FDA's Hamburg: Focus Remains On Innovation, Partnerships, And Quality

By Ed Miseta, Chief Editor, Clinical Leader

Margaret Hamburg, MD, commissioner, FDA

Margaret Hamburg is now four and a half years into her tenure as commissioner of the FDA. That makes her the second longest serving individual in that position. Four and a half years might not seem like a long time, but some agency changes under her rule are noteworthy. For one, the budget of the agency, during that timeframe, has grown from $2.7 billion to $4.2 billion. She casually shrugs off the achievement, joking that it takes a long time to learn how to do the job.

Hamburg's comments came at the 2013 FDA/CMS Summit held in Washington D.C. in December. Her keynote presentation, which ran just under 30 minutes, was noteworthy in that it gave insight into what she sees as the most significant accomplishments of the department, and where the focus will be going forward. Quality and innovation were themes that came up throughout.

Hamburg began her presentation by discussing advances in science and technology, which have not only had an impact on Big Pharma and FDA in the past, but will continue to impact the industry going forward. Noting important changes that have spurred human progress, she mentioned the Industrial age, jet age, and the age of computers before referring to the current age as one of the most remarkable and productive in human history for achievements in medical science.

"Life sciences research, advances in information technology, engineering, and other disciplines are coming together in extraordinary ways," she said. "More than at any other time, scientific innovation today offers us extraordinary potential to transform the prevention, diagnosis, and treatment of disease through targeted therapies. Advancements are happening so fast, that what might have been termed science fiction not long ago is now just plain old science."

Ticking off a list of significant advancements, Hamburg notes recent progress in regenerative medicine and stem cell therapy, the regeneration or replacement of a patients missing or damaged tissues, 3-D printing for the replacement of body parts, and advances in sequencing the human genome, which when combined with greater insights into diseases, is making it possible to develop new therapies tailored to the specific characteristics, needs, and preferences of individual patients.

"The treatment of diseases such as cancer is quite literally being transformed as the result of new drugs and new treatments," she says. "We are entering an era when next generation DNA sequencing technology offers the ability to identify the genetic mutations present in a patients' tumor. This information will enable physicians to choose the best therapeutic regimen for that individual and rule out drugs likely to be ineffective or to have side effects that would outweigh the benefits."

New Challenges And New Approaches

Hamburg notes FDA is enormously supportive of the new direction, stating the rapid pace of scientific advancement will require everyone in the industry to act in new ways. While spurring on innovation is important, so, she says, is protecting patient safety through smart, science-based regulation. Toward that end, the FDA is adapting and changing regulatory policies in response to, and in anticipation of, scientific opportunities.

Hamburg believes patients are already seeing the benefits of these advances, via recent drugs that have been approved by FDA. "Last week we gave the green light to Sovaldi (sofosbuvir), an oral drug that's the first to demonstrate safety and efficacy to treat certain types of hepatitis C virus infection without the need for co-administration of interferon and its known side effects," she says. "And last month the FDA approved Gazyva for previously untreated chronic lymphocytic leukemia. Also last month the FDA approved Imbruvica (ibrutinib) as a breakthrough therapy to treat patients with mantle cell lymphoma. Each of these drugs is a significant advance for patients and also represents examples of how new scientific insights are leading to exciting and important innovation in laboratories all across the nation."

Hamburg believes the approval of these new medicines demonstrate how FDA is pursuing new strategies to better support the industry in transforming scientific opportunities into products for patients. She notes FDA is working collaboratively with companies and other stakeholders to expedite the development, review, and availability of promising new drugs. The three previously mentioned drugs are also among the first to gain approval via the FDA's breakthrough therapy designation.

An increase in the rate of scientific development will also bring about new challenges for FDA. Keeping up with those challenges will be an enormous responsibility, but one that FDA takes seriously. "Our underlying responsibility remains the same: to ensure the safety and efficacy of drugs and other medical products," she states. "Ultimately, the review of each new product we approve and send to market is based on vigorous study, the evaluation of hard data, and the best available science. Regardless of the speed of the development or review, that product must demonstrate that its benefits outweigh its risks. We will not compromise our safety or efficacy standards in exchange for rapid approval and our responsibility for oversight extends after approval when the products are in the marketplace."

Regulation Leads To Innovation

Hamburg took some time to dismiss claims by some in the industry who believe regulation can have a detrimental effect on innovation. She believes regulation, when done right, is a key driver of innovation in both the laboratory and across society, noting it can support as well as shape more appropriate, streamlined, and time and cost effective development. She believes smart, science-based regulation will also instill in consumers a confidence in both products and treatments. Regulation can level the playing field for business and promote economic development, and can serve to decrease the threat of litigation, prevent recalls that threaten industry reputations and consumer trust, and spur industry excellence.

"In the area of personalized therapies, the FDA can play a particularly significant role as a driver of innovation," she notes. "Our efforts encourage the development of new tools to evaluate targeted therapeutics and promote greater collaboration in key areas of research. They define and streamline regulatory pathways and policies and apply new knowledge to product reviews. The addition of rigorous regulatory science from the FDA helps ensure the safety and effectiveness of innovative new products, sees that the scientific achievements quickly reach their full potential, and builds a pathway for continued innovation."

To be effective, however, the agency must continue to focus on partnerships. Increased collaboration, in Hamburg's opinion, will significantly further the advances being made and ultimately transform how the industry approaches research, clinical care, and patient engagement. She believes the entire industry needs to develop new ways to work with government, pharma, academia, the private sector, non-government organizations, philanthropic groups, and the public. Only by enhancing these collaborative ventures with everyone involved will the industry be able to overcome barriers to innovation while optimizing safety and benefits for patients.

"Nowhere is the need to expand the approach to developing new partnerships greater than in response to our growing challenges created by the expanded global marketplace," she says. "As you likely know, products used here at home are increasingly manufactured in whole or in part in other countries. Forty percent of all finished drugs used in this country are actually made elsewhere. Eighty percent of the active ingredients are made outside of the United States. As sourced materials are turned into finished goods, their ultimate distribution in the U.S. may follow an astonishingly complex supply chain. All of this clearly creates potential vulnerabilities in the U.S. drug supply and increased pressure on regulatory authorities to ensure the quality and safety of these products. How we respond on a domestic level and how we interact with other nations in a productive and forward leaning way will have an enormous impact on public health."

Different Agencies, Common Problems

In meeting with the heads of regulatory authorities from other countries, Hamburg notes the common challenges they all face include:

• Globalization
• Protecting the integrity of supply chains
• The increasing complexity of new drug products and drug development
• Keeping up with the fast pace of change in science and technology
• Greater demands for public accountability and transparency
• Budgetary and political challenges to regulatory oversight
• And maintaining quality in the face of other pressures

Focusing on the quality issue, Hamburg notes it has to be the backdrop for all other challenges. "Millions of people depend on thousands of products, and we need to continue to develop even more with improved outcomes," she says. "Without adequate attention to quality, none of us can feel completely comfortable that a product is either safe or effective. These concepts are inseparable. We are all too aware of how lapses in quality really matter, wherever and however they occur."

Pointing out how instances of product contamination have caused harm to individuals as well as put communities at risk, Hamburg tied these events to product recalls, shortages, and the reputation and trust of producers. She notes quality is one of the reasons the U.S. pharmaceutical industry is the standard against which the rest of the world is measured. While quality is the responsibility of individual companies, she states FDA clearly plays a major role, and has increasingly focused on the issue of quality through strengthening enforcement and inspections and supporting new developments and opportunities to build quality into the system.

"We are working to encourage advances in pharmaceutical manufacturing technology made over the last decade which offer significant opportunities to strengthen quality," she says. "Forms of continuous manufacturing, which includes chemical synthesis of active ingredients, offer the means to prevent shortages and ensure product quality can be precisely controlled. It allows for a range of strengths or doses of drugs to be prepared more easily, which has important implications for healthcare options and for the quality and quantity of available and critically needed drugs."

Congress Acts To Strengthen Oversight

Hamburg ended her presentation by touching on recent actions by Congress, and how they will affect the agency and the industry. She is pleased Congress was able to come together in a bi-partisan way to pass the Drug Quality and Security Act, which the president later signed into law.  

According to Hamburg, the track and trace component of the act will establish critical steps necessary to build an electronic interoperable system to identify and trace certain prescription drugs as they are distributed in the U.S. It will enhance FDAs ability to protect consumers from exposure to drugs that may be counterfeit, stolen, contaminated, or otherwise harmful, and will strengthen the ability of the agency to protect and remove potentially dangerous drugs from the supply chain.

The compounding component of the act, among other things, will provide a regulatory framework for entities that prepare compounded drugs and are registered with FDA as outsourcing facilities. "If a facility registers as an outsourcing facility, to qualify for the exemptions from certain requirements, such as new drug approval requirements, they must follow the requirements in the law that are applicable to outsourcing facilities," notes Hamburg. "In addition, outsourcing facilities are subject to current good manufacturing practice requirements and FDA will be conducting risk-based inspections of these facilities. This new level of FDA oversight engagement will make a difference with respect to these important and high risk products."   

Although the law is progress and makes significant steps forward, Hamburg notes it did not give the agency all of the new authorities she would have liked. She notes the law will complement the goals of the FDA Safety and Innovation Act (FDASIA) in important ways. While that law gave FDA additional authorities to secure the safety and integrity of drugs imported into the U.S., the agency now has further track and trace capabilities and is moving towards a system that will provide a more integrated system for assuring the integrity of drugs regardless of where they are made or how they move, both within and outside U.S. borders. "I'm hopeful that along with this recognition, Congress will also supply us with real resources that are equal to the challenge, not just mandates and authorities," she adds.

In response to a question regarding FDA guidance on social media, Hamburg noted it is moving forward and is a high priority, but would not commit to a specific release date.