On January 19, 2017, the United States Food and Drug Administration (“FDA”) unveiled a new drug designation process for regenerative advanced therapies, an important first step toward implementation of the regenerative medicine provisions of the 21st Century Cures Act.  Products for which a designation as a regenerative advanced therapy (“RAT”) is obtained are eligible for accelerated approval under the 21st Century Cures Act, which was signed into law by former President Obama on December 13, 2016 with sweeping bipartisan support.

The accelerated approval provisions for RATs under the 21st Century Cures Act are intended to facilitate expedited review and approval of stem cell therapies and other cellular and tissue products for use in serious or life threatening diseases, which are currently subject to regulation as unapproved drugs. Under the 21st Century Cures Act, regenerative medicine therapies eligible for a RAT designation may include any “cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, except for those products regulated solely under Section 361 of the Public Health Service Act (“PHS”), and part 1271 of Title 21, Code of Federal regulations.”[1]

Under the 21st Century Cures Act, the sponsor of a product must show the following to be eligible for a RAT designation:

  • The drug is a regenerative medicine therapy;
  • The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition;[2] and
  • Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition.

Pursuant to the FDA website on the Regenerative Advanced Therapy Designation, a sponsor requesting a RAT designation for its product must make such a request either concurrently with submission of an Investigational New Drug application (“IND”), or as an amendment to an existing IND. Consistent with requests for fast track and breakthrough therapy designations, the FDA only requires that a sponsor describe the preliminary clinical evidence that supports a RAT designation, and does not require the sponsor to submit primary data.  Information that will be considered includes: a description of any available therapies for the disease or condition already in existence, the study design, the population studied, the endpoints used, and a description of the study results and statistical analyses.

The RAT designation process will be overseen by the newly created Office of Tissues and Advanced Therapies (OTAT). The OTAT will manage the application process for RAT designation, and will notify the sponsor within 60 days of receiving an application as to whether the RAT designation is granted. If a sponsor does not receive a RAT designation for its product the OTAT will provide an explanation in writing of its rationale for the denial.

A sponsor that obtains a RAT designation for its product is entitled to meet with the FDA early in its development program to discuss the potential use of surrogate or intermediate endpoints that may be used to support accelerated approval of the product. RATs may be eligible for accelerated approval based upon surrogate or intermediate endpoints reasonably likely to predict a long-term clinical benefit, and based on data obtained from a “meaningful number of sites” with subsequent expansion to additional sites, along with the collection of additional data in the post-market phase.

The implementation of the RAT designation process will enable manufacturers to begin to take advantage of the less burdensome review process enabled by the 21st Century Cures Act.  While some patient advocates have expressed concern that the availability of an accelerated approval pathway for regenerative medicine products may impede the development of robust evidence establishing their safety and effectiveness, and may ultimately result in patient harm, 21st Century Cures’ accelerated approval provisions are likely to be a harbinger of a new wave of regenerative medicine therapies that provide additional options for patients facing serious or life threatening conditions.


[1] 21st Century Cures Act Sec., Sec. 3033(8).  Human Cells, tissues, and cellular and tissue-based products (HCT/Ps) are regulated solely under section 361 of the PHS Act and the regulations of 21 C.F.R. Part 1271 if all of the following criteria are met: the HCT/P is minimally manipulated, intended for homologous use (as reflected in labeling and advertising), is not manufactured by combining cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving or storage agent, and does not have a systemic effect nor is dependent upon the metabolic activity of living cells for its primary function. Therefore, if a product meets all of the aforementioned criteria, the HCT/P will still be regulated under 21 C.F.R. Part 1271 and will not be subject to regulation as a drug product.

[2] The FDA will use its standard definitions found in its Expedited Program Guidance as a guide to determining whether a product meets the required criteria, such as whether a condition is “serious or life-threatening” or whether a drug is “intended to treat a serious disease or condition.”

Our colleagues Joshua A. Stein and Frank C. Morris, Jr., at Epstein Becker Green have a post on the Health Employment And Labor blog that will be of interest to many of our readers: “The U.S. Access-Board Releases Long-Awaited Final Accessible Medical Diagnostic Equipment Standards.”

Following is an excerpt:

As part of a flurry of activity in the final days of the Obama Administration, the U.S. the Architectural and Transportation Barriers Compliance Board (the “Access Board”) has finally announced the release of its Accessibility Standards for Medical Diagnostic Equipment (the “MDE Standards”).  Published in the Federal Register on Monday, January 9, 2017, the MDE Standards are a set of design criteria intended to provide individuals with disabilities access to medical diagnostic equipment such as examination tables and chairs (including those used for dental or optical exams), weight scales, radiological equipment, mammography equipment and other equipment used by health professionals for diagnostic purposes. …

Read the full post here.

Recent federal and state legislative efforts signal an increased focus on a significant and largely underappreciated public health threat – antimicrobial resistance (i.e., when a microorganism (such as a bacteria or virus) is able to resist the effects of medications such as antibiotics and antivirals, causing such medications to be ineffective). The results of a 2014 study underscore the magnitude of the threat of so-called “superbugs,” estimating that the number of deaths worldwide attributable to antimicrobial resistance will reach 10 million by 2050.  By comparison, the same study projected 8.2 million deaths from cancer, and 1.2 million deaths from traffic accidents by 2050.  Legislative efforts to address antimicrobial resistance span from encouraging development of new pathways to market for antimicrobial drugs to expanding data collection and monitoring efforts to better understand the scope of the problem.  The combination of new data and less-restrictive pathways to market simultaneously provide pharmaceutical companies with a faster entry into the market for antimicrobial drugs and a better understanding by local health departments and hospitals of the need for new drugs to combat resistant strains of microorganisms.

Federal Initiatives

On the federal side, the 21st Century Cures Act (the “Act”), signed into law by President Obama on December 13, 2016, includes several measures related to antimicrobial resistance.  For example, the Act creates a new approval pathway for “limited population drugs,” which are antibacterial or antifungal drugs “intended to treat a serious or life-threatening infection in a limited population of patients with unmet needs.” While the Act allows FDA to approve limited population drugs with less data than typically would be required, the approval is restricted to “the intended limited population,” and the manufacturer must meet additional labeling requirements to inform physicians of the drug’s limited approved use.  In addition, manufacturers of drugs approved through this pathway are required to submit any promotional materials to FDA at least 30 days before they plan to use them.

While adding specific labeling requirements for new drugs approved for limited populations, the Act also changes labeling requirements for susceptibility test interpretive criteria. Susceptibility test interpretive criteria includes the myriad of testing options used to determine whether a patient is infected with a specific microorganism or class of microorganism that can effectively be treated by a drug.  The Act requires pharmaceutical manufacturers to replace the currently existing susceptibility test interpretive criteria from the drug’s packaged insert or labeling with a reference to a FDA website to be built where such criteria for all drugs will be held.  Manufacturers have one year from the day the website is established to move its susceptibility test interpretive criteria to the so-called “Interpretive Criteria Website.”

The Act also increases monitoring and reporting of antimicrobial drug use and antimicrobial resistance at federal healthcare facilities, like VA hospitals and facilities run through the Indian Health Service or the Department of Defense. Further, it requires annual federal data reporting on aggregate national and regional trends related to antimicrobial resistance. A broad base of reliable data on antimicrobial resistance and the associated morbidity and mortality does not currently exist. However, along with the federal government, certain states are also making efforts to improve data collection in this space.

State Initiatives

Many states receive funding from the Centers for Disease Control (CDC) to collect data about patients with extremely resistant strains of microoganisms, like carbapenem-resistant Enterobacteriacea, or “CRE” – a bacteria that kills an estimated 600 Americans each year. The Illinois Department of Health, for example, developed a registry in 2014 that tracks positive lab tests for extremely drug-resistant organisms, including CRE.  Illinois began tracking this information following a deadly outbreak of CRE in 2013.  Health care facilities participating in the registry receive alerts when an infected patient is transferred in and must report CRE-positive culture results of patients within seven calendar days.  The most recent annual report shows a 7% increase in overall cases; however, a recent article posits that the increase may be somewhat attributable to better reporting efforts by hospitals gaining experience identifying CRE.  Similar programs exist in many states, but these programs typically do not track the outcomes of CRE cases.

A recently proposed bill in California (California Senate Bill 43) would require hospitals to include information within death certificates that identifies whether “any antimicrobial-resistant infection…was a factor in the death.”  Specifically, the bill would require the “attending physician [who] is legally obligated to file a certificate of death” to determine whether, in the physician’s professional judgment, an antimicrobial-resistant infection was a factor in the patient’s death.  State law already mandates tracking of over 80 communicable diseases, like HIV and Hepatitis (A-E), but only tracks antibiotic-resistant infections of VRE and MRSA if they are contracted while a patient is already in the hospital.

Given the magnitude of the potential threat, it is reassuring that legislative initiatives are showing an increased focus on antimicrobial resistance. New pathways to market for antimicrobial drugs and increased public awareness of the rising threat of “superbugs” should lead to additional innovation by drug manufacturers.  The limited population pathway may also cause some manufacturers to reassess their pipelines and strategies to market drugs toward limited populations.  For manufacturers facing expensive and burdensome FDA requirements to market new antimicrobials to a general population, the limited population pathway may provide a cheaper and faster entry into the market.  Early entry into the market can then fund additional efforts expand the label beyond a limited population.

By Stuart M. Gerson

The three days of arguments about the constitutionality of the Patient Protection and Affordable Care Act are complete. The Justices of the Supreme Court of the United States have conducted their post-argument conference and are now turning their attention to the drafting and the discussions that will lead to a majority opinion and, likely, several dissents and concurrences. The Court’s decision should be issued before the end of June. Health care companies and employers, like the rest of the population, await the ultimate decision. However, there are several matters that can be identified in the short run.

Read the full alert here

Now that we have sweeping new health care legislation, the Patient Protection and Affordable Care Act ("the Act"), let’s look at the rollout of the accountable care provisions–i.e., those changes to the payment and delivery system that hold the most long-term promise of improving quality and cost-efficiency. They are discussed in my most recent article: "The Timeline for Accountable Care: The Rollout of the Payment and Delivery Reform Provisions in the Patient Protection and Affordable Care Act and the Implications for Accountable Care Organizations," published last week in the BNA’s Health Law Reporter.  Click here to read the full article (PDF).


Barack Obama signed an executive order on April 8, 2009 to formally lay infrastructure in the executive branch to facilitate health care reform activities. The executive order officially creates the White House Office of Reform (the “Health Reform Office”) and lays out its principle functions, including coordination across executive departments and agencies, outreach activities with state and local policymakers, and working with Congress for the purpose of enacting and implementing health care reform. As we reported on March 6, 2009, Nancy Ann DeParle was selected to be the Director of the Health Reform Office. The order grants DeParle the discretion to work with “established or ad hoc” committees, task forces, or interagency groups. It remains to be seen how DeParle will use this authority to promote the goal of the Obama Administration to have an open, inclusive and transparent process for health care reform.

The order also creates the HHS Office of Reform “to coordinate closely” with the White House office. InsideHealthPolicy reports that Jeanne Lambrew is the lead candidate to head the HHS office. Lambrew originally was tapped as the deputy director of the White House office when Tom Daschle was nominated for HHS Secretary and selected for the Health Reform Office in December 11, 2008. Prior to joining the Obama Administration, Lambrew was an associate professor of public affairs at the Lyndon B. Johnson School of Public Affairs at the University of Texas at Austin where she specialized in health care policy.

In yesterday’s post on The Health Care Blog, Bill Kramer remarks upon a key difference in the health reform discourse this go-round. Simply put, “the Obama Administration is changing the debate in a fundamental way.” As President Obama stated in his opening remarks to last week’s White House Forum on Health Reform, “[h]ealthcare reform is no longer just a moral imperative, it is a fiscal imperative.”

Kramer explains that past attempts at reform suffered from political sticker shock over concerns that health reform would dramatically enlarge the federal deficit. However, this time, the Obama Administration is emphasizing that reform will not pose an additional burden to the already laden deficit. Indeed, health reform is a necessary tool to “tame” the deficit over the long term.

And framing health reform as an economic necessity is already having an effect. As Nancy-Ann DeParle, director of the White House Office for Health Reform, pointed out in her Wednesday op-ed in The Boston Globe: there are no defenders of the status quo. Two happenings from yesterday, both involving key stakeholders, echo this sentiment:

Regional White House Forum on Health Reform – Dearborn Michigan
Underscoring the link between long-term economic prosperity and health reform, the White House chose Michigan, the state with the highest unemployment rate in the nation, as the site for the first of five Regional White House Forum on Health Reform. In his announcement of the Regional White House Forum series, President Obama called on participants of these forums to “put forward their best ideas about how we bring down costs and expand coverage for American families."

Among the 250 attendees were doctors, patients, insurers, policy experts and health care advocates. The forum was hosted by Governors Jennifer Granholm of Michigan and Jim Doyle of Wisconsin. Notable politicos in attendance included Congressmen John Dingell and John Conyers, Jr., as well as White House Domestic Policy Director Melody Barnes, who helped to moderate the event. Reports of the town hall-style event indicate that “guests in the room uniformly supported broad and sweeping reform focused on expanding access to the uninsured, improving medical records and emphasizing preventative care.”

The remaining four regional forums will take place in Burlington, VT (March 17th), Des Moines, IA (March 23rd), Greensboro, NC (March 31st), and Los Angeles, CA (April 6th).

Business Roundtable urges lawmakers to act quickly on health reform
Yesterday heard from another key stakeholder group, Business Roundtable. The association released a study showing that American companies were losing out to other countries with cheaper healthcare and healthier workers. As reported by Reuters, Business Roundtable “wants changes that would reduce costs through greater use of technology and other efficiencies and require everyone to obtain health coverage. The group also supports plans to provide government aid to help those who cannot afford insurance, but said they do not want to see a government insurance plan that dominates the market.”

Members of the Business Roundtable also heard from President Obama yesterday on the critical need for health reform. A transcript of the President’s speech is posted on the Wall Street Journal’s Washington Wire blog.

If yesterdays goings-on are any indication, Kramer and DeParle are right: the landscape has changed and the health form battle will be fought on different grounds. Everyone is in favor of change. The devil, of course, will be in the details.

Thursday’s White House Forum on Health Reform brought together people who have a stake in our health care system with people who have the ability to change it. Prior to his inauguration, President Obama called on Americans to hold community discussions about health care. More than 9,000 Americans signed up to host discussions in all 50 states and more than 30,000 Americans attended these discussions. These community groups submitted reports to the White House that detailed their concerns about the health care system and their suggestions for reform. At the Forum, several of these community participants joined health care experts to participate in the Forum discussions.

Did these community representatives have any meaningful impact on Thursday’s discussion? Let’s hope so – engaging members of our nation’s communities adds a necessary human element to these debates as they begin to take shape and hopefully will demonstrate to those who can effect change that every ordinary person must be involved in this important national discussion. The President expressed his desire see change by the end of this year. We should harness the energy generated by yesterday’s discussions to promote actions that result in health reform efforts and engage all Americans – all "stakeholders" – in these efforts. 

On Tuesday, President Obama announced Kansas Governor Kathleen Sebelius as his nominee for Secretary of Health and Human Services. She is known for her bipartisan approach to politics and her efforts as a governor in the health care arena. If confirmed, Governor Sebelius has a once in a lifetime opportunity to execute health care reform – a President enjoying positive public opinion, a national sense of urgency, and resources to get the job done.

The President also announced his choice for Director of the White House Office of Health Reform, Nancy-Ann DeParle, a former Administrator of HCFA (now CMS) during the Clinton administration who also has extensive experience in the private health care sector. Although this private sector experience has prompted criticism from some, Ms. DeParle’s appointment has drawn praise from both sides of the aisle because, despite her career-long identification with Democrats, DeParle has credibility with Republicans as well. Ms. DeParle is comfortably familiar with Washington and, drawing upon her previous White House, HCFA and Hill experiences, should be able to integrate herself within the White House policy operation easily while also serving as a powerful ally to Governor Sebelius. When it comes to crafting a health reform plan and then actually enacting it, Ms. DeParle’s role is likely to be unique and pivotal.

The President’s choices of Governor Sebelius and Ms. DeParle reflect a commitment to change that is likely to move us forward in our health reform efforts!