1. health and fitness

InsideHealthPolicy.com’s
FDA Week
an exclusive weekly report on Food and Drug Administration policy, regulation and enforcement
Vol. 21, No. 3 — January 23, 2015
Upton Calls On Obama To Support Upcoming 21st Century Cures Bill
House Energy and Commerce Committee chair Fred Upton (R-MI) called on President Barack Obama ahead of
Tuesday’s (Jan. 20) State Of The Union address to come out in support of the panel’s bipartisan 21st Century Cures
Initiative. Upton and Rep. Diana DeGette (D-CO) plan to release a discussion draft of the legislation in the coming days
and outlined a broad framework for the measure in a CNN op-ed last week. Up to now administration officials have
expressed support for the initiative’s overall goal of spurring innovation but have warned against inclusion of proposals
to dramatically overhaul current clinical trial policies.
continued on page 4
Stakeholders: Obama’s Precision Medicine Effort To Complement ‘Cures’
President Barack Obama’s newly announced Precision Medicine Initiative would double funding for antibiotic
development while continuing investment in Alzheimer’s and brain research, and while the details remain scant the
personalized medicine initiative is viewed by key stakeholders as complementary to the House Energy and Commerce
panel’s emerging 21st Century Cures Initiative. One stakeholder says the initiative may have roots in a bipartisan bill that
Obama sponsored while senator.
Obama described the initiative during his State of the Union Address Tuesday night (Jan. 20), and a White House
continued on page 7
SCOTUS’ Pass On Generic Labeling Case Puts FDA Rule In Spotlight
The Supreme Court’s decision this week not to take up a lower court’s ruling that a generic drug company should
have immediately updated its product label to include new safety data puts the spotlight back on FDA, which is already
facing intense pressure from generic drug makers not to finalize a proposed rule that would impose similar labeling
requirements. Generic drug makers last year urged lawmakers to intervene and also signaled they would sue if FDA
moved forward with the rule, which has been hung up in the administrative review process and was recently delayed on
FDA’s regulatory agenda.
continued on page 10
Court: FDA Can Review Data Not Referenced By 505(b)(2) Applicants
A federal judge, in a D.C. Circuit Court memorandum opinion unsealed Tuesday (Jan. 20), ruled that the HatchWaxman Act gives drug makers the right to choose which listed drugs they reference in 505(b)(2) applications but that
FDA can look at data on similar drugs without requiring the applicants to reference relevant patents for those drugs.
One industry attorney says U.S. District Court Judge Ketanji Brown Jackson’s lengthy opinion is a well-reasoned “must
read” for Hatch-Waxman practitioners and says the judge’s opinion on FDA looking at other data will “raise eyebrows,”
particularly of brand drug makers, but the issues are far from decided as the case heads to appeal.
continued on page 12
FDA Invites Device Manufacturers To Join International MDSAP Pilot
FDA this week invited device and in-vitro diagnostic makers to begin participating in a voluntary Medical Device
Single Audit Program (MDSAP) pilot that lets them rely on a single audit by an authorized auditing organization to
satisfy requirements of regulatory authorities in the United States, Canada, Brazil and Australia in lieu of individual
inspections by each individual jurisdiction. The agency said that MDSAP pilot audits will substitute for biannual FDA
routine inspections and manufacturers, but cannot be used for pre-approval or post-approval inspections necessary for
premarket approval applications or for compliance follow-ups. As an incentive to participate, FDA will provide a longer
continued on next page
time frame for companies to respond to problems found during an MDSAP pilot audit — 30 days as opposed to the 15
business days for an FDA audit.
Regulatory agencies in Japan are expected to join the pilot program, which runs through December 2016, this
summer, the agency said.
Device manufacturer lobbying group Advanced Medical Technology Association (AdvaMed) said it supports the
MDSAP in theory and will monitor the pilot to see how the policy works in practice.
“Under this pilot, manufacturers that market medical devices and in vitro diagnostics in Australia, Brazil, Canada,
and the US can volunteer to be inspected by a MDSAP-recognized third-party organization. Medical device regulators in
the participating countries will be able to use these inspection reports when making their regulatory decisions. This will
decrease the number of regulatory audits manufacturers have to host, thereby minimizing manufacturing plant and
personnel disruptions,” FDA said in an announcement to manufacturers Tuesday (Jan. 20).
FDA said any medical device manufacturer can participate in the pilot by simply contacting a participating auditing
organization directly to see if the regulatory agencies have authorized the auditor to perform MDSAP audits. Manufacturers do not need to give prior notification to the regulatory authorities to or receive authorization from those agencies to
take part in the pilot, FDA said.
All auditing organizations recognized the Canadian Medical Device Conformity Assessment System, which are listed
on FDA’s website, have been invited to apply to take part in the pilot. Once authorized as MDSAP auditors the organizations will use a standard template to conduct audits. Some MDSAP audits will be “witnessed” by officials from the
regulatory agencies, but these officials will only be monitoring how the auditing organization conducts the audit and will
not be conducting a concurrent audit.
Auditing organizations will share their outcomes with the regulatory agencies and upon successful completion of a
certification or recertification audit will issue an MDSAP certification showing compliance with the MDSAP criteria.
FDA said it plans to have an internet portal regulatory agencies and participants in the MDSAP program can
use to share information once the program is fully operational in 2017. Last year the agency said it is courting the
World Health Organization, which is an official observer of the program, to help fund and maintain the portal. At
the time an FDA official said if the portal, which is expected to cost several million dollars, isn’t ready in 2017 the
regulatory agencies, auditing organizations and manufacturers could use an encrypted email system to share information.
The agency said MDSAP pilot audits will take the place of biannual FDA routine inspections, but not those for
necessary pre-approval and post approval inspections nor inspections conducted “For Cause” and “Compliance Followup.”
In a statement to FDA Week, AdvaMed said it supports the goals of the MDSAP program to bring international
regulations in line with each other and lower regulatory red tape.
“AdvaMed supports the goals of the MDSAP program and is in favor of mechanisms to harmonize regulations
internationally and reduce regulatory burdens. While FDA has been working for some time on the MDSAP pilot, which
has the potential to reduce the number of redundant regulatory audits of manufacturing facilities, we will be monitoring
its implementation closely to see how it works in practice,” the organization said. — Todd Allen Wilson
Rep. Chaffetz Reintroduces Drug Combination Incentives Bill
Rep. Jason Chaffetz (R-UT) reintroduced legislation Tuesday (Jan. 20) that would incentivize drug manufacturers to
create new combination of drugs by offering them five years of market exclusivity, the same exclusivity granted to a
single drug product containing a new active ingredient. Combinations that have a new drug alongside an approved drug
would receive three years of exclusivity.
At the time of its original introduction a year-and-a-half ago, the bill came on the heels of three citizen petitions
requesting FDA to modify its interpretation of the Hatch-Waxman Act to give combinations containing novel and approved existing drugs five years of exclusivity, instead of three years, which has been the standard for years.
“This may well be the first time ever that the research-based and generic pharmaceutical companies have joined on
an issue involving market exclusivity,” said Chaffetz in a statement. “The bill extends to new combination drugs containing molecules already approved by the FDA the same five-year market exclusivity as a drug product containing an
entirely new active ingredient.”
The bill was originally introduced in August 2013 but died in the House Energy and Commerce Committee. But
Chaffetz, now chairman of the powerful House Committee on Oversight and Government Reform, could use his new
clout to persuade lawmakers to reconsider the bill.
Kurt Karst, an attorney at Hyman Phelps McNamara, said that the bill’s most likely vehicle is the 21st Century Cures
Initiative legislation to be unveiled by the Energy and Commerce Committee.
“This legislation is intended to allow companies to develop new medicines that are not financially or economically
feasible under existing law,” Chaffetz said. — David Hood
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Pew Maintains Drive To Incorporate UDIs Into Electronic Health Records
As a proposed rule to revise electronic health records is under review at the White House, Pew Charitable Trusts and
nine other health organizations urged the Office of the National Coordinator to re-include a provision from an earlier
proposal that would modify EHRs to include an optional field for unique device identifiers, laying out their request in a
letter sent Tuesday (Jan. 20) to FDA, ONC, CMS and HHS. The UDI provision was in last year’s proposed EHR rule but
was ultimately nixed by the office before the rule was finalized in September.
FDA commissioned the Brookings Institution to write a report on how UDIs should be integrated across the entire
health care system. A major portion of the report outlined why adding a UDI field to EHRs should be a priority, and FDA
officials have said the agency will “push on all fronts” to get full implementation. Since FDA only has jurisdiction over
medical devices and not health records, the agency could only force device manufacturers to apply the device labeling
rule.
With its letter, Pew intends to get out in front of the proposed EHR rule which is set to be released at the beginning
of this year. The group hopes that once UDI information is available in patients’ health records, it can be merged with the
massive database of medical devices FDA has set up, which went live this month and will be populated starting Jan. 26.
with Class III devices. That will allow patients and healthcare workers to access data on their devices and watch for
recalls or other adverse events in near-real time. In addition, Pew argues, clinical decision-making would be enhanced
and the data could provide better analysis on how each product is working or how it is being used.
“I think the Brookings report and a lot of other stakeholder groups have really called out the importance of
ensuring that the UDI is utilized by the health care system in areas such as the electronic health records, claims
forms, in a variety of different ways,” Josh Rising, director of Healthcare Programs at Pew, told FDA Week. “It’s important for FDA to be working with other agencies and HHS as a whole to really look at this issue and understand public
health and use this new tool.”
Pew outlines four other capabilities that it says EHR certification criteria should support. The first is automatic
identification and data capture (AIDC) capabilities like bar coding. Pew argues that since a UDI could be several dozen
characters long, there is a high probability that the lack of AIDC capabilities would deter providers from manually
entering UDI data into EHRs and the possibility of incorrectly entering information. The second capability is that the
certification criteria should “allow providers to generate a list of patients with a particular device, thus aiding hospitals
with recalls and letting facilities perform analyses of device outcomes.” The third is to support merged data from external
databases to allow physicians to make more informed clinical decisions. Fourth, the letter says, EHRs should automatically notify clinicians if a device has any risks.
The second part of the letter from Pew and others lays out a framework to include UDIs in separate CMS rule
on meaningful use of EHRs, which is under review by the White House Office of Management and Budget. The letter
contends that the meaningful use program is “an appropriate and essential avenue to support the frequent, consistent and
accurate documentation of devices used in care, enhancing recall resolution, ensuring more precise adverse event reports
and providing primary care providers, specialists and patients with detailed information on implanted products.” The
group cited a Health Information Technology Policy Committee recommendation to create a Stage 3 Meaningful Use
objective to capture the UDI of implanted devices at the time of implantation. — David Hood
FDA Sends Proposed Healthcare Antiseptics Monograph To OMB
FDA asked the White House budget office over the weekend to review a proposed rule required by a court consent
decree that lays out what data industry must submit to demonstrate the safety of over-the-counter healthcare antiseptic
active ingredients. The framework for the proposed rule received unanimous support last year from an FDA advisory
panel, but industry at the time blasted the proposal as unnecessary due to what it viewed as lack of evidence that the
active ingredients in such products cause adverse health effects in humans.
The proposed over-the-counter drug review monograph for topical antimicrobial drug products will use “significant
agency resources,” says FDA, and has been classified as economically significant.
According to the rule description, the monograph establishes conditions under which OTC drugs are considered
generally recognized as safe and effective, and not misbranded. The rule addresses antimicrobial agents in healthcare
antiseptic products.
The agency sent the monograph to OMB as part of a consent decree it entered with the Natural Resources Defense
Council in November 2013.
“With respect to the TFM for Healthcare Antiseptic Products, at this time, FDA expects to publish the TFM by April
30, 2015, in accordance” with the consent decree, said FDA in an update to the U.S. District Court for the Southern
District of New York in December.
“This will require the expenditure of significant agency resources, including the draft TFM (taking recommendations
and comments of the Advisory Committee into consideration), responding to any comments provided by the United States
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Department of Health and Human Services (“HHS”), and responding to any comments provided by the Office of Management and Budget,” says the court document.
FDA turned to the advisory committee to weigh in on its framework for the monograph in September. The framework
proposes the “minimum data FDA believes necessary to establish the safety of long-term, daily, repeated exposure to
healthcare antiseptic active ingredients,” says the agency in the briefing document for the meeting.
The data FDA proposes to require in order to demonstrate safety for all healthcare antiseptic active ingredients include: human safety studies, nonclinical studies described in current FDA guidance, data to characterize potential
hormonal effects, and data to evaluate the development of resistance.
The committee voted unanimously that the proposed safety standards were appropriate to demonstrate that a
healthcare antiseptic active ingredient is generally recognized as safe (GRAS). But committee members also provided
some feedback, which FDA says it incorporated in the draft monograph for health care antiseptic products and
which will likely influence the agency’s development of the consumer antiseptic hand rub monograph, according to
court documents.
Christianne Roumie, associate professor of internal medicine and pediatrics at the Institute for Medicine and Public
Health at Vanderbilt University, questioned the use of animal studies.
“[A]re animal studies really the right data?” she asked. “We’re talking about chronic use among patients, providers,
people at home, your kids who Purell every time they come in. And the question is, there’s enough widespread use,
shouldn’t we be looking at the effects in populations instead of going back to the animal?”
But Thomas Moore, clinical professor at the University of Kansas School of Medicine, said looking at effects in
populations could be difficult to do.
“Just as an infectious disease practitioner, I think that would be great,” he said. “However, executing that is going to
be — I’m not speaking for industry, but I think it would be very difficult to do. It would be great. It would be fantastic.
But both financially and ethically, it would be difficult to do without doing animals.”
Industry members, however, have pushed against the framework. The American Cleaning Institute filed a brief
for the meeting saying that there is no evidence of the antiseptic active ingredients causing adverse health effects in
humans, and that any “suggestion that the benefit or risk of these products is in question, especially by FDA, could lead to
unintended adverse consequences if usage patterns were to change in the healthcare setting.” — Erin Durkin
Upton Lobbies Agency Heads For Support . . . begins on page one
Upton said he reached out to HHS Secretary Sylvia Burwell, FDA Commissioner Margaret Hamburg and NIH
Director Francis Collins, all of whom have testified at 21 st Century Cures Initiative hearings conducted by Upton over the
past year, to urge them to press Obama to commit to supporting the bipartisan legislation.
But Upton has only unveiled a broad outline of his upcoming bill, the details of which could drive the
administration’s position.
While top FDA officials have backed the lawmakers’ overall goal of spurring developing of new cures and treatments, they have warned that innovation should not come at the expense of safety — a view likewise expressed last year
by consumer advocates and some Democrats on the committee. FDA has been particularly worried by proposals to move
away from phase III clinical trials and rely more heavily on post-market data collection.
Avalere Health last week pegged clinical design reform as a key policy to watch for in lawmakers’ upcoming discussion draft, but the consulting firm also suggested the likelihood of such revisions actually moving forward is slim.
“[S]tudy design will be a major hurdle to any large shift on FDA’s part,” says the report. “The Agency has long maintained that Randomized Controlled Trials (RCTs) are the ‘gold standard’ for evidence generation, and it is unlikely to
significantly alter this stance to allow widespread reliance on real-world evidence (RWE) for post-market approval
studies.”
Last summer Peter Lurie, FDA’s acting associate commissioner for planning and policy, sought help from
research stakeholders in staving off efforts to undermine current clinical data policies. FDA Commissioner Margaret
Hamburg, speaking at a June 13 conference hosted by the National Center for Health Research, likewise warned
against too much emphasis on innovation, saying, “Just because something is new doesn’t mean that it’s better,
doesn’t mean that it will make a meaningful enduring difference in the lives of individuals.” And a former CMS
official said at the time that greater reliance on postmarket data would only work if payers are involved in the
process.
Upton and DeGette last week indicated their discussion draft will call for greater reliance on postmarket
studies for new drugs and devices designed for “unmet medical needs,” but they offered no details. It is unclear how
broadly the lawmakers hope to shift to postmarket studies and whether any potential limits on such a shift would be
enough to garner FDA support.
The lawmakers wrote in a CNN op-ed that the upcoming discussion draft of the bill will focus on: targeting clinical
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trials to the “right group” of patients; better integrating the patient perspective into the regulatory process through publicprivate partnerships; promoting better access to and sharing of data among researchers; increasing and targeting funding
for scientific research; and incentivizing new drugs and devices for unmet medical needs by relying more on post-market
studies and possibly offering exclusivity or reimbursement incentives.
Upton has said he will release the discussion draft this month, and file formal legislation in March with the goal of
the bill reaching the House floor for a vote by Memorial Day in May. Upton hopes the measure will reach the president’s
desk by the end of the year.
Stakeholders at a recent IIR-sponsored FDA/CMS Summit said they view work on the 21st Century Cures
Initiative this spring to be a staging ground for negotiations over the sixth iteration of the Prescription Drug User
Fee Act (PDUFA) in 2016 and 2017, and Janet Woodcock, director of FDA’s Center for Drug Evaluation and
Research (CDER), said working with lawmakers on the 21st Century Cures initiative is a “front burner” priority for
the agency.
One idea advocated by FDA has been development of new clinical trial networks. Woodcock told Energy and
Commerce members at a roundtable discussion last year that development of clinical trial networks spearheaded by
patient groups and that enable testing of multiple drugs and biomarkers could spur innovation.
Upton, in his press release Tuesday, said: “21st Century Cures is about hope. We seek to provide hope to patients
and families all across the country who are desperate for new cures and treatments. We also seek to provide hope to those
who have seen Washington as a partisan city incapable of getting things done. As we look toward this new year and new
Congress, I am encouraged by the bipartisan achievements we have already made throughout the 21st Century Cures
initiative and grateful for the support of top administration officials.”
He added: “I hope that President Obama will consider joining our effort to boost jobs, ensuring the United States
remains the epicenter of innovation, and help bridge the gap between the incredible advances made in science and
how we in Washington actually regulate those therapies. There is no issue more important to families all across the
country.”— Todd Allen Wilson
Hatch, Bennet Push Antibiotics Pathway Bill In New Congress
Legislation to create a new drug approval pathway that would streamline access and innovation of antibiotic drugs
was reintroduced by Sens. Orrin Hatch (R-UT) and Michael Bennet (D-CO). The bill specifically addresses serious or
life-threatening conditions, but the lawmakers envision the pathway to be extended to other drugs. Initially introduced in
December, the bill has since garnered support from multiple stakeholder and advocacy groups.
The bill comes as the White House launches a new Precision Medicine Initiative that calls for doubling the investment in new antibiotics and as House lawmakers prepare to unveil a draft 21st Century Cures Initiative bill that is
expected to propose ways to streamline drug development.
The Promise for Antibiotics and Therapeutics for Health (PATH) Act would set up a limited population pathway for
anti-bacterial drugs to treat serious or life-threatening diseases, conditions or infections and address unmet medical need.
Sponsors of the antibacterial drugs would be required to demonstrate safety and effectiveness within the limited population, and would not be denied approval if there is a lack of evidence of a favorable benefit-risk profile in a broader
population.
“America has always been a beacon for innovation and discovery,” said Hatch. “The PATH Act will allow health
experts to more easily develop new treatments for antibiotic-resistant bacteria, and make real progress in preventing a
great number of illnesses and deaths in the United States. I was pleased our proposal received such a positive response
when we introduced it in the end of the last Congress, and I look forward to working with Senator Bennet and others to
enact it into law.”
According to a press release from Bennet’s office, the act has garnered the support of the Infectious Diseases Society
of America (IDSA), Pew Charitable Trusts, Science in Service to Humanity Foundation, and National Venture Capital
Association (NVCA).
“There is clear agreement among medical, scientific, and public health leaders that the federal government must act
to stimulate development of urgently needed new antibiotics,” said Steve Calderwood, president of IDSA. “There is
broad support for the limited population antibacterial drug pathway which the PATH Act would establish. Congress must
continue the momentum driving this issue on behalf of patients. IDSA looks forward to working with Senators Bennet and
Hatch to enact the PATH Act.”
Pew Charitable Trusts’ senior director of health programs, Allan Coukell, said that the new pathway tackles an
important problem with an approach that is “good for both public health and drug development.”
However, Pew also cautioned the lawmakers against extending such a pathway to other drugs, saying it is not clear
that a limited population approach would be suited to other therapeutic areas (see FDA Week, Dec. 12). — Erin Durkin
FDA Week - www.InsideHealthPolicy.com - January 23, 2015
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FDA Puts Onus On lndustry To Push Device Accessory Classifications
FDA, in draft guidance laying out its plans to regulate medical device accessories, encourages manufacturers to use
the de novo process to request classification determinations for new types of accessories. An industry attorney said the
guidance, while responding to calls for the agency to decrease regulation of low-risk products, instead puts the onus on
industry to “blaze the trail” for their competitors.
The agency committed to releasing the guidance in the FDA Safety and Innovation Act Health IT Report released last
April, following recommendations from the FDASIA Health IT Working Group that FDA provide greater clarity in this area.
Bradley Merrill Thompson, an attorney for Epstein Becker & Green who serves as general counsel for the mHealth
Regulatory Coalition, said the group had urged FDA to use guidance to develop categories of accessories that would be
unregulated through enforcement discretion and to follow up with rulemaking to formally declassify these devices.
However, Thompson said FDA decided instead to put the burden on industry to reclassify accessories.
“FDA does not want to shoulder the burden unilaterally to reclassify these accessories,” he said. “They want industry
to put together submissions that include all of the data necessary to support the reclassification. I understand that, but in
the real world, many companies hate the de novo classification process for a very simple reason. In the de novo process,
the company has to be magnanimous in the sense that it has to pursue de novo classification at pretty significant cost, only
to blaze the trail for its competitors to follow.”
Thompson suggested that trade associations, such as the Advanced Medical Technology Association, may have to
take the lead on addressing these issues.
On the positive side, Thompson said the guidance does address problems surrounding how to determine the risks of
accessories separately from those of their parent device, and tackles the definition of an accessory.
The agency explains it will regulate accessories based on the risks they present when used with their parent
devices, but not solely based on the risks of their parent devices. FDA also encourages the use of the de novo classification process to request risk-based classifications of new types of accessories.
“Determining the risks of accessories according to their use with parent devices does not mean that all risks of a
parent device are imputed to the accessory; the risk profile of an accessory can differ significantly from that of the parent
device, warranting differences in regulatory classification,” says FDA. “In determining the classification of an accessory,
FDA will evaluate the risks imposed by the accessory’s impact on the parent device and any unique risks of the accessory
independent of its parent device.”
Thompson said FDA had been grouping accessories with the parent device and were regulated them all as one — a
move he argued didn’t make sense for some accessories that had a far lower risk profile.
In order to classify a device accessory, FDA says it will address the following two questions: Is the article an accessory? What is the risk of the accessory when used as intended and what level of regulatory controls are necessary to
provide a reasonable assurance of its safety and effectiveness?
FDA also addressed what would be considered an accessory, explaining that an accessory is a product that is intended for use with one or more parent devices; and is intended to support, supplement, and/or augment the performance
of one or more devices.
The agency goes even further to clarify what it means to support, supplement and augment a device: A device
supplements a parent device if it adds a new function or a new way of using the parent device, without changing the
intended use of the parent device; it augments the performance of a device by enabling the device to perform its intended
use more safely or effectively; and it supports the performance of a parent device by enabling or facilitating that device to
perform according to its intended use.
“[W]e were not sure that everyone was using the same definition of accessory to begin with,” said Thompson. “It was
unclear under what circumstances an article would be considered to accessorize a medical device, with FDA seemingly to
apply certain rules that potentially differed from the international community. In this guidance, FDA seems to have come
much closer to international norms with regard to what is an accessory.” — Erin Durkin
Bill Eases Limits On ‘Customer Service’ For Research-Only Medical Tests
Reps. Michael Burgess (R-TX) and Jackie Speier (D-CA) are pushing legislation that would allow communication
between a manufacturer of a “Research Use Only” medical test product and an end user, including technical support,
customer service and assistance with the installation of the product. An attorney said the legislation would allow manufacturers to provide services that otherwise would be at odds with FDA’s guidelines for these products, which often serve as
foundations for laboratory developed tests (LDTs).
The legislation “Medical Testing Availability Act of 2015,” which is a second iteration of a bill released by Burgess
in 2013, states that products with a research use only label will not be held as adulterated or misbranded if the end user
uses the product in a way that is inconsistent with the label, and if the manufacturer engages in business communications
regarding the product with the user. The 2013 bill garnered support from the American Clinical Laboratory Association,
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FDA Week - www.InsideHealthPolicy.com - January 23, 2015
California Healthcare Institute, the Coalition for 21 st Century Medicine and AdvaMedDx (see FDA Week, Aug. 9, 2013).
Business communications in this context means contact between the manufacturer and the end user of the product
regarding the function, and includes: communication of technical support, customer service, assistance with the installation of such product, communication relating to ensuring the performance of the product and other similar contacts.
The issue of customer service and business communications between a manufacturer and a customer is still a
gray and uncomfortable area, said Bradley Merrill Thompson, an attorney for Epstein Becker & Green. He said the bill
would allow manufacturers to answer unsolicited requests for assistance from laboratories that may be using the product
clinically, communication that currently might be at odds with FDA guidance in this area.
“Manufacturers are telling labs that if you’re planning to use the product clinically, we can’t provide customer
service,” said Thompson. “[The bill] would allow vendors to provide those supporting services.”
FDA released final guidance in November 2013 around RUO products, stating: “Overt expressions by the manufacturer, such as those present in labeling and advertising, may be sufficient to show determine that an IVD product is
inappropriately labeled RUO or IUO, when such expressions demonstrate that the device is actually intended for clinical
use despite the RUO or IUO labeling.”
The guidance says inclusion of clinical interpretive information, discussion of clinical significance, or other indications of clinical applicability included with any RUO products would “suggest that such products are not intended for
research use only, but rather that they are intended for non-research clinical diagnostic purposes.”
The final guidance scaled back FDA’s initial approach in the draft, which said manufacturers could not sell products
to labs they have reason to know are using the products for clinical diagnoses.
Concerns over FDA’s stance prompted lawmakers to draft legislation deeming these products would not be
considered misbranded if the customer does not use the product in accordance with its label.
Thompson said the bill not only codifies in law that FDA can’t regulate manufacturers in this way, but it also
broaches the issue of business communications that could be seen as promoting clinical use. He added that the language
of the bill may need to be refined so that it is limited to unsolicited requests from labs for assistance, so vendors will not
promote clinical practice.
“Incredible advances in personalized medicine hold great potential for patients and healthcare providers to detect,
diagnose and treat disease,” said Burgess. “But physicians and medical professionals must be able to access them in order
to provide the best care for their patients. Our bill is an important step towards improving medical innovation in the
United States and, ultimately, finding cures to ailments that affect thousands of Americans each year.”
Speier said that the bill strikes a clear balance between developments in personalized medicine and “the rights
of patients to safely explore new care options.”
Thompson also noted that research use only products often serve as the foundation for LDTs. While Thompson said
he could not see this piece of legislation serving as a basis for broad reforms to FDA’s draft LDT framework, he said he
could see this “possibly chipping away at the LDT issue.” — Erin Durkin
Obama Pushes Precision Medicine . . . begins on page one
blog posted the same day described it as an “emerging approach to treatment that takes into account patients’ individual
characteristics, and a kind of research the President hopes to expand.”
Although the initiative is new, this is not Obama’s first venture into personalized medicine. Amy Miller, the executive
vice president of the Personalized Medicine Coalition, said that clues on what shape the new initiative may take can be
found in Obama’s past efforts in personalized medicine.
While serving as senator for Illinois, Obama proposed the Genomics and Personalized Medicine Act in 2007,
and was joined by Sen. Richard Burr (R-NC). The objective of the legislation was to speed the development of customized healthcare, particularly by encouraging drug and device manufacturers to develop diagnostic tests to accompany
their products. It also called for FDA to update its oversight of diagnostics, requiring that FDA regulate direct-toconsumer advertising of the tests.
Miller and other stakeholders also expect the new White House plan to complement the Energy and Commerce
Committee’s cures initiative, although the administration hasn’t formally taken a position on the congressional
effort.
The committee said in a released statement Wednesday (Jan. 21) that president’s remarks signal support for “exploring policies that encourage and embrace the advancements made in science and health care over the past several years.”
The morning of the State of the Union, committee chair Fred Upton (R-MI) called on the president to come
out in support of the panel’s upcoming bill, expected to be unveiled by the end of the month. Upton said he reached out
to HHS Secretary Sylvia Burwell, FDA Commissioner Margaret Hamburg and NIH Director Francis Collins to urge them
to press Obama to commit to supporting the cures legislation (see related story).
Though the president didn’t mention the congressional effort in his Tuesday remarks, stakeholders say the White
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House plan shares the goal of advancing medical research.
A brief posted on the White House website Tuesday states: “The President is calling for a major increase in R&D
investments, including precision medicine, combating antibiotic resistance, and the President’s signature BRAIN Initiative. The President’s proposal would invest in precision medicine, an innovative field that provides healthcare professionals
with tools, knowledge, and treatments to tailor care to a person’s unique characteristics — such as their genetic makeup.”
The brief adds that the proposal will engage patients and healthcare providers in delivering the “new era of medicine,” will double the investment in antibiotic discovery, and will continue investment in Alzheimer’s research and the
Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative.
Miller said the Personalized Medicine Coalition was excited the president announced his personalized medicine
initiative as the Energy and Commerce Committee was gearing up to release its draft legislation.
“I assume the president’s personalized medicine initiative will be complementary to the bipartisan House effort,” said
Miller.
The president’s comments also garnered support from Research!America; AdvaMedDx, a diagnostics arm of the
Advanced Medical Technology Association; Alzheimer’s Association; and National Association of Chain Drug
Stores.
“Current funding levels for federal health agencies put researchers at an extreme disadvantage in pursuing studies
that have the potential to cure disease and improve quality of life, and tax policies have stymied the development of new
drugs,” said Research!America President and CEO Mary Woolley.
She added: “Policymakers must pivot from short-sighted thinking to formulating a long-term strategy that will bring
new treatments across the finish line and spur growth in quality jobs. We think it’s past time to adopt a national policy
that will assure the U.S. retains its world leadership in science and innovation.”
The Manhattan Institute’s policy research senior fellow and director of the Center for Medical Progress, Paul
Howard, described precision medicine as “the future of medicine.”
“We have the ability to personalize treatments for cystic fibrosis and many other diseases,” said Howard in a release.
“To do so, we need an FDA and a regulatory system rooted in 21st century technologies, which American companies and
researchers excel at. Congress’s bipartisan 21st Century Cures initiatives is a very promising step toward rebooting the
FDA and streamlining clinical trial regulations to take advantage of our globe-leading biotech companies, world-class
universities, and nimble tech sector.” — Erin Durkin
Obama Launches Precision Medicine Initiative In State Of The Union
President Barack Obama announced the launch of a new initiative that he said would give patients “access to the
personalized information” they need to stay healthy and receive the “right treatment at the right time,” during the State of
the Union Address Tuesday (Jan. 20).
In a White House blog, the administration appears to make a connection to the effort through the story of a cystic
fibrosis patient who was able to receive treatment through the collaboration of the Cystic Fibrosis Foundation, patients,
researchers and a pharmaceutical company.
“His story is a testament to the promise of precision medicine, an emerging approach to treatment that takes into
account patients’ individual characteristics, and a kind of research the President hopes to expand,” states the blog posted
Tuesday.
Obama, in his State of the Union remarks, said: “I want the country that eliminated polio and mapped the human
genome to lead a new era of medicine — one that delivers the right treatment at the right time.” He added: “In some
patients with cystic fibrosis, this approach has reversed a disease once thought unstoppable. Tonight, I’m launching a new
Precision Medicine Initiative to bring us closer to curing diseases like cancer and diabetes — and to give all of us access
to the personalized information we need to keep ourselves and our families healthier.”
The president offered no details about the new initiative, which comes as the House Energy and Commerce Committee is poised to release draft legislation aimed at spurring development of new medical treatments as part of the panel’s
21st Century Cures Initiative. Tuesday morning Energy and Commerce chair Fred Upton (R-MI) pushed Obama to
endorse the upcoming bill as an “area of bipartisan agreement to pursue in 2015.”
“We seek to provide hope to patients and families all across the country who are desperate for new cures and
treatments,” said Upton. “We also seek to provide hope to those who have seen Washington as a partisan city incapable of
getting things done. As we look toward this new year and new Congress, I am encouraged by the bipartisan achievements
we have already made throughout the 21st Century Cures initiative and grateful for the support of top administration
officials. I hope that President Obama will consider joining our effort to boost jobs, ensuring the United States remains
the epicenter of innovation, and help bridge the gap between the incredible advances made in science and how we in
Washington actually regulate those therapies.”
It was unclear at press time how the president’s new initiative fits in with the upcoming legislative proposal. — Erin
Durkin
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FDA Week - www.InsideHealthPolicy.com - January 23, 2015
Obama’s Pushes Antibiotic Funding Hike As Congress Eyes Incentives
The president’s plan to nearly double investment in antibiotics and tackle antibiotic resistance complements lawmakers’ efforts to create incentives for development of such products and likewise combat resistance, said a public health
advocate. A consumer advocate also said the president’s past efforts on antibiotic resistance indicates that the administration has “a real public health understanding of medical issues.”
President Barack Obama’s antibiotic plan, unveiled as part of a new Precision Medicine Initiative in the State of the
Union Address Tuesday night (Jan. 20), calls for almost double federal investment in antibiotic discovery to combat
antibiotic-resistant bacteria, according to a brief on the White House website.
Pew Charitable Trusts’ director of public health, Elizabeth Jungman, said the president’s proposed efforts join a
three-pronged strategy to combat antibiotic resistance. She noted that Congress is addressing economic incentives
through proposed legislation, the Generating Antibiotics Incentives Now (GAIN) Act, which would add five years of
additional market exclusivity for antibiotics that target qualified pathogens; and lawmakers are also addressing regulatory
barriers through two bills that would create a streamlined pathway for antibiotics that address serious or life-threatening
conditions — the Promise for Antibiotics and Therapeutics for Health (PATH) Act, and the Antibiotic Development to
Advance Patient Treatment (ADAPT) Act.
The president is addressing the scientific barriers to developing new antibiotics, said Jungman. “I think it’s part
of a larger pattern of what the administration has focused on for the last few months... There are some real challenges to
antibiotic drug discovery, and some real challenging scientific problems,” she said.
The announcement came a few months after the President’s Council of Advisors on Science and Technology recommended
that the federal government create incentives for antibiotic drug development. The September report also recommended that
FDA and the National Institutes of Health create a national infrastructure to support clinical trials for new antibiotics.
Diana Zuckerman, president of the National Center for Health Research, said the PCAST report also shows that the
president has a understanding of medical issues from the public health perspective, which she says the House Energy and
Commerce Committee’s 21st Century Cures efforts may lack.
During the months the House committee convened hearings around its initiative, Zuckerman said she worried that the
lawmakers were favoring industry-backed patient groups.
“There is more than one point-of-view,” said Zuckerman at the time. “There are a lot of people in between, but it
seems like the Energy and Commerce Committee has focused on the groups who are pushing for faster approvals and not
pushing for better safeguards” (see FDA Week, July 7).
She notes that the PCAST report discusses the importance of well-designed clinical trials. “We are hopeful that the
president will continue to get really good advice when it comes to this initiative,” she said.
The report had recommended the development of a national clinical trials network for antibiotic testing to make
trials more efficient and less expensive. “Such a network would allow rapid initiation of clinical trials by commercial sponsors and academic researchers and would optimize the identification and enrollment of patients,” states the
report.
The president’s new funding announcement also comes after the Antimicrobial Innovation Alliance released a
report pushing for more federal incentives. “Unfortunately, the marketplace for novel antibacterial and antifungal
products is economically and scientifically challenging,” said the report. “Federal incentives are critical, both to
keep existing antimicrobial companies focused on product development and to encourage new ones to enter this
arena.”
The group of antibacterial and antifungal researchers and developers recommended six types of incentives: inpatient
reimbursement reform, transferable exclusivity, new commercialization models, enhanced federal partnerships for
antibiotic development, special medical use pathway and corporate tax reform. — Erin Durkin
GPhA President And CEO Ralph Neas To Step Down This Fall
Generic Pharmaceutical Association President and CEO Ralph Neas will step down this fall, the industry group
announced Tuesday (Jan. 20). After around four years of service to GPhA, Neas is leaving to explore entrepreneurial
opportunities and to work on issues such as non-partisan election reform.
“It has been an honor and a pleasure to work with my GPhA colleagues to help ensure access to safe and affordable
medicines, which save patients and the health care system hundreds of billions of dollars annually,” said Neas in a
released statement. He added: “I am especially proud of the exceptional GPhA team that has been built and how together
we have achieved numerous legislative victories; protected the historic Hatch-Waxman Act; promoted future access to
biosimilars medicines at the state, national and international levels; and enhanced our relationships with the FDA,
Republican and Democratic Members of Congress, and the Executive Branch.”
The group will begin its search for a new CEO immediately, and Neas will be available through spring of 2016 to
support and advise the new leadership. — Erin Durkin
FDA Week - www.InsideHealthPolicy.com - January 23, 2015
9
SCOTUS Declines Generic Labeling Case. . . begins on page one
The high court’s decision not to intervene is significant because FDA launched its rulemaking in response to safety
concerns arising from a landmark 2011 Supreme Court decision that generic drug makers can’t independently add new
safety information to their labels. The 2011 Pliva v. Mensing case shielded generic drug companies from failure-to-warn
claims stating that FDA regulations prevent generic firms from changing their labels.
The drug at issue in Teva Pharmaceuticals v. Superior Court of Orange County is Teva’s generic equivalent for
Merck’s Fosamax, an osteoporosis treatment. The plaintiff who brought suit against the company alleged that Teva didn’t
immediately update its label to match new information included in the Fosamax label.
“Unless and until this Court provides clarity, however, this entrenched nationwide division in authority threatens to
subject thousands of similarly situated parties to irreconcilable rulings in cases involving scores of different drug products,” argues Teva in its petition. “The problem will only grow as decisions like the one here lead plaintiff’s lawyers to
file suit every time the FDA’s website reveals a labeling change that generic companies cannot possibly implement
instantaneously.”
The Supreme Court’s reluctance to weigh in on the issue comes as FDA wades through comments on its controversial
proposed rule. If finalized, the rule would require that generic drug makers independently update their labels when new
safety data become available while FDA reviews the information to decide whether to urge both brand and generic
makers to change their labels.
The Generic Pharmaceutical Association has strongly opposed FDA’s rulemaking, with President and CEO Ralph
Neas recently telling reporters that litigation could ensue. “If you’re going to change the law you’ve got to go to the
correct forum,” he said (see FDA Week, Sept. 23). — Erin Durkin
FDA Says Finalizing Opioid Guide A Priority, Doesn’t Commit To Deadline
An FDA official said issuance of a final abuse-deterrent opioid evaluation and labeling guidance is a priority but
wouldn’t publicly commit to the June 30 deadline set by Congress. Lawmakers included language in the year-end
spending package that withholds $20 million in salaries and expenses from the FDA commissioner’s office pending
finalization of the guidance and warns the funding will be shifted if the document isn’t out by the due date.
“Although an exact release date cannot be determined at this time, the FDA considers the development of abuse
deterrent technologies a priority and is working to complete the final guidance as soon as possible,” an FDA spokesperson told Inside Health Policy Tuesday (Jan. 20).
The spokesperson, in response to an IHP story last week on the topic, clarified the reason the final guidance is not
included on the drug center’s newly released guidance agenda is because the agenda only includes anticipated draft and
revised draft guidances, not anticipated final guidances.
The agency didn’t respond to queries prior to publication of the article on why the document wasn’t on the agenda.
The draft version of the “Guidance for Industry Abuse-Deterrent Opioids — Evaluation and Labeling” was unveiled in
January 2013.
The FDA spokesperson also clarified Tuesday that the drug center will not be releasing a list of final guidances it
expects to publish this year. “While the FDA’s Center for Drug Evaluation and Research releases a list of expect draft
guidances, it does not release a list of expected final guidances,” said the spokesperson. — Erin Durkin
Warren Takes Shot at Pharmaceutical Companies With NIH Funding Bill
Sen. Elizabeth Warren (D-MA) announced an initiative to improve NIH funding at a Families USA conference in
Washington Thursday (Jan. 22) ahead of legislation she plans to introduce next week that would require pharmaceutical
companies that enter settlement agreements with the federal government to avoid a trial for violating federal antifraud laws to pay a small portion of their overall profits over five years to help fund research at NIH and FDA. The
pharmaceutical lobby pushed back, saying that her bill would kill jobs and would result in fewer medicines for
patients.
Warren likened her bill to a “swear jar: whenever a huge drug company that is generating enormous profits as a result
of federal research investments gets caught breaking the law— and wants off the hook — it has to put some money in the
jar to help fund the next generation of medical research.”
A fact sheet from Warren’s office on the forthcoming legislation says the bill would only apply to companies that
break the law and enter into a settlement agreement with the federal government; sell “blockbuster” drugs with annual
sales over $1 billion; and relied on federally funded research in whole or in part to develop those drugs.
But the Pharmaceutical Research and Manufacturers of America blasted the proposal. PhRMA spokesman
Robert Zirkelbach told FDA Week in a statement that Warren’s policy is “misguided “ and would “siphon funding from
the groundbreaking medical research happening in the biopharmaceutical industry (and) will have devastating conse-
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FDA Week - www.InsideHealthPolicy.com - January 23, 2015
quences for patients and society. “
“The proposed legislation would result in fewer medicines for patients and lost jobs at a time when our economy can
least afford it,” he added.
Warren maintained that under her plan NIH would receive $6 billion more a year without raising new taxes, a
roughly 20 percent increase in funding for the agency.
Warren plans to formally introduce the bill when Congress returns next week. —David Hood
FDA’s Device Compliance Chief Steve Silverman Stepping Down
Steve Silverman, director of the FDA device center’s compliance shop, is leaving the agency after 13 years. Jan
Welch, the center’s deputy director for regulatory affairs, will be the acting compliance director while a search for a
permanent director is underway, said Silverman in an email to staff.
According to the email, Silverman’s last day is slated for Feb. 27 although he will be on leave starting Monday, Jan.
19. “I go with mixed emotions... I’ve seen again and again that it is a superb agency with a world-class staff,” Silverman
said. “And I’ve never had a better job than my current one. Even so, I feel that it’s time for me to gain experience in other
areas.”
Silverman oversaw implementation of the medical device portion of the federal Food, Drug, and Cosmetic Act and
directed more than 170 staff in the office of compliance. — David Hood
Court Tells CA Firm To Stop Selling Supplements Until It Meets FDA Regs
A U.S. District Court judge recently ordered California-based dietary supplement manufacturer Health One Pharmaceuticals Inc. to stop selling its products until it comes into compliance with FDA dietary supplement manufacturing
regulations and hires an independent inspector to regularly verify the company’s compliance.
In agreeing to the court’s consent decree ordering the injunction, Health One Pharmaceuticals, which bills itself as a
private label and contract manufacturer for health supplement products, and its president and founder Richard Yeh
attested to the court that the company has already stopped manufacturing all articles of food, drugs and dietary supplements.
“When a company puts consumers at risk, the FDA will take action to protect public health,” said Melinda Plaisier,
FDA associate commissioner for regulatory affairs, in a press release. “Our goal is to ensure that consumers have access
to dietary supplements that meet federal standards for safety and quality.”
As part of the consent decree detailing the injunction issued by U.S. District Judge Beverly Reid O’Connell of the
Central District of California, Health One Pharmaceuticals must also recall and destroy all dietary supplements that were
manufactured, prepared, packaged, labeled, held or distributed from Sept. 1, 2011 through Jan. 15, 2015.
Health One Pharmaceuticals did not respond to requests for comment from FDA Week, and did not have any information on the injunction posted on its website.
FDA sent the manufacturer a warning letter in March 2012 detailing several violations of the agency’s current good
manufacturing practice (cGMP), including the company’s failure to perform tests verifying that identity of dietary
ingredients used to manufacture supplements; to establish appropriate manufacturing controls; and to maintain, clean and
sanitize equipment based on inspections of Health One Pharmaceuticals in the fall of 2011. Additionally FDA said the
company’s products were mislabeled because the labels didn’t list ingredients by their common or usual names.
Following the warning letter, the agency said it received assurances from Health One Pharmaceuticals that the
company that is rectifying the situation, but FDA said further inspections showed the company was still not in compliance
with cGMP regulations.
Under the consent decree, Health One Pharmaceuticals will face a $7,500 per violation per day fine for failing to
meet the terms laid out by the court. — Todd Allen Wilson
ONC Hires Chief Health Information Officer With Focus On Interoperability
The Office of the National Coordinator for Health Information Technology announced James McCoy will be the
ONC’s first Chief Health Information Officer.
McCoy will lead development of ONC’s clinical policy for standards and regulatory matters, National Coordinator
for HIT and Acting Assistant Secretary for Health Karen DeSalvo said in an email to staff. McCoy will also be ONC’s
lead clinical subject matter expert on interoperability. ONC’s roadmap on interoperability is expected to be released this
month.
“He is passionate, as am I, on making effective use of interoperable healthcare IT while ensuring a person-centered
health system that results in the best outcomes possible,” DeSalvo says. — Michelle M. Stein
FDA Week - www.InsideHealthPolicy.com - January 23, 2015
11
Decision Has Hatch-Waxman Implications . . . begins on page one
The case involved FDA approval of a 505(b)(2) application for a drug for prophylaxis of gout.
In the case, Takeda Pharmaceuticals U.S.A. (Takeda), which markets Colcrys (colchicine) tablets for prophylaxis of
gout and the treatment of acute gout flares, and Elliott Associates L.P., Elliott International L.P. and Knollwood Investments L.P. (collectively Elliott), that have investment interests in Colcrys, asked the court for a summary judgment of an
injunction against FDA’s September approval of Hikma Pharmaceuticals LLC’s (Hikma) Mitigare (colchicine) capsules
for prophylaxis of gout.
Jackson ruled against Takeda and Elliott, which argued that FDA’s approval of Hikma’s 505(b)(2) application —
which is a middle ground pathway established by Hatch-Waxman between new drug applications (NDAs) and abbreviated new drug applications (ANDA) — violated both the Food Drug and Cosmetics Act and the Administrative Procedure
Act by allowing Hikma to submit an application that didn’t reference Colcrys and without requiring a label that contained
“critical safety data” developed by Takeda’s predecessor, Mutual Pharmaceutical Company Inc, as part of its 2009
application for a single ingredient colchicine product. Takeda and Elliott plan to appeal Jackson’s decision.
Takeda’s fight with the FDA and Hikma is part of a long, convoluted history of colchicine products that Jackson lays
out in detail in her 80-page opinion. The drug has been used to treat gout for centuries and colchicine products were
unregulated by FDA for decades, until FDA in 2009 approved Mutual Pharmaceutical Company’s Colcrys (now owned
by Takeda). Within a year FDA moved to push all unapproved colchicine products from the market.
During the 505(b)(2) application process, Mutual, which relied on Colbenemid as its reference product, submitted
studies that forwarded the science on the toxicity of colchicine, especially when taken with certain inhibitors. FDA
included findings in terms of dosage recommendation when used to treat acute gout flare ups on the Colcrys label and
issued an alert about the safety information. FDA cited absence of this information on labels for unapproved colchicine
products with regard to acute gout flare ups and drug-drug interactions to go after those products and suggested it was
important for this information to be on all labels for colchicine products.
Hikma subsidiary West-Ward Pharmaceutical Corp. removed its unapproved colchicine tablet from the market on the
heels of the agency’s enforcement actions and then submitted a 505(b)(2) application after getting the go ahead from FDA
to use Col-Probnecid as its reference product rather than Mutual’s Colcrys. West-Ward opted to use Col-Probnecid
because its patents had expired, while Colcrys’ patents run through 2028 and 2029, and it didn’t want to submit a HatchWaxman Paragraph IV certification of Mutual’s patents.
With the submission of West-Ward’s 505(B)(2) application, Mutual filed a citizen petition that the FDA only accept
ANDA applications for approval products identical to Colcrys and make sure they reference Colcrys and include the same
safety and dosing information that are on its label — essentially asking the agency to reject any 505(b)(2) application for
orally-administered colchicine products.
FDA partially approved and rejected Mutual’s citizen petition, saying that applications for products identical to
Colcrys must reference that product and use the ANDA rather than 505(b)(2) pathway. The agency also asked West-Ward
to withdraw its 505(b)(2) application and resubmit it as an ANDA application. But the FDA also said it would accept
505(b)(2) applications for colchicine products as long as they were not identical to Colcrys without referencing Mutual’s
product as long as the applicant provided its own safety and efficacy data. Recognizing “new, quantitative information”
provided by Mutual’s studies, the agency also said the label “for any single-ingredient colchicine product needs to include
adequate information on drug-drug interactions, including relevant dose adjustments to prevent unnecessary toxicity,” and
for the treatment of acute gout flare for people already taking colchicine for prophylaxis must inform healthcare providers
of the lower-dose regimen in Mutual’s trials.
West-Ward withdrew its application and reformulated its product as Mitigare, a colchicine capsule as opposed to
tablet — thereby making it no longer identical to Colcrys. The company also conducted its own drug interaction studies
on the same class of drugs — though not the same exact drugs — that Mutual used, the results of which differed substantially from Mutual’s findings. Because these results were unexpected, FDA extensively compared Mutual’s data to West-Wards.
FDA approved West-Ward’s Mitigare in September, based on West-Ward’s studies, for prophylaxis of gout — though
not for acute gout flares which the company did not seek — with a substantially different label from Colcrys. Mitigare’s
label does not include dosage recommendations for acute gout flares, saying “[t]he safety and effectiveness of Mitigare
for acute treatment of gout flares during prophylaxis has not been studied,” and that patients taking taking certain drugs in
combination of Mitigare should avoid combining the drugs entirely, or if that’s not possible “by either reducing the daily
dose or reducing the dose frequency, and the patient should be monitored carefully for colchicine toxicity.”
In their combined suit Takeda and Elliott allege that the FDA was wrong to approve Mitigare without having
West-Ward reference Colcrys and certify Takeda’s patents, and that Mitigare is unsafe as labeled because it does not
include “FDA-approved low-dose-treatment notation for acute gout nor the the drug-drug interaction dosing adjustments.” Takeda also contends that because FDA looked at Mutual’s studies when evaluating West-Wards safety data
submitted with its application, West-Ward should be required to certify Takeda’s patents — the Colcrys’ studies are
mentioned more than 200 times in FDA’s approval of Mitigare. And Elliott argued that FDA’s failure to make West-Ward
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FDA Week - www.InsideHealthPolicy.com - January 23, 2015
certify Colcrys’ patents went against both longstanding agency policy and the FDCA.
Jackson disagreed, concluding “that Plaintiffs are wrong to characterize FDA’s actions with respect to Mitigare as
unauthorized, unsafe, or unreasoned; to the contrary, it is clear on the record presented that FDA’s approval of Mitigare
was consistent with the FDCA, the regulations the agency has promulgated pursuant to the FDCA, the Citizen Petition
Responses FDA has issued, and the policies and practices under which the agency operates.”
Jackson found that it was irrelevant to West-Ward’s application — which did not use Colcrys data — that the
FDA of its own volition decided to use Mutual’s studies in reviewing the application, and that “prior applicant’s
voluntary submission of its proprietary data to FDA waived any right that applicant may have had to prohibit FDA from
‘open[ing] th[e] locked file drawer’ to access the applicant’s data in the future.”
Writing in Hyman, Phelps &McNamara’s, P.C.’s FDA Law Blog, industry attorney Kurt Karst says this part of
Jackson’s ruling “might raise some eyebrows among those in the brand-name industry, particularly given previous FDA
statements on the matter.” Kurst then links to a previous post quoting FDA as saying in response to prior citizen petitions
assuring industry that it would “not disclose any trade secret or confidential information, and [that] FDA did not impermissibly use or rely upon any such information in developing them.”
Kurst told FDA Week that while Jackson’s opinion is well-reasoned, it is just the opinion of a lower court. He
said given that Takeda and Elliott have appealed the decision the argument is far from over. Brand drug makers will
probably file amicus briefs on the “locked drawer” issue on Takeda and Elliott’s behalf, he said.
On the issue of whether it is the 505(b)(2) applicant’s choice as to which drug to reference as opposed to making
them reference and certify the patents of the most similar drug, Jackson writes, “FDA’s prior statements confirm that,
other than where duplicate drug products are involved, a Section 505(b)(2) applicant has the discretion to select a
reference drug, and to make that selection in relation to the scope of the materials the applicant desires to submit,” and
that the FDC Act requires 505(b)(2) to certify only to patents associated with the reference drug.
Kurst told FDA Week that over the years there has been a lot of confusion over the choice of listed drug issue, and
notes that in FDA Law Blog he wrote that “we think there’s room in the 505(b)(2) space for an applicant to argue that
even where there is an approved pharmaceutical equivalent, such drug does not necessarily have to be cited by a
505(b)(2) applicant as a listed drug relied on for approval.”
Jackson also dismissed Takeda’s argument that Mitigare was unsafe because the label did not include the same
labeling as Colcrys’ label and that there was no change of FDA policy regarding colchicine products. “[FDA’s] scientific
determination that Mitigare is safe and effective as labeled is entitled to the highest degree of deference, meaning that,
even if this Court had the expertise to reevaluate FDA’s safety and efficacy decision, it could not freely supplant the
agency’s scientific judgments about what a drug product’s label must include in order to ensure safe use of that product,
any more than it could roll up its sleeves and dig into the data or run its own clinical experiments in order to determine
whether FDA was wrong to conclude that such drug product was, in fact, safe.” — Todd Allen Wilson
Klobuchar Reintroduces Gov’t Drug-Price Control Bill
Sens. Amy Klobuchar (D-MN) and Tim Kaine (D-VA) introduced Wednesday (Jan. 7) a bill that would give the HHS
secretary power to directly negotiate with drug makers the price of pharmaceuticals under Medicare. Klobuchar introduced
similar legislation in past sessions of Congress, when Democrats controlled the Senate, and those bills did not gain traction.
The bill would undo a provision that was part of the GOP-sponsored 2003 law called the Medicare Prescription
Drug, Improvement, and Modernization Act, which created the Medicare prescription drug benefit called Part D. Although hepatitis C drugs Sovaldi and Harvoni made waves last year with their price, most lobbyists do not expect a
Republican-controlled Congress to entertain government price controls this year.
Sens. Richard Blumenthal (D-CT), Angus King (I-ME), Bernie Sanders (I-VT), and Jeanne Shaheen (D-NH)
cosponsored the bill. — John Wilkerson
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FDA Week - www.InsideHealthPolicy.com - January 23, 2015
13
House E&C Insists On Paying For SGR Bill In Ways That Won’t Draw Veto
The opening statement and questions by House Energy & Commerce health subcommittee Chair Joseph Pitts (R-PA)
at Wednesday’s (Jan. 21) hearing on Medicare physician payment reform does not bode well for those hoping to replace
the Sustainable Growth Rate formula without paying for it or for repeating last year’s strategy of delaying the ACA’s
individual mandate as an offset. Some House Republicans have said they are comfortable with not paying for the legislation, but Pitts and full Energy & Commerce Chair Fred Upton (R-MI) said an SGR replacement must be offset, and with
pay-fors that wouldn’t draw a White House veto.
“Now with the policy agreed to, the question we face is how to responsibly pay for SGR reform in a manner that can
pass both Houses of Congress and be signed by the president,” he said at the outset of the hearing.
Last year’s deal stalled when House GOP leaders began by saying they would pay for SGR reform by axing the
ACA’s individual mandate and then revised that to a mandate delay. The Senate responded by proposing to simply not
pay for the bill, which Republicans refused to go along with and lawmakers ended up passing a temporary pay patch
instead.
Pitts said Wednesday he worries that organizations pushing for an unpaid SGR fix aren’t serious about replacing the
formula. He added that GOP leadership has made it clear the bill must be paid for. He asked former Sen. Joe Lieberman
(I-CT), a witness at the hearing, what advice he has for such trade groups, and Lieberman said stakeholders must give a
little to preserve Medicare.
Pitts and Lieberman also said 98 percent of the SGR patches have been paid for and Congress shouldn’t break with
that history when it replaces the SGR for good. That assessment is based on research by the Committee for a Responsible
Federal Budget.
But ranking member Gene Green (D-TX) and other Democrats pointed out the House didn’t pay the $53
billion cost of a bill it passed Jan. 8 to change the Affordable Care Act’s definition of full-time work week from 30
hours to 40 hours for the purpose of the employer mandate. The 252-172 vote fell mostly along party lines, with 12
Democrats voting for the bill and no Republicans opposing the measure.
“What’s good for the goose is good for the gander,” he said.
Green also said Democrats aren’t against paying for the SGR so much as they oppose paying for it on the backs of
seniors.
A a source close to Lieberman said the former senator was invited to testify at Wednesday’s hearing because he and
former Sen. Tom Coburn (R-OK) wrote a Medicare-reform bill in 2011 that was estimated to reduce spending by $600
billion and those reforms could be used as a way to pay for an SGR replacement bill.
That bill called for raising Medicare’s eligibility age from 65 to 67, increasing Part B premiums from 25 percent to
35 percent of program cost, making wealthier Americans pay full Part B premiums, combining deductibles for Medicare
Part A and Part B, capping out-of-pocket spending at $7,500, and reforming Medigap. The plan also relied on some
provisions of the Affordable Care Act, such as pay cuts to the home health industry. The Coburn-Lieberman proposal
called for speeding those home health pay cuts by two years for a savings of $9 billion. The plan also called for phasing
out Medicare payments to hospitals for bad debt for $23 billion in savings, and it included Coburn’s legislative proposal
to reduce waste, fraud and abuse.
Democrats and the AARP strongly opposed the Coburn-Lieberman bill in 2011. — John Wilkerson
Senators Reintroduce Rx Import Bill Amid Debate Over Prices
Sens. John McCain (R-AZ) and Amy Klobuchar (D-MN) last week reintroduced legislation allowing Americans to
import drugs from Canada, a proposal that lay dormant for a good decade and that still isn’t getting much attention from
advocates of lower drug prices. The Affordable Care Act gradually closes Medicare’s drug benefit coverage gap, and the
law led to many more people receiving drug coverage outside of Medicare, but some say the fear of rising drug prices
keeps the reimportation legislation in the picture, if just barely.
“Not really our top priority,” said National Coalition on Health Care Director John Rother, who also leads the
Coalition for Sustainable Rx Prices.
Asked why the legislation is still needed with the closing coverage gap, Klobuchar told Inside Health Policy it has as
much to do with pressuring drug companies to lower their prices as it does with giving people a way to find less-expensive drugs that otherwise are identical to those sold here. She said that even though individual seniors might be less
exposed to high prices than in the past, tax payers must still foot the bill for brand drugs that are on average twice as
expensive here as in Canada. Generics in the United States are cheaper than in Canada.
Likewise, an AARP spokesperson said reimportation and other price-containment policies are needed now as much
as ever because of the high cost of brand-name and specialty medicines.
The drug price debate reared its head last year after Gilead priced its hepatitis C drug Sovaldi at $84,000 for a
12-week course. FDA late in the year approved the second generation of that drug, called Harvoni, which costs
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FDA Week - www.InsideHealthPolicy.com - January 23, 2015
$94,500 and is taken as a once-daily pill without interferon, which makes patients very sick. FDA then approved
AbbVie’s Viekira Pak in December, which also is interferon-free and has a similarly stellar cure rate but a more
complicated regimen. Viekira Pak costs $83,319 for a treatment course. Pharmacy benefit managers and health
plans began negotiating discounts on the drugs following Viekira Pak’s approval, but the amount of the discounts is
not public.
FDA already allows people to import a 90-day personal supply of drugs, which happens to match the typical
12-week course of hepatitis C drugs. Despite broader drug coverage in recent years, many people have plans that
restrict coverage of hepatitis C drugs to people with advanced liver disease. Gilead discounts its hepatitis C drugs in other
countries — Sovaldi sells for less than $1,000 per 12-week course in Egypt. Sources say it might make sense for those
people to turn to health care tourism and “drug reimportation,” but for the most part, the fight over drug costs is between
drug makers and health plans, not drug makers and beneficiaries.
Under the McCain/Klobuchar bill, imported prescription drugs would have to be purchased from approved Canadian
pharmacies and dispensed by licensed pharmacists. Drugs would have to be the same dosage, form, and potency as drugs
sold here. — John Wilkerson
Health Care Not A Focus Of Obama’s 2015 State Of The Union
President Barack Obama touted 10 million uninsured Americans gaining health care over the past year, but otherwise
rarely mentioned healthcare in his 2015 State of the Union Tuesday (Jan. 20), while Sen. Joni Ernst (R-IA) in the GOP
response to the State of the Union repeated Republicans’ vow to replace the Affordable Care Act.
“At every step, we were told our goals were misguided or too ambitious; that we would crush jobs and explode
deficits,” Obama said after touting the number of Americans gaining health insurance over the past year. Instead, Obama
added, health care inflation is at its lowest rate in 50 years.
Obama also said that if a bill comes to his desk to repeal the ACA, “it will earn my veto.”
Ernst, however, reiterated concerns about canceled health care plans and higher monthly insurance costs in the
Republican response to the State of the Union before saying that the new Republican majority will “keep fighting to
repeal and replace a health care law that’s hurt so many hardworking families.”
Obama did not mention reforms to Medicare and Medicaid in the State of the Union, though he did promise to
address health care, among other topics, in his upcoming budget request. Maya MacGuineas, head of the Fix the Debt
Campaign, called on Obama to use his “bully pulpit” to push for entitlement reform and to work with Congress to
enact it. Senate Finance Chair Orrin Hatch (R-UT) hours before the State of the Union address outlined an agenda
that includes entitlement reform, and the House Energy and Commerce Committee plans to address cost-saving
Medicare reforms at a hearing Wednesday (Jan. 21) that is expected to look at ways to pay for reforming the
physician payment system.
The president also announced in the State of the Union that he is launching a “Precision Medicine Initiative,” though
details were scarce. – Michelle M. Stein
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FDA Week - www.InsideHealthPolicy.com - January 23, 2015
15
SCOTUS Backs Teva, Says Appeals Court Can’t ‘Set Aside’ District Ruling
The Supreme Court handed Teva Pharmaceuticals a major win this week by ordering a federal appeals court to revisit
its decision to shoot down a subset of Teva’s patents for a complex multiple sclerosis drug, demanding the U.S. Court of
Appeals for the Federal Circuit consider information generated by the district court unless it is found to be in “clear
error.” The high court’s ruling may make it harder for brand and generic companies to get appeals courts to review patent
cases “de novo,” and industry attorney suggest the added weight given to district court rulings could favor brand companies that have resources to call in extra witnesses and submit additional data.
The Supreme Court’s decision prevents generic drug makers from releasing versions of Teva’s complex multiple
sclerosis drug, Copaxone, as the case is remanded to the federal appeals court.
The appeals court earlier found a subset of Teva’s patents around the drug were invalid for indefiniteness in the
claims, reversing decisions made in the U.S. District Court of the Southern District of New York. Most of the patents
expired in May, except for one, which expires in Sept. 1, 2015. The Supreme Court ordered the federal circuit to consider
the case on remand and consider the district court’s opinion.
Justice Stephen Breyer, writing for seven of the justices, noted that the Federal Rules of Civil Procedures state the
court of appeals must not set aside a district court’s finding of fact unless “clearly erroneous.”
“Even if exceptions to the Rule were permissible, we cannot find any convincing ground for creating an exception to
that Rule here,” wrote Breyer. “The Rules Advisory Committee pointed out that, in general, exceptions ‘would tend to
undermine the legitimacy of the district courts..., multiply appeals..., and needlessly reallocate judicial authority.’”
Breyer later notes that “practical considerations” favor the federal circuit applying the clear error review, because
patent law is “a field where so much depends upon familiarity with specific scientific problems and principles not usually
contained in the general storehouse of knowledge and experience.” He says the district court has an opportunity to gain
familiarity with the issue, rather than an appeals court that reads a written transcript or “perhaps just those portions to
which the parties have referred.”
The ruling provides different implications for brand and generic companies who may go through the litigation
process in the future, according to industry attorneys.
Sunit Talapatra, senior counsel at Foley & Lardner LLP, said such a ruling would provide more certainty to the
district court decisions. He said that currently if companies do not receive a favorable district court decision, they can
turn to the Federal Circuit Appeals Court as a second chance.
“I think this would be helpful for smaller companies,” he told FDA Week prior to the oral arguments. “Bigger
companies with deep pockets wouldn’t mind going to court twice... it probably [would] reduce the costs and the budgets
that are expected to arise from litigation” (see FDA Week, July 21).
But another lawyer argued that a decision in favor of Teva would be giving deference to extrinsic evidence — the use
of outside experts and artisans to provide general understanding of a patent, which Teva argues are factual findings and
should be given deference.
Robert Brunelli, an attorney at Sheridan Ross, said brand-name drug companies would likely spend more money to
bring in experts to help argue their patent claims, leaving generic drug companies at a disadvantage.
“I think there is going to be a lot more evidence submitted...further burdening the district court and slowing down
decisions in patent cases and making cases more expensive,” he said (see FDA Week, Nov. 13).
Sandoz and Mylan, which filed generic Copaxone applications, contended there were ambiguities within the patent
claims when dealing with the term “average molecular weight,” but the U.S. District Court of the Southern District of
New York rejected this argument, saying the term was not “insolubly ambiguous.”
Justice Clarence Thomas, who wrote the dissent joined by Justice Samuel Alito, said he agrees that the court should
apply clear error review for “findings of fact,” but argued the case surrounds “conclusions of law,” and says that the
Federal Circuit was correct in reviewing the case de novo.
“Bearing these differences in mind, the subsidiary facts relevant to the construction of patents, on the one hand, and
contracts and deeds, on the other, differ substantially,” wrote Thomas. “As explained above, we have justified treating
subsidiary determinations about the actual intentions of parties to contracts and deeds as findings of fact. But the subsidiary determinations about patent claims that the majority identifies as factual do not concern historical facts, such as what
the parties agreed to do or how a given parcel of land is situated.”
He further notes that although the lower court relied on expert testimony to understand the science underlying Teva’s
claims, the court made no “findings of fact.”
Google, Dell, Hewlett-Packard, Twitter and Yahoo had all weighed in on the case in support of Sandoz, describing
Teva’s argument as “radical.”
“As this Court held just last Term, patents must provide the public with clear notice of their meaning, so the public
can determine the boundaries of a patentee’s exclusive property right with reasonable certainty... According to petitioners,
however, claim construction should turn on a battle of paid experts and other extrinsic ‘evidence’ found nowhere in the
public record of a patent application,” said the groups in an amicus brief. “That position would revolutionize claim
construction itself (not just appellate review) and defeat the public notice function of patent documents.” — Erin Durkin
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FDA Week - www.InsideHealthPolicy.com - January 23, 2015