Strong Review Performance Brings Innovative Medical Products to Patients

By: Margaret A. Hamburg, M.D.

There are many ways FDA supports biomedical innovation as part of our mission to protect and promote public health. We are committed to finding ways to ensure that safe and effective products can get to the people who need them as swiftly as possible. With that in mind, we were pleased with new data in two reports, one looking at FDA’s review performance for prescription drugs, the other for medical devices.

Margaret Hamburg, M.D.A study by the London-based Centre for Innovation in Regulatory Science (CIRS) looked at trends in the number of drug approvals and approval times by FDA and our regulatory counterparts in Europe and Japan for new active substances (NASs). These are similar to what FDA refers to as New Molecular Entities (NMEs). As the study authors said, approvals are often a measure of the pharmaceutical industry’s output and are, along with approval times, used as markers of the regulatory environment.

The study found very little difference between the agencies in approvals of new drugs in 2013: FDA approved 29, Japan approved 28, and Europe approved 30. According to the report, Europe experienced a significant increase in approvals compared to 2012, in part because it was “catching up” on a number of compounds that had been approved by FDA in previous years.

But where the agencies really differed was in drug approval times. FDA’s median approval time in 2013 was 304 days. In Japan it was 342 days, and in Europe it was 478 days. You can read more about our 2013 NME approvals in FDA’s Novel New Drugs Summary, which we blogged about in January 2014.

And it turns out that FDA was consistently faster than its regulatory counterparts over the time frame 2004-2013. In this period, the overall median approval time for new drugs in the United States was 304 days, compared to 459 days in Europe, and 487 days in Japan. Moreover, of the 21 new drugs approved by all three agencies during the latter part of that period – from 2009-2013 – 76% of those drugs were approved first by FDA.

Regulatory systems vary, and making these direct comparisons can be a challenge. Indeed, the CIRS report doesn’t discuss why FDA’s review times are faster than those of our regulatory counterparts. However, our review times certainly benefit from our innovative and flexible approach to drug development and approvals that includes such mechanisms as priority review, fast track designation, and accelerated approval. In the 2004-2013 timeframe, for example, the study pointed out that 44% of the NMEs received priority review from FDA, meaning that FDA’s goal is to take action on the submission within six months rather than 10 months under standard review.

And FDA’s accelerated approval pathway has helped bring innovative drugs to market for patients suffering from serious or life-threatening illness but who have limited treatment options. Such drugs include Sirturo (bedaquiline), to help patients with multi-drug resistant tuberculosis, and Ferriprox (deferiprone), to help patients with thalassemia (a genetic disorder causing anemia) to avoid iron overload from blood transfusions.

Our most recent approach to expedited drug review and approvals, the breakthrough therapy designation, went into effect in July 2012 with the enactment of the Food and Drug Administration Safety and Innovation Act (FDASIA) – so it isn’t well captured during the timeframe for this particular study. But the breakthrough designation is already helping to ensure that products that treat unmet needs get to patients as quickly as possible. Since July 2012, FDA has received 178 breakthrough designation submissions, granted 44 designations and already approved six of the designated drugs. Just last week we approved a late-stage lung cancer drug under the breakthrough designation – four months ahead of its goal date, using evidence from a trial with 163 patients.

I’m also happy to report new data for medical devices showing that FDA is on track towards meeting the review performance goals that were agreed to with industry and approved by Congress – under the Medical Device User Fee Amendments (MDUFA) of 2012, also part of FDASIA.

FDA committed to posting a quarterly performance report under the medical device user fee program. The latest report, issued in the last few days, covers performance reported through March 31, 2014. Review times, as measured in average total days for 510(k) submissions, have continued to decline since last year. With nearly all of the fiscal year (FY) 2012 submissions now closed, average review times have dropped from a high of 154 total days for submissions received in FY 2010 to 144 total days for FY 2012.   

FDA’s review times for higher risk devices that must go through the premarket approval (PMA) process are showing similar improvements. The same report we recently issued, for example, demonstrates the average time to decision for a PMA has been dropping, from a high of 464 days in FY 2009.

While we continue our efforts to reduce the time for the premarket review of medical devices, we’re also focused on reducing the time associated with product development. A few weeks ago we proposed a new program aimed at providing earlier access to certain medical devices that are intended to treat or diagnose patients with unmet needs for life threatening or irreversibly debilitating diseases or conditions.

The Expedited Access Premarket Approval Application for Unmet Medical Needs for Life Threatening or Irreversibly Debilitating Diseases or Conditions (“Expedited Access PMA” or “EAP”) program features earlier and more interactive engagement with FDA staff. This includes the involvement of senior management and a collaboratively developed plan for collecting the scientific and clinical data to support approval. These features, taken together, should provide patients with earlier access to safe and effective medical devices.

In addition to the Expedited Access PMA Program, the FDA published a separate draft guidance that outlines the agency’s current policy on when data otherwise collected prior to approval can be collected after product approval. To ensure that a device is safe and effective and to provide timely patient access to important devices, it’s critical to get the right balance between pre-market and post-market data collection.

While FDA is always striving to improve in the area of medical product review performance, I’m pleased to be able to report on the progress we’re making. The FDA of the 21st Century, through the creation of new pathways, designations and programs for drug products and medical devices, is actively encouraging innovation and speeding the availability of promising medical products to patients who need them.

Margaret A. Hamburg, M.D., is Commissioner of the Food and Drug Administration

FDA Goes 3-D

By Steven K. Pollack, Ph.D., and James Coburn, M.S.

Dr. Steven Pollack (left) holds a 3D-printed RoboHand, a prosthetic for children with amnionic banding syndrome, an illness that can prevent fingers from developing in children. Research engineer James Coburn (right) uses the 3-D printer (background) in his work in the FDA lab.

Dr. Steven Pollack (left) holds a 3D-printed RoboHand, a prosthetic for children with amnionic banding syndrome, an illness that can prevent fingers from developing in children. Research engineer James Coburn (right) uses the 3-D printer (background) in his work in the FDA lab.

This Snap-Together RoboHand Prosthetic, sized for a small child, was created at FDA with a 3-D printer.

The Snap-Together RoboHand prosthetic was invented by South African carpenter Richard van As and made available for free on the Internet. Before printing, the hand can be individually sized, and all connecting pieces are also printed. The device can now be printed for less than $100.

A hospital in Michigan implants a 3-D printed medical device into a 3-month-old boy with a rare bronchial condition and saves a young life.

A man has 75 percent of his skull replaced with a 3-D printed implant.

3-D printing—the process of making a three-dimensional solid object of virtually any shape from a digital model—is making headlines these days, and the technology, once considered the wave of the future, is rapidly becoming part of the present.

It’s spurring innovation in manufacturing, dramatically reducing the time required to design new products and allowing designs to be built that were not possible before.

Here at FDA, we’re using it to expand our research efforts and expand our capabilities to review innovative medical products. In fact, 3-D printing is fast becoming a focus in our practice of regulatory science—that is, the science of developing new tools, standards and approaches to assess the safety, effectiveness, quality and performance of FDA-regulated products.

With 3-D printing, the conversion from a virtual computer model to a physical object can occur almost in real time. The printer translates virtual models into digital cross-sections for use as a blueprint for printing, laying down successive layers in different shapes.

FDA Research Engineer James Coburn operates a RapMan kit 3D printer.

James Coburn adjusts the tension on the feed mechanism for the ABS plastic filament that is the raw material for the RapMan kit 3D printer.

Two laboratories in the FDA’s Office of Science and Engineering Laboratories (OSEL) are investigating how the technology may affect the manufacturing of medical devices in the future.

At our Functional Performance and Device Use Laboratory we’ve developed and adapted computer-modeling methods to help us determine the effect of design changes on the safety and performance of devices when used in different patient populations. The 3-D technology enables us to tweak the design in ways large and small, and to see precisely how those tweaks will change both fit and functionality. In an era of increasingly personalized medicine, which involves the development of treatments that are tailored to an individual patient or a group that shares certain characteristics, including anatomical features, it helps us to fine-tune our evaluation of patient-fitted products.

At our Laboratory for Solid Mechanics we’re investigating how different printing techniques and processes affect the strength and durability of the materials used in medical devices. What we’re discovering will be valuable to our reviews of devices down the road; it will help us to develop standards and set parameters for scale, materials, and other critical aspects that contribute to product safety and innovation.

In August 2012, President Obama launched the National Additive Manufacturing Innovation Institute (NAMII), a national effort bringing together industry, universities and the federal government to provide innovation infrastructure to support new technologies and products created with additive manufacturing, the formal term for 3-D printing.

FDA has a long history of researching and regulating innovative technological practices. Regulators regularly review some of the newest technologies coming onto the market and, through our research, FDA has first-hand knowledge of these advanced techniques so we can evaluate advanced technology at an early stage—a crucial step in facilitating innovation and protecting the public health. We will continue to facilitate device innovation and keep on the cutting edge of technology and regulatory science to help ensure that the products we regulate are safe and effective.

To see more photos of how FDA is using 3-D printing technology, visit our Flickr photostream.

Steven K. Pollack, Ph.D. is Director of FDA’s Office of Science and Engineering Laboratories (OSEL) at FDA’s Center for Devices and Radiological Health. James Coburn, M.S. is a Research Engineer in OSEL.