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DIA's Content Currents provides you with new and important global regulatory developments and their impact on pharmaceutical, biotechnology, and medical product development.

EDITION PUBLISHED: October 17, 2014

SECTION 1 FDA GUIDANCES & MAPPS

CDER List of Guidance Documents

CDER Guidances: New/Revised/Withdrawn through 6/30/14

The links above lead to the List of Guidance Documents (CDER) updated on July 7, 2014, and to CDER Guidances that are new, revised, or withdrawn through the second calendar quarter of 2014.

Guidance Agenda: Guidance Documents CBER is Planning to Publish During Calendar Year 2014 (PDF - 31KB)

CDRH FY 2014 Proposed Guidance Development

On October 14, 2014, FDA announced the availability of a draft guidance entitled “Flow Cytometric Devices.” This draft guidance addresses the current major review concerns regarding submissions for flow cytometric devices used as in vitro diagnostic devices for leukocyte immunophenotyping and provides suggestions on the content of submissions for these types of devices. This draft guidance is not final nor is it in effect at this time.  Comments should be submitted by January 12, 2015.  [Federal Register]

On October 15, 2014, FDA announced the availability of the guidance entitled “Distinguishing Medical Device Recalls from Medical Device Enhancements.”

When a firm’s recall process is operating effectively, the firm identifies a device defect or failure, determines that a recall is appropriate, and triggers the initiation of the recall process.  When a new iteration of a device has improved design or other quality improvements, this does not necessarily mean that the prior version of the device should be recalled. Such changes may be appropriately characterized instead as product enhancements. In addition to determining whether a proposed change to a marketed device meets the definition of a device recall or a product enhancement, a firm must assess whether it is required to report the change to FDA. This guidance is intended to clarify when a potential change to a device is a medical device recall, distinguish those instances from product enhancements, and explain reporting requirements.  [Federal Register]

On November 5, 2014, the FDA will hold a webinar to explain the guidance and to provide a forum for asking questions.   Registration is not necessary.  See link at right for more information.  [FDA.gov]

On October 16, 2014, FDA announced the availability of a draft guidance entitled “New Chemical Entity Exclusivity Determinations for Certain Fixed-Combination Drug Products.”  This guidance sets forth a change in the Agency’s interpretation of the 5-year NCE exclusivity provisions as they apply to certain fixed-combinations. Fixed-combinations have become increasingly prevalent in certain therapeutic areas and FDA recognizes that these products play an important role in optimizing adherence to dosing regimens and improving patient outcomes. Therefore, to further incentivize the development of fixed- combinations containing previously unapproved active moieties, the guidance sets forth the Agency’s revised interpretation regarding the eligibility for 5-year NCE exclusivity of certain fixed-combinations. Under the revised interpretation, the term ‘‘drug’’ in the relevant provisions is interpreted to mean ‘‘drug substance’’ or ‘‘active ingredient,’’ and not ‘‘drug product.’’ [Federal Register]
(See also related commentary below in Section 2: Will an FDA Policy Shift on Fixed Dose Drug Approvals Anger Pharma?)

On October 17, 2014, FDA announced a publication containing modifications the Agency is making to the list of standards FDA recognizes for use in premarket reviews (‘‘FDA Recognized Consensus Standards’’). This publication, entitled ‘‘Modifications to the List of Recognized Standards, Recognition List Number: 037’’ (‘‘Recognition List Number: 037’’), will assist manufacturers who elect to declare conformity with consensus standards to meet certain requirements for medical devices. [Federal Register]

SECTION 2 FDA NOTES & RELATED NEWS

Updated List of CDER Key Officials Posted

FDA Shortens Review Period for Ebola Medicines
The National Journal (10/17, Koren, Subscription Publication) reports that “the Food and Drug Administration is in crisis mode, and its process of reviewing applications for new drugs has been pushed into overdrive” as a result of the Ebola crisis. The FDA is now “reviewing new drug applications to fight Ebola in a matter of days instead of months or years.”
        Roche Considers Getting Approval For Ebola Test. The Wall Street Journal (10/17, Morse, Subscription Publication) reports that Roche Holding AG, a Swiss company, in considering submitting an Ebola test it has developed for emergency use approval. The company has already filed for approval from European Regulators. The company did not specify when it would officially file with the FDA.
        Meanwhile, The Wall Street Journal (10/17, Loftus, Subscription Publication) reports North Carolina-based Chimerix Inc. will begin clinical trials for its Ebola drug brincidofovir after receiving authorization from the FDA.
        HHS Fast-Tracking Development Of Third Ebola Vaccine. The Hill (10/17, Kamisar) reports that, according to a press release, “The Department of Health and Human Services will fast-track the development of a third Ebola vaccine that had a 100 percent success rate with non-human primates.” Robin Robinson, the director of the agency’s Biomedical Advanced Research and Development Authority, stated, “We are pushing hard to advance the development of multiple products as quickly as possible for clinical evaluation and future use in preventing or treating this deadly disease.”
        The Baltimore Sun (10/17) reports that HHS “is giving $5.8 million to Baltimore company Profectus BioSciences for its efforts to develop an Ebola vaccine.” Profectus is preparing “to apply to the Food and Drug Administration to begin human clinical trials,” and “the money from HHS’s Biomedical Advanced Research and Development Authority will go toward manufacturing a vaccine for those trials.” Modern Healthcare (10/17, Frank, Subscription Publication) also covers the story.  (DIA Daily, Subscription a member benefit)

FDA Will Study Impact of Size and Other Pill Characteristics on Adherence
To what extent does a change in the shape, size or color of a pill determine whether you remember to take that medicine?

The FDA wants to know, especially when it comes to generic drugs. Distributors and, therefore, pharmacies frequently change suppliers, depending upon pricing and availability. As a result, consumers can refill a prescription and receive a supply that looks different from the previous supply. And so, the FDA plans to conduct a survey of about 3,000 pharmacists and consumers in hopes of gaining insight into patient adherence, according to a notice in the Federal Register.

The effort is part of ongoing interest the FDA has in gauging how patient adherence is affected by any change in the physical characteristic of a medicine. In fact, the agency issued a draft guidance last December suggesting manufacturers attempt to produce pills that are similar in shape and size as the underlying brand-name drug. More at link above. (WSJ, Pharmalot)

Regulatory Science Collaborations Support Emergency Preparedness
Coordinating government agencies, healthcare providers, and numerous additional partners to protect public health in emergency situations is a challenge.  FDA’s Medical Countermeasures Initiative (MCMi) is working with federal agencies (through the Public Health Emergency Medical Countermeasures Enterprise), product developers, healthcare professionals, and researchers, among other partners, to help translate cutting-edge science and technology into safe, effective medical countermeasures.

Data are critical to help FDA evaluate the safety and effectiveness of medical countermeasures—products that can save lives—during public health emergencies. But collecting data in the midst of an emergency is exceptionally challenging. Working with the Biomedical Advanced Research and Development Authority (BARDA), FDA is teaming with critical care physicians nationwide to help address these challenges.

Under a contract awarded last month, FDA and BARDA will work with the U.S. Critical Illness and Injury Trials Group (USCIITG) to gather important information about medical countermeasures used during public health emergencies. Physicians will help address challenges with collecting and sharing data rapidly in emergencies, including streamlining electronic case reporting for clinical trials and rapidly disseminating key findings to FDA and other stakeholders to support clinical decision-making.

When it is not ethical or feasible to test the effectiveness of products in humans—such as countermeasures for potential bioterror agents—products may be approved under the Animal Rule. When products are approved under the Animal Rule, FDA requires additional studies, called phase 4 clinical trials, to confirm safety and effectiveness. In addition to the MCMi work, BARDA is funding USCIITG to investigate conducting phase 4 clinical studies during public health emergencies.  More at link above.  (FDA.gov)

FDA Announces January 1 2015 Launch of Office of Pharmaceutical Quality
OPQ is a new office within CDER that creates a single unit dedicated to product quality. The new structure, to be stood-up in January 2015, is expected to provide better alignment among all drug quality functions at CDER, including review, inspection, and research.

OPQ will combine non-enforcement-related drug quality work into one super-office, creating one quality voice and improving FDA oversight of quality throughout the lifecycle of a drug product. OPQ creates a uniform drug quality program across all sites of manufacture, whether domestic or foreign, and across all drug product areas – new drugs, generic drugs, and over-the-counter drugs.

Changes include:
•    Realignment of functions and personnel from the Office of Pharmaceutical Science to OPQ
•    Realignment of preapproval and surveillance inspection activities from the Office of Compliance (OC) to OPQ
•    Realignment of inspection-related activities for bioequivalence/bioavailability and non-clinical studies from OC’s Office of Scientific Investigations to the Office of Translational Sciences
Janet Woodcock will serve as the Acting Director of the OPQ and has appointed Lawrence Yu, PhD as Deputy Director.  More at link above.  (FDA.gov)

Will an FDA Policy Shift on Fixed Dose Drug Approvals Anger Pharma?
After months of anticipation, the FDA has issued a final guidance for approving new treatments that contain more than one drug. And the agency decision is likely to stir controversy because untold amounts of money may be at stake.

Here’s why. Such drugs are known as fixed-dose combinations and, until now, five years of valuable marketing exclusivity are available if all of the drugs in the combination are new chemical entities. Simply put, these would be drugs that were not previously approved for any use. A fixed-dose combination containing an older drug would be eligible for three years of exclusivity instead.

Those two years can make a difference for drug makers that have a big-selling product and have additional time to ring the register before another version arrives in pharmacies or hospitals. And so, a few drug makers petitioned the FDA last year to change its rules so that a fixed-dose combination with at least one new chemical entity was eligible for five years of marketing exclusivity.

The final guidance confirms agency plans released earlier this year to reconsider how new chemical entities are treated, but the FDA will only alter its policy for fixed-dose combinations as of the date of the publication of the guidance.
Some suggest the cut-off date may prompt litigation.  More at link above. (WSJ Pharmalot)

Hemophilia Patients Seek Comparative Data on Inhibitor Side Effects
Summary:  FDA hears calls for more post-approval monitoring of products at drug-development meeting, a reminder to sponsors that patient pressure can prod the agency for more than just streamlined approvals.

The hemophilia community is telling FDA that it wants access to post-market safety surveillance data on factor replacement therapies in order to better understand the development of inhibitors, or neutralizing antibodies, that many patients experience.

Patients aired their concerns at a Sept. 22 patient-focused drug development meeting organized by the agency’s Center for Biologics Evaluation and Research to receive input on a range of issues related to treatment for hemophilia A, hemophilia B, von Willebrand Disease and other heritable bleeding disorders.

Speaking at the hemophilia meeting, patients said that treatment needs were very dependent on the individual and consequently, they appreciate as many options as possible and hope to continue to have access to new therapies through insurance companies. They also noted the importance of quality of life, which can be improved by longer-acting treatments, their interest in better administration in subcutaneous or pill formulations, the desire for ways to reverse damage from prior bleeding episodes and their hope for a cure.

The hemophilia meeting is a reminder to sponsors that patients can press FDA for more than a streamlined, more humane approval process.  More at link above.  (Pink Sheet, paid subscription required)


SECTION 3 AGENCY AND ADVISORY COMMITTEE MEETINGS

Patient-Focused Drug Development: Disease Area Meetings Planned for FY2013-2015

Public Workshop (and Request for Comments). Collaborative Approaches for Medical Device and Healthcare Cybersecurity. October 21-22, 2014. National Intellectual Property Rights Coordination Center Auditorium, Arlington, VA. FDA, in collaboration with other stakeholders within the Department of Health and Human Services (HHS) and the Department of Homeland Security (DHS), seeks broad input from the Healthcare and Public Health (HPH) Sector on medical device and healthcare cybersecurity. The vision for this public workshop is to catalyze collaboration among all HPH stakeholders. [Federal Register]

CDRH Webinar.  Clarifications Questions on the Proposed LDT Regulatory Oversight Framework.  October 23, 2014.  FDA will address clarification questions on the proposed framework for oversight of Laboratory Developed Tests (LDTs).  The webinar is intended to provide clarification on the proposed framework only; comments should be submitted to the docket.  [FDA.gov]

New:  Brookings Webinar:  Roundtable on Active Medical Product Surveillance. Likelihood Ratio-Based Tests for Longitudinal Drug Safety Data.  October 24, 2014.  This webinar will highlight a recent development of longitudinal likelihood ratio test (LongLRT) methods with application to a pooled clinical trial dataset for drugs treating osteoporosis with concomitant use of proton pump inhibitors (PPIs). [FDA.gov]

Panel Session.  “Competing Regulatory Oversight of Investigational Tests, including LDTs, for Co-Development Programs.”  October 29, 2014.  Washington, DC. FDA, industry, IVD manufacturer, and laboratory stakeholders will discuss their perspectives on the impact of the FDA proposed LDT oversight framework on safety, clinical validity, innovation, and accessibility of investigational tests.   [DIA Companion Diagnostics]
 
Public Meeting.  Patient-Focused Drug Development and Scientific Workshop on Female Sexual Dysfunction.   October 27-28, 2014.  White Oak Campus, Silver Spring, MD.  FDA is conducting a Patient-Focused Drug Development public meeting and scientific workshop on Female Sexual Dysfunction (FSD).  [Federal Register]

Day 1 – October 27th Patient-Focused Drug Development Public Meeting
FDA is interested in obtaining patient input on:

  1. The impact of the most common form of FSD, female sexual interest/arousal disorder (FSIAD) on daily life
  2. Patients’ views on currently available therapies to treat the condition

Day 2 – October 28th Scientific Workshop
The scientific workshop will include discussion on scientific challenges related to:

  1. Diagnosis of the condition for clinical trials and in clinical practice
  2. Ensuring valid patient-reported outcome measures for the key efficacy endpoints used in clinical trials

New:  First Annual Neonatal Scientific Workshop – Roadmap for Applying Regulatory Science to Neonates.  October 28-29, 2014.  Silver Spring, MD.  The purpose of this scientific workshop is to accelerate the development of therapeutics for the neonatal population. The workshop will also serve to map out the priorities of this new consortium devoted to applying regulatory science to the neonatal population, as well as ensuring that the leading academic experts in the US, Canada and Europe, interested companies, regulatory agencies, patient groups, NIH institutes, and non-profit organizations, all have an opportunity to shape priorities and eventually join the new consortium. [FDA.gov]

Public Meeting.  Development and Regulation of Abuse-Deterrent Opioid Medications.  October 30-31, 2014.  Silver Spring, MD.  The purpose of the meeting is to discuss the development, assessment, and regulation of abuse-deterrent formulations of opioid medications. The meeting will focus on scientific and technical issues related to the development and in vitro assessment of these products, as well as FDA’s approach towards assessing the benefits and risks of all opioid medications, including those will abuse-deterrent properties. [FDA.gov]

Public Advisory Committee Meeting. Risk Communications Advisory Committee. November 3-4, 2014. White Oak Campus, Silver Spring, MD.  The Risk Communication Advisory Committee will discuss methods for effective risk communication with a focus on messages about the importance of eating adequate amounts of fish, while avoiding certain fish with higher amounts of methyl-mercury. These messages are especially important for women who are pregnant or nursing, or for anyone who prepares food for young children. [Federal Register]

Clinical Investigator Training Course. November 4-6, 2014. College Park, MD.  This training course, a co-sponsored event of FDA CDER and Duke University Office of Continuing Medical Education, is intended to provide clinical investigators with expertise in the design, conduct, and analysis of clinical trials; improve the quality of clinical trials; and enhance the safety of trial participants.  [Federal Register]

Public Advisory Committee Meeting. Cellular, Tissue and Gene Therapies Advisory Committee. November 6, 2014. White Oak Campus, Silver Spring, MD. The committee will discuss the draft guidance for industry entitled ‘‘Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene Therapy and Oncolytic Products’’ and the Dear Gene Therapy IND or Master File Sponsor Letter.  [Federal Register]

Science Advisory Board to the National Center for Toxicological Research (NCTR) Advisory Committee Meeting.  November 6-7, 2014. NCTR, Jefferson, AR. On November 6, a Center-wide update on scientific initiatives and accomplishments during the past year will be presented. An overview of the Division of Microbiology Subcommittee and the Subcommittee Site Visit Report will be presented.  On November 7, 2014, the Office of the Chief Scientist will update the SAB on their research needs, and discuss opportunities for collaboration to help address these needs.  The Center for Biological Evaluation and Research, the Center for Drug Evaluation and Research, the Center for Devices and Radiological Health, the Center for Veterinary Medicine, the Center for Tobacco Products, the Office of Regulatory Affairs, and the Center for Food Safety and Applied Nutrition will each briefly discuss their Center-specific research strategic needs. [Federal Register]

New:  Public Meeting and Request for Comments.  Regulatory Science Considerations for Software Used in Diabetes Management.  November 13, 2014.  White Oak Campus, Silver Spring, MD. The goals of this public workshop are to foster greater stakeholder collaboration in the area of diabetes device interoperability and to seek input from the clinical community, academia, government, industry, and other stakeholders regarding usability considerations for appropriate information consumption (e.g., notifications, indicators, data, and displays) based on user skill and knowledge.  [Federal Register]

Science Board to the Food and Drug Administration Advisory Committee Meeting.  November 19-20, 2014. White Oak Campus, Silver Spring, MD. On November 19, the Science Board will review the existing nonclinical and clinical data related to the use and potential toxicity of anesthetics and sedation drugs in the pediatric population. The Science Board will be asked to make recommendations on steps the FDA should take to further evaluate and to mitigate the risks associated with the use of these drugs in the pediatric population and mechanisms to best communicate with the public regarding this issue. On November 20, among the agenda items will be consideration of a request to form a new subcommittee to evaluate the Centers of Excellence in Regulatory Science and Innovation program. [Federal Register]

Public Workshop. Brain-Computer Interface Devices for Patients With Paralysis and Amputation. November 21, 2014.  White Oak Campus, Silver Spring, MD.  The purpose of this workshop is to obtain public feedback on scientific, clinical, and regulatory considerations associated with BCI (Brain-Computer Interface) devices. Ideas and suggestions generated during this workshop may facilitate development of draft guidance to provide our initial thoughts regarding the content of premarket submissions for emerging BCI technologies to help speed development and approval of future submissions.  [Federal Register]    On September 30, 2014, FDA released a discussion paper in preparation for this workshop.  [FDA.gov]

Public Advisory Committee Meeting. Anesthetic and Analgesic Drug Products Advisory Committee. November 24-25, 2014. White Oak Campus, Silver Spring, MD. The committee will discuss the risk of serious neurologic adverse reactions associated with epidural steroid injections (ESI) administered to reduce inflammation for pain management. The committee will also consider the efficacy of ESI and the overall risk benefit balance of injecting steroids in the epidural space to treat pain. These considerations will assist the FDA in its discussions of possible regulatory options, including but not limited to changes to the product labeling. [Federal Register]

Meeting. Realizing the Benefits of the Unique Device Identifier in Health Care.  Office of the National Coordinator and Pew Charitable Trusts.  December 9, 2014. Washington, DC. This meeting will present discussion on the benefits and challenges of integrating the unique device identifiers (UDI) into clinical care, registries, the supply chain, and other facets of health care delivery. [FDA.gov]


SECTION 4 OTHER REGULATORY AUTHORITIES & ORGANIZATIONS

White House Appoints Ebola Czar
Ron Klain, a former White House adviser, has been appointed to head U.S. efforts to combat Ebola.

A White House official says Klain "will report directly to the president's Homeland Security Adviser Lisa Monaco and ... National Security Adviser Susan Rice as he ensures that efforts to protect the American people by detecting, isolating and treating Ebola patients in this country are properly integrated but don't distract from the aggressive commitment to stopping Ebola at the source in West Africa."

Klain, a former chief of staff to vice presidents Joe Biden and Al Gore, is currently president of case holdings and general counsel at Revolution LLC, a technology-oriented venture capital firm based in Washington, D.C.

The White House official tells NPR's Tamara Keith that Klain's role "is consistent with the view the president articulated in the Oval Office last night that Monaco, Rice and others have done outstanding work in confronting this challenge so far — but given their management of other national and homeland security priorities, additional bandwidth will further enhance the government's Ebola response." More at link above. (NPR.org)

PhRMA Statement on Ebola Czar
Pharmaceutical Research and Manufacturers of America (PhRMA) President and CEO John Castellani today (10/17/14) issued the following statement on the selection of Ron Klain to manage the U.S. government’s response to preventing the spread of the Ebola virus:

“Protecting patients and their families from the devastating effects of Ebola is a national priority. As Mr. Klain takes on the important and challenging role of coordinating the government’s response to the Ebola outbreak, our industry stands ready to support these efforts by using our resources and expertise to assist patients and their families affected.

“Stopping the spread of Ebola will require close collaboration and engagement from a wide range of stakeholders, including health care providers, relief organizations, government agencies, and biopharmaceutical companies. Over the past several years, researchers have been working to develop vaccines and treatments to prevent infection and fight its effects, and there are at least two Ebola vaccines currently in the biopharmaceutical pipeline. PhRMA members are also helping to expand capacity on the ground in West Africa to take care of affected patients, including donating medicines, providing funding to relief organizations for infrastructure improvements, medical products and protective equipment for health care workers, and donating funds for disease education and prevention efforts within the region.”

To learn more about the biopharmaceutical industry’s commitment to preventing the spread of Ebola, visit the PhRMA website at www.phrma.org/ebola as well as the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) website at http://www.ifpma.org/global-health/ebola-outbreak.html.  (PhRMA.org)

Some in Ebola Trials Wouldn't Get Test Drugs in US Plan
U.S. health officials want some patients to forgo potentially life-saving Ebola treatments when they’re being tested so researchers can compare their response to those who get the medicines, said an official involved in the discussions.

Some experimental drugs have already been used on an emergency basis. In a formal trial, the U.S. wants one group of patients to get the treatments and a second to get only standard supportive care, said the official, who asked not to be identified because the person isn’t authorized to speak on the record. Supportive care includes replacing fluids and using medicines to fight off other infections.

The Food and Drug Administration oversees trials that generate data for approval of medical products. Many of the Ebola trials may be done in Western Africa, where an outbreak has killed more than 4,400 in Liberia, Sierra Leone and Guinea.

“At the moment, it is just so urgent to figure out what works and what doesn’t work, and to do it with a reasonable degree of certainty,” said Steven Joffe, at the University of Pennsylvania’s department of medical ethics and health policy.

Trials where everyone gets an experimental drug may be misleading, making doctors think a treatment is more or less effective than it actually is. It could also mask harm in critically ill patients. More at link above.  (Bloomberg News)

IOM Announces Workshop: Research Priorities to Inform Public Health and Medical Practice for Domestic Ebola Virus Disease (EVD)
An ad hoc committee, under the auspices of the Institute of Medicine in collaboration with the National Research Council will organize a one-day workshop on November 3, 2014, that will explore potential research priorities arising as a result of the emergence of Ebola Virus Disease (EVD), a hemorrhagic disease caused by a filovirus, in the United States.

The workshop will focus primarily on basic science and environmental health research issues of specific concern to affected and potentially affected U.S. communities. The workshop will help inform future research that could be conducted under real-world conditions (i.e., during an event) that would provide public health officials and the general public with additional accurate information about virus transmission, mitigation of health risks, and appropriate measures to prevent the spread of disease. Specific topics that may be discussed include routes of transmission and persistence of the virus to inform public health practice, and strategies to address issues of concern to healthcare workers and the general public, including the use of PPE and personal protective behaviors to prevent spread and reduce exposure.  More at link above.  (IOM)

Institute of Medicine Report:  Antimicrobial Resistance A Problem without Borders
The Centers for Disease Control and Prevention identified antimicrobial resistance as one of five urgent health threats facing the United States this year. Antimicrobial resistance is a global health security threat that will demand collaboration from many stakeholders around the world.

The Institute of Medicine's 2014 Richard & Hinda Rosenthal Symposium: Antimicrobial Resistance: A Problem Without Borders explored the current and future impact of antimicrobial resistance, implications for our nation's health and that of the world, and obstacles and successes in the development of solutions and steps to mitigate this global public health challenge. This report highlights the crosscutting character of antimicrobial resistance and the needs for many disciplines to be brought together to be able to deal with it more effectively. More at link above.  (IOM)

NIH Ebola Update: Working Toward Treatments and Vaccines
We are all alarmed by the scope and scale of the human tragedy occurring in West African nations affected by the Ebola virus disease epidemic. While the cornerstones of the Ebola response remain prompt diagnosis and isolation of patients, tracing of contacts, and proper protective equipment for healthcare workers, the National Institutes of Health (NIH), led by its National Institute of Allergy and Infectious Diseases (NIAID), is spearheading efforts to develop treatments and a vaccine for Ebola as quickly as possible.

Highlights of the NIH update:  

NIAID has supported and collaborated with Mapp Biopharmaceutical, Inc., San Diego, in its development of the product known as ZMapp, which has been administered experimentally to several Ebola-infected patients.

NIAID is supporting a broader effort to advance development and clinical testing of ZMapp to determine if it is safe and effective.

The U.S. Biodefense Advanced Research and Development Agency (BARDA) has announced plans to optimize and accelerate the manufacturing of ZMapp, which is in limited supply, to enable clinical safety testing to proceed as soon as possible.

NIAID is also supporting the development of other potential treatments, including BCX4430, a drug that BioCryst Pharmaceuticals, Research Triangle Park, NC, plans to enter into a Phase 1 human clinical trial by early 2015. Another potential drug, brincidofovir, developed by Chimerix of Durham, N.C., has been evaluated in more than 1,000 patients for two non-Ebola viruses (cytomegalovirus, adenovirus). Broader evaluation of the drug will likely take place in the coming months.

The HIV drug, lamivudine, has also been used in some Ebola patients in Liberia, under the supervision of a Liberian physician. Cell culture testing of the drug is being conducted in the United States, and if promising, clinical trials could be performed.

Several Ebola vaccine candidates are undergoing Phase 1 human clinical testing this fall after proving effective in animals. One of these is a vaccine candidate developed by NIAID and GlaxoSmithKline, London; this product entered a small Phase 1 study at the NIH Clinical Center in Bethesda, MD, last month, and the study is now expanding to additional sites.

NIH will collaborate with the Department of Defense and NewLink Genetics Corp., Ames, IA, on Phase 1 human safety studies of another investigational Ebola vaccine candidate, which was developed by and licensed from the Public Health Agency of Canada. Other vaccine candidates are in earlier stages of development in animal models. More at link above.  (NIH.gov)

USTR Launches Review of Intellectual Property Rights in India
The Office of the U.S. Trade Representative (USTR) announced its planned review of intellectual property rights (IPR) in India. The review, promised in April when USTR published its "2014 Special 301 Report," noted India remains on the U.S. government's "priority watch" list for IPR. The review also noted bilateral engagement to improve IP protection and enforcement in India would support that nation's efforts to achieve a "decade of innovation."

In its April report, USTR cited a variety of concerns related to the effects of India's IPR policies on pharmaceutical and medical device innovators, including higher bars to obtain patents on inventions; the ongoing prospect of compulsory licenses to innovator IP; disparities between domestic and foreign requirements on local manufacturing of pharmaceutical goods; and lack of guaranteed data protections.

USTR also cited U.S. customs data showing that India is the "top supplier of counterfeit pharmaceuticals to the United States."
Public comments are due by Oct. 31; foreign government comments are due by Nov. 7. (BioCentury)

HHS Officially Delays Compliance Deadline for ICD-10 to October 1, 2015
In August, the Department of Health and Human Services (HHS) issued a final rule which delayed the transition to ICD-10 until October 1, 2015. Prior to the enactment of the Protecting Access to Medicare Act of 2014 (PAMA), the health care industry was preparing to transition to ICD-10 by October 1st of this year. Last week the Centers for Medicare and Medicaid Services (CMS) published the official ICD-10 Guidelines for Coding and Reporting.

CMS explains that these guidelines should be used in conjunction with the official version of the ICD-10-CM as published on the National Center for Health Statistics (NCHS) website.

The International Classification of Diseases, 10th Revision (ICD-10) is an update to ICD-9, the official system for assigning codes to medical diagnoses. The codes provide an alphabetical index to all disease entries and a classification system for procedures.

Due to the vast amount of new data in the update, many doctors and other stakeholders have urged CMS to delay implementation to give everyone involved enough time to prepare for the changes. More at link above.  (Policy and Medicine)

Data Sharing, Year 1 — Access to Data from Industry-Sponsored Clinical Trials
Excerpts from the online article published by the New England Journal Medicine:

Since May 2013, investigators have been able to request access to deidentified patient-level data from clinical trials sponsored by GlaxoSmithKline, subject to review and oversight by an independent review panel (https://clinicalstudydatarequest.com/Default.aspx). As the members of this panel, we now have more than 12 months of experience with this initiative — and can report that it has been a productive and successful first step.

The system was launched on May 7, 2013, and initially included approximately 200 clinical trials that had been started since January 1, 2007 — the date on which more consistent data standards began to be required for GlaxoSmithKline-sponsored trials.  Between May 2013 and May 2014, a total of 36 research proposals were approved (or approved with conditions) by the independent review panel. Of these, 23 had progressed to a signed data-sharing agreement. Each of these proposals included requests for data from 1 to 11 studies (average, 2 studies).

There were requests for 97 GlaxoSmithKline studies that were not included in the system. Of these, 20 turned out to be general inquiries that did not require data access through the system; of the others, 3 are still undergoing feasibility assessment, and 74 have been approved.

There is considerable interest in open access to clinical trial data on the part of both the research community and the wider public. Limited but important evidence suggests that reanalyses of previously published data can lead to conclusions about the types of patients who should receive a given treatment that differ from the conclusions drawn by the original investigators.

A number of other companies have since joined this system, which naturally permits easier aggregation of data from multiple companies. Some companies have elected to join other data-access systems. The system described here will undoubtedly evolve considerably over time. Management of the proposals is likely to be turned over to an independent organization, a development that should make it more appealing for other manufacturers to join and should enhance public confidence in the process.  More at link above.  (NEJM)

Research Data Warehouse Project Shows Promise but Issues Remain
Health researchers learned vital lessons from building a data warehouse to help care for safety net populations, and highlight those findings in a new paper at eGEMS (Generating Evidence & Methods to improve patient outcomes.)

The Community Health Applied Research Network, funded by the Health Resources and Services Administration, organized 18 community health centers (CHCs) into four research nodes, each with an academic partner, aimed at furthering patient-centered outcomes research (PCOR). The data warehouse was intended to serve multiple purposes, including characterizing the safety net population as well as supporting research and quality improvement efforts.

In version 1 of the warehouse content focused on seven diseases: diabetes, HIV- and AIDS-related conditions, hepatitis B, hepatitis C, cardiovascular disease, hypertension, and dyslipidemia, and included patient demographics, encounter data, diagnosis data, lab results and medications ordered.

The project "paved the way for low impact, but active clinic engagement in research," allowing clinicians to ask questions about their patient population, help clinicians not particularly interested in research to find information relevant to their practices and learn the value of documenting care in a standardized way, according to the paper.

The warehouse now is in version 2, which includes more clinical data and the full population of patients from each CHC.  More at link above.  (Fierce Health IT)

ONC interoperability road map draft outlines governance, certification standards goals
An updated draft version of the Office of the National Coordinator for Health IT's 10-year road map to interoperability, published online late Monday, outlines goals for governance and certification standards and calls for "unprecedented collaboration" in ensuring that technology can seamlessly support the health of patients on a day-to-day basis.

By 2017, "explicit rules that address organizational, trust, business and technical issues" must be established, the report notes.

"With broad input from stakeholders across the health IT ecosystem" ONC will establish a voluntary nationwide government framework, according to the draft road map. The framework will define the responsibilities of different stakeholders, as well as technical standards, a governance structure and privacy and security rules.

ONC plans to publish a road map for public comment in January 2015 that includes feedback from its Health IT Policy and Standards Committees, which gathered for a joint meeting in the District of Columbia on Wednesday (10/15/14) to discuss the current iteration of the document. By March of next year, ONC anticipates that version 1.0 of the road map will be complete.  More at link above.  (Fierce Health IT)

Concept paper on the need for revision of the points to consider on the clinical investigation of new medicinal products for the treatment of acute coronary syndrome
An update of the Committee for Medicinal Products for Human Use points to consider on new medicinal products for the treatment of acute coronary syndrome is foreseen. This document covers a number of points that are proposed to be addressed in the update.  

Cardiovascular diseases are currently the leading cause of death in industrialized countries and are expected to become so in emerging countries by 2020 (1,2). Among these, coronary artery disease (CAD) is the most prevalent manifestation and is associated with high mortality and morbidity. Acute coronary syndrome (ACS) has evolved as a useful operational term to refer to any constellation of clinical symptoms that are compatible with acute myocardial ischemia. It encompasses ST-segment elevation myocardial infarction (STEMI), Non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina (UA).

Two CHMP documents have been developed to address ACS, one in 2000 and one in 2003.  Since that time, major developments have taken place in the definitions, diagnosis, interventions and management of ACS. These developments are reflected in the relevant ESC clinical practice guidelines (1,2). Currently, an update is considered necessary to take these new developments into consideration, based on literature review and expert advices concerning treatment initiated during the acute phase and beyond.  

Comments may be submitted until January 15, 2015. More at link above. (EMA.europa.eu)

EFPIA Touts Innovative Medicines Model in China
China’s status as the “world’s factory” continues to shift as other Asian countries such as Vietnam attract greater investment due to lower costs. So China is stepping up investment in areas such as education in a bid to move investments to higher-value sectors such as drug research.  

The pharmaceutical industry fits in solidly with that plan and has invested heavily in translational research because of the importance of achieving improved results and outcomes, Chris Viehbacher, chairman of the European Federation for Pharmaceutical Industries and Associations said in Beijing Sept. 26. Viehbacher was leading the first-ever EFPIA delegation to China.

The federation, representing 34 national industry organizations and 40 pharmaceutical companies, spent its two-day mission meeting Chinese regulators, reimbursement agency officials and industry associations such as the R&D-based Pharmaceutical Association Committee (RDAPC).

Touting a collaborative model which brings diverse sets of disciplines to accelerate innovative pharma research, Viehbacher opened a panel discussion on the benefits of translational medicine and how to foster it.  Among the speakers were Guido Rasi, European Medicine Agency Executive Director, and Innovative Medicines Initiative Executive Director Michel Goldman.  More at link above. (Pink Sheet, paid subscription required)


SECTION 5 LEGAL AND COMPLIANCE

SCOTUS Challenges on Teva Patient Case
U.S. Supreme Court justices on Wednesday voiced skepticism about arguments from both sides in the petition by Teva Pharmaceutical Industries Ltd. to overturn an appeals court decision that invalidated the company's process patent for multiple sclerosis blockbuster drug Copaxone glatiramer acetate.

The high court will decide whether the U.S. Court of Appeals for the Federal Circuit (CAFC) overreached by reviewing de novo certain questions of fact in Teva's lawsuit against the Sandoz International GmbH generics unit of Novartis AG, rather than deferring to the findings of the U.S. District Court for the Southern District of New York.

Teva's suit alleges Sandoz's ANDA for generic Copaxone infringed on Teva's patents. The district court ruled in favor of Teva in 2012. In 2013, the CAFC reviewed the facts of the case and instead invalidated the process patent for Teva's daily formulation of Copaxone, set to expire on Sept. 1, 2015.

The SCOTUS decision is due by the end of June 2015.  More at link above.  (BioCentury)

RICO: Offering Co-Pay Coupons Does Not Constitute A Racketeering “Enterprise,” Rules Federal Court
Pharmaceutical manufacturer co-payment coupons have come under a lot of scrutiny recently. HHS-OIG recently warned these coupons may violate the anti-kickback statute if they encourage the purchase of Medicare Part D drugs. Manufacturers seem to be safe, however, from co-pay challenges under RICO—the federal Racketeer Influenced and Corrupt Organizations Act which was originally enacted to combat organized crime. Last week, a Federal Court judge dismissed an insurance company’s claim that they overpaid for drugs in which Abbott Laboratories and AbbVie allegedly committed mail and wire fraud by offering co-pay coupons for their brand name drugs. The Court did not find that a racketeering “enterprise” existed between the companies and the pharmacies distributing the drugs.  More at link above.  (Policy and Medicine)

THR Chief Clinical Officer testifies to Congress about EHR changes in wake of Ebola situation
Testifying before the House Energy and Commerce subcommittee on oversight and investigations on Oct. 16, Texas Health Resources Chief Clinical Officer Daniel Varga spoke about electronic health record documentation and updates made to the hospital's system in the wake of treatment for Ebola (EVD) patient Thomas Eric Duncan, who died last week.

On Oct. 2, Texas Health Presbyterian Hospital Dallas (THD) issued a statement that an EHR flaw may have led hospital clinicians to misdiagnose and release Duncan upon his first visit to the hospital's emergency room. A day later, the hospital clarified that, in fact, an EHR flaw was not responsible for Duncan's misdiagnosis.

“Where we fell short initially was in our ability to detect and diagnose EVD, as evidenced by Mr. Duncan's first visit to the ED."

To that end, Vargas told federal legislators, the hospital has changed its screening process to more quickly and accurately capture a patient's travel history "at the first point of contact with ED staff."

"We have modified our electronic health record in multiple ways to increase the visibility and documentation of information related to travel history and infectious exposures related to EVD," Varga said. In addition to the updates made, Varga said the hospital retrained clinicians on how to use the EHR in such a scenario.  More at link above.  (Fierce Health IT)

Energy and Commerce Committee Releases Dallas Ebola Timelines
The House Energy and Commerce Committee today released documents obtained in its investigation of the ongoing Ebola outbreak. The documents were submitted to the committee by Texas Health Resources. One outlines the preparedness timeline from August 1, 2014, through September 24, 2014, and the other document details the sequence of events at Thomas Duncan’s first visit to the Emergency Department on September 25, 2014. Documents available at link above.  (Energy and Commerce)


SECTION 6 SOURCES REVIEWED FOR THIS NEWSLETTER

A partial listing of sources reviewed for this newsletter:  AdvaMed Smartbrief; AHRQ Newsletter; Alzheimers Association; Alzheimers Research Forum Newsletter; BioCentury; Biopharma Reporter; BIOtechNow; CDISC Monthly Newsletter; CER Daily Newsfeed (NPC); Daily Dose (Becker); DIA Daily; Drug Daily Bulletin;  EMA website; EP Vantage; Evaluate Pharma; Eye on FDA; FDA.gov; FDA Law Blog; Federal Register Table of Contents; Fierce Medical Devices; Fierce Diagnostics; Fierce Pharma; Fierce Vaccines; FDLI Smartbrief; Genomeweb; Health Industry Washington Watch; Government Health IT; Health IT Security; Institute of Medicine News; MedCityNews; Medical Device Daily; Medical Device & Diagnostic Industry; MedPage Today; NPC Bulletin; Nutra Ingredients USA; Pharmabiz; Pharmafile; Pharma IQ; PharmaTimes; PhRMA website; PM Live; Policy and Medicine (newsletter); Regulatory Focus; RegLink News; US FDA Daily Digest Bulletin.