Remarks by Commissioner Califf to the 2024 FDA Regulatory Education for Industry Annual Conference (REdI) May 29, 2024

Speech | Mixed

• Speech by: Robert M. Califf, M.D., MACC

(Remarks as prepared for delivery)

I am delighted to once again help kick off this important conference. Its focus -- innovation in medical product development -- is at the core of the FDA’s mission.  One of our primary goals to support innovation and scientific advances that can be translated into viable, safe, and effective medical products that make a meaningful difference for patients and their families.  

At the outset, I should point out that the FDA’s support of innovation is not limited to medical products, but also involves the many other areas in which we have oversight, including food safety, nutrition, cosmetics, dietary supplements and tobacco regulation, to name several of our more prominent responsibilities.  

For the next few days, however, you will be focused on medical products and some of the many ways we are working across the entire agency to support you and your innovation efforts.    The companies represented at this conference are a key focus of the support and guidance we provide to businesses, especially smaller businesses involved in the development of new medical products in the areas we regulate. 

As you know, we have three different Centers whose work encompasses these issues -- our Center for Drug Evaluation and Research (CDER), our Center for Devices and Radiological Health (CDRH), and our Center for Biologics Evaluation and Research (CBER) -- as well as many other offices across the agency who play a role.  You’ll have the chance to hear and exchange information from representatives of all three Centers during this conference.   In fact, during the next session you’ll have the opportunity to participate in a discussion with all three directors of our medical product Centers.

That conversation will reinforce the fact that while each Center has specific responsibilities, their work also overlaps.  This collaborative, cross cutting approach is central to the FDA’s success and is based in our agency’s underlying commitment to biomedical science, clinical research and inquiry with a focus on research, data collection, and analysis that forms the evidence to support decision making. Moreover, as developers like you embrace the latest scientific and technological advances, our capabilities to support your work and engage with you as appropriate only grows. 

This morning, I want to give you just a flavor of some of the initiatives we’ve undertaken to support the work you do and advance medical product innovation. Throughout the meeting you’ll have the opportunity to discuss in greater detail many of these and other programs and supports available to you.

CDER 

Let’s start with a topic near and dear to my heart, clinical trials and some of the work CDER has been doing in this area. Over the years, CDER has championed clinical trial innovation with programs such as Model-Informed Drug Development (MIDD), Complex Innovative Trial Design (CID), Drug Development Tools Qualifications, and other initiatives.  Each of these efforts has enhanced the design and conduct of clinical trials intended to generate evidence of safety and effectiveness of therapies to meet the growing demands of drug development.  

I’m excited to announce that last month CDER launched its new Center for Clinical Trial Innovation (or C3TI).  Using targeted projects, the C3TI Demonstration Program will explore scalable improvements in the adoption of select clinical trial innovations, expand opportunities for sponsors of innovative clinical trials to engage with CDER staff, and enhance the existing body of knowledge and precedents for clinical trial innovations to improve the efficiency and effectiveness of drug development.  There are several sessions during the meeting focusing on clinical trials, so you’ll be able to explore this topic in greater depth.

CDER is not alone in its work in this area. For instance, it is collaborating on a new pilot program initiated by CBER to accelerate the development of new treatments for rare diseases, particularly the rare genetic disorders that affect children and result in severe disability or death in the first decade of life. In addition to working together on this effort, called Support for Clinical Trials Advancing Rare Disease Therapeutics (or START), both Centers also continue to participate together in the ongoing Rare Disease Endpoint Advancement Pilot Program.

One of the topics that will be included in C3TI is artificial intelligence and machine learning.  But this is just one of the ways we are incorporating AI, which is one of the most exciting and promising areas of science, into our work across the agency.  I know many of you are also beginning to find application for this technology, and we look forward to supporting those efforts. 

The FDA and each of our Centers has been working for years to anticipate and prepare for the challenges of AI, and to harness its potential to enable major advances in the development of more effective and less risky medical products. 

Consider, for example, since 1995 the FDA has received over 300 submissions for drugs and biological products with AI components, and more than 800 submissions for AI-enabled devices.  These submissions have included drug discovery and repurposing, enhancing clinical trial design elements, dose optimization, endpoint and biomarker assessment, and postmarket surveillance. They also cover a growing diversity of medical devices that leverage AI to improve clinical workflows and patient experiences or outcomes in addition to sophisticated prediction algorithms. 

We’ve issued several helpful papers on our work and role in this area.  The first of these, “Artificial Intelligence & Medical Products: How CBER, CDER, CDRH, and OCP are Working Together,” outlines and reaffirms our commitment to promoting the responsible and ethical development, deployment, use, and maintenance of safe and effective medical products that incorporate or are developed with AI, as well as prioritizing collaboration, consistency, and mutual learning.  Another discussion paper, ”Using Artificial Intelligence & Machine Learning in the Development of Drug & Biological Products,” seeks to foster dialogue with interested parties in the medical products development community on using AI/ML in drug and biological product development, and the development of medical devices to use with these treatments. 

As the AI landscape continues to expand and evolve, we will continue to develop new ways to use this technology.  I know there are several sessions of this conference that focus on this exciting area.  

I also want to mention the drug development tool qualification program developed by CDER and CBER, which provides a route to qualify novel drug development tools (or DDTs) for use in drug development programs.  Examples of innovative DDTs accepted into the biomarker qualification program include AI and ML-based readings of liver histopathology slides in NASH/MASH (also known as non-alcoholic steatohepatitis/metabolic dysfunction-associated steatohepatitis); and an AI/ML-based multi-component biomarker to assess risk of cardiovascular outcomes.

CBER

Although I’ve already mentioned CBER’s work several times (an indication of just how closely our Centers work together), let me offer a few other exciting CBER-focused developments in the Center’s continuing efforts to help develop and review innovative therapeutic products. 

In 2023, CBER approved 23 biologics device applications, 20 original biologics license applications and 17 biologics license application supplements.   There were many highlights, including two new gene therapy treatments.  One is the first product using a new type of genome editing technology for the treatment of severe sickle cell disease, and a second indicated for the treatment of children with different forms of a rare disorder called metachromatic leukodystrophy (MLD), which affects the brain and the peripheral nervous system. 
CBER is also considering ways to leverage data related to platform technologies for cell and gene therapies to further promote development of treatments for patients with rare diseases. This includes and complements the ongoing collaboration with the Bespoke Gene Therapy Consortium.  

And CBER also continues to support global harmonization efforts related to the evaluation and regulation of cell and gene therapy products to help facilitate more efficient clinical development for these and other product categories. The international collaboration of regulators and the clinical community of medicine is extremely important and has spurred many important developments, including another new pilot program—the Collaboration on Gene Therapies (CoGenT) Global Pilot.

In 2023, CBER published numerous draft and final guidance documents for developers on topics including blood and blood components, tissues, vaccines, and cellular and gene therapy.  For example, to further promote incorporation of gene editing technology into new treatments available to patients, CBER published the guidance for industry, Human Gene Therapy Products Incorporating Human Genome Editing earlier this year. 

CBER also has continued to strengthen its patient engagement efforts to help facilitate the development of medical products that make the biggest differences in patients’ lives. In 2023, CBER participated in 35 patient-focused drug development meetings and patient listening sessions, in addition to four CBER-led or co-led public meetings with patient groups.

CDRH

Let me now turn to CDRH, our Center that is responsible for assuring that medical devices on the U.S. market are high-quality, safe and effective, and that works to facilitate timely patient access to these technologies, while advancing medical device innovation.  

Last year, CDRH gave marketing authorization to 124 novel devices (excluding EUAs) – the highest on record in the Center’s history.  It’s worth noting that one of the most important factors in CDRH’s continuing evolution has been the importance of medical device user fees, which provide critical resources to support program improvements including new hiring targets, greater engagement with developers of innovative technologies based on lessons learned from the pandemic, broadened international harmonization efforts, and expanded opportunities to ensure patient perspectives are an integral part of medical device development and evaluation. 

One essential component of the most recent MDUFA agreement is The Total Product Lifecycle Advisory Program (TAP) Pilot, a voluntary program intended to help innovators avoid pitfalls in early product development and help ensure a clear, predictable path to market from development to bedside, TAP will provide industry participants with earlier and more frequent interactions with CDRH, more strategic input from stakeholders, and proactive, strategic advice from CDRH to spur more rapid development of high-quality, safe, effective, and innovative medical devices first in the world that are critical to public health. You’ll be hearing in much greater detail about TAP from CDRH director Jeff Shuren a little later in the program.

Before I close, I want to mention a few other important CDRH-related developments. The first is last month’s final rule on LDTs or Laboratory Developed Tests. As this audience understands, LDTs are today used more widely than ever before – in everything from newborn screenings, to helping predict a person’s risk of cancer, or aiding in diagnosing heart disease and Alzheimer’s.  

But even as 70% of today’s medical decisions depend on laboratory test results, some of these tests perform poorly or don’t work at all. As a result, patients may initiate unnecessary treatment, or delay or forego proper treatment altogether, which could result in harm. I am particularly concerned right now about the ”diagnostic oddysey“ experienced by patients with rare disease as they often go to multiple medical centers before the diagnosis is made.  The FDA’s oversight and enforcement of the requirements for LDTs dates to a time when tests were generally simple, often made to address local individual needs, and mostly manufactured in small volumes and often in a single lab. In contrast, today’s LDTs can be far more complex and offered nationally. Hence, our decision to craft a new rule to ensure the safety and effectiveness of LDTs today. 

After seeking extensive public comments, we announced a final rule in April that will better protect the public health.  The final rule amends the FDA’s regulations to make explicit that in vitro diagnostic products (IVDs) are devices the FDA&C Act, including when the manufacturer of the IVD is a laboratory.  The rule also describes a policy under which we will increase our oversight of LDTs through phasing out the agency’s general enforcement discretion approach for LDTs.

The second recent CDRH initiative I wanted to call to your attention is the Home as a Health Care Hub, which is designed to help reimagine the home environment as an integral part of the health care system, with the goal of advancing health equity for all people in the U.S. 

In today’s world, home care is an essential aspect of health care.  But very few care options consider the structural and critical elements of the home that will be required to absorb this transference of care, and devices for home use may be designed to operate in isolation, rather than as part of an integrated environment. CDRH is collaborating with patient groups, clinicians and  provider organizations, the medical device industry, and housing design experts to build the Home as a Health Care Hub. Once this concept is established, it will provide a systematic approach to enable people to get the care they need, when they need it. Stay tuned as this exciting initiative takes shape.

As I hope this brief outline of recent developments has made clear, support for innovation in medical products is at the heart of what the FDA does.  And I hope you will take the time during the conference to connect with our outstanding FDA staff and leadership on these and other initiatives. Working together, we can truly achieve the best possible outcomes for patients.  

I want to add one final note in closing, which goes to a related responsibility of the FDA – how we communicate trustworthy scientific information to industry and the public.  As we know, misinformation is being used today to undermine public confidence in science generally, and biomedical science in particular, and to subvert the credibility of our agency’s work. 

So, as we focus on your efforts to innovate, I want to underscore just how important it is that we – and you – get it right.  We are committed to doing our best to produce reliable scientific work, to communicate facts and evidence, and to the use of the most scrupulous and sophisticated scientific methods and tools to achieve this result.  This communication challenge includes the daunting responsibility to communicate uncertainty while also maintaining the public trust.  In so doing, we will increase the likelihood that the public and developers will trust and rely upon the FDA’s decisions in support of innovation in medical products. 

Thank you again for your commitment to this process and for your participation here.