the course of review). For greater collaboration, a cross-disciplinary team will be assigned to work on a new drug application at the outset.
  • Prioritizing operational excellence – Staff throughout CDER face a staggering pace of work, much of which involves attention to detailed administrative procedures. Our proposal would centralize project management functions within OND. CDER currently has 19 separate review divisions that regulate drugs. Over time, many divisions have developed procedures specific to their areas of review. We are proposing a single and consistent process: One organization with one process. Our aim is to enable our scientific and clinical experts to focus on what they know best – science and medicine – and our regulatory experts to manage the many processes we conduct.
  • Improving knowledge management – The information we process in our work is vast and diverse. Knowledge management is essential to control the data we receive from outside sources as well as what we generate from within the FDA. We plan to enhance our IT capabilities and access to information to better enable the storage and management of the collected experience of our scientific review staff. Accurate historic information from many past drug reviews is essential to informing current and future reviews – and to assure consistent regulatory decision-making. We want to make it easy for staff to find and use scientific and regulatory data, information and precedents. We’re also proposing changes that will increase the number of offices that oversee our review divisions from five to nine – and we’re envisioning 30 review divisions within those offices – up from our current 19. In addition to enabling greater efficiency, these envisioned changes will help us to better understand the diseases intended to be treated by the drugs we evaluate for approval – another way we aim to enhance our knowledge management.
  • Emphasizing the importance of safety across a drug’s lifecycle – Safety remains a key component of our new plans. We will work to establish a unified post-market safety surveillance framework to monitor the benefits and risks of drugs across their lifecycles, both before and after approval.
  •  Incorporating the patient voice – Patients are the FDA’s most important stakeholder and our vision includes incorporating the patient voice in modern patient-focused drug development. In fact, all the elements in our proposal have a common thread: they ultimately serve to improve health for patients.

Last year, CDER approved 46 novel drugs, 100% of which were reviewed on time – fulfilling our commitments under the Prescription Drug User Fee Act (PDUFA). Our system is effective, but we can always improve. Our new plan is designed to help us generate efficiencies so we can build stronger external collaboration capabilities and enhanced support for the scientific, clinical and technological innovation necessary for new drug therapies.

This proposal to modernize our new drug review processes will help us maintain and advance our global leadership, and better support our deeply committed staff. Both science and technology are changing at a blistering pace, and we need to keep up. Patients depend on the FDA to do what is necessary to provide access to safe and effective drug therapies. They take FDA-approved drugs because they trust us. While we have many steps to go before we can realize these changes, we feel confident that they will reinforce that trust and align us for ongoing success.

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

Statement from FDA Commissioner Scott Gottlieb, M.D., on proposed modernization of FDA’s drug review office