Good morning.  I am delighted to be with you today for this important meeting. 

The title of today’s symposium, “Innovations in a Changing World,” truly captures the essential dynamic that we face as medical scientists, researchers, and regulators in our work to get safe, effective, quality medical products to more patients. 

Not coincidentally, perhaps, it also typifies two key principles that we advance and balance in our work at the FDA -- supporting and speeding innovations that make medicines safer and more effective, while helping to ensure that the public has the accurate, science-based information it needs to use those medicines to improve their health.

This work is is meticulous and must be responsive to the dynamic nature of medical science. What that means is that we are constantly acquiring, reviewing, and evaluating new data and expanding the evidence on which we base our decisions to ensure those decisions are as comprehensive as possible and that Americans can be confident in the quality of the products the FDA approves.  It also means developing and embracing new technologies and regulatory tools that support innovation and the decisions that lead to the development and manufacture of new products. 

It is an approach that involves the entire drug lifecycle, from the earliest stages of product development to manufacture, distribution, and post-market safety.

Quality, Manufacturing, and Supply Chain

One of the most important tools in our arsenal for ensuring the safety, effectiveness, and quality of the products we regulate is our review, surveillance, and compliance efforts, including the inspections we conduct of manufacturers.

As drug manufacturing has globalized over the years, we have modernized our policies to ensure that every manufacturer of a drug, whether it is made in the U.S. or overseas, meets the FDA’s strict standards for producing medicines for U.S. patients and undergoes the same, rigorous application process, with the information carefully reviewed by our highly trained scientific staff.

The FDA’s global inspection efforts focus on higher risk facilities to prevent, uncover, and combat data integrity issues and manufacturing problems. We also monitor reports from industry, patients, and healthcare providers to identify and resolve potential quality problems.

During the COVID-19 pandemic, we have been forced to adjust some of our processes and guidance to maintain the appropriate level of review to fulfill our mission to protect public health. Thus, we ensure the safety of FDA regulated products, as well as protect the safety of our inspectors and the staff of firms subject to FDA inspection.

We employed a number of novel tools in support of this risk-based approach , including remote assessments and interactive evaluations, and import alerts.

For example, we have used our authority under section 704(a)(4) of the Food, Drug, and Cosmetic Act to request records in advance or in lieu of an inspection for drug and biological products. 

As a result, the FDA has been able to act on applications in a timely manner over 90 percent of the time across our User Fee programs.

I’m pleased to say that as of July, we began resuming normal operations for domestic inspections, what we call the “base case” scenario of our Resiliency Roadmap for FDA Inspectional Oversight. 

Even as we have begun this process, we also recognize that the actions we’ve taken and tools we’ve used to adapt can play an important role going forward in prioritizing risk-based deployment of our inspection resources, and we look forward to building on these. 

Regulatory Innovations

Inspections are not the Agency’s only area of innovation. Another program involves the development of quality management maturity, or QMM ratings.  What these do is help establish and maintain consistent, reliable, and robust business processes to achieve quality policies and objectives. To fully realize the FDA’s modern pharmaceutical quality vision requires a focus on continual process and system improvement, and a transparent method of evaluating, characterizing, and communicating the state of QMM for manufacturing sites.

The system we’ve developed has helped us understand which drug manufacturing sites go above and beyond the minimum practices required by CGMP regulations.  They also inform purchasers about the state of, and commitment to, quality management at the facility that makes the drugs they buy.

Currently, there are two QMM Pilot Programs, one for domestic sites for finished dosage forms (or FDF) manufacturers, and another for foreign sites for active pharmaceutical ingredients (or API) manufacturers.

The FDA also has formed a multidisciplinary, multi-center working group to facilitate the development of the QMM rating program for drug manufacturers.  The goal is to develop a framework to objectively assess and rate the QMM of manufacturing sites using facilitated assessments along with other surveillance intelligence related to the site.

Advanced Manufacturing

Yet another important way the FDA is working to provide a safer and more secure drug supply is through the development of, and investment and application in advanced manufacturing technology.

The FDA has long recognized the importance and potential of advanced manufacturing, which can be more cost-effective than traditional manufacturing technology and may enable the United States to play a larger role in pharmaceutical manufacturing. 

Advanced manufacturing can improve products and processes, advance drug quality, address shortages of medicines, and speed time-to-market. 

It is a key component of the broader U.S. strategy to strengthen domestic drug manufacturing and increase the domestic supply of quality medical products for consumers, thereby improving the global competitiveness of U.S. manufacturing.

When manufacturers are able to produce medications in newer, more expedient, and more flexible ways, patients suffering from a variety of diseases, including cystic fibrosis, HIV, breast cancer, leukemia, and asthma, can experience added benefits.

With congressional support, the FDA has invested in a number of advanced manufacturing-related projects, and we continue to work with manufacturers looking to implement these new technologies to benefit even more patients and foster growth.

Our Center for Drug Evaluation and Research (CDER) has established a variety of initiatives in this area, including the development of a research program to better understand the science of advanced manufacturing and support the FDA’s ability to approve quality, safe and effective drugs made by manufacturing technologies that ensure a seamless supply of these medicines.

To date, this program has supported nearly 60 research projects, including many collaborations with experts in the field. The knowledge gained has helped us provide guidance for applicants seeking to use new technologies.  These include continuous manufacturing, a technology that produces medicines in an integrated flowing process, as opposed to the traditional “batch” process that employs stops and starts between steps.

To help reduce barriers to entry for advanced manufacturing, CDER created the Emerging Technology (or ETP) program.  This is designed to provide a gateway for the early, pre-submission discussion of innovative technologies and approaches, even before a candidate drug is identified. The technology may be used at a facility that manufactures multiple products, meaning it potentially could have an impact for multiple drugs. 

Our Center for Biologics Evaluation and Research (CBER) established the Advanced Technologies Team (CATT) to offer pre-submission support for applicants looking to adopt advanced manufacturing technologies for the development of human drugs.

And our colleagues in the Office of Regulatory Affairs are focused on strengthening their advanced manufacturing training for field investigators through strategic personnel additions.

Recent data suggests these efforts are working. In 2015, the FDA approved the first regulatory submission for a human drug produced by continuous manufacturing and the first produced by 3D printing. We have now approved finished dosage forms, an active pharmaceutical ingredient, and biological molecules produced using advanced manufacturing technologies. . More than 80% of the drugs made using advanced manufacturing technologies are produced in the U.S.
 
We are confident this trend will continue. To date, the FDA has accepted more than 100 proposals spanning a wide range of innovative technologies and has sponsored more than 100 meetings.

In fact, the workload of the ETP has increased to the point that we are creating ETP 2.0 to meet workload challenges and enhance communication with companies that would like to adopt advanced manufacturing technologies in the future.

One last point on Advanced Manufacturing.  Since most pharmaceutical firms have a global operations footprint, the FDA is also collaborating with our international regulatory counterparts in this area. 

We are encouraging industry investment in advanced manufacturing methods through our leadership in the International Council on Harmonization (ICH) to harmonize global regulatory standards for continuous manufacturing.  And we are spearheading the new draft ICH Q13 guideline on Continuous Manufacturing of Drug Substances and Drug Products, which is now available for public comment. 

Science & Research

Clearly, it’s an exciting time with extraordinary opportunities.  

There’s one final point I want to make about our efforts to strengthen manufacturing and improve pharmaceutical quality.  And that is that all of these exciting regulatory tools and promising new technologies are buttressed by the core element of the FDA’s work – our focus on applying the best available science and most rigorous data to inform our decisions.

Let me close by offering an example of the impact strong science has on effective regulatory action. 

It involves Nitrosamines, an impurity in human drugs that may increase the risk of cancer if people are exposed to them above acceptable levels and over long periods of time.   Their presence has led us to recall certain drugs, schedule for-cause inspections of manufacturing sites, issue warning letters based on violative inspections, and place manufacturers on import alert based on violative findings. 

Before we took those actions, however, we needed to be able to detect the nitrosamines.  CDER scientists developed the means to do just through testing to detect for impurities. 

We then shared the methods with industry and international regulators, and developed recommendations for industry to conduct risk assessments for their drugs and make necessary manufacturing and supply chain changes to prevent or reduce the presence of nitrosamines, including in a published guidance for industry.

We also continue to work closely with our regulatory scientist partners around the world on intake limits for nitrosamines and to monitor safety signals for products that may include higher than accepted limits.

In short, science was our north star, guiding us in our development of regulatory tools and actions to help ensure that the medications that people take are safer and of higher quality. 

We will continue to remain vigilant in addressing potential issues in the global drug supply chain and using all of the technologies and regulatory tools at our disposal to do so.  In this way we can continue to ensure that Americans have confidence in the safety and quality of their medicines, and that we fulfill our mission to protect and promote the health of the public. 

Thank you.