Naming and Biological Products

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

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

Janet Woodcock

Janet Woodcock, M.D.

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

So today we are releasing a draft guidance that details the FDA’s proposal on the nonproprietary naming of biological products.

Our draft guidance proposes that reference products and biosimilars have nonproprietary names (also called proper names) that share a core drug substance name and, in order to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

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

The proposed naming convention seeks to address two main issues:

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

Karen Midthun, M.D.

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

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

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

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

For more information: www.fda.gov/biosimilars

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

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

FDA, From a Distance

By: Claudia Heppner, Ph.D.

It is a great honor for me, as a European, to be working for FDA. I am one of the two Locally Employed Staff (Foreign Service nationals) currently working in FDA’s Europe Office in Brussels, Belgium.

Claudia HeppnerI came to this position after serving for 12 years in the European Food Safety Authority (EFSA), which is the European Union (EU) institution that provides independent scientific advice on existing and emerging food safety issues.

Before joining EFSA, I worked with the Secretariat of the EU’s Scientific Committee on Food. I’ve also worked for a multinational company in Belgium and the United Kingdom in the areas of pesticides product discovery and product development, including genetically-engineered plants.

With seven months at FDA under my belt, I enjoy and receive a great deal of satisfaction from my challenging new duties. Together with my colleagues, I am analyzing the range of science and policy issues under discussion in the EU’s decision-making framework. These EU issues span the breadth of FDA-regulated products and may sound familiar to some: updating and streamlining the food safety system; rapid access to innovative medicines; biotech, nanotech, novel foods, mobile and e-health; and, implementation of new legislation on tobacco and electronic cigarettes.

The EU has a complex environment for decision making, involving the “three pillars” (the European Commission, the European Parliament, and the Council of the EU) along with EU organizations that are counterparts to FDA such as the European Medicines Agency, EFSA, and various EU scientific committees.

In addition, each EU Member State (countries that are members of the EU) has its own national law-making bodies and regulatory organizations.

Only the European Commission can propose an EU law. The preparatory steps include: concept papers; a roadmap describing the timeline and significant events; impact assessments examining potential economic, social and environmental consequences; and public consultations.

I quickly learned that the European system is quite different from the legislative process and the notice-and-comment rule making system in the United States. In the Europe Office, we look at each step along the way in the EU decision-making process as a potential opportunity for strategic engagement.

Recently, I wrote a paper that analyzed what the EU is doing to strengthen food regulatory systems in Africa, China, and India. I was struck by the possibilities of what could be achieved through FDA and EU cooperation to help assure the safety of foods shipped to the United States and Europe and to improve public health around the world.

I feel fortunate to be working at FDA and to have the opportunity to broaden my professional horizons. I enjoy the dual focus on science and policy, working on medical product issues as well as foods issues, and observing how a non-EU organization like FDA works.

I look forward to continued learning and to the possibility of contributing to both the U.S. public health and – through FDA’s engagement with the EU – the EU public health.

Claudia Heppner, Ph.D., is a Senior Policy Analyst in FDA’s Europe Office

Find out more about FDA’s Europe Office

Kicking off the PDUFA VI Reauthorization Process

By: Theresa M. Mullin, Ph.D.

The Prescription Drug User Fee Act (PDUFA) authorizes FDA to collect fees from pharmaceutical companies to help fund the agency’s drug review work. PDUFA’s intent is to provide additional funding for FDA to hire staff, improve systems, and establish a better-managed review process that enables us to do more timely reviews of human drug applications.

Theresa MullinAs a result, many important new drug therapies have been made available to patients sooner without compromising FDA’s high standards for safety, efficacy, and quality.

As part of FDA’s agreement with industry during each reauthorization of the Act, the agency agrees to certain performance goals to enhance the process of drug review. The goals, now 30 in total, apply to many review processes, including the review of original new drug applications, resubmissions, and supplemental applications. Since the first user fee law was passed in 1992, PDUFA has been reauthorized four times. The current legislation, PDUFA V, is set to expire in September 2017.

On July 15, 2015, FDA gathered stakeholder perspectives during a meeting on what features the agency should propose in the reauthorization of PDUFA for fiscal years 2018 – 2022. Attendees included patient advocates, consumer advocates, representatives of professional health care associations, biopharmaceutical industry representatives, academic researchers, policy analysts, and others. FDA received mostly positive feedback on our progress under PDUFA V and helpful input about the future for PDUFA VI.

Highlights of progress noted during this meeting include:

  • FDA continues to meet or exceed most review goals.
  • The program is experiencing high rates of approvals for novel products during their first submission. This includes a historically high number of approvals for novel products treating rare diseases (17 orphan drug approvals in 2014).
  • There are improved and increased communication functions and practices between FDA and new drug companies, or sponsors. This includes implementation of a structured risk-benefit framework within the review process.
  • The Patient-Focused Drug Development program has been successful in systematically obtaining patient perspectives on certain diseases and related treatments.

Meeting participants also contributed a number of ideas for further enhancements, including:

  • Further efforts to involve the patient perspective in drug development processes;
  • Building on FDA’s Sentinel System for active surveillance of safety issues for medical products, including expanding its use as a source of data; and
  • Enhancing regulatory science initiatives, including the use of patient-reported outcomes and biomarkers.

More detailed information about the meeting is available at PDUFA Meetings, which includes a webcast of the one-day meeting, the agenda, access to the docket for online public comments, and (soon to follow) a complete written transcript of the public meeting’s proceedings.

PDUFA was designed to enable FDA to fulfill its mission to protect and promote public health by helping to more effectively bring to market critical new medicines for patients. FDA is strongly committed to the components, enhancements, and initiatives that constitute this program and have made it so successful. The public feedback received during the July 2015 meeting indicates that we are on the right track in achieving our goals under PDUFA V, and FDA looks forward to PDUFA VI.

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

Frances Oldham Kelsey, Ph.D., M.D.: A Pioneer in Public Health and Protection of Patients

By: Stephen M. Ostroff, M.D.

Acting FDA Commissioner, Stephen Ostroff, M.D.

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

Last week our nation lost a true pioneer in public health and consumer protection.

Frances Oldham Kelsey, Ph.D., M.D., who joined FDA in 1960 as a medical officer, was known worldwide as a leader in drug safety and the protection of patients. She established that reputation in one of first FDA assignments: reviewing the marketing application for a drug called thalidomide, which was already available in dozens of countries around the world.

Despite constant pressure from the company, Dr. Kelsey refused to approve thalidomide because of inadequate evidence about its safety. As a result of Dr. Kelsey’s expertise, diligence, and integrity, the drug was never approved in the United States and Americans were largely spared the tragic birth defects and deaths experienced by patients in those countries where thalidomide was available.

This “near miss” spurred Congress and the White House to revive pending proposals to revitalize the oversight and regulation of pharmaceutical products. In the wake of the thalidomide episode, the Kefauver-Harris Drug Amendments became law in 1962. That law mandates “substantial evidence” of a drug’s effectiveness (in addition to evidence of safety that was previously required) and today continues to provide this road map for how unapproved pharmaceutical products are tested in humans.

Dr. Kelsey

Frances Oldham Kelsey, Ph.D., M.D.

It is fair to state that these amendments, as implemented by FDA, ushered in the modern era of science-based proof that the medicines we use are both safe and effective, a level of evidence that created a standard still in effect today.

Dr. Kelsey’s original work on the thalidomide application stands today as a legendary example of how FDA carries out its public health mission: judicious exercise of authority and oversight to protect consumers and patients.

Dr. Kelsey joined FDA during a different era and was a trailblazer in many ways, including the role of women in science. And yet, although this is a new era, our mission endures: to promote innovation while protecting the health and welfare of Americans. And FDA continues to be defined by the same rigor, dedication, and integrity that informed Dr. Kelsey’s work.

Our nation owes a great debt of gratitude to Dr. Frances Oldham Kelsey for her decades of service to public health.

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

More information about Dr. Kelsey’s life and career is available in her “Autobiographical Reflections,” which FDA released on the occasion of her 100th birthday in 2014.

Need a Guidance Document? We’ve Got You Covered

By: Chris Mulieri, PMP

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

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

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

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

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

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

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

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

How are we doing?

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

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

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

Advancing precision medicine by enabling a collaborative informatics community

By: Taha A. Kass-Hout, M.D., M.S., and David Litwack, Ph.D.

FDA plays an integral role in President Obama’s Precision Medicine Initiative, which foresees the day when an individual’s medical care will be tailored in part based on their unique characteristics and genetic make-up. Yet while more than 80 million genetic variants have been found in the human genome, we don’t understand the role that most of these variants play in health or disease. Achieving the President’s vision requires working collaboratively to ensure the accuracy of genetic tests in detecting and interpreting genetic variants. We are working towards that goal by developing an informatics community and supporting platform we call precisionFDA.

Taha Kass-Hout

Taha A. Kass-Hout, M.D., M.S., FDA’s Chief Health Informatics Officer and Director of FDA’s Office of Health Informatics.

Sophisticated, relatively inexpensive technology known as next generation sequencing (NGS) already exists to sequence a person’s genome quickly. Developers and users of NGS tests must then comb these sequences to look for segments that suggest potentially meaningful differences and determine whether those differences provide useful and actionable information about the state of a person’s health, and their future risk of disease, behavior, or treatment choices.

Special features of this technology pose novel regulatory issues for FDA. Most diagnostic tests follow a one test-one disease paradigm that readily fits FDA’s current device review approaches for evaluating a test’s accuracy and clinical interpretation. Because NGS tests may be used in many ways in the clinic and can produce an unprecedented amount of data about a patient, we are working to evaluate whether a better option might simply be requiring each NGS test developer to show that the test meets certain standards for quality. Similarly, to demonstrate a test’s clinical value, we are assessing whether it may be more efficient for developers to refer to evidence in well-curated, validated, and shared databases of mutations instead of independently generating data to support a mutation-disease association.

David Litwack

David Litwack, Ph.D., Policy Advisor, Office of In Vitro Diagnostics and Radiological Health, at FDA’s Center for Devices and Radiological Health.

To begin to realize this new vision, precisionFDA is designed as a crowd-sourced, cloud-based platform to advance the science needed to develop the necessary standards. PrecisionFDA will supply an environment where the community can test, pilot, and validate new approaches. For example, NGS test developers, researchers, and other members of the community can share and cross-validate their tests or results against crowd-sourced reference material in precisionFDA.

Planned for beta release (work in progress) in December 2015, precisionFDA will offer community members access to secure and independent work areas where, at their discretion, their software code or data can either be kept private, or shared with the owner’s choice of collaborators, FDA, or the public. Initially, precisionFDA’s public space will offer a wiki and a set of open source or open access reference genomic data models and analysis tools developed and vetted by standards bodies, such as the National Institute of Standards and Technology (e.g., Genome in a Bottle). We believe precisionFDA will help us advance the science around the accuracy and reproducibility of NGS-based tests, and in doing so, will advance consumer safety. We look forward to continuing to update the community on the development of these new tools.

Taha A. Kass-Hout, M.D., M.S., is FDA’s Chief Health Informatics Officer and Director of FDA’s Office of Health Informatics.

David Litwack, Ph.D., is Policy Advisor, Office of In Vitro Diagnostics and Radiological Health, at FDA’s Center for Devices and Radiological Health.