PDF Version - InsideHealthPolicy.com

FDA Week
an exclusive weekly report on Food and Drug Administration policy, regulation and enforcement
Vol. 21, No. 2 — January 16, 2015
Avalere: Generics, CMS, Insurers Largely Absent From Cures Debate
Comments and testimony submitted to House lawmakers working on a 21st Century Cures initiative have largely
focused on orphan and rare diseases, addressing issues from approval pathways, regulatory burdens on innovators and
health IT, according to a report put out by Avalere Health, a healthcare analyst group. The report suggests proposals to
create broad new market incentives and to change clinical trial designs will face major hurdles.
Avalere’s report, “21st Century Cures: Who’s In, Who’s Out, and What’s Next,” also says there was heavy engagement among patient groups, biopharmaceutical and device industries around the initiative; but generic drug manufacturcontinued on page 5
Upton, DeGette Lay Out Basic Framework For 21st Century Cures Bill
House Energy & Commerce chair Fred Upton (R-MI) and Rep. Diana DeGette (D-CO) on Tuesday laid out five
broad goals of the 21st Century Cures draft bill they plan to introduce later this month: targeting clinical trials to the
“right group” of patients; better integrating the patient perspective into the regulatory process through public-private
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.
continued on page 6
FDA Urged To Clarify LDT Risk Classification, Harmonization With CMS
Stakeholders are pushing for more clarity on key aspects of FDA’s proposed framework for regulating laboratory
developed tests (LDTs), including how the agency will classify risks and harmonize its requirements with those of CMS.
The issues came up at a public workshop held by FDA last week on challenges related to its proposed LDT framework, which has received backlash from the laboratory community as being a statutory overreach and burdensome (see
FDA Week, Jan. 9). The agency laid out in draft guidance last year its plan to apply the existing device classification
system to LTDs over a nine-year implementation period.
continued on page 8
Opioid Guide Not Included On FDA Agenda, Despite Congressional Push
FDA’s anticipated final guidance on evaluation and labeling of abuse-deterrent opioids is absent from the recently
released list of guidances the drug center plans to publish this year — a notable omission considering Congress’ yearend spending package withheld $20 million in salaries and expenses for the FDA commissioner’s office pending
finalization of the guidance.
While FDA did not respond to inquiries about the guidance, HHS Secretary Sylvia Burwell told press Thursday
(Jan. 15) that she hopes to work with Congress to drive down opioid dependency and overdose death. “We have an
continued on page 11
FDA To Open GUDID Accounts For Class III I/LS/LS Devices Jan. 26
The massive Global Unique Identifier Database that tracks medical devices will open for labelers of Class III
implantable, life-supporting, life-sustaining devices on Monday, Jan. 26, the agency announced in a webinar on Wednesday (Jan. 14). Stakeholders have been in a holding pattern since the final UDI rule went into effect for Class III I/LS/LS
in September of last year.
The announcement from FDA came in the middle of a webinar guiding stakeholders on GUDID submissions, an
effort by the agency to ramp up outreach efforts to medical device manufacturers looking to comply with the rule. While
continued on next page
the database has already gone live, the database has yet to be populated by device identifiers, or the mandatory, fixed
portion of the UDI that denotes the specific version or model of a device and the labeler of that device. The database is
accessible via FDA’s GUDID Web Interface, a secure web portal where anyone can search for a medical device.
FDA followed up with a letter to UDI stakeholders Thursday (Jan. 15) urging them to make necessary preparations before requesting a GUDID account or submitting device identifier records. “FDA’s experience and feedback from
industry indicate that device labelers often take a number of actions related to organizing, collecting and validating data
— before they get a GUDID account or submit device identifier (DI) records. We strongly encourage all device labelers
to take such actions to ensure their readiness to meet UDI requirements and streamline the GUDID submission process.
Suggested steps can be found on the UDI website,” the letter states.
The first population of entries will be a benchmark for the rest of medical devices, with Class I devices required
to be properly labeled by 2018. FDA has set up a series of webinars, such as the one hosted Wednesday, to help
industry understand all the provisions in the rule. In addition, FDA’s Center for Devices and Radiological Health is
planning to release two draft guidance documents in 2015 with respect to UDIs: direct marking and a frequently
asked questions list.
Navigating the rule has been tricky for some stakeholders, as the rule has built-in ambiguities that allow labelers to
be flexible in implementing the rule. For example, FDA does not specify where a UDI should be placed, only that a UDI
needs to be affixed to the device. But regulations governing single-use devices, reprocessed devices, packaging and
software-only components were the main concerns brought up by members on the call. FDA officials offered help but
directed most to the UDI help desk.
Until Jan. 26, said Indira Konduri, GUDID program manager at FDA, manufacturers have “plenty of homework to
do,” familiarizing themselves with navigating the UDI rule and setting up accounts to begin inputting data into the
massive database. Eventually, other FDA officials have said, patients and others will be able to look up their devices and
monitor adverse events or recalls.
The database is intended to serve as a reference catalog of information about every FDA-approved device with a
barcode identifier, which will be accessible to allow provider systems, payers, clinicians, patients and industry to search,
download and use information. The database is structured in a way so that in the future hospitals can scan devices to
automatically upload the information to a patient’s EHR for insurance providers as well as the GUDID for near-real time
analysis. FDA has assured patients and manufacturers that no patient information or proprietary information will be
available in the GUDID database.
In Thursday’s letter, FDA notes that it has also updated two important GUDID resources: HL7 SPL Implementation
Files (Jan. 13) and GUDID Data Elements Reference Table (Jan. 14). Plus, the agency says it is continuing to work with
the National Library of Medicine as part of its plan to give the public search and download access to published records in
the GUDID in the spring of 2015. “GUDID search will allow GUDID data to be retrieved based on parameters of interest
to the user. The GUDID download function will let users download all GUDID data at once,” the letter says.—David
Premarket-Postmarket Data Collection On FDA’s Device Guidance Agenda
FDA has pegged as “A-list” priorities 12 device guidance documents it hopes to finalize this year that include
guidances on balancing premarket and postmarket data collection for devices subject to premarket approval; and on
crafting 510(k) submissions for devices that include antimicrobial agents. FDA last week issued its list of of final
guidance documents it plans to develop in 2015, with the intention of clarifying or assuaging industry concerns on hotbutton issues left over from 2014.
FDA’s Center for Devices and Radiological Health also lists regulatory oversight of laboratory developed tests,
validation methods and labeling, reprocessing medical devices in clinical settings, and safety measures for 510(k)
submissions on the priority list.
In addition, eight draft guidance topics are slated to be updated. Among them: UDI direct marking and an update to
UDI “frequently asked questions” document to assist industry in implementing UDI labeling rules.
“B-list” items, or second-priority guidances, the center is considering include documents on medical device
interoperability, questions and answers to transfers of ownership of a premarket motification, direct access genetic in
vitro diagnostics testing (also known as direct-to-consumer genetic testing), patient access to information, 3D printing,
manufacturing site change supplements, the use of symbols in labeling, and finalizing other existing draft guidance
documents. – David Hood
FDA Week - www.InsideHealthPolicy.com - January 16, 2015
IOM Report Pushes Framework For Public Sharing Of Clinical Trial Data
The Institute of Medicine recommends clinical trial data be made public at specific points during the study process,
while also suggesting safeguards be put in place to protect participants and the legitimate economic interests of sponsors
as well as ensure original researchers get proper credit for their work. An IOM report released Wednesday (Jan. 14) says
the “responsible sharing” of clinical trial data, including from unsuccessful trials, is in the public interest and can advance
new discoveries, stimulate new ideas for research, improve clinical care and and avoid unnecessary duplicative trials, and
notes that academic researchers and several big pharmaceutical companies are already sharing clinical data and the
European Medicines Agency plans to do so in the near future.
IOM calls for the sponsors of its report — which include the National Institutes of Health, National Academy of
Sciences, FDA and a number of charitable foundations and pharmaceutical companies — to take the lead in developing a
“multistakeholder body with global reach” to address standards as well as infrastructure, technological, sustainability and
workforce development challenges that come with clinical sharing data.
The report says an independent panel including patient advocates should be set up to address data requests, and says
more discussion is needed on a way for data-sharing costs to be distributed equally between the people that generate the
data and those who use the information.
“The rapidly changing landscape of clinical trials and the movement toward greater transparency create a need to
establish professional standards and set expectations of how to share clinical trial data,” said Victor Dzau, president of
IOM. “Numerous approaches and models for sharing clinical trial data are being implemented across the globe, and more
and more organizations are taking the initiative to share their data. The time is right to have the principles in this report
serve as a guide for what specific clinical trial data to share, at what time, and under what conditions.”
IOM lays out a clear timeline for when specific data should be shared, which begins with sponsors and researchers developing a plan for which data will be shared when and under which conditions publicly at a third-party site that
meets the specifications of the World Health Organization’s International Clinical Trials Registry Platform at the time of
trial registration before the first participant is enrolled. IOM suggests researchers, where possible, build standardized
common data elements into study reports to make sure the information is easily accessible and usable by others.
IOM also calls for sponsors to set up independent review panels that include representatives of patient and disease
advocacy groups to address questions surrounding data access. “If the trial sponsor or investigator, rather than an independent review panel, reviewed data requests and made decisions regarding access, concerns about conflicts of interest
could lead to mistrust,” says the IOM report, titled “Sharing Clinical Trial Data: Maximizing Benefits, Minimizing
Under the proposal, summary-level results of the data would be made available, with a simultaneous release of lay
summaries for participants, no later than 12 months after the completion of a study. Full data packages, which include the
entire analyzable data set, full protocol, statistical analysis and analytic code, would be released within 18 months of
completion of the study unless the trial is in support of a regulatory application, IOM says. In the case of studies that
support regulatory approval, IOM says, data should be released 30 days after regulatory approval or 18 months after
completion of the study, whichever comes later.
For studies of new products or indications that are abandoned, IOM says, data should be shared within 18 months of
abandonment of the study unless the product is licensed to another party for development — in that case the data should
be shared after publication, approval or final abandonment.
Bernard Lo, president of The Greenwall Foundation and chair of the IOM committee responsible for the report, said
at a public meeting on the report Wednesday that the timelines laid out are not hard and fast and the committee hopes that
as a culture of data sharing develops the information is made publicly available sooner rather than later.
To ensure protection of privacy of participants, the report says, data should be deidentified, and sharing
agreements should make clear that the information cannot be reidentified and agreed to by secondary users of the data,
and participants need to know and consent to the data being shared.
“People need to understand that while there will be measures taken to protect the anonymity of the data that there are
not absolute guarantees about that,” said committee member Deven McGraw, a lawyer that works in the healthcare
practice at Manatt, Phelps & Phillips, LLP.
The report recognizes four major challenges to creating an environment where public sharing of clinical trial
data is the norm — infrastructure, technology, workforce and sustainability — and says the multistakeholder body called
for should continue to work on these issues.
With regards to infrastructure and technological challenges, the report points out that currently there are insufficient
platforms to store and manage clinical trial data over a variety of access models and the existing platforms are not
interoperable and are not consistently discoverable and searchable.
“Special attention is needed to the development of common protocol data models and common data elements to
ensure meaningful computation across disparate trials and databases,” the report says.
The report points out that there is not a sizable workforce at this point that has the skills and knowledge to manage
FDA Week - www.InsideHealthPolicy.com - January 16, 2015
the operational and technical aspects of data sharing. Committee members said this is an area where research universities
can take the lead in the development of the needed workforce.
In order for the sharing of clinical trial data to be sustainable, the report says, the costs involved need to be
distributed equally between the people that generate the data and the people who use the data.
Lo pointed out that at this point when clinical trial data sharing occurs the costs are being borne solely by sponsors
and researchers who produce the data.
“That’s not a sustainable model,” Lo said. “It’s also not a fair model. We recommend that those who benefit from
sharing clinical trial data should also bear a fair share of the cost. How that is going to be worked out is something that
needs to be worked out in the future.”
The report does not detail a timeline for when its recommendations for clinical data sharing should begin, but says
the proposals are intended as a guideline for creating a culture where public sharing of clinical trial data is the norm.
“This is not the end of the conversation, it’s just the beginning,” Lo said. — Todd Allen Wilson
FDA Urged To Use ‘Influence’ With CMS To Hike Reimbursements For LDTs
Stakeholders urged FDA to involve CMS and payers in its oversight of laboratory developed tests (LDTs), as lab
stakeholders noted at a public workshop last week that many labs don’t have resources to go through FDA’s approval
The public meeting invited stakeholders to weigh in on FDA’s proposed LDT framework, which applies the agency’s
medical device risk classification system under a nine-year implementation timeline for LTDs that qualify.
A diagnostic industry consultant suggested that FDA use its influence with CMS and the HHS secretary to push for
better reimbursements of these tests.
“I urge FDA to recognize this is a significant unfunded mandate for laboratories,” said Katherine Tynan, president of
Tynan Consulting LLC. “You should use your influence to raise the issue with CMS and HHS Secretary. Labs are under
huge financial constraints and this has been exasperated by poor reimbursements for many tests.”
The idea was also floated to include payers on FDA’s expert advisory panels to help determine risk classifications for devices that had not been previously classified by the agency. Andrew Fish, Advanced Medical Technology
Association Diagnostics executive director, said he supported this idea, as payers are looking to FDA’s review to make
coverage decisions.
The call for payers to be involved in the approval discussions comes as laboratories bring forth concerns that they do
not have the resources to keep up with FDA approval.
“The prohibitive costs of obtaining FDA premarket clearance or approval for each such test would leave many
laboratories unable to continue offering them, despite patient need and physician demand,” states a white paper from the
American Clinical Laboratory Association released the day before the meeting (see FDA Week, Jan. 9). “Even where
supported by well-accepted, peer-reviewed research and scientific studies, ‘low-volume’ tests designed for individual
patients or small patient populations often generate only modest financial returns for laboratories.”
Lawrence Hertzberg, medical director of CSI Laboratories, said that small reference labs like his would effectively
be driven out of business if FDA were to enforce its proposed framework as is.
“We in essence completely lack the resources necessary to submit any 510(k) documentation to the FDA,” he said.
“The effect of regulations like this for a laboratory like mine could well mean that there are very few remaining reference
laboratories in the country.” — Erin Durkin
Senate Device-Tax Repeal One Dem Shy Of Passage, Warren Not A Cosponsor
A bipartisan Senate bill repealing the ACA’s contentious medical device tax appears to be only one Democrat shy
from passage. Five Democratic senators cosigned the legislation, introduced Tuesday (Jan. 13), but Sen. Elizabeth Warren
(D-MA), a long-time supporter of repealing the tax who reportedly was courted as a cosponsor, is not on the bill.
Warren has supported repealing the device tax since winning her Senate seat in 2012. Her office did not respond to
Inside Health Policy for this article, and other news reports also say she has declined to discuss whether she will support
the bill, called the “Medical Device Access and Innovation Protection Act.”
Senate Finance Committee Chair Orrin Hatch (R-UT) introduced the bill, and nine other senators cosponsored it:
Sens. Amy Klobuchar (D-MN), Pat Toomey (R-PA), Joe Donnelly (D-IN), Richard Burr (R-NC), Al Franken (D-MN),
Rob Portman (R-OH), Bob Casey (D-PA), Dan Coats (R-IN) and Jeanne Shaheen (D-NH).
“Every dollar medical device manufacturers spend on this onerous tax is a dollar taken away from American innovation, job growth, and the ability to provide groundbreaking medical technologies to patients in need,” Hatch said. “Both
Republicans and Democrats understand just how bad this tax really is, and we owe it to the American people to ensure the
development of life-saving medical devices are not plagued by high costs that will, ultimately be passed on to patients.
FDA Week - www.InsideHealthPolicy.com - January 16, 2015
This is a common-sense bill, and I’m hopeful Congress will act swiftly to repeal this misguided tax once and for all.”
The Advanced Medical Technology Association (AdvaMed), the Medical Imaging & Technology Alliance (MITA)
and the Medical Device Manufacturers Association (MDMA) support Hatch’s bill.
“This tax is an anchor on American economic growth,” said Stephen Ubl, president and CEO of AdvaMed.
The legislation comes on the heels of a similar House bill that at 254 cosponsors, including 27 Democrats, and was
also supported by the three medical device industry groups. — Erin Durkin
FDA Opts Against Updating Proposals On Pregnancy And Pain Medication
FDA, after reviewing studies on concerns about the use of over-the-counter and prescription pain medication, has
decided not to make any new recommendations on the issue. The agency said Jan. 9 that research studies published in the
medical literature are too limited for FDA to make a decision, and instead the agency will stick with its current recommendation that all pregnant women discuss all medicines with their doctor’s before taking them.
“We found all of the studies we reviewed to have potential limitations in their designs; sometimes the accumulated
studies on a topic contained conflicting results that prevented us from drawing reliable conclusions. As a result, our
recommendations on how pain medicines are used during pregnancy will remain the same at this time,” FDA said in a
drug safety communication.
The agency looked at studies that reported the potential risks associated with three types of pain medication:
Prescription nonsteroidal anti-inflammatory drugs — including ibuprofen, naproxen, diclofenac and
celecobix — and the risk of miscarriage in the first half of pregnancy.
Opioids — including oxycodone, hydrocodone, hydromorphone, morphine and codeine — and the risk of
brain, spine and spinal cord defects in babies born to women who took these medications during pregnancy.
Acetaminophen and the risk of attention deficit hyperactivity disorder.
In the communication the agency said severe and persistent pain that is not treated during pregnancy can lead to
depression, anxiety and high blood pressure in the mother, and pain medication can help treat the pain.
“However, it is important to carefully weigh the benefits and risks of using prescription and OTC pain medicines
during pregnancy,” FDA said. — Todd Allen Wilson
Avalere Names ‘Cures’ Items To Watch . . . begins on page one
ers, CMS and health insurers were noticeably absent from the debate. The report states that patient groups account for
almost half of all public comments submitted to the House Energy and Commerce Committee.
“[W]hile America’s Health Insurance Plans (AHIP) and Blue Cross Blue Shield submitted comments and a representative from the pharmacy benefit manager Express Scripts testified at a hearing, other payers (including the Centers for
Medicare and Medicaid Services (CMS)) were noticeably absent,” the group says. “This may be a missed opportunity, in
light of the critical role that payers have in covering new treatments and spreading payment reform methodologies.”
The report identifies legislative items to watch in five major areas — regulatory, post-market evidence, innovative data collection, patient focus and data access/ transparency — and predicts what might transpire.
Among those items, Avalere notes the consistent call for increased funding for the National Institutes of Health and
FDA. However, the report points out that the funding would still need to be appropriated, and that finding additional
funding for NIH may be difficult in the current fiscal climate. “With the Center for Drug Evaluation and Research
currently about 70% funded by user fees, this policy focus also highlights the need for a greater balance of federal
appropriations within FDA’s budget relative to user fees,” the report says.
The report also touches upon development incentives suggested by industry comments and testimony, including
increased market exclusivity. The brand drug industry and some patient groups have pushed for added exclusivity for a
range of cases such as for small molecule drugs and first-in-class treatments. Energy and Commerce health panel chair
Joe Pitts (R-PA) had said company incentives could be included in the upcoming bill stemming from the 21st Century
Cures initiative (see FDA Week, Oct. 27). In an op-ed published this week, committee chair Fred Upton (R-MI) and Rep.
Diana DeGette (D-CO) signaled they haven’t closed the door on such incentives.
Avalere says that Congress is unlikely to fundamentally revisit exclusivity incentives, but adds that lawmakers
have a history of advancing targeted incentives for specific therapies and areas of need. “Members may take cues
from FDA’s Patient-Focused Drug Development series to choose focus areas for incentives,” says the group.
Legislation relating to shifting premarket data burdens to postmarket surveillance duties was also named as something to watch for, but Avalere says changing study designs will be a challenge.
“[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
FDA Week - www.InsideHealthPolicy.com - January 16, 2015
to significantly alter this stance to allow widespread reliance on real-world evidence (RWE) for post-market approval
FDA’s device center pegged a guidance document balancing premarket and postmarket data collection for devices
subject to premarket approval as a priority for this year (see related story).
Lawmakers may also direct FDA to create evidentiary standards for patient reported outcomes (PROs) to supplement
an expected guidance on off-label communication, the report says. Avalere notes that comments to the committee have
included calls for incorporation of patient-focused data such as PROs into FDA’s approvals process, and that the life
sciences industry has long sought clarity on how it may differentiate products using PROs.
The op-ed by Upton and DeGette outlines five broad goals of the 21st Century Cures draft bill: targeting clinical 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 (see related story). — Erin Durkin
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
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
Stakeholders View ‘Cures’ As Prequel To PDUFA . . . begins on page one
In a Jan. 13 CNN op-ed on the upcoming bill, Upton and DeGette write that after a year of hearings on the initiative
they are ready to put forward bipartisan legislation that will promote finding cures for 7,000 diseases and ensure the
United States is a leader in the field of medical innovation.
“Our legislation will modernize all of these categories, removing outdated hurdles that can prevent innovation from
flourishing or from fleeing the United States ,” Upton and DeGette write.
The bipartisan duo do not detail specific provisions of the forthcoming draft, but lay out brief justifications of the
four goals laid out in the piece that offer a framework for the legislation.
Streamlining clinical trials. The lawmakers say clinical trails should use technology like genetic screening to create
smaller, more-targeted clinical trials that ensure the “right treatments” are developed for “the right group of patients.”
They say the legislation will also streamline the paperwork process for clinical trials to make it easier to recruit patients
and adapt the operation of trials as new information becomes available.
“[T]he old approach of automatically applying a therapy to a broad group of patients is no longer the best path
forward, particularly for those diseases for which we do not have a treatment or cure,” Upton and DeGette write.
Integrating the patient perspective into the regulatory process. The lawmakers say they want to build off the
FDA’s Patient-Focused Drug Development Program to incorporate patients perspectives into the regulatory process by
using public-private partnerships to help “build the science” around biomarkers and patient-reported outcomes.
“We also will create a predictable process for the qualification of biomarkers and patient-reported outcomes so we
can utilize these tools in the development process,” they write.
Promoting better access to and sharing of data. Upton and DeGette say the bill will promote better access and
sharing of genomic and other clinical data among researchers and foster interoperability. The bill will also “assist developers and entrepreneurs” develop patient-focused technologies by reducing regulatory uncertainty as they design new
apps and products.
“With the explosion of technology, we can collect, monitor and analyze information like never before, helping
patients stay healthy and adopt healthy habits while also making treatments safer and more effective,” they write.
Increasing and targeting funding for scientific research. The pair says the legislation help young scientists have
more access to resources to fund their research and encourage them to conduct their research in the U.S.
“Many of our most promising investigators — many with great ideas and cutting edge training — are hamstrung by
FDA Week - www.InsideHealthPolicy.com - January 16, 2015
the challenges of securing much-needed support,” they write.
Incentivizing new drugs and devices for unmet medical needs. Upton and DeGette say the legislation will
streamline the premarket process and create mechanisms to “better capture” evidence post-market in the development of
drugs and devices designed to target unmet medical needs. They say the bill will also “examine incentives” like exclusivity and simplifying the reimbursement process.
“America has a strong history of finding solutions to diseases through medical innovation. Today, partnerships with
patients and advocates, health care workers and researchers, and government and the private sector can speed the cycle of
finding faster cures,” Upton and DeGette write.
Upton has said he expects to have final language for the bill in March, and hopes to have a vote on the legislation by
Memorial Day with the goal of having the measure on 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 the
21st Century Cures initiative is a “front burner” priority for the agency. — Todd Allen Wilson
Merkley Brings Anti-Tobacco Stance To FDA Approps Panel
Sen. Jeff Merkley (D-OR), a strong advocate for FDA controls over tobacco, was tapped Friday (Jan. 9) as ranking
member of the Senate Appropriations agriculture panel that oversees FDA’s budget. Merkley served on the committee
during the last session and was expected to be ranking member of a subcommittee though it had been unclear which one.
He was selected for the agriculture and FDA subcommittee because of his roots in rural Oregon and his position as an
anti-tobacco advocate who will push FDA to crack down on illegal uses of tobacco, including protecting children from
tobacco and nicotine addiction, according to a release from his office. — David Hood
Study Finds Little Bias Among FDA Advisors, Public Citizen Disagrees
A study by George Mason University School of Law finds that there is “almost no” evidence that members of
FDA advisory committees with conflicts of interest have biases in favor of drug company interests when their votes
are measured against final FDA approval of a product or company stock prices in reaction to advisers’ recommendation. But the consumer advocacy group Public Citizen, which has long complained about conflicts of interest among
those serving on FDA advisory panels, says the benchmarks used by GMU’s Searle Civil Justice Institute are
The study released last week looked at advisory committee votes from January 1997 through December 2012 on
whether the agency should approve a new drug.
Decisions by advisory panels with conflicted members and individual votes by conflicted members are more likely to
be in line with FDA decisions and stock market predictions than non-conflicted ACs and non-conflicted members, the
study, titled “FDA Advisory Committees: Conflicts of Interest and Voting Relative to Benchmarks,” says.
“The presence of conflicts appears to have no statistically measurable impact on the accuracy of AC decisionmaking, measured as either consistency with the FDA or stock market predictions. If anything, conflicts lead to too few
approval recommendations, which is the opposite of the concern that has motivated recent AC [advisory committee]
reforms,” the study says.
In FDA Amendments Act of 2007 placed a 13 percent cap on the number of conflicted members that could serve on
an advisory committee, and the maximum financial interest a conflicted member could have and still receive a waiver to
serve on a committee was reduced from $100,000 to $50,000.
The study says the law’s restrictions may be the real problem as opposed to having conflicted members on
committees because they make it difficult for FDA to find highly qualified people to serve.
“The same specialized education and scientific experience that makes these experts attractive candidates to serve on
ACs also puts them in contact with drug companies. Conflicts arise because biopharmaceutical firms often employ or
contact these same expert physicians, researchers, and clinicians to help them develop and market their products. For
instance, companies seek out these experts to monitor or run their clinical trials, speak at various company-sponsored
meetings, consult, write briefs, or serve on review boards. Drug companies, moreover, fund research studies at universities and research institutes that employ these experts,” the study says.
Relative to final FDA decisions the study found that conflicted members’ votes recommending drug approvals are
more consistent with the agency’s ultimate decisions than are those of non-conflicted members, with conflicted members
40 percent less likely to disagree with FDA.
“If the FDA decision represents an unbiased benchmark of ‘correct’ voting, these results may imply that ACs with
conflicted members vote too infrequently to approve drugs, but it is contrary to a claim that ACs with conflicted members
FDA Week - www.InsideHealthPolicy.com - January 16, 2015
tend to be biased toward drug approval,” the study says.
But Sammy Almashat, a researcher with Public Citizen, said FDA decisions are not a useful benchmark
because the agency’s ultimate determinations on whether to approve a drug are made by management rather than the
agency’s scientists. Almashat noted that instances of scientists at FDA being overruled by management are very frequent
— a problem he said is also a concern to Public Citizen.
“In those instances according to the study that was put out the FDA’s management would be ‘correct,’ and the FDA
scientists are not accounted for at all,” Almashat said. “That’s the reason why we think the FDA’s [decisions] are not
necessarily a useful benchmark.”
The study also found that the stock market is “rarely surprised” by advisory committee recommendations, and those
made by conflicted panels are less likely than those by non-conflicted panels to surprise investors. The study notes that
many investment firms hire drug industry experts to evaluate expected advisory committee recommendations and final
FDA decisions.
“The meeting level analysis shows that ACs with a larger proportion of conflicted members are less likely to make
decisions contrary to investor expectations. To the extent that investor expectations are a proxy for ‘correct’ decisions,
these results suggest that conflicts improve the accuracy of decision making,” the study says.
Almashat said using stock market predictions as a benchmark is “highly flawed” for two reasons. The first he
said should seem obvious in that “what is good for investors is not necessarily good for the public.”
The second, Almashat said, is that it is a circular argument to say that voting patterns of people who are connected to
the industry correlate to predictions made by investors who financially benefit from the industry. He said this benchmark
speaks more to the predictive ability of investors than voting patterns of members.
“It doesn’t say anything about the validity of the decisions themselves,” he said. “It just relates to the fact that
investors see the same way as conflicted members. So it doesn’t really tell us much about how good the decision ultimately is.”
Pointing to previous studies, Almashat said that the bias of conflicted members is very difficult to measure and there
is an evident trend of higher approval levels by FDA. Rather than explicit bias on the part of conflicted members, there
seems to be a high level of “group think” that takes place among committee members and FDA officials that potentially
make conflicted members less skeptical than they objectively should be when considering evidence for approval of drugs,
he said.
Almashat said that the public puts its trust in these committees whose decisions can have “enormous public health
importance.” He said the “absence of evidence” that conflicted members of advisory committees are biased isn’t the
“evidence of absence.”
“Having members who receive tens of thousands of dollars from the same industry that is affected by their vote in a
public committee, to us, doesn’t seem to be the ideal scenario. Undermining public trust is a huge problem,” Almashat
said. — Todd Allen Wilson
FDA Holds LDT Public Workshop . . . begins on page one
At the public workshop stakeholders urged FDA to release more guidance around the area of risk assessment.
“It probably would be helpful if the agency would consider publishing... a document laying out a way risk should be
assessed,” said Advanced Medical Technology Association Diagnostics Executive Director Andrew Fish. He raised
concerns that everyone would have a different idea of what high risk is unless FDA provides more information in this
FDA’s draft guidance explains that the agency will rely upon the existing medical device classification system to
evaluate the risk of a category of LDTs and will use expert advisory panels to help classify devices not previously
classified by FDA.
“The entire framework is predicated on risk classification,” said Amy Miller, executive vice president of the
Personalized Medicine Coalition (PMC). “I think there’s a lot of confusion about what is the highest risk, and about
that line where the highest risk ends and where moderate risk begins.”
Fish also suggested that advisory panels be convened for specific clinical areas and health conditions. “A bunch of
risk considerations are situational,” said Fish. He also added that he supports the idea of allowing payers to provide input
to the advisory panels, as these stakeholders are looking to FDA’s review to make a decision.
Miller, in public comments, also pushed for harmonization between the CMS’ Clinical Laboratory Improvement Amendments requirements and FDA’s manufacturing recommendations.
“Two large critical pieces of the framework are missing,” she said. “First, guidance on LDT risk classification, and
second, harmonization between the CLIA program and FDA’s manufacturing recommendations.”
She said these two pieces of information are substantial enough that the agency should release another draft, and
FDA Week - www.InsideHealthPolicy.com - January 16, 2015
recommended releasing the requested documents as a draft package as it would lead to more robust revision of the
Sheila Walcoff, CEO and founder of Goldbug Strategies LLC and prior senior counselor to the HHS secretary, also
pushed for the harmonization between FDA and CLIA requirements, adding that where there is overlap, FDA should rely
on previously existing CLIA requirements.
FDA said it will consider several factors in determining the risk an LDT poses to patients, including: whether
the device is intended for use in high risk disease/conditions or patient populations; whether the device is used for
screening or diagnosis; the nature of the clinical decision that will be made based on the test result; whether a physician
or pathologist would have other information about the patient to assist in making a clinical decision; the alternative
diagnostic and treatment options available to the patient; the potential consequences or impact of erroneous results; and
the number and type of adverse events associated with the device. — Erin Durkin
Burwell Lists 2015 Priorities For Administration, Congressional Agreement
HHS Secretary Sylvia Burwell said at the New America Foundation Thursday (Jan. 15) that she believes Congress
and the administration can find bipartisan agreement on CHIP and Medicare’s sustainable growth rate, signaling an effort
to move on to priorities other than the Affordable Care Act.
Burwell outlined areas where politicians may be able to progress this year: higher quality of care with more responsible health spending; reducing substance abuse disorders and overdose deaths; improving global health security; boosting America’s research, innovation and scientific capabilities; and growing “precision medicine” by looking at people’s
DNA to customize care.
“I hope that we can move beyond the back and forth of the Affordable Care Act and focus on the substance of access,
affordability and quality,” she said.
When asked if she is confident that the administration will hit its goal of 9.1 million effectuated enrollments by the
end of the sign-up period Feb. 15, Burwell did not give a direct answer but said efforts like “Latino Week of Action,” a
recent push to enroll the Hispanic community, and other targeted outreach will aid them in moving toward the final goal.
“I believe that we’ve made strong progress,” she said. “We have a ways to go.”
Burwell also reiterated that reducing health care costs is important to reducing the long-term federal deficit.
“When you start to see that 2011, 2012, 2013, those numbers in terms of the lowest per capita health care costs
growth that we have seen on record, when you see that downward pressure on Medicare in terms of its per capita growth
being nearly flat, over an extended period of time, I think we are starting to see that,” she said.
“Are those structural changes that will last for an extended period of time? How that incorporates with more people
getting care, we need to keep our eye on,” Burwell added. “That’s why I was emphasizing so much delivery system
reform because while that’s an issue that’s about quality, it is about changing the way we do things so we get some of that
long-term cost savings that we are talking about.”
Despite continued the GOP’s ongoing effort to repeal Obamacare, Burwell said she will work with those who have
expressed interest in moving forward Medicaid expansion and other provisions of the ACA.
GOP lawmakers this week headed to a party retreat and scheduled breakout sessions on health care, and on the
budget and reconciliation. GOP leadership is expected to include reconciliation instructions in its budget, which would
allow certain ACA provisions to be repealed under a simple majority, however some sources believe it is unlikely the
mechanism will be used due to its complexity. The GOP will also huddle on tax reform, which could end up being a larger
priority than health in the 114th Congress.
Burwell during the speech gave no indication that HHS officials have been in discussions with GOP so far this
year. “We are hopeful and look forward to that opportunity,” Burwell said when asked if she has spoken to any Republicans who stray from the GOP leadership line of repealing the ACA. “We want to find places where the Act can be
improved … We welcome the conversation.”
Senate health committee Chairman Lamar Alexander (R-TN) said in a statement that he welcomes Burwell’s comments and looks forward to working with her.
“We have plenty we disagree on, but we also have plenty of issues that are important to millions of Americans upon
which we should be able to get results, including, for example, getting life-saving drugs, treatments and devices through
the FDA to patients faster; remodeling the health care delivery system; and improving global health security,” Alexander said.
Burwell’s mention in her speech that she hopes to work with Congress on reducing substance abuse disorders
and overdose deaths comes as FDA’s recently released guidance agenda excludes an opioid guidance sought by
lawmakers — Rachel S. Karas
FDA Week - www.InsideHealthPolicy.com - January 16, 2015
CMS Sued For Retroactively Changing Drug Compounding Reimbursement
An Alabama company is suing CMS after receiving a re-pricing letter saying the company owed the government
about $25 million due to billing changes for compounded drugs. A lawyer for the company questioned whether CMS can
retroactively change prices and an industry attorney said the case may change how much authority the agency is willing to
give Medicare Administrative Contractors.
James Hoover, a lawyer for Alabama Pain Center, questions CMS’ use of the sub-regulatory process and says the
agency’s bid to retroactively apply a local coverage decision is unconstitutional. Stephanie Trunk, an industry attorney
following the case, predicts the controversy could spur CMS to come up with more uniform rules for Part B reimbursement and to reduce Medicare Administrative Contractors’ authority at the local level.
According to the brief filed on behalf of Alabama Pain Center, the company had been working with Medicare
Administrative Contractor Cahaba and getting guidance on billing since 2008. In 2013, Alabama Pain Center received a
local coverage article (LCA) from Cahaba setting a new fee schedule for the compounded drugs they administer. In 2014,
Alabama Pain Center was investigated by AdvanceMed, a Zone Program Integrity Contractor that concluded Cahaba had
overpaid for the drugs over a four-year span. After much back and forth, AdvanceMed said a re-pricing of the drugs was
underway and later alleged the company owed about $25 million based on a review of about 60 claims.
Hoover said it is unconstitutional and violates rulemaking for the government to apply the new prices set forward in
the LCA or re-pricing letter retroactively.
Hoover also argues the re-pricing letter is a substantive rule and should have been subject to prior notice and
Others in the compounding world have said they haven’t seen a case like this before.
Trunk, a partner at Arent Fox who specializes in drug pricing, said this is her first time seeing retroactive pricing.
The Alabama Pain Center makes and administers these drugs in its office and bills them under Medicare Part B.
Trunk said Part B is a section of Medicare in which reimbursement rules might be less clear for compounded drugs than
for drug prices under Part D, especially given that the center is mixing drugs with potentially different prices.
Trunk said Hoover gave a solid argument that what CMS did could not be applied retroactively, but regardless of
how the case turns out, she thinks it could lead to some changes.
“This may ultimately lead to CMS coming up with more uniform national rules on the Part B side,” she said,
possibly modeling the rules after Part D and giving less authority to MACs on the local level.
The International Academy of Compounding Pharmacists said the group is not involved in the case, but sees disparities in which entities can bill Medicare for compounded drugs. —Rebecca Beitsch
Attorney Points To Compounding Regs To Guide FDA In LDT Oversight
An industry attorney is urging FDA to use its drug compounding policies as a roadmap as it weighs how to oversee
laboratory-developed tests. How the agency distinguishes between medical practice and manufacturing in the pharmaceutical compounding setting could guide the agency as it similarly tries to determine which LDTs should be regulated as
medical devices, the attorney said at an FDA public meeting last week.
Disagreement over whether FDA has authority over LDTs was sparked when the agency unveiled a draft framework
applying the medical device classification system to LDTs over a nine-year implementation period. The American
Clinical Laboratory Association has argued that FDA’s proposed requirements are a statutory overreach, but the Advanced Medical Technology Association views the lab group’s effort as “an attempt to obscure the fact tests are a regulated tool that doctors use in the care of patients” (see FDA Week, Jan. 8).
At a public workshop discussing the draft framework, an attorney representing the Combination Products Coalition
drew comparisons between the legal questions surrounding LDTs and pharmacy compounding.
“In my opinion there is no legal issue [for FDA] to regulate IVDs, I am using that term carefully, [in vitro diagnostics] produced by laboratories,” said Bradley Merrill Thompson, an attorney at Epstein Becker & Green who discussed
the topic on a panel. “There’s no question at all. The question is when does the LDT process merge into or become an
IVD process regulatable by FDA. At the end of the day, there are legal issues distinguishing those two activities.”
Thompson said the LDT debate is similar to legal questions surrounding pharmacy compounding, where FDA set a
line marking when pharmacists crossed over from pharmacy practice and began pharmaceutical manufacturing.
In a draft blog he shared with FDA Week, the industry attorney refers to a compliance policy guide put forth by the
agency in 1992 and 2002, but was declared obsolete when the Drug Quality and Security Act (DQSA) was passed in
“[T]he pharmacy compounding rules offer us guidance as to how we might approach the dividing line between
legitimate laboratory services regulated by CLIA, and IVD manufacturing that FDA regulates, even if both are conducted
in a clinical laboratory,” says Thompson.
He lists factors FDA could use to make the distinction between the LDT process and IVD manufacturing
FDA Week - www.InsideHealthPolicy.com - January 16, 2015
based on the “pharmacy compounding precedent,” considering whether:
Test materials are made in advance of receiving an order from a physician for the test, and stored until such time
as a physician places an order.
The tests duplicate already manufactured tests, with a similar narrow exception as described under pharmacy
Test materials are made using manufacturing equipment and manufacturing processes not customarily used in
laboratory testing services.
Promotion of the protocol is evidence that it is really the protocol that is being sold.
The LDT is designed, manufactured and used by a single laboratory.
The LDT is comprised only of components and instruments that are legally marketed for clinical use.
The LDT is both manufactured and used by a health care facility laboratory for a patient that is being diagnosed
and/or treated at that same health care facility or with the facility’s healthcare system.
The LDT is interpreted by qualified laboratory professionals, without the use of automated instrumentation or
software for interpretation.
Thompson’s discussion came as other stakeholders at the meeting fell on either side of the debate as to whether FDA
should be enforcing requirements upon LDTs.
“I am absolutely outraged at the FDA guidance,” said Edward Ashwood, president and chief executive officer at
ARUP Laboratories, who went on to describe the draft framework as “misguided” and “naive.”
But Christopher Newton-Cheh, an assistant professor of medicine at Harvard Medical School representing the
American Heart Association, told FDA Week that the group is very supportive of the framework.
“We don’t support regulation just for the sake of regulation,” said Newton-Cheh. “There’s been a proliferation of
tests that are of variable clinical utility.” — Erin Durkin
Opioid Guide Not On CDER’s List . . . begins on page one
opportunity to work together on improving opioid prescribing practices by enhancing prescription monitoring, data
sharing, and clinical decision-making,” she said. “We also want to incentivize the development of abuse-deterrent opioids
and expand the utilization of naloxone — a drug that’s used to reverse overdoses.”
The agency’s draft version of the document, “Guidance for Industry Abuse-Deterrent Opioids — Evaluation and
Labeling,” unveiled in January 2013, lays out the agency’s preliminary thinking on studies that should be conducted to
demonstrate that a given formulation has abuse-deterrent properties, how those studies will be evaluated and what
labeling claims may be approved based on the results of those studies.
The “cromnibus” spending package passed in December gives FDA until June 30 to release the final guidance, and
stating if the deadline is not met the $20 million withheld from the commissioner’s office will be transferred to FDA’s
Office of Criminal Investigation to assist federal, state and local agencies in combating the diversion and illegal sales of
controlled substances.
The Alliance for a Stronger FDA described the language as an “unusual (if not unprecedented)” challenge from
Congress. The provision was originally included in earlier versions of House appropriations bills, moves that drew White
House veto threats at the time.
The push from Congress comes as the agency faces increasing pressure to curb opioid abuse and misuse. FDA has
sought comments from stakeholders on possible enhancements the agency could make to opioid packaging, storage or
disposal systems to deter misuse and abuse.
The drug center’s guidance agenda does include several other high-profile documents, including a guidance on
current good manufacturing practices for outsourcing compounding facilities, six separate drug tracing guidances, a
guidance addressing development of drugs for Duchenne Muscular Dystrophy, and four guidances addressing biosimilar
drugs, including labeling. — Erin Durkin
703-416-8500 or
[email protected]
Fax: 703-416-8543
[email protected]
Health Group Publisher:
Associate Editors:
Donna Haseley ([email protected])
Erin Durkin ([email protected])
David Hood ([email protected])
Todd Allen Wilson ([email protected])
Production Manager:
Production Specialists:
Lori Nicholson ([email protected])
Daniel Arrieta, Michelle Moodhe
FDA Week is published every Friday by Inside Washington Publishers, P.O. Box 7167, Ben Franklin Station,
Washington, DC 20044. Subscription rates: $705 per year in U.S. and Canada; $755 per year elsewhere (air
mail). © Inside Washington Publishers, 2015. All rights reserved. Contents of FDA Week are protected by
U.S. copyright laws. No part of this publication may be reproduced, transmitted, transcribed, stored in a
retrieval system, or translated into any language in any form or by any means, electronic or mechanical,
without written permission of Inside Washington Publishers.
FDA Week - www.InsideHealthPolicy.com - January 16, 2015
Public Citizen Pushes Against Approval Of Twice-Rejected Drug
Public Citizen urged FDA to reject for the third time a Ferring Pharmaceuticals drug manufactured to treat frequent
nighttime urination, which the consumer group says dangerously lowers blood sodium levels.
According to the group’s press release, the drug, Nocdurna, has been rejected twice before because the product’s
effect in reducing nighttime urination was determined to be modest and unclear as compared with a placebo.
After Ferring submitted a third application, an FDA reviewer commenting on the quality-of-life effects concluded
that the evidence does not meet standards for listing such a benefit on the medication’s label, according to Public Citizen.
“Additionally, a separate FDA reviewer assessing the possible sleep benefits of Nocdurna noted an absence of objective
evidence to support such a claimed benefit,” Public Citizen says.
Ferring proposed to mitigate the risk of low blood sodium levels by recommending that patients undergo monitoring
of their sodium levels during the first week of use and at the one-month mark, the group notes. But FDA noted that “there
is still a persistent risk for hyponatremia which may become more apparent if the drug is used in a larger and more
diverse population,” Public Citizen adds.
“We hope the FDA will once again recognize that the risks of this medication strongly outweigh the benefits, and
flush this application away,” said Michael Carome, director of Public Citizen’s Health Research Group. — Erin Durkin
Key UDI Claims Document Moves Closer To Approval By ASC Committee
A critical document designed to make recommendations to CMS on including unique device identifiers (UDI) on
claims forms cleared a major hurdle last week when the document moved to a second Accredited Standards Committee
X12 Insurance (ASC X12N) panel for review. The committee has until 2017 to send final recommendations to CMS,
which has been a “dissenting voice” in the process.
ASC X12N, a group of industry representatives tasked with developing standards for the insurance industry, convened in July to determine how to incorporate UDIs into claims forms with the intent of making the 2017 deadline, when
the next round of modifications are due. The document, called the Business Requirements and Technical Solutions
(BRTS), has been through 13 revisions since July and has been passed on to a subcommittee that will review it and return
it to the original UDI workgroup.
Margaret Weiker, chairwoman of the ASC X12N committee and president of the Weiker Group, told FDA Week that
the meeting on Jan. 8 was a step in the right direction but the actual meeting itself was rocky. Weiker said the process is
slow-moving, with experts reviewing each individual section and subsection of the 25-page document the UDI workgroup
came up with.
“The document’s purpose is to capture the business requirements and, based upon those business requirements,
develop a technical solution that meets them,” Weiker said.
Incorporating UDIs into insurance claims has been a priority for FDA since its 2013 ruling that every medical device
needs to have an affixed alphanumeric label readable by humans and a scanning device. The labels contain critical
information about the device such as manufacturer, size, serial number and expiration date. FDA went live this month
with its Global Unique Device Identifier Database, which contains all medical devices in a searchable database. Since
FDA does not have jurisdiction over insurance claims forms, the agency said it was working with its sister agencies CMS
and ONC to incorporate the information into claims and patient electronic health records.
The ASC X12N committee is helping to fulfill that role with its BRTS document — going through a lengthy approval
process to meet an industry need. “EDI transactions currently do not include details on the specific medical devices used
by clinicians. As a result, health plans and health systems lack a process to efficiently collect data on the safety and
quality of different medical devices. ASC X12 in conjunction with the other SDOs can explore ways to remedy the
deficiency,” the document states.
In a recent letter to CMS Commissioner Marilyn Tavenner, Sens. Elizabeth Warren (D-MA) and Chuck
Grassley (R-IA) said that CMS was a “dissenting voice” on the UDI committee, potentially preventing private health
plans from collecting and utilizing UDI data. Weiker confirmed CMS’ dissent on the committee but would not give any
specifics on the points of disagreement. CMS and other government entities are allowed to sit on ASC committees to
offer input on discussions.
Weiker said the claims panel has until the end-of-month to make changes to the document before it goes back to the
UDI workgroup, which will approve the changes and turn it over to a technical subcommittee.
Because the group is made up of a wide range of industry stakeholders, Weiker said the biggest challenge is getting
individual members to look past their parochial experiences and consider the industry as a whole. She said the group had
no problem deciding how and where the UDI field should be placed within claims, but is struggling with broader, longterm solutions.
“The next challenge is to have a broader understanding of the industry or the benefits. People tend to focus on what
FDA Week - www.InsideHealthPolicy.com - January 16, 2015
they know and in many instances, you have people that know about the claims adjudication process, that know about the
billing process and it’s getting them to go outside their comfort zone,” Weiker said.
The claims workgroup meets every week via phone conference to discuss changes in each section, and Weiker said
she is confident the panel will meet its deadline. — David Hood
Woodcock Promotes Kathleen Uhl As New Director Of OGD
FDA drug center chief Janet Woodcock has tapped Kathleen (Cook) Uhl as director of the Office of Generic Drugs.
Uhl has been acting director of OGD since 2013, when then-Director Greg Geba stepped down over differences in vision
and leadership.
The last time the office had a director before Geba was 2010. While FDA put out a notice for the job a few months
ago, the move is not unexpected, said Kurt Karst, attorney at Hyman Phelps McNamara.
“She brings to the position more than 30 years of regulatory and medical policy, scientific, and government leadership experience,” said Woodcock in a statement. “I am confident in Cook’s continued exceptional leadership of OGD and
its support of our Center’s mission. She brings extensive knowledge and skills in developing and implementing standards
for the safety and effectiveness of generic drugs.”
Since the Generic Drug User Fee Amendments was enacted in 2012, Uhl has overseen its implementation in 2013,
marking one of the more sizable changes in policy since the office’s inception. Stable leadership will be key, said Karst,
especially since GDUFA is transitioning into its third year. — David Hood
AdvaMed Seeks Device Approval, Reimbursement Reforms In Cures Bill
The medical device industry is hopeful House lawmakers will advocate a slew of device approval and reimbursement
reforms when they unveil a draft 21st Century Cures bill later this month. The Advanced Medical Technology Association
has urged lawmakers to shorten device review times, revamp approval policies for drug-device combination products,
encourage use of CLIA waivers for diagnostic tests, mandate CMS reliance on trials approved by FDA or any other
government agency and streamline the process for applying billing codes to devices.
AdvaMed outlined these and other proposals in an 11-page submission to the House Energy and Commerce Committee last summer. JC Scott, senior executive vice president of Government Affairs at AdvaMed, told FDA Week this week
that reimbursements are still a top priority for the group as the bill’s provisions are still being ironed out.
“We certainly see this as an opportunity to make even further progress and improve the process at FDA,” said Scott.
“I think they’ve done a great job so far but I think there’s a lot more work to be done and we think this legislative process
provides opportunity for that. And I think there may be opportunities as well given the committee’s jurisdiction to being
looking at what the challenges are on the reimbursement and coverage front at CMS,” he added.
AdvaMed said that while wait times have improved under the Medical Device User Fee Act, they could still be
better. The lack of timeliness and consistency in FDA review have been major reasons clinical trials and first
product introductions have moved abroad, the group says in its response. Reversing that trend would attract more
venture investors and keep business domestic. In addition, the group points out that improving procedures for
evaluation and approvals for drug-device combination treatments have been slow. “FDA’s current procedures result
in inappropriately long reviews for these products and difficulty in coordinating work between the FDA centers
involved,” the response says.
Device approvals wait times could also be improved by the Clinical Laboratory Improvement Amendments waiver
application process . The group argues that CLIA waivers are necessary to allow diagnostic tests at patients’ bedside and
in doctor’s offices, as opposed to the requirement of drawing specimen and sending it to a lab. AdvaMed maintains that
FDA’s CLIA waivers could cut costs and produce more rapid test results.
AdvaMed also recommends Medicare begin relying on clinical trials approved or sponsored by FDA, NIH or any
other government agency. “Most trials are ultimately approved for coverage by Medicare, but the process for gaining
approval can be time-consuming and costly,” the response says. “The new centralized approval requirement that Medicare is establishing could turn into an unnecessary bottleneck for launching trials.” AdvaMed reasons that separate
Medicare review of clinical trials should be unnecessary if they have already been scrutinized and evaluated by other
agencies like FDA or NIH.
The group also says that streamlining the process for assigning billing codes to new technologies takes up to 18
months after FDA approves a new technology for a code to be provided, “effectively depressing the timeliness of reimbursement and delaying patient access to new treatments and cures.”
A draft 21st Century Cures bill is expected to be released by the Energy and Commerce Committee this month.
Committee leaders hope to have it on the House floor by Memorial Day and to the president’s desk by the end of the
year. — David Hood
FDA Week - www.InsideHealthPolicy.com - January 16, 2015
PBMs Call For Greater Focus On FDA’s Indirect Role In Drug Pricing
The pharmacy benefit manager lobby is distributing a white paper that calls on lawmakers and regulators to pay closer
attention to how FDA policies affect drug pricing, even though the hot-button topic doesn’t formally fall within the agency’s
jurisdiction. The paper, written by Matrix Global Advisors, contends that a heavy focus on innovator product approvals, a
backlog of generic drug applications, a long delay in bringing biosimilars to market, abuse of the Risk Evaluation and Mitigation Strategies (REMS) and underfunding of the agency all contribute to FDA impeding competition in the drug industry.
FDA’s role in pharmaceutical competition needs to be carefully examined and statutory and regulatory agendas need to be
developed to address problems, concludes the paper distributed by the Pharmaceutical Care Management Association.
“While drug prices are not (and should not be) a factor when the FDA determines if a drug should be approved for
marketing in the United States, how the FDA makes such a determination can ultimately contribute to the market dynamics that affect a product’s price. Without a statutory and regulatory agenda for the FDA that carefully examines the
agency’s effect on pharmaceutical competition, some consumer welfare may be unnecessarily lost,” states the paper, titled
“Considerations of the FDA’s Impact on Competition in the Drug Industry.”
The paper argues that the FDA’s focus on promoting innovation often comes at the expense of competition in terms
of a backlog of generic drug applications and the delay in getting the first biosimilars to market. The Food and Drug
Safety and Innovation Act of 2012 created a new way for the agency to speed approval of innovative medicines with a
breakthrough therapy designation, and FDA has promoted innovation with the agency’s drug center listing “scientific
innovation” as one of its four primary strategies, the paper says.
As FDA focuses on expediting priority new drug applications (NDA) and biologics license applications (BLA),
which have a six-month deadline for agency review as opposed to the 10-month timeline for regular NDAs and BLAs,
generic drug companies are seeing a backlog of abbreviated new drug applications (ANDA). The paper notes the median
time for an ANDA approval is 36 months — more than three times longer than it takes to approve regular NDAs and
BLAs, and six time longer than the time for priority NDAs and BLAs. As a result of 2012 legislation the FDA got
additional funding from user fees that is supposed to help clear the ANDA backlog, but FDA has said it doesn’t foresee
reducing application review times to 10 months until at least 2017.
The agency’s dedication of resources to expedited approvals of innovative drugs has limited “brand vs.
brand” competition in a given drug class, the paper says.
“Because the FDA does not prioritize approving competitive products, the first brand drug in a given class may
benefit from additional market access with limited or no competition,” the paper says.
The agency also has been slow to get biosimilars — which are expected to increase competition and lower prices in
the biologics sector — approved for market. The pathway for biosimilar approval was established in 2010 by the Affordable Care Act and the Biologics Price Competition and Innovation Act, and at the time the Congressional Budget Office
predicted the first biosimilars would enter the market place in 2012, with budgetary savings coming in 2014.
The first biosimilar approval is expected to come in early-March as an FDA panel recommended this month that the
agency license Sandoz’s filgristam as a copy of Amgen’s Neupogen. But as FDA Week has reported extensively, and the
white paper points out, policies questions remain over biosimilar naming, interchangeability and labeling that will affect
how the products are marketed.
FDA has yet to issue any guidance on naming of biosimilars, and should the agency require unique names for
biosimilars distinct from their reference products — as favored by biologics makers — it could impede prescribing and
utilization, making it difficult for biosimilars to find market success, the paper contends.
FDA recently said it plans to issue draft guidance this year on biosimilar interchangeability and labeling, but naming
was absent from the list. Some stakeholders believe that FDA might include naming in the labeling draft guidance, while
others think the agency may offer de facto guidance with the name it assigns Sandoz’s product.
“While the FDA has released draft guidance on various issues related to biosimilars, the agency’s delay in issuing
final guidance for biosimilar manufacturers has thwarted the development of a U.S. biosimilars industry—thus preventing
the savings that competition would generate,” the paper says.
The paper also contends that misuse of the REMS programs — risk management plans that the FDA requires for
some drugs — by brand manufacturers are keeping generics from coming to market.
Last month FDA issued draft guidance that aimed to curb the innovators’ use of REMS to keep generics from the
market, but a week later admitted that the guidance does not go far enough to address the full scope of the problem.
“The problem is the use of REMS blocking generic competition,” said John Jenkins, director of FDA’s Office of New
Drugs, during a panel discussion at an industry conference. “Innovators have really become very aggressive in using that
strategy [and] hiring the best lawyers to back up that strategy.”
The white paper concludes that while making innovation a priority and implementing strict policies and regulations
to ensure the safety and efficacy of drugs are necessary parts of FDA’s role, policies in these areas must be crafted in a
way that strikes a balance that ensures competition.
The paper, referring to ways in which FDA hinders competition, concludes “the consequences of these impediments
need to be better understood and rectified.” — Todd Allen Wilson
FDA Week - www.InsideHealthPolicy.com - January 16, 2015