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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: May 15, 2015

SECTION 1 FDA GUIDANCES, RULES & 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.

April 28 Update: New & Revised Draft Guidances CDER is Planning to Publish during CY2015
The link above is the new CDER list of guidances planned for new issue or revision in Calendar Year 2015.  In this revision, FDA has added a new title to the Biosimilarity category: “Nonproprietary Naming for Biological Products.”

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final guidances for which CDRH would appreciate external feedback on whether these final guidances should be revised or withdrawn.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 May 11, 2015, FDA announced a “Request for Nominations on the Vaccines and Related Biological Products Advisory Committee.” FDA is requesting that any industry organizations interested in participating in the selection of a nonvoting industry representative to serve on the Vaccines and Related Biological Products Advisory Committee for the Center for Biologics Evaluation and Research (CBER) notify FDA in writing. FDA is also requesting nominations for a nonvoting industry representative(s) to serve on the Vaccines and Related Biological Products Advisory Committee. A nominee may either be self-nominated or nominated by an organization to serve as a nonvoting industry representative. Nominations will be accepted for current vacancies effective with this notice.  Expressions of interest and nominations will be due by June 10, 2015. [Federal Register]

On May 12, 2015, FDA issued a draft guidance for industry entitled ‘‘Revised Recommendations for Reducing the Risk of Human Immunodeficiency Virus Transmission by Blood and Blood Products.” This guidance document provides blood establishments that collect blood or blood components, including Source Plasma, with FDA’s revised donor deferral recommendations for individuals with increased risk for transmitting human immunodeficiency virus (HIV) infection. FDA is also recommending that corresponding revisions to donor education materials, donor history questionnaires and accompanying materials, along with revisions to donor requalification and product management procedures.  This guidance also incorporates certain other recommendations related to donor education materials and testing contained in the memorandum to blood establishments entitled, “Revised Recommendations for the Prevention of Human Immunodeficiency Virus (HIV) Transmission by Blood and Blood Products,” dated April 23, 1992 (1992 blood memo).  [FDA.gov]

On May 13, 2015, FDA announced the availability of a draft guidance for industry, FDA staff, and other stakeholders entitled “Patient Preference Information – Submission, Review in PMAs, HDE Applications, and De Novo Requests, and Inclusion in Device Labeling.” This draft guidance document takes the next step beyond the March 2012 guidance “Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications” and provides guidance on patient preference information that may be used by FDA staff in decision-making relating to PMAs, Humanitarian Device Exemption (HDE) applications, and de novo requests. The objectives of this draft guidance are: 1) to encourage voluntary submission of patient preference information by sponsors or other stakeholders, in certain circumstances; 2) to outline recommended qualities of patient preference studies, which may result in valid scientific evidence; 3) to provide recommendations for collecting patient preference information to FDA; and 4) to provide recommendations for including patient preference information in labeling for patients and health care professionals.  This draft guidance also includes several hypothetical examples that illustrate how patient preference information may inform FDA’s regulatory decision-making. Comments will be due 90 days after publication of the draft guidance in the Federal Register. [FDA.gov]

On May 13, 2015, FDA announced the availability of a draft guidance for industry entitled “Investigational Enzyme Replacement Therapy Products: Nonclinical Assessment.” This draft guidance is intended to advise the sponsors and individuals involved in the design and implementation of nonclinical studies on the substance and scope of nonclinical information needed to support first-in-human clinical trials, ongoing clinical development, and eventual approval of enzyme replacement therapy (ERT) products for the treatment of rare, life-threatening conditions. It is intended as an adjunct to the ICH guidances for industry entitled ‘‘M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals,’’ ‘‘M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals—Questions and Answers,’’ and ‘‘S6 Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals.’’ Comments should be submitted by July 13, 2015. [Federal Register]

On May 13, 2015, FDA issued a revised draft guidance for industry entitled “Biosimilars: Additional Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009.” This draft guidance is intended to provide answers to common questions from sponsors interested in developing proposed biosimilar products, biologics license application (BLA) holders, and other interested parties regarding FDA’s interpretation of the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). This guidance revises the draft guidance entitled ‘‘Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009,’’ issued February 15, 2012, to provide new and revised questions and answers (Q&As). Comments should be submitted by July 13, 2015. [Federal Register]

On May 14, 2015, FDA published in the Federal Register a notice entitled “Electronic Study Data Submission; Data Standards; Support for the Logical Observation Identifiers Names and Code.” Through this notice, FDA is encouraging sponsors and applicants to provide Logical Observation Identifiers Names and Codes (LOINC) codes (available at http://loinc.org/) for clinical laboratory test results in investigational study data provided in regulatory submissions submitted to the Center for Drug Evaluation and Research and to the Center for Biologics Evaluation and Research. LOINC code is defined as electronic messages for laboratory test results and clinical observations. The decision to adopt LOINC for lab test results is part of a larger FDA effort to align the use of data standards for clinical research with ongoing nationwide health information technology initiatives. FDA invites public comment on appropriate steps the Agency could take to promote the use and utility of LOINC-coded clinical data submitted to the Agency.  [Federal Register]

On May 14, 2015, FDA announced a that a proposed collection of information entitled “Survey of Pharmacists and Patients; Variations in the Physical Characteristics of Generic Drug Pills and Patients’ Perceptions” While generic drugs are required to be pharmaceutically equivalent and bioequivalent to their brand-name counterparts, generics made by different manufacturers may differ substantially from their brand-name therapeutic equivalents and from each other in their physical appearance (e.g., color, shape, or size of pills). When pharmacists switch generic drug suppliers, patients refilling their generic prescriptions may therefore experience changes in their drugs’ appearances. These changes may result in patient confusion and concerns about the safety and effectiveness of the generic drug products. To provide additional information that may help guide regulatory policy or pharmacy business practices, we intend to conduct surveys of pharmacists and patients about their perceptions about and experiences with generic drug product pill appearance change. These surveys are intended to further our understanding of the relationship between changes in pill appearance and non-adherence to prescribed therapeutic regimens.  Comments on the proposed collection of information should be submitted by June 15, 2015. [Federal Register]

On May 15, 2015, FDA issued a draft guidance for industry entitled “Investigational New Drug Applications Prepared and Submitted by Sponsor-Investigators.” This draft guidance is intended to assist sponsor-investigators in preparing and submitting complete investigational new drug applications (INDs) to the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) at FDA.  The document highlights certain elements of this process to facilitate a sponsor- investigator’s successful submission of an IND and discusses the IND review process and general responsibilities of sponsor-investigators related to clinical investigations. Details of the informational content of an IND as well as information needed to complete required forms also are provided throughout this guidance.  Comments should be submitted by July 14, 2015, to assure consideration prior to FDA’s work on the final version. [Federal Register]

On May 15, 2015, FDA issued a draft guidance for industry entitled “Revised Recommendations for Reducing the Risk of Human Immunodeficiency Virus Transmission by Blood and Blood Products.” This draft guidance provides blood establishments that collect blood or blood components, including Source Plasma, with revised donor deferral recommendations for individuals at increased risk for transmitting human immunodeficiency virus (HIV) infection. The draft guidance document recommends corresponding revisions to donor education materials, donor history questionnaires and accompanying materials, along with revisions to donor requalification and product management procedures. The document also incorporates certain other recommendations related to donor education materials and testing contained in the memorandum to blood establishments entitled, ‘‘Revised Recommendations for the Prevention of Human Immunodeficiency Virus (HIV) Transmission by Blood and Blood Products,’’ dated April 23, 1992 (1992 blood memo). The draft guidance, when finalized, is intended to supersede the 1992 blood memo. Comments should be submitted by July 14, 2015, to assure consideration prior to FDA’s work on the final version. [Federal Register]


SECTION 2 EMA CONSULTATIONS, GUIDELINES, & NEWS

Safety monitoring of medicines: EMA to screen medical literature for 400 active substance groups
A new service will improve safety monitoring of medicines and simplify pharmacovigilance activities for companies. The European Medicines Agency (EMA) has published the list of active substances and a reference to the journals that will be covered by its new medical literature monitoring service. This service will start with a limited number of active substances on 1 July 2015 and will be fully rolled out in September 2015. A guide, a training video and a document detailing the inclusion and exclusion criteria to be used when screening the literature are also available on a dedicated webpage [Medical Literature Monitoring].   

This initiative aims to improve the safety monitoring of medicines by enhancing the quality and consistency of data reported in EudraVigilance. It is provided as a service to industry which, for the active substances and literature covered by the EMA activities, will no longer be obliged to enter the information on suspected adverse reactions into EudraVigilance. Individual cases of suspected adverse reactions found in the literature will be made available to marketing-authorisation holders so they can include them in their safety databases and meet their reporting obligations outside the European Economic Area.

As of 1 July 2015, the service will cover the top 50 chemical active substance groups (ID 1 to ID 50) which are listed in the document published today. Companies with medicines containing one of these active substances will benefit from the EMA service from 1 July and will need to adapt their processes by that date. All the other substances, including the herbal active substances that are listed, will be included in the EMA service as of September 2015. More at title link above. (EMA.eu)

Public Consultation on Inventory of Paediatric Therapeutic Needs - Endocrinology
Based on Article 43 of the European Union Paediatric Regulation the Paediatric Committee at the European Medicines Agency (PDCO) is working to establish an inventory to identify the needs in the different therapeutic areas where there should be research and development of medicinal products for children. The inventory is based on the results of a survey of all paediatric uses of medicines in Europe and on the existing list of paediatric needs established by the former Paediatric Working Party; it will be published progressively by therapeutic area. Further information can be found on the [EMA Website]. Deadline for comments is June 5, 2015. List at title link above. (EMA.eu)

Inventory of Paediatric Therapeutic Needs - Gastroenterology
Based on Article 43 of the European Union Paediatric Regulation the Paediatric Committee at the European Medicines Agency (PDCO) is working to establish an inventory to identify the needs in the different therapeutic areas where there should be research and development of medicinal products for children. The inventory is based on the results of a survey of all paediatric uses of medicines in Europe and on the existing list of paediatric needs established by the former Paediatric Working Party; it will be published progressively by therapeutic area. Further information can be found on the [EMA Website]. Deadline for comments is June 5, 2015. List at title link above. (EMA.eu)

Draft guideline on clinical development of fixed combination medicinal products
EMA has published a draft guideline covering fixed combination (also referred to as fixed dose combinations, FDCs) medicinal products containing two or more active substances within a single pharmaceutical form. The active substances may be known active substances or substances that have not yet been authorised in the EU. This guideline addresses the clinical development requirements of fixed combination medicinal products, which shall reflect their intended therapeutic use and indication. This revised guideline revisited scientific requirements for the development of an FDC independent of chosen legal basis for submission of an application for marketing authorisation. Deadline for comments is November 15, 2015. More at link above. (EMA.eu)


SECTION 3 FDA NOTES & RELATED NEWS

Califf Seeks New “Ecosystem” for Clinical Trials
Current clinical trials are regarded as “too slow, too expensive, not reliable, and not designed to answer the important questions,” according to FDA’s new deputy commissioner for medical products &tobacco, Robert Califf. A veteran of multiple initiatives to modernize the biomedical clinical research enterprise, Califf emphasized the importance of improving the quality and efficiency of clinical trials as key to improving public health and to encouraging biomedical innovation.

Califf has long advocated for building a “learning health care system,” where information from individual health records can be accessed to inform treatment decisions and support medical product development. Now we’re “on the verge of a tipping point” in clinical trial reform, Califf predicated at a Washington seminar addressing the topic of re-engineering clinical trials.

Multiple efforts so far have realized “incremental improvements” in research operations, many negotiated as part of drug user fee agreements, Califf observed; he sees real change on the horizon due to important advances in data systems, integration of health care delivery operations, plus greater public attention to the flaws in the clinical research enterprise.

FDA staff is implementing initiatives designed to achieve more efficiencies in clinical research, such as electronic informed consent, adoption of mobile technologies to measure clinical response, use of e-health records in designing research protocols, and adoption of common data standards and terminologies in research studies to support applications filed with FDA. Further development of research networks at the National Institutes of Health (NIH) and the Patient-Centered Outcomes Research Institute (PCORI), along with expansion of FDA’s Sentinel System, will provide added infrastructure for conducting more efficient clinical research.

Califf similarly described a new “ecosystem” for clinical research as key to supporting the Precision Medicine Initiative and efforts by FDA to “put patients first.” More at link above. (Applied Clinical Trials)

Biosimilars: New guidance from FDA to help manufacturers develop more treatment options
In her May 14, 2015 FDA Voice blog, Leah Christl, PhD, FDA’s Associate Director for Biosimilars, Office of New Drugs, Center for Drug Evaluation and Research, writes:

FDA has taken important new steps to continue to help manufacturers develop biologic products called biosimilars. Biosimilars are highly similar to, and have no clinically meaningful differences from, an already approved biological product. Biosimilars can provide more treatment options for patients, and possibly lower treatment costs.

Over the past few weeks, we have released four guidances for industry — useful tools to help manufacturers navigate the new terrain of biosimilar development.
  • One assists companies in demonstrating that a proposed product is indeed biosimilar to an existing biologic product, and is intended to provide clarity to manufacturers about the expectations for a biosimilar development program.
  • A second focuses on the analytical studies that demonstrate that the product is “highly similar” to an existing biological product, which supports the demonstration of biosimilarity.
  • A third guidance answers common questions about the biosimilar development and application process and contains information intended to provide a better understanding of the law that allows biosimilars development.  
  • A fourth, still in draft form — which means we are accepting public comment — answers a variety of additional questions that have arisen regarding the biosimilars development process.
Having more approved biosimilars is good for public health. FDA looks forward to continuing to help manufacturers develop these important products. More at link above. (FDA.gov)

FDA to hold public meeting on off-label use
FDA said it intends to release new draft guidance on acceptable manufacturer communications with physicians and other entities concerning off-label use of approved drugs. The Agency will also hold a public meeting this summer to address drug company concern that restrictions on what they can say about off-label use of drugs violate their First Amendment right to free speech.

The meeting, announced last month by FDA chief counsel Elizabeth Dickinson, comes as a bill known as 21st Century Cures, designed to speed new drugs to market, is moving through Congress. Language in the bill is adding pressure on the agency to relax its guidelines.

Efforts by drug companies to change the rules gained steam after a 2012 decision from the Second Circuit Court of Appeals, which overturned the conviction of Alfred Caronia, a sales representative for Orphan Medical, which was later acquired by Jazz Pharmaceuticals Inc. After Caronia was caught talking to physicians about various off-label uses of the narcolepsy drug Xyrem, the court said the First Amendment protected truthful and non-misleading off-label speech.

Under current rules, physicians are allowed to prescribe medicines off-label for whatever condition they want. But drug companies are not allowed to promote them for uses that have not been approved by the FDA.

Pharmaceutical companies are citing the Caronia and similar rulings to pressure the FDA to let them talk more freely about off-label use.  More at link above. (Reuters)


SECTION 4 AGENCY AND ADVISORY COMMITTEE MEETINGS

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

New:  Public Workshop. Dose Finding of Small Molecule Oncology Drugs.  May 18-19, 2015.  Washington, DC.  The purpose of the public workshop is to discuss the best practices of dose finding and dose selection for small molecule kinase inhibitors developed for oncology indications. To permit the widest possible opportunity to obtain public comment, FDA is also soliciting either electronic or written comments on all aspects of the public workshop topics. The deadline for submitting comments related to this public workshop is June 18, 2015. [Federal Register]

Public Webinar.  Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses of Medical Devices Draft Guidance.  May 19, 2015.  Online.  FDA will host a webinar to provide clarification, answer questions and encourage feedback during the open comment period for the above-referenced draft guidance. The webinar is intended to help manufacturers and other interested stakeholders understand the information provided in this draft guidance document. Access information at link. [FDA.gov]

Public Meeting. Interim Assessment of the Program for Enhanced Review Transparency and Communication. May 20, 2015.  White Oak Campus, Silver Spring, MD.  FDA is holding this public meeting to discuss the above referenced interim assessment and to provide an opportunity for public comment on the assessment and the Program to date. [Federal Register]

Public Workshop. FDA Science Forum 2015.  May 27 - 28, 2015.  White Oak Campus, Silver Spring, MD.  The public workshop will highlight science conducted at the FDA by showcasing how scientific research informs regulatory decision making and to provide a forum for developing collaborations within FDA and with external organizations. The focus of the forum will be the eight FDA Regulatory Science priority areas. [Federal Register] Podcast brief of Science Forum content by Dr. Luciana Borio, FDA’s Acting Chief Scientist: [FDA.gov]

Annual Workshop. European Network of Pediatric Research at the EMA.  May 28, 2015. Canary Wharf, London, UK.  The aim of the annual workshop is to promote the conduct of high quality paediatric clinical studies.  Enpr-EMA is a network of research networks, investigators and centres with recognised expertise in performing clinical studies in children. Its main objective is to facilitate studies in order to increase the availability of medicines authorised for use in children. [EMA.eu]

Public Advisory Committee Meeting. Transmissible Spongiform Encephalopathies Advisory Committee. June 1, 2015.  White Oak Campus, Silver Spring, MD.  The Advisory Committee will meet to hear updates on the variant Creutzfeldt-Jakob Disease (vCJD) situation worldwide, followed by presentations by FDA on current measures to reduce vCJD from transfusion in the US and additional topics. [Federal Register]

Public Hearing. Regulatory Science Initiatives under the Generic Drug User Fee Amendments of 2012.  June 5, 2015.  White Oak Campus, Silver Spring, MD.  This public hearing will provide an overview of the current status of regulatory science initiatives for generic drugs and an opportunity for public input on research priorities in this area. FDA is seeking this input from a variety of stakeholders—industry, academia, patient advocates, professional societies, and other interested parties—as it fulfills its commitment under the Generic Drug User Fee Amendments of 2012 (GDUFA) to develop an annual list of regulatory science initiatives specific to generic drugs. FDA will take the information it obtains from the public hearing into account in developing the fiscal year (FY) 2016 Regulatory Science Plan.  [Federal Register]

Public Advisory Committee Meeting. Risk Communications Advisory Committee. June 8-9, 2015.  White Oak Campus, Silver Spring, MD.  The Committee will discuss approaches to communicating information about fetal effects in product labeling for methadone or buprenorphine maintenance therapy for opioid addiction, and about the maternal benefits and risks of treatment, to best enable patients and health care providers to make informed decisions about the use of these drugs during pregnancy. [Federal Register]

Public Meeting and Request for Comment. Generic Drug User Fee Amendments of 2012. June 15, 2015.  White Oak Campus, Silver Spring, MD.  Before FDA begins negotiations with the regulated industry on GDUFA reauthorization, it will hold a public meeting at which the public may present its views on the reauthorization, including specific suggestions for changes to the goals referred to in the Generic Drug User Fee Act Program Performance Goals and Procedures (i.e., the Commitment Letter). A docket is also established for public comments. [Federal Register]

New: Public Meeting.  Prescription Drug User Fee Act.  July 15, 2015.  White Oak Campus, Silver Spring, MD.  FDA will begin the PDUFA reauthorization process for fiscal years 2018 through 2022 by requesting public input and holding a public meeting where the public may present its views on the reauthorization. FDA invites public comment as the Agency begins the process to reauthorize the program in FYs 2018–2022. [Federal Register]

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 5 OTHER ORGANIZATIONS & AUTHORITIES

Medical Device Innovation Consortium Patient-Centered Benefit Risk Framework Report Available
Medical Device Innovation Consortium (MDIC) released the first-of-its-kind Framework report, “A Framework for Incorporating Information on Patient Preferences Regarding Benefit and Risk into Regulatory Assessments of New Medical Technology,” (http://mdic.org/pcbr/) on how to incorporate patient preferences into the development and submissions of medical devices.

The Framework report is a result of collaborative work that came after the U.S. Food & Drug Administration (FDA) issued a guidance document in 2012 “Factors to Consider When Making Benefit- Risk Determinations in Medical Device Premarket Approval and De Novo Classifications.” This Benefit-Risk Guidance discusses how the patient’s perspective on benefits and risks is valuable in the regulatory assessment of new medical devices, but does not provide detail on when or how to collect such information. MDIC undertook its Patient Centered Benefit-Risk (PCBR) Project both to catalog the methods available to assess patient preferences and to create a framework to guide thinking about when and how to collect information on patient preferences in the development and regulatory evaluation of medical devices. More at link above. (MDIC)

Economist Leading UK Review: Multibillion-Dollar Investment Needed to Fight Drug-Resistant ‘Superbugs’

A multibillion-dollar investment into the global pharmaceuticals industry is needed to ward off the threat of drug-resistant “superbugs,” according to Jim O’Neill, the economist leading a review into antimicrobial resistance for the U.K. government.

Mr. O’Neill estimated that as much as $37 billion is needed over the next 10 years to spur the industry to develop innovative antibiotics, since there is little market incentive to do so.

The economist said he was “open” to different sources of funding but said that some will “almost certainly come from the global taxpayer.” Mr. O’Neill added that this sum was “modest” in comparison with the economic cost of ignoring the problem.

Mr. O’Neill said extra investment was needed at every stage of the antibiotic development process to “radically overhaul” the antibiotics pipeline over the next 20 years.  While he didn’t specifically call on pharmaceutical companies to foot the bill for the innovation fund, he did urge the industry to act with “enlightened self-interest” in tackling AMR, “recognizing that it has a long-term commercial imperative to having effective antibiotics, as well as a moral one.”

He said these measures, along with efforts to link up early research with companies, could bring 15 new drugs a decade to market, at least four of which would be “truly novel.” More at link above. (Wall Street Journal)

Prescription Drug Costs Rose Faster Than Ever for Many Americans: Report
The prices for new hepatitis C and cancer treatments are driving the cost of prescription drugs to new highs for more Americans, according to a new report. Specifically, the estimated number of people in the U.S. who took medicines worth more than $50,000 annually rose 63% last year, to 576,000, up from 352,000 the year before. And the number of Americans who are estimated to be taking at least $100,000 worth of drugs jumped 193% to 139,000 people, from 47,000.

“The bottom line is that the number of people with very high prescriptions is increasing very rapidly,” says Glen Stettin, senior vice president for clinical research at Express Scripts, the pharmacy benefits manager, which reviewed data for 31.5 million people covered by commercial insurers, Medicare and Medicaid. “And a lot of people are being treated with expensive, life-long drugs and so they will be in this category for a long time.” More at link above. (Pharmalot)

PhRMA: Express Scripts Releases Misleading Report on Medicine Prices
Express Scripts released yet another misleading report to promote a false narrative about medicine spending in the United States.

For more than 50 years, spending on medicines has consistently accounted for just 10 percent of U.S. health care spending.

Yet this report ignores this reality and instead focuses solely on the costs of treating the sickest patients with the most health conditions. In fact, less than one percent of patients included in the report are at the top of the cost spectrum and one-third of those are being treated for ten or more different medical conditions.

The report also found that nearly 70 percent of patients incurred less than $1,000 in medicine expenditures in 2014.  More at link above.  (PhRMA.org)

Paying for Personalized Medicine: How Alternative Payment Models Could Help or Hinder the Field
In a white paper released today by the Personalized Medicine Coalition (PMC), the nonprofit education and advocacy organization encourages health care policymakers to consider how alternative payment models (APMs) may promote or impede access to personalized medicine tests and treatments that have the potential to improve patient outcomes while lowering systemic costs.

Following the U.S. Department of Health and Human Services’ recent announcement of a plan to tie 50 percent of fee-for-service Medicare payments to quality or value in three years by linking them to APMs, PMC Executive Vice President Amy M. Miller, Ph.D., said thinking about these issues now is imperative. “We must consider the downstream implications of these policies,” Miller said. “These reforms will impact patient access and influence the pace of innovation. It is therefore imperative that they support personalized medicine.”

The report explores the potential positive and negative consequences that APMs might have on personalized medicine, with a particular focus on how Accountable Care Organizations (ACOs), bundled payments, medical homes and clinical pathways might impact the field. As stated in the conclusion of the paper, PMC believes that “through open dialogue and transparent processes that include all stakeholders, a more efficient and high-quality health system is within reach.” (Personalized Medicine Coalition)

Patient-Centered Research Can Improve Chronic Pain Care and Address Opioid Abuse
From the blog of PCORI (Patient Centered Outcomes Research Institute) Executive Director Joe V. Selby, MD:

For more than a decade, the United States has faced an escalating opioid abuse crisis. The number of deaths associated with abuse of these prescription painkillers more than tripled between 1999 and 2012 and now outstrips the number associated with any other drug, according to the US Centers for Disease Control and Prevention. The problem is estimated to approach $56 billion in costs to society.

Researchers, policy makers, clinicians, and their professional organizations are working hard to stem the opioid abuse epidemic, seeking ways to reduce overprescribing of these drugs by expanding the use of alternative and supporting therapies, as well as identifying more effective treatments for addiction.

These are important steps, but we clearly need more evidence-based information about how to better treat chronic pain. We at the Patient-Centered Outcomes Research Institute (PCORI) believe that when it comes to this issue, we can help by funding research that compares what works best, for whom, under which circumstances. In the last three years, we’ve funded at least 16 such projects that, as in all of our work, focus on the questions and outcomes most important to patients.

People suffering pain, or caring for someone in pain, want information that is relevant, trustworthy, and clear to inform their healthcare choices. That’s what PCORI-funded comparative clinical effectiveness research (CER) seeks to do – provide patients, their caregivers and clinicians with more and better information on the pain care options available to them and which therapies are most likely to help them achieve the outcomes they desire.

Since 2012, PCORI has built a sizeable portfolio of studies on chronic pain, two of which specifically address opioid treatment.  We also plan future research relevant to pain treatment. For example, the topics in our research prioritization process pipeline include long-term use of opioids in treating chronic pain generally as well as treatment of chronic low-back pain and musculoskeletal pain specifically. In June, we are hosting two multi-stakeholder workshops to discuss whether CER studies can help to address these issues; the discussion may lead to the creation of a targeted PCORI funding announcement or the listing of other topics related to pain as high-priority areas in funding announcements for pragmatic clinical studies.  More at link above. (PCORI.org)  

Personalized Medicine Is Gaining Traction, but Faces Multiple Challenges
While development of personalized medicines has grown since the human genome was first sequenced in 2001, biopharmaceutical sponsors face a number of hurdles that are impeding more rapid market uptake, according to a recently completed study by the Tufts Center for the Study of Drug Development.

Fourteen years after the human genome was initially sequenced, paving the way for development of personalized medicine, 13% of drugs marketed in the United States today post pharmacogenomic information on the label, but developers continue to encounter challenges relating to basic science, regulatory and reimbursement policies, and, equally critical, clinical adoption, according to Tufts CSDD.

Says Joshua Cohen, associate professor at Tufts CSDD, “In particular, the continued development of personalized medicine depends on identifying biomarkers and developing clinically useful diagnostic tests.”

These assessments, based on a survey of major drug manufacturers and interviews with leading drug and diagnostics companies, were reported in the May/June Tufts CSDD Impact Report, released Thursday (5/14/15). Other highlights include the following:

  • Biopharmaceutical firms said they expect investment in personalized medicine to increase 33%, and medicines in development to increase 69%, over the next five years.
  • Biomarker identification and diagnostic test development rank highest in terms of scientific challenges, followed by regulatory and reimbursement issues.
  • Oncology products continue to rank highest in terms of average share of personalized medicines in development across all phases, followed by neurology and cardiovascular drugs.

More at link above.  (Tufts CSDD Release)

ASCO Chief Medical Officer: Creating a Collective Path Forward to Optimize Value in Cancer Care
The Centers for Medicare and Medicaid Services projects that U.S. health-care spending will reach $4.3 trillion and account for 19.3% of the nation’s gross domestic product by 2019.  Although cancer care represents a small fraction of overall health-care costs, the cost of cancer care is rapidly increasing, now estimated to reach $158 billion in 2020—an increase of 26% over just a decade.

Cost is only one component of a complex calculus that must weigh health outcomes against dollars spent to assess the true value of health care…Value must be considered from the varying perspectives of consumers of health care, providers of health care, payers for health care, purchasers of health care, and innovators of health-care products. Value must be considered from the varying perspectives of consumers of health care, providers of health care, payers for health care, purchasers of health care, and innovators of health-care products.

For product innovators, value is determined in the context of research and development investment and shareholder expectations. From the innovator’s perspective, value is often assessed over the life cycle of the product, as product performance varies across patient populations, by line of therapy, and based on whether a biomarker selection strategy is employed.

Pricing and reimbursement typically depend on marketplace competition, region of the world, and duration of patent exclusivity and less so on treatment indication and magnitude of incremental benefit achieved. To be sure, cancer drugs take years to develop and billions of dollars in research investment, and for every success, there are dozens of failures. Yet even drugs that successfully reach the market sometimes produce only modest incremental improvements in clinically important endpoints—nevertheless, they still enter the market with extraordinarily high prices.

For all stakeholders, the definition of value ultimately comes down to the price that must be paid to achieve meaningfully improved health outcomes at the level of individual patients or for the broader population of affected individuals. Optimizing the value of a new product begins with innovation to address an unmet medical need followed by defining and achieving clinically meaningful improvements in health outcomes through well-designed and efficiently conducted clinical trials. Effectiveness research is essential to determine how well the new product performs compared to available alternatives and in more diverse populations than those typically included in the clinical trials used to establish efficacy.

Regulatory and policy initiatives (such as adaptive licensing, value-based insurance, and indication-specific pricing, which impact marketing approval, reimbursement, and price, respectively) based on treatment effectiveness all deserve careful consideration. Further research must also be conducted to determine the impact of these initiatives on aligning cost with benefit while insuring patient access to life-prolonging therapies and continuing innovation in product development.  More at link above. (ASCO Post)


SECTION 6 LEGAL AND COMPLIANCE

21st Century Cures Unveils Updated Draft in Advance on Health Subcommittee Markup
Bipartisan leaders of the House Energy and Commerce Committee unveiled on Wednesday, May 13, an updated draft of the 21st Century Cures Act, to be considered by the Health Subcommittee during a mark-up the next day.

“Every step in this process has been hard fought, not for our own interests, but for those who suffer. Every policy has been scrutinized, every voice considered. We’ve pushed harder and faster than anyone thought possible, because we know patients cannot wait. They need 21st Century Cures now,” commented full committee Chairman Fred Upton (R-MI).   

Read the updated draft online here and a section-by-section online here.  More at title link above. (Energy & Commerce)

#Cures2015 Moves Forward
After more than a year of listening to and engaging with patients and other experts across the country, the Energy and Commerce Subcommittee on Health today advanced the 21st Century Cures Act by a voice vote. The full committee will consider the legislation next week. The bipartisan discussion draft was introduced by full committee Chairman Fred Upton (R-MI), Rep. Diana DeGette (D-CO), Health Subcommittee Chairman Joe Pitts (R-PA), full committee Ranking Member Frank Pallone, Jr., (D-NJ), and Health Subcommittee Ranking Member Gene Green (D-TX).

“Our time is now. For more than a year we have been listening and diligently working on policies that we believe will truly make a difference in the lives of families and patients. 21st Century Cures is for them. It is their optimism, hope, and drive that has kept us moving forward. In the coming days we will continue working to make improvements to this important bill and prepare for a full committee markup next week,” said Upton, DeGette, Pitts, Pallone, and Green. More at link above. (Energy & Commerce)

Full Committee to Convene for Markup of 21st Century Cures Bill
On Tuesday May 19, the Energy and Commerce Committee will convene a markup of the 21st Century Cures Act. This nonpartisan legislation is the product of more than a year of listening to patients, researchers, caregivers, and innovators. It seeks to modernize the nation’s health care innovation ecosystem, encourage greater biomedical innovation, and help get more cures and treatments to patients faster. Members will deliver opening statements on Tuesday and reconvene Wednesday morning to consider the bill. The Majority Memorandum, legislation, and amendments will be available here as they are posted.  See link above for more information. (Energy & Commerce)

Pharma and Biotech Industry Trade Groups asked to Offset Cost of 21st Century Cures Act
U.S. House Energy & Commerce Committee staff have asked the pharmaceutical and biotech industry trade groups to offset some or all of the cost of the proposed 21st Century Cures Act, BioCentury writes. But the trade associations adamantly refused to consider the proposal because their members feel the current discussion draft, which was released last week, contains few provisions that would benefit them. Provisions in the first discussion draft that would have provided generous additional market exclusivity for many drugs were stripped out due to objections from Democrats. (WSJ Pharmalot)

Next Generation Cures
On Tuesday, May 12th, PhRMA and The Hill convened a symposium with legislators and leading health care experts on “Next Generation Cures.” Speakers and panelists focused on how all health care stakeholders can work together to create a policy and regulatory environment conductive to encouraging innovation and investment in the research and development needed for new therapies and cures for patients.

Senator Richard Burr kicked off the event by discussing the state of health care in America and what Congress can do to improve quality of care and access to medicines for patients. “We have to make sure there’s a pathway that’s understandable, not only through approval but reimbursement,” said Sen. Burr. Addressing 21st century breakthroughs, Sen. Burr stated that focusing on innovation is imperative to encourage research for new medicines, enabling us to reach the next level of treatments and cures. Giving President Obama credit for launching a new precision medicine initiative, Sen. Burr reiterated that this is a significant opportunity to get legislation right and help increase access to clinical trials and new treatments for patients.  More at link above. (PhRMA.org)

Subcommittee on Oversight and Investigations to Continue Hearing Series on Opioid Abuse Epidemic
The Subcommittee on Oversight and Investigations has scheduled a hearing for Thursday, May 21, entitled “What are the State Governments Doing to Combat the Opioid Abuse Epidemic?”

The subcommittee will continue its hearing series to review how states are combatting the opioid abuse epidemic and explore how state and federal policies can most effectively incentivize the development and broadened use of evidence-based practices and treatments in their communities. Next week the subcommittee will hear from several state health leaders about their experiences in coordinating efforts with the federal government. Witnesses from Colorado, Indiana, Massachusetts, and Missouri will testify.

Subcommittee members recently heard from a panel of federal health care officials about what steps the federal government is taking to combat the epidemic. Members have also recently heard from health professionals and academics about treatment options currently available, as well as local community leaders who discussed their efforts to confront the growing cycle of prescription drug and heroin abuse. More at link above. (Energy & Commerce)

Sanders Asks VA to Break Patents on Gilead and AbbVie Hep C Drugs
U.S. Sen. Bernie Sanders (I-VT.) has asked the U.S. Department of Veterans Affairs to use emergency powers to break – or override – the patents on high-priced hepatitis C medicines sold by several drug makers. The new hepatitis C treatments cure more than 90% of those infected and, in the U.S., cost from $63,000 to $94,500, depending upon the drug and regimen, before any discounts.

Sanders notes the VA stopped enrolling veterans who need treatment for hepatitis C due to budget constraints and that the agency has treated about 20,000 vets for hepatitis C but needs fund for an estimated 180,000 more vets who are enrolled in VA health care and are believed to be infected with the chronic disease. The agency has already reallocated $400 million on hepatitis C drugs.  

It is not clear whether the VA will consider breaking patents. We asked a VA spokesman about the idea and he did not directly respond, but did say the agency is working with Congress to find ways to address the financial shortfall.  More at link above. (WSJ Pharmalot)

Opinion: Drug Safety Benefits from Off-Label Promotion
Jim Davis, The American Journal of Managed Care, comments “...Unless there is a dramatic reversal by FDA, all off-label promotions will be required to be based on published studies. Pharmaceutical companies are the chief sponsor for most late stage and post-marketing drug research and they have the most to gain—and more importantly, lose—if their data fails to meet healthcare decision maker and market demands. Allowing for off-label promotion, supported by published studies, will require more research to be sponsored by the drug manufacturer. This will also cause their competitors to respond in-kind, providing for more balanced data.”  More at link above.  (via National Pharmaceutical Council)


SECTION 7 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.