Life Science Compliance Update

294 posts categorized "FDA"

April 21, 2015

FDA Acting Commissioner Ostroff Addresses the "State of the FDA"


The 2015 FDLI Annual Conference kicked off yesterday in Washington, DC. The conference hosted a variety of impressive speakers from the Food and Drug Administration, as well as FDA lawyers and in-house counsel. Dr. Stephen Ostroff, the Acting Commissioner at FDA, spoke as the conference's keynote speaker. After congratulating previous Commissioner Margaret Hamburg on an impressive tenure as FDA Commissioner, Ostroff ran through a long list of recent FDA accomplishments--"hitting the highlights," as he called it. Following Ostroff's address, a panel of industry experts provided a "to do list" for the agency for the coming year.

State of the FDA

First, Ostroff acknowledged the "extraordinary number of new approvals," by FDA in 2014, which included 51 new molecular entities and biological products--41 from CDER and 10 from CBER. Ostroff was especially impressed with the broad scope and significance of the products. Indeed, last year saw numerous revolutionary treatments for cancer, Hepatitis C, Type 2 Diabetes, as well as a meningococcal vaccine. Seventeen of these new treatments were “first in class,” and almost two-thirds were approved in the U.S. before receiving approval abroad.  Ostroff noted that many of these new products targeted specific characteristics of patients, exemplifying President Obama’s State of the Union call for “precision medicine.”

Second, Ostroff discussed FDA's approval of products to treat serious disease or that address unmet needs. “We have effectively employed expedited review programs including priority review, fast track, accelerated approval, and the much touted breakthrough therapy designation,” he stated. “Fully two-thirds of the new drugs approved last year took advantage of at least one of these programs.” The breakthrough therapy program has been surprisingly popular--FDA received 246 requests for breakthrough designation and granted 71, Ostroff noted.

Ostroff next spoke to FDA's Expanded Access program. Earlier this year, FDA streamlined the application procedures for expanded access, and last week, the Center for Devices and Radiological Health (CDRH) launched a similar expedited access program for devices.

The fourth area Ostroff listed was the agency’s reaction to the 2012 fungal meningitis outbreak concerning oversight of compounding pharmacies. Congress enacted the Drug Quality and Security Act in 2013.  “Since then, we have made great progress in implementing the provisions of DQSA,” stated Ostroff, who noted that the agency has issued three final guidances, ten draft guidances, and one proposed rule. FDA has also conducted over 140 inspections of compounders, issuing approximately 40 warning letters, and are working with the Department of Justice on civil and criminal enforcement actions, according to Ostroff.

Fifth, Ostroff stated that FDA has been focusing on more diverse clinical trial participants. They recently issued a guidance document on the “Evaluation of Sex-Specific Data in Medical Device Clinical Studies,” and are working “to promote clinical trial participation by women and minorities.” They have also posted Drug Snapshots about the age, race, and sex of participants in clinical studies of new drugs,” stated Ostroff.

Ostroff next addressed the first biosimilar approval—what he called a "game changer." In reference to Zarzio, a biosimilar to Neupogen, Ostroff noted: “Although this is the first, there will certainly be more to come, even as we work to educate the public and providers about this new category of products.”

Seventh, Ostroff spoke about antimicrobial resistance. President Obama’s National Strategy on Combating Antibiotic Resistant Bacteria, also known as the CARB, is intended to “ensure that the miracle drugs developed over the last 80 years will remain available and effective for future generations,” Ostroff stated. Last year FDA approved four novel antibiotics for several categories of infections. “As a comparison, just five new antibiotics had been approved in the previous ten years,” said Ostroff.

Opioid abuse was another highly publicized subject the FDA has worked to mitigate. “Interest in producing abuse-deterrent formulations has risen dramatically,” stated Ostroff. FDA has already received around 30 investigational new drug applications from manufacturers seeking to conduct clinical trials on potential abuse-deterrent formulations. “Recent steps taken by FDA include approval of an auto-injector form of naloxone to treat overdoses, which took the agency a mere 15 weeks from application to approval. Just recently, the agency issued final guidance on development of abuse-deterrent opioid formulations,” Ostroff stated.

Ninth--and finally on the drug and device side--Ostroff noted that FDA played a “critical, although somewhat unsung, role in the response” to Ebola, he stated, “involving more than 200 people across the agency, including several dozen deployed FDA commissioned officers to provide care in Liberia.”

Ostroff also noted accomplishments on the food and tobacco side, including the Food Safety Modernization Act. 

“We live in an era of unprecedented innovation in pharmaceuticals, diagnostics, medical devices, and food and nutrition science,” stated Ostroff.  “This innovation offers unprecedented opportunities to advance and improve public health.” He concluded: “It is essential that we at FDA keep pace with these changes, especially the evolving science that underpins them, in order to fulfill our regulatory responsibilities effectively and efficiently.”

FDA To Do List

Ostroff was followed by a group of experts who offered their predictions—or hopefuls—for FDA’s keynote at next year’s 2016 FDLI Conference.

Geoff Levitt, Senior VP & Associate General Counsel, Regulatory & Policy, at Pfizer applauded FDA on a successful 2014. In terms of future priorities for the agency, he responded that FDA must “acknowledge that there has been a paradigm shift in the information environment for medical products.” There are two key trends, Levitt states. One is the fact that control of information about the safety, efficacy, and value of medical products has moved away from FDA and sponsors toward academia, media, and payors. Second, Levitt noted that FDA should acknowledge broader and more diverse categories of data beyond the traditional adequate and well-controlled definition to include real world data and meta-analysis, for example. Levitt suggests that FDA continue to participate even more actively in setting quality standards to ensure that data from these sources is as reliable and comparable as possible. Levitt also calls for FDA to update the rules on communication to allow sponsors—who are uniquely restricted—to contribute their distinct knowledge on their own products.

Levitt also discussed FDA’s first biosimilar approval. He noted that FDA’s initial draft guidance stated that biosimilar labeling should include all information necessary for healthcare professionals to make fully informed decisions, including a clear statement that the product is an approved biosimilar and other pertinent clinical data for that product. He stated that the most recent approval did not include this information and, without arguing for any particular side, called for FDA to put forth reasoned decision-making through a transparent review process. FDA has promised guidance on biosimilar labeling this year. 

Sheila Hemeon-Heyer, President at Heyer Regulatory Solutions, LLC, spoke to the importance of streamlining the path to market for low risk devices. She noted that while the premarket approval pathway is appropriate for high-risk products, the vast majority of devices are very low risk and in many cases are handled with a “heavy stick,” where the FDA-required testing “far exceeds the risk of the product." 

Hemeon-Heyer also argued that the 510(k) process is “outliving its tenure.” It is increasingly difficult to demonstrate substantial equivalence, she states, for the “98-99 percent of all medical devices” that are low risk. In today's innovative environment, products can be low risk, but utilize technology for which there is no predicate. To avoid the onerous de novo process, however, companies in such a case may have to artificially find a substantially equivalent product on which to base their 510(k) application. Hemeon-Heyer concluded that products should be regulated based on their risk level, not necessarily on finding a predicate, and that changing this regulatory process would put the U.S. in line with the rest of the world.

Marta Villarraga, PhD, Principal in Exponent’s Biomechanics practice, spoke to the importance of a public and private partnership to promote bringing safer, cost effective devices to market. She specifically referenced the Medical Device Innovation Consortium (MDIC), which seeks to “coordinate the development of methods, tools, and resources used in managing the total product life cycle of a medical device to improve patient access to cutting-edge medical technology.” 

It will be interesting to follow FDA’s activity throughout 2015, and to see what trends make their way into the 2016 keynote presentation.  


April 13, 2015

FDA Finalizes Two Guidances To Speed Approvals For Innovative Medical Devices; Expedited Access Program Starts April 15

CME E-Learn

The Food and Drug Administration last week finalized two guidances intended to speed the process of getting innovative medical devices to patients in need. The Agency discussed its guidances in an article entitled “Providing Timely Patient Access To High-Quality, Safe and Effective Medical Devices.”

“We know that patients with life-threatening or irreversibly debilitating conditions lack treatment and diagnostic options,” states Jeffrey Shuren, M.D., J.D., Director of FDA’s Center for Devices and Radiological Health. “For these patients, earlier access to promising new devices is critically important, and [a]t the same time, delayed access may mean the difference between life and death, or may result in irreversible disability.”

“In weighing the benefits and risks of new technologies for these patients, we understand the need to place greater weight on the benefit of earlier access, and to also account for the risks of delayed access,” Shuren states.

To this end,  FDA has developed the Expedited Access Program (EAP), a voluntary program for certain medical devices “that demonstrate the potential to address unmet medical needs for life threatening or irreversibly debilitating diseases or conditions that are subject to premarket approval applications (PMA) or are eligible for de novo requests,” states FDA. The EAP relies on similar policy to the FDA’s accelerated approval program for pharmaceuticals, designed to fast-track breakthrough drug therapies.

Devices subject to premarket approval applications (PMAs) or requests for de novo designation are eligible for EAP designation if the following three criteria are met:

The device is intended to treat or diagnose a life-threatening or irreversibly debilitating disease or condition



The device meets at least one of the following:

(1) No appropriate alternative treatment or means of diagnosis exists.

(2) The device represents a breakthrough technology that provides a clinically meaningful advantage over existing legally marketed technology.

(3) The device offers significant, clinically meaningful advantages over existing legally marketed alternatives.

(4) The availability of the device is in the best interest of patients.

The sponsor submits an acceptable draft Data Development Plan.


Once an eligible device sponsor chooses to go down the EAP path, the FDA works with the sponsor to try to reduce the time and cost from development to marketing without changing the FDA's PMA approval standard of reasonable assurance of safety and effectiveness, the standards for granting de novo requests, or the agency’s standard of valid scientific evidence.

Components of the program include priority review, more interactive review, senior management involvement, and assignment of a case manager.  The extent to which the FDA provides these features depends on the availability of resources.

"Starting April 15th, this program will be up and running and we will begin to accept requests for EAP designation," states Shuren. 

Another important aspect of this program is FDA's interest in shifting some of the premarket data responsibilities to the postmarket setting, when appropriate. "If, after careful analysis, FDA determines that some data can be collected after the device is on the market, then patients in need will benefit sooner," states Shuren. "A few of the factors that can enter into this analysis include a low probability of serious harm, a high likelihood that postmarket surveillance can quickly identify instances of serious patient harm and a high likelihood that postmarket data collection will be completed in a timely manner."

"We consider this balancing of premarket and postmarket data collection to be so important that we made it one of our three 2014-2015 strategic priorities, along with strengthening the clinical trial enterprise and providing excellent customer service," Shuren concludes.


Released April 8, 2015, FDA's first guidance explains the the Agency's Expanded Access Program at length. The second goes into more detail about when FDA will shift premarket data collection to postmarket in certain cases. "Getting the right balance between premarket and postmarket data collection – specifically, where appropriate, a greater reliance on postmarket collection, including real-world data collection, can reduce the extent of premarket data collection and directly impact when patients will have access to high-quality, safe and effective medical devices," states the guidance. "But, greater reliance on postmarket data collection could undermine patient safety if the necessary and timely data collection does not occur." FDA wrangles with this issue in the guidance. 

  • Expedited Access for Premarket Approval and De Novo Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions (available here)
  • Balancing Premarket Postmarket Data Collection for Devices Subject to Premarket Approval (available here)


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