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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: February 27, 2015

SECTION 1 FDA GUIDANCES & MAPPS

Guidance Documents CBER is Planning to Publish in 2015
This is the list of guidance topics CBER is considering for development during Calendar Year 2015.  The list includes topics that currently have no guidance associated with them, topics where updated guidance may be helpful, and topics for which CBER has already issued Level 1 drafts that may be finalized following review of public comments.

CDER 2015 Plan for New & Revised Guidances
The link above is the new CDER list of guidances planned for new issue or revision in Calendar Year 2015.

Searchable Database of All Official FDA Guidance Documents and Other Regulatory Guidance
FDA has created a database that provides a convenient way y to search for all FDA guidance documents from a single location. You can search for documents using key words, and you can narrow or filter your results by product, date issued, FDA organizational unit, type of document, subject, draft or final status, and comment period. Access the database at the link above. (FDA.gov)

CDRH FY 2015 Proposed Guidance & Focused Retrospective Finalized Guidance
The lists below include guidance documents that CDRH intends to publish this fiscal year (FY2015) as well as previously-issued final guidances for which CDRH would appreciate external feedback on whether these final guidances should be revised or withdrawn. We have provided three lists: (1) a list of guidance documents that the Agency fully intends to publish (the “A-list”); (2) a list of guidance documents that the Agency intends to publish as resources permit (the “B-list”); and (3) a list of final guidance documents that issued in 2005, 1995, and 1985 subject to focused retrospective review. Although resource constraints and new issues that emerge over the course of the year may preclude CDRH from issuing every guidance document on the A-list and B-list and may require that CDRH issue guidance documents not on the lists, the A-list and B-list are intended to provide helpful information about CDRH’s current priorities for the upcoming fiscal year. CDRH plans to update all three lists every year.  (FDA.gov)

On February 24, 2015, FDA announced final order for a medical device classification for “Physical Medicine Devices; Classification of the Powered Exoskeleton.” FDA is classifying the powered exoskeleton into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the powered exoskeleton’s classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.  This order is effective March 26, 2015. The classification was applicable on June 26, 2014. [Federal Register]

On February 25, 2015, FDA announced the opening of a docket for “Request for Information on Specific Areas of Public Health Concern Related to Racial/Ethnic Demographic Subgroups for Additional Research by the Office of Minority Health.” FDA is opening a docket to obtain information and comments on specific areas of public health concern for racial/ethnic demographic subgroup populations, focusing on certain disease areas where significant outcome differences may be anticipated. The Agency is seeking public input on identifying areas that can be addressed through regulatory science research. Submit either electronic or written comments or information by April 27, 2015. [Federal Register]

On February 25, 2015, FDA announced the availability of the report and web site location where the Agency has posted the report entitled ‘‘Strengthening Patient Care: Building an Effective National Medical Device Surveillance System,’’ developed by the National Medical Device Postmarket Surveillance System Planning Board. In addition, FDA has established a docket where stakeholders may provide comments. Submit either electronic or written comments by April 27, 2015.  [Federal Register]

On February 25, 2015, FDA announced the availability of the draft guidance entitled “Technical Performance Assessment of Digital Pathology Whole Slide Imaging Devices.” This draft guidance provides industry and Agency staff with recommendations regarding the technical performance assessment data that should be provided for regulatory evaluation of a digital whole slide imaging (WSI) system. Comments should be received by May 26, 2015. [Federal Register]

On February 25, 2015, FDA announced a revision to the Manual of Policies and Procedures (MAPP) for “Tertiary Review of Genetic Toxicology Studies Resulting in a Recommendation for a Clinical Hold or Conduct of Additional Studies.” The ICH guidance for industry S2(R1) Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use specifies the genetic toxicology assays that should be performed and submitted in support of investigational new drug applications (INDs) and new drug applications. This MAPP establishes policies and procedures in the Office of New Drugs (OND) for tertiary review of data from genetic toxicology studies. This MAPP also establishes a Genetic Toxicology Review Committee (GTRC) within OND to perform the tertiary review. [FDA.gov]

On February 26, 2015, FDA announced final order for a medical device classification for “Obstetrical and Gynecological Devices; Classification of the Assisted Reproduction Embryo Image Assessment System.” FDA is classifying the Assisted Reproduction Embryo Image Assessment System into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the Assisted Reproduction Embryo Image Assessment System classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.  This order is effective February 26, 2015. The classification was applicable on June 6, 2014. [Federal Register]

On February 27, 2015, FDA announced it is amending its regulation regarding postmarket   “Medical Device Reporting: Electronic Submission Requirements.” In the Federal Register of September 24, 2013 (78 FR 58786), FDA published the ‘‘Unique Device Identification System’’ final rule (UDI rule). The eMDR rule, among other things, revises part 803 in its entirety. As published in the Federal Register, the eMDR rule will, upon its effective date, unintentionally remove the amendments made by the UDI rule to part 803 of the Code of Federal Regulations (CFR), Title 21. This document addresses the unintentional removal by amending part 803 to include the UDI requirements. The rule is effective August 14, 2015. [Federal Register]


SECTION 2 FDA NOTES & RELATED NEWS

Moving Toward a National Medical Device Postmarket Surveillance System
In his February 23 FDA Voice blog, Dr. Jeffery Shuren, Director of FDA’s Center for Devices and Radiological Health and Thomas Gross, MD, MPH, Director, Office of Surveillance and Biometrics in FDA’s CDRH discussed the release of the Medical Device Postmarket Surveillance System Planning Board’s report Strengthening Patient Care: Building an Effective National Medical Device Surveillance System, which outlines recommended steps toward achieving the MDS and strategies for implementation. The report provides a pathway to realizing a national system that harnesses novel data sources, modern analytical techniques and the participation of all stakeholders to optimize patient care. Interested stakeholders will be able to share their feedback on the report through a public docket.

Shuren and Gross said that in the coming months, FDA will also get reports from the Medical Device Registry Task Force. These reports will address significant issues such as defining effective registry governance and data quality practices, which will enrich the national dialogue on development of registries as a crucial source of data on device performance.  More at title link above. (FDA.gov)

FDA Sentinel Transition Will Involve Expanding Rx Safety Data Sources
Summary:  Moving Mini-Sentinel pilot program to a fully operational and sustainable Sentinel postmarket safety surveillance system will take place over next year, CDER Director Woodcock says.

Article: FDA’s plans for expanding its Mini-Sentinel postmarket drug and biologics safety surveillance pilot program to a “fully operational” and sustainable Sentinel system will include increasing the sources of electronic data used by the system and broadening the research methods employed.

After five years of preparatory work through Mini-Sentinel, FDA awarded the contract for coordinating the full-fledged Sentinel program in September 2014 to Harvard Pilgrim, under the direction of Richard Platt, which has been coordinating the operations of Mini-Sentinel. The agency will spend the next year integrating the program into its routine functions.
The Mini-Sentinel distributed-data network includes information, mainly claims data, on 178 million individuals. FDA is exploring the possibility of linking the Sentinel network more closely with other government payers including the Department of Defense, the Department of Veteran’s Affairs and CMS (Medicare, Medicaid and the Children’s Health Insurance Program) to enrich the data available, Woodcock noted. Electronic health records will be an important source of data once they can be standardized and appropriate methods for extracting information from the records are developed, she said.

In preparation for transitioning to Sentinel, FDA has shifted the management and development responsibilities for the initiative from the agency’s Office of Medical Policy to its Office of Surveillance and Epidemiology.

FDA will continue to work toward developing Sentinel as a national resource that could be used by outside organizations for research or other purposes beyond safety surveillance, Woodcock said. “That would help us share the financial load a bit,” she pointed out. “I’ve long been seeking that.” In line with that goal, Pfizer is working with the public-private Innovation in Medical Evidence Development and Surveillance (IMEDS) program on the first pilot to test safety management queries from an entity outside of FDA to the data partners participating in Sentinel. More at link above. (The Pink Sheet, paid subscription required)

FDA Posts Deputy Director for Office of Generics Position
This position is located in the Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA). The incumbent will serve as the Deputy Director of the OGD and participate fully in the day-to-day operations of the Office. In the absence of the Director, s/he acts with full authority in carrying out the variety of scientific, technical and administrative duties required of that position. More at link above. (FDA.gov)

35th Edition of Orange Book Posted on FDA Site
FDA has posted the 2015 (35th Edition) of “Approved Drug Products with Therapeutic Equivalence Evaluations” (commonly known as the Orange Book) to its website.

The publication identifies drug products approved on the basis of safety and effectiveness by FDA under the Federal Food, Drug, and Cosmetic Act (the Act). Drugs on the market approved only on the basis of safety (covered by the ongoing Drug Efficacy Study Implementation [DESI] review [e.g., Donnatal® Tablets and Librax® Capsules] or pre-1938 drugs [e.g., Phenobarbital Tablets]) are not included in this publication. The main criterion for the inclusion of any product is that the product is the subject of an application with an effective approval that has not been withdrawn for safety or efficacy reasons. In addition, the List contains therapeutic equivalence evaluations for approved multisource prescription drug products. These evaluations have been prepared to serve as public information and advice to state health agencies, prescribers, and pharmacists to promote public education in the area of drug product selection and to foster containment of health care costs. Full text at link above.  (FDA.gov)

Continuous Manufacturing For Generics Is Easy Path To Quality, Woodcock Says
Summary: Production flexibility and less regulatory interaction are among advantages, CDER director tells GPhA in effort to woo converts to the technique.

Article: When Center for Drug Evaluation and Research Director Janet Woodcock extolled the virtues of the process at the Generic Pharmaceutical Association’s annual meeting in Miami, she talked about how it offered production and regulatory flexibility, all from a basic upfront investment. She presented continuous manufacturing as a relatively straightforward process that would make generic production easier.

The advocacy for continuous manufacturing is part of FDA’s new all-carrot/no-stick approach to getting generic firms on board with the agency’s overhaul of GMP oversight.

“There are different meanings of continuous manufacturing,” Woodcock acknowledged. “Some people are talking about raw materials to finished products, soup to nuts. Granted, that’s a little bit complicated.”

However, for finished dosage forms “it ain’t rocket science, and the point of it is it’s better,” Woodcock said. “You can monitor your product, you can modulate your production, you can ramp up, you can ramp down, without at all needing to file supplements with the FDA.” More at link above. (The Pink Sheet, paid subscription required)


SECTION 3 AGENCY AND ADVISORY COMMITTEE MEETINGS

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

Public Advisory Committee Meeting. Science Board to the Food and Drug Administration. March 4, 2015.  White Oak Campus, Silver Spring, MD.  Among other agenda items, the Science Board will be provided with a progress or final draft report the Commissioner’s Fellowship Program Evaluation subcommittee and will hear a progress report from Science Moving Forward subcommittee. The Science Board will be asked to provide feedback on FDA’s public access policy. FDA will seek the Science Board’s input regarding approaches to regulatory science training coordination. [Federal Register]

Public Advisory Committee Meeting. Vaccines and Related Biological Products. March 4, 2015.  Silver Spring, MD.  The committee will meet in open session to discuss and make recommendations on the selection of strains to be included in the influenza virus vaccines for the 2015–2016 influenza season.  [Federal Register]

Public Conference. Serious Drug-Induced Liver Injury: The Importance of Getting It Right: How To Measure and Interpret Drug-Induced Liver Injury Information and Make Correct Diagnoses.  March 18-19, 2015.  Hyattsville, MD.  The purpose of the public conference is to discuss, debate, and share views among stakeholders in the pharmaceutical industry, academia, health care providers, patient groups, and regulatory bodies on how best to detect and assess the severity, extent, and likelihood of drug causation of liver injury and dysfunction in people using drugs for any medical purpose. [Federal Register]

New.  Public Advisory Committee Meeting. Pediatric Ethics Advisory Committee.  March 23, 2015.  White Oak Campus, Silver Spring, MD.  The Pediatric Ethics Subcommittee of the Pediatric Advisory Committee will meet to discuss the general topic of how procedural sedation for nontherapeutic (research) interventions or procedures in the pediatric population should be considered under the Additional Safeguards for Children in Clinical Investigations at 21 CFR 50 subpart D. A brief summary of the subcommittee’s discussion will then be presented to the FDA Pediatric Advisory Committee on Tuesday, March 24, 2015. [Federal Register]

New.  Public Meeting. Pediatric Stakeholder Meeting.  March 25, 2015.  White Oak Campus, Silver Spring, MD.  The FDA Office of Pediatric Therapeutics (OPT), the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) are announcing a public meeting seeking input from patient groups, consumer groups, regulated industry, academia and other interested parties to obtain any recommendations or information relevant to the report to Congress that FDA is required to submit concerning pediatrics, as outlined in section 508 of the Food and Drug Administration Safety and Innovation Act (FDASIA).  The report will address the implementation of the Best Pharmaceuticals for Children Act (BPCA) and Pediatric Research Equity Act (PREA).  [Federal Register]

Public Meeting. Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products. March 27, 2015.  White Oak Campus, Silver Spring, MD.  The purpose of the meeting is to provide a public forum for FDA to listen to comments on the proposed rule on ‘‘changes being effected’’ supplements that was published in the Federal Register of November 13, 2013, and alternatives offered to this proposed rule. [Federal Register]

Public Workshop. Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics.  March 30-31, 2015.  White Oak Campus, Silver Spring, MD.  The purpose of this workshop is to provide a forum to consider issues related to selection of endpoints and clinical outcome measures appropriate for drug development in the following disease areas: Inflammatory bowel diseases and celiac disease. [Federal Register]

Public Meeting. Patient-Focused Drug Development for Breast Cancer. April 2, 2015.  White Oak Campus, Silver Spring, MD.  The public meeting is intended to allow FDA to obtain patient perspectives on the impact of breast cancer on daily life and patient views on treatment approaches. More information and materials as they become available at  Breast Cancer Patient-Focused Drug Development    [Federal Register]

Public Workshop. Assessment of Neurocognitive Outcomes in Inborn Errors of Metabolism and Advancing the Development of Pediatric Therapeutics: Assessment of Neurocognitive Outcomes. April 16-17, 2015.  White Oak Campus, Silver Spring, MD.  Day 1 of the workshop will focus on approaches for assessing the efficacy of therapeutic products based on neurocognitive outcomes in patients diagnosed with inborn errors of metabolism disorders. On Day 2 of the workshop, participants will discuss identification of signals in animal studies and clinical trials that warrant further clinical investigation and testing that may be predictive of neurocognitive outcome in children. [FDA.gov]

New.  Public Advisory Committee Meeting. Neurological Devices Panel of the Medical Devices Advisory Committee. April 17, 2015.  White Oak Campus, Silver Spring, MD.  The committee will discuss the current knowledge regarding the conduct of clinical studies and evaluation of clinical study data for flow diverter technology. FDA is convening this committee to seek expert opinion on scientific and clinical considerations relating to the study design and existing clinical studies, for flow diverter technology indicated for the neurovasculature. [Federal Register]

New.  Public Workshop. 2015 Office of Regulatory Science and Innovation Science Symposium. April 27, 2015.  White Oak Campus, Silver Spring, MD.  The purpose of the public workshop is to increase scientific collaborations with government institutions, academia, industry and other stakeholders, working to improve science, training, and networking in accordance with the FDA mission of the advancement of regulatory science. This venue will also enhance knowledge and awareness of the FDA ORSI resources and provide guidance of its available services. [Federal Register]

Public Meeting. Chagas Disease Patient-Focused Drug Development. April 28, 2015.  White Oak Campus, Silver Spring, MD.  FDA is interested in obtaining patient input on the impact of Chagas disease on daily life and patients’ views on currently available therapies to treat the condition. [FDA.gov]

Public Meeting. Patient-Focused Drug Development for Functional Gastrointestinal Disorders. May 11, 2015.  White Oak Campus, Silver Spring, MD.  FDA is holding this public meeting and an opportunity for public comment on Patient-Focused Drug Development for functional gastrointestinal (GI) disorders, including irritable bowel syndrome, gastroparesis, chronic persistent symptomatic gastroesophageal reflux despite standard therapeutic interventions, and chronic idiopathic constipation. [Federal Register]

New.  Public Workshop. Robotically-Assisted Surgical Devices: Challenges and Opportunities. July 27-28, 2015.  White Oak Campus, Silver Spring, MD.  FDA is holding this public workshop to obtain information on the current challenges and opportunities related to robotically- assisted surgical medical devices, which are classified as Class II medical devices. The purpose of this workshop is to obtain public feedback on scientific, clinical, and regulatory considerations associated with RAS devices.  [Federal Register]


SECTION 4 OTHER REGULATORY AUTHORITIES & ORGANIZATIONS

Health Information Management Systems Society to Focus on Transforming Health
Chicago welcomes the 2015 HIMSS Annual Conference & Exhibition, April 12-16, 2015, at McCormick Place. More than 38,000 healthcare industry professionals are expected to attend to discuss health IT issues and view innovative solutions designed to transform healthcare.

DIA is proud to support this annual event that helps health IT professionals find the right solutions for their organizations.
Conference education sessions include preconference symposia on clinical and business analytics, HIEs, innovation, mobile health, nursing informatics, physicians’ IT and more. More than 300 peer-reviewed sessions, including workshops and roundtables, round out education offerings at HIMSS15.

George W. Bush, 43rd President of the United States, leads a strong roster of speakers that also includes Alex Gourlay, President, Walgreens; Bruce  D. Broussard, President and CEO, Humana; and Jeremy Gutsche, Founder of Trendhunter.com and Author of “Exploiting Chaos.”

The HIMSS15 Exhibit Hall will feature the Connected Patient Gallery, Federal Health IT Solutions Pavilion, HIMSS First-Time Exhibitors Area, HIMSS Health IT Value Suite, HIMSS Interoperability Showcase™, Intelligent Health™ Pavilion (formerly known as Intelligent Hospital Pavilion), and three Knowledge Centers focused on clinical and business intelligence, disaster preparedness and mobile health.

As a HIMSS15 Endorser, DIA members are eligible to receive the member discount to attend the conference. To receive the discount, go to the online registration at www.himssconference.org/registration, and select DIA from the “Conference Endorsing Organizations” drop-down in the registration process. Enter Endorser Number “2015”.  More information at title link above. (HIMSS.org)

MD Anderson Cancer Center Leukemia Chairman Launches Online Petition Urging Control of Cancer Meds
For the past two years, Hagop Kantarjian has complained about the price of cancer medications. As the chairman of the leukemia department at the M.D. Anderson Cancer Center in Houston, one of the premier facilities in the U.S., he says that he sees a growing number of patients who have difficulty affording treatment. In response, he has become an outspoken critic of the cost of medicines and last year told CBS’s ’60 Minutes’ that prices are “unreasonable, unsustainable and, in my opinion, immoral.” Yet he has seen little change. And so this week, he is leading a new effort – an online petition in which he hopes to gather up to 1 million names to convince the White House and Congress to take action.

Kantarjian suggests the following solution: First, allow Medicare to negotiate drug prices. Two, allow the Patient-Centered Outcomes Research Institute [which was created as part of the Affordable Care Act to assess treatments] to put the prices of drugs in their evaluations of benefits. Three, allow importation of drugs across borders. Prices in Canada are half of what they are in the U.S., so insurance companies would save money, patients would save on out-of-pocket costs and drug companies would make money because the patient who can’t afford the drug here would then make a purchase. Fourth, we should prevent drug companies from making deals to protect patents, like pay for delay, and prevent patent evergreening [which allegedly involves tweaking a patent to extend its life]. And fifth, we should encourage organizations that represent patients with cancer to develop treatment pathways that incorporate drug prices – what they call drug value or treatment value.

Says Kantarjian, “We’re going to use all aspects of social media- Facebook, Twitter. I’m going to ask for organizations and people with a lot of followers to publicize it and include a hashtag.” More at link above. (WSJ Pharmalot)

PCORI Awards $64.2 Million to Support Five Pragmatic Clinical Studies
The Patient-Centered Outcomes Research Institute (PCORI) Board of Governors today approved awards totaling more than $64 million to fund five large patient-centered comparative effectiveness research (CER) studies that will answer critical clinical questions about care for cancer, back pain, and stroke.

The awards are the first to be made through PCORI’s Pragmatic Clinical Studies Initiative, an effort to produce results that are broadly applicable to a greater variety of patients and care situations and can be more quickly taken up in routine clinical practice.

Ranging from $7.75 million to $14.5 million each, the five awards will fund studies involving thousands to tens of thousands of patients in efforts to fill critical evidence gaps. More at link above. (PCORI.org)

PCORI Board Adopts Process for Peer Review and Public Release of Research Findings
The PCORI Board of Governors adopted PCORI’s process for peer review and public release of the results of the comparative clinical effectiveness research (CER) studies it funds.

This process details how PCORI will meet its legislative mandate to ensure the scientific integrity of the primary research it supports and make study findings widely available and useful to patients, clinicians, and the general public within a specific timeframe. It is part of PCORI’s broader efforts to disseminate and implement research findings.

The process for public release of research approved by PCORI’s Board of Governors today is the most transparent and comprehensive policy adopted by a major research funder to date,” said PCORI’s Executive Director Joe Selby, MD, MPH. “It includes release of both scientific and lay abstracts and publication of final reports, which will ensure that reliable, useful new clinical evidence reaches those who need it in ways that they can readily understand it and use it to make better-informed healthcare decisions.”

PCORI’s process aligns with others’, including those of federal agencies, in requiring registration of studies with appropriate web-based public registry sites and submission of results to the National Library of Medicine’s ClinicalTrials.gov site no more than 12 months after a study is completed. More at link above. (PCORI.org)

First Independent U.S. Psoriasis Registry Will Track Drug Safety
People with psoriasis and their health care providers will have the opportunity to participate in research that aims to improve treatments and disease outcomes when the first independent U.S. psoriasis registry begins recruiting patients in 2015.

The registry, a joint collaboration with the National Psoriasis Foundation and Corrona, LLC, will initially track the drug safety reporting for secukinumab, a new biologic medication by Novartis Pharmaceuticals for moderate-to-severe psoriasis. The Corrona Psoriasis Registry will enroll at least 3,000 people with psoriasis on secukinumab and follow their treatment for at least eight years. Novartis is the first subscriber to the registry and did incur a subscriber fee.

By collecting and analyzing data from thousands of people with psoriasis over many years, the registry will help clinicians, researchers and the pharmaceutical industry compare the effectiveness and safety of different psoriasis treatments. Data will be gathered through comprehensive questionnaires completed by patients and their dermatologists during appointments. More at link above. (Drug Discovery & Development)

Harvard Researchers Propose New Model of Alzheimer's Disease
Although natural selection is often thought of as a force that determines the adaptation of replicating organisms to their environment, Harvard researchers have found that selection also occurs at the level of neurons, which are post-mitotic cells, and plays a critical role in the emergence of Alzheimer’s disease.

Using the principles of natural selection, Lloyd Demetrius, a researcher in population genetics at Harvard’s Museum of Comparative Zoology, and Jane Driver, an assistant professor of medicine at Harvard Medical School, have proposed a new model of Alzheimer’s that suggests mitochondria — cellular power plants — might be at the center of the disease. The study, which builds on earlier work by Demetrius and David Simon, an associate professor of neurology at HMS, was described in a recent paper in the Journal of the Royal Society Interface.

“We felt that, in order to explain the exponential increase in Alzheimer’s with age, we had to move away from the nuclear genome and look at what is going on with the energy-producing organelles,” Demetrius said. “That led us to a completely different model for the disease. We do not rule out the nuclear genes as playing a role … but, for the late-onset form of Alzheimer’s, we envision a mechanism based on the fact that mitochondrial DNA has a high mutation rate and that the organelles generate less energy with age.”

The prevalent model of Alzheimer’s is known as the amyloid cascade model. An accumulation of beta amyloid in neurons is thought to be triggered by a mutation in the nuclear genome. The genetic mutation model could explain early onset Alzheimer’s, but this form of the disease accounts for only about 5 percent of cases.

“The late-onset cases, however, are quite different,” Demetrius said. In the model Demetrius and Driver describe, the disease’s first step is what they call “mitochondrial dysregulation.” The process is largely part of the natural course of aging. More at link above. (Drug Development & Discovery)

National Institute on Aging Posts Webcasts of Alzheimer's Disease Research Summit 2015
In case you missed the Alzheimer’s Disease Research Summit 2015: Path to Treatment and Prevention on February 9-10, 2015, the National Institutes of Health has posted video of the Summit online. You can view all or parts of the Summit at any time and for free.

Video of Summit Day 1 includes plenary lectures on the socioeconomic burden of Alzheimer’s in the U.S. and globally and what we now understand about the complexity of the disease. The day also covered sessions on the biology of Alzheimer’s disease, updates on drug and therapy development, and new strategies for prevention.

Video of Summit Day 2 explores innovations in disease monitoring, assessment, and care; engaging and empowering people in research, and enabling partnerships for collaboration. More at link above. (NIH.gov)

New Report: Transforming Rare Disease Patients' Lives Through Innovation
The Pharmaceutical Research and Manufacturers of America (PhRMA) released a new report, “A Decade of Innovation in Rare Diseases,” to document the significant progress made in the last 10 years in understanding a broad range of rare diseases and translating this knowledge into groundbreaking therapies for a variety of patient populations.

The report illustrates that more than 230 new medicines to treat rare or “orphan” diseases were approved by the U.S. Food and Drug Administration (FDA) in the last decade, and there are currently more than 450 orphan drugs in development.

It also explores significant treatment advances seen over the past decade in five rare diseases which have led to improvements in patient survival and quality of life: chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), pulmonary arterial hypertension (PAH), hereditary angioedema (HAE), and cystic fibrosis (CF). Furthermore, the report spotlights additional rare conditions where major milestones transformed treatment —including several in which first-ever treatment options have become available to patients.  More and full report at link above. (PhRMA.org)

Pricing Reforms Debated In EU
Summary: European policymakers look at options such as greater information exchange between countries to strengthen price negotiation, joint procurement, and more collaborative HTA reviews to help hold down the high prices of certain medicines.

European health care policymakers could step up efforts to share information on drug pricing and expenditures, in order to strengthen their individual negotiating power with pharmaceutical companies wanting to charge high prices for some medicines.

During a debate in the European Parliament Feb. 11 on access to medicines, Zanda Kalnina-Lukasevica, EU affairs minister for Latvia, the country currently holding the presidency of the EU, said European countries had met in December and agreed there was a need to co-operate on exchanging information to manage pharmaceutical expenditures, while at the same time assuring patient access to medicines.

There are also calls for the Transparency Directive, the legislation underpinning pricing and reimbursement processes in the EU, to be revised to help address pricing issues. Previous plans to introduce a new directive were abandoned last year because the likelihood of European countries agreeing to new rules was thought to be slim.

The EU Commission has been put to work to find solutions on patient access: commission representative Christos Stylianides said the commission’s expert group on Safe and Timely Access To Medicines for Patients just begun work on the issue. It is examining the way existing regulatory tools and pharmaceutical legislation could be used to foster innovation, assure faster access to medicines, and hold down prices.

Ideas include the possibility of European countries joining forces to buy medicines under their joint procurement mechanism, originally set up to counter cross-border health threats like pandemic flu. There could also be greater cooperation on health technology assessment programs. The commission also will look at the practice of countries using prices in other member states as a benchmark for their own pricing; this tendency may be contributing to higher prices in some countries, Stylianides said.  More at link above.  (The Pink Sheet, paid subscription required)

EMA Supports Rare Disease Day 2015
The European Medicines Agency (EMA) supports Rare Disease Day 2015, taking place on Saturday 28 February.

A rare disease affects not more than 5 in 10,000 people; however, altogether about 30 million people suffer from these diseases in the European Union (EU).

The Agency plays an important role in the development and authorisation of medicines for rare diseases, known as orphan medicines. EMA’s Committee for Orphan Medicinal Products (COMP) issues recommendations to grant orphan designation to medicines, and marketing-authorisation applications for designated orphan medicines are assessed by EMA rather than in each Member State separately.

Companies that have been granted an orphan designation for their medicine benefit from a number of incentives, including reduced fees for marketing-authorisation applications, scientific advice (protocol assistance) and paediatric investigation plans, as well as protection from market competition once the medicine is authorised through a 10-year market-exclusivity period. These incentives aim to bring more medicines for rare diseases to patients.

Since the entry into force of the EU orphan regulation in 2000, more than 100 medicines for rare disease have been brought to the EU market. More at link above. (EMA.eu)

Adjusted fees for applications to European Medicines Agency from 1 April 2015
The European Medicines Agency reminds applicants and marketing-authorisation holders that adjusted fees will be coming into effect on Wednesday 1 April 2015.

Every year, the Agency adjusts its fees on 1 April, in line with the European Union (EU) inflation rate for the previous year. The European Commission is currently in the process of adopting a regulation adjusting the fees payable to the Agency in line with the 2014 inflation rate. Although the final adjustment is not yet known, the Agency expects its fees to decrease by around 0.1%.

The Agency will publish full details of the revised fees at the end of March, once the European Commission has adopted the regulation and published it in the Official Journal of the European Union and the Agency's Management Board has reached a decision on its implementation. More at title link above. (EMA.eu)

Sparring Begins Over a European Policy for Disclosing Clinical Trial Data
Once again, there is a clash in Europe over disclosing clinical trial data. The latest flare up is over proposed rules for managing a European Union database of clinical study information, which will be overseen by the European Medicines Agency.

The database will not launch until next year, but already there is substantial disagreement about the extent to which commercial information should remain confidential, according to comments submitted to the EMA by pharmaceutical industry trade groups, consumer advocates and one government panel.

Data disclosure is a contentious topic following scandals over safety or effectiveness data that was not publicly shared. Drug makers argue that disclosing certain data may compromise trade secrets or patient privacy. Consumer groups counter that such information is kept out of reach at the expense of patients.

The EMA notes that comments will be reviewed as the agency works toward developing a final version of the database rules. “The outcome will need to balance the public interest and value of immediate transparency with the need to ensure Europe re-establishes itself as the leading location for innovation and research on medicines, which is itself in the public interest,” an EMA spokeswoman writes us. More at link above. (Pharmalot WSJ)

Hepatitis C Treatments win NICE Approval
NICE has issued final guidance recommending two new innovative hepatitis C drugs - Gilead's Sovaldi (sofosbuvir) and Janssen's Olysio (simeprevir) - but patients will not be able to access Gilead's treatment until the summer.  

While Solvadi is now NICE-approved, the drug will not actually be paid for by the NHS until August, more than two months later than this would usually happen. This is because healthcare bodies in England are concerned about the high cost of the drug, which comes with a price tag of around £35,000 and could cost the health service £1bn per year if all eligible patients are treated with the pill. To try and prepare for this, NHS England has asked NICE for the guidance to be delayed until July 31.

NHS has not asked for a delay in the funding of Olysio.

Professor Carole Longson, director of the NICE centre for health technology evaluation, said: “New treatments, like sofosbuvir and simeprevir, can shorten the length of interferon-based therapy and in some situations don't need to be taken with interferon at all. Both drugs can also be given to people who have previously been treated but did not clear the virus, in people whose condition has relapsed, or in people who have become re-infected after treatment.

“Sofosbuvir and simeprevir could therefore be valuable treatment options for people with chronic hepatitis C. This is good news, not just for people with chronic hepatitis C, but also because having more effective treatments for the condition could reduce the spread of the virus.”  More at link above. (PM Live)

Amended Chinese GCP Could Aid Development of CRO Industry
The China Food and Drug Administration (CFDA) is proposing to amend its GCP (good clinical practices) to add more specific responsibilities for sponsors, Ethics Committees (ECs) and sites as part of efforts to further protect study subjects, experts say.

The release of new draft guidelines includes new details on interactions between sponsors and CROs and may help boost the local CRO industry.  

Under the revised GCP, sponsors are permitted to outsource certain tasks in clinical studies to CROs, as long as CROs responsibilities are clearly documented in contracts.  Responsibility and liability were often outsourced as well, prior to the release of these latest new standards.

Sponsors are now required to evaluate and inspect CROs, and like in the US, are ultimately responsible for the quality of the work performed.  More at link above.  (Outsourcing Pharma)


SECTION 5 LEGAL AND COMPLIANCE

FDA Budget Increase Relies on Higher User Fees
Although President Obama’s proposed budget for fiscal year 2016 includes increases for both the FDA and the National Institutes for Health (NIH), the 9-percent boost to the FDA’s budget – to roughly $4.9 billion — would come largely from industry user fees.

An article posted on Genetic Engineering and Biotechnology News states that Obama requested roughly $2.187 billion in user fees, up about 10% from FDASIA. “The president is proposing to collect 15% or $277.2 million more in user fees than in FY 2015. The largest share of user fees, $826.072 million, would be prescription-drug user fees,” according to the article. “Those would rise 3.5% or $28.072 million from the current fiscal year. … In 2016, user fees would account for 44% of FDA’s total budget, up from 35% in FY 2012.” More at link above. (Coalition for Healthcare Communication)

Bill Introduced in House to Exempt Almost Half of FDA Budget from Sequestration
A bill introduced in the House of Representatives on February 25, the FDA Safety Over Sequestration (FDA SOS) Act, would specifically exempt FDA's user fees from the effects of future budget sequestration. The user fees, which come from the pharmaceutical and medical device industries, are meant to help fund FDA's regulatory activities, and have been a key source of the agency's funding since they were first introduced in the Prescription Drug User Fee Act (PDUFA) of 1992.

If passed, the legislation would exempt about 42% of the FDA budget from austerity measures meant to help balance the federal budget.

Under the Budget Control Act of 2011, FDA's user fees were subject to sequestration measures. In plain terms: FDA was forced to give back more than $100 million in funding to the US Treasury. While the agency eventually regained access to much of this money, it was unable to touch it for months, putting product reviews and its regulatory staff in fiscal jeopardy.

The bill's passage remains uncertain. While an identically titled bill was introduced in 2013, it was not approved. The legislation could have a better chance at passage now that both the House and Senate are considering FDA reform legislation, however. More at link above.  (Regulatory Focus)

Permanent R&D tax credit bill reintroduced in Senate
Sens. Tom Carper (D-Del.) and Pat Toomey (R-Pa.) reintroduced a bill that would increase and make permanent the alternative simplified R&D tax credit. The bill would increase the tax credit to 25% from the 14% credit that expired last year and enable CROs to claim a portion of the credit. Carper introduced a similar bill last July.

The bill is known as the Competitiveness and Opportunity by Modernizing and Permanently Extending the Tax Credit for Experimentation, or COMPETE Act. (BioCentury)

Has the Physician Payment Sunshine Act Reduced Participation in Blinded Market Research?
One of the most difficult aspects of compliance with the Sunshine Act is accounting for "indirect payments" that pharmaceutical and device manufacturers make to third parties—such as market research firms—that end up going to physicians (covered recipients).

Manufacturers must report indirect payments under the Sunshine Act, but there is an “indirect payment exclusion,” that excludes otherwise reportable indirect payments where the manufacturer is “unaware of the identity of the covered recipient.” In implementing the Sunshine law, the Centers for Medicare and Medicaid Services (CMS) decided to create an “ongoing” awareness standard. Thus, indirect payments are only excluded if the manufacturer does not find out the identity of the covered recipient during the reporting year or by the end of the second quarter of the following reporting year.” CMS specifies that manufacturers may not act in “deliberate ignorance or reckless disregard” of a physicians’ identity.

Amidst the regulatory uncertainty, market research companies were unsure how either manufacturers or physicians would react--from a funding and a participation perspective, respectively.  Late last year, MedPanel, a market research firm for the life sciences, invited expert physicians to participate in a survey about the Sunshine Act and the Open Payments website. A total of 461 physicians across diverse specialties contributed their perspective. The participants received no honoraria for their answers.

Among other findings, the survey results indicated that passage of the Physician Payment Sunshine Act did not drive an increase in paid market research or consulting participation, with only 3% of surveyed physicians indicating such a trend," stated the report. “The large majority of our expert physicians say that their participation has remained stable since passage of the Act, but 21% of physicians say that their participation has decreased." MedPanel speculated that physicians' fear a stigma attached to the payments maybe driving some of this behavior.

With only five months of data so far published in the system, it is tough to know what the true deterrent effect the Sunshine Act will be on various industry-physician interactions. Even with third party intermediaries keeping a firewall between manufacturers and physicians, both manufacturers and doctors have moved tentatively due to ambiguity around Sunshine reporting. Hopefully within the next few reporting cycles, the process is demystified a bit and accredited CME, blinded market research, and other important informational exchange will continue to thrive.  More at link above.  (Policy and Medicine)
 
Judge Strikes Down Maine Law for Importing Prescription Medicines
A federal judge has invalidated a controversial Maine law that allows residents to buy prescription drugs from some foreign pharmacies.

The Maine Pharmacy Act was enacted two years ago in response to the growing cost of prescription medicines. The law was passed in an effort to lower the cost of medicines for state residents and had the support of the state business community. Residents were permitted to purchase prescription drugs through a broker from pharmacies that are licensed in Canada, the U.K., New Zealand and Australia.

But in a 19-page ruling, filed February 23, U.S. District Court Judge Nancy Torresen decided that the first-in-the-nation law is pre-empted – or superseded – by federal law. The terminology, essentially, means that the state did not have the right to enact such a law because the federal government – in this case, the FDA – has jurisdiction over importation.

The ruling is a big win for the pharmaceutical industry and pharmacists in Maine, who filed lawsuits challenging the law. They argued that the law, which was enacted in 2013, was an ill-conceived attempt to usurp FDA regulatory authority. And in a bid to win wider attention, they repeatedly cautioned that patient safety may be compromised by the prospect of an influx of counterfeit medicines. More at link above. (WSJ Pharmalot)
 
California Lawmaker wants Pharma to Reveal Costs for Pricey Drugs
As the prices of prescription medicines strain budgets, one California lawmaker wants to force drug makers to reveal their costs in a bid to provide some transparency to the pricing process.

Specifically, the bill would require drug makers to report profits and various operational costs for any medicine that has a price tag of more than $10,000 a year. And these costs would have to be reported to the California Office of Statewide Health Planning and Development, which would then compile an annual report that would be submitted to the state legislature and posted publicly online.

Which costs would have to be reported? The list in the bill includes R&D costs incurred by a drug maker or a company from which a compound was acquired; R&D grants, including those from any government agency; costs for clinical trials, manufacturing and marketing; any costs associated with acquiring a compound, such as patents or licensing fees; and financial assistance provided to patients.  More at link above. (WSJ Pharmalot)


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 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.