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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: July 10, 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final guidances for which CDRH would appreciate external feedback on whether these final guidances should be revised or withdrawn.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)

Collections of Information:

On July 1, 2015, FDA announced that a collection of information entitled “General Licensing Provisions; Section 351(k) Biosimilar Applications” has been submitted to the Office of Management and Budget (OMB) for review and clearance. Fax written comments on the collection of information by July 31, 2015. [Federal Register]

On July 1, 2015, FDA announced that a collection of information entitled “Registration of Producers of Drugs and Listing of Drugs in Commercial Distribution” has been submitted to the Office of Management and Budget (OMB) for review and clearance.  Fax written comments on the collection of information to OMB by July 31, 2015. [Federal Register]

Guidances and Draft Guidances:

On June 29, 2015, FDA announced the availability of draft guidance for industry entitled “Assessment of Radiofrequency-Induced Heating in the Magnetic Resonance Environment for Multi- Configuration Passive Medical Devices.”  The purpose of this guidance is to provide an assessment paradigm for radiofrequency (RF)-induced heating on, or near, multi-component, or multi- configuration, passive medical devices in the magnetic resonance environment.  To ensure that the Agency considers your comment of this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by August 28, 2015. [Federal Register]

On June 30, 2015, FDA announced the availability of additional draft and revised draft guidances for industry entitled “Product-Specific Bioequivalence Recommendations.”  The recommendations provide product- specific guidance on the design of BE studies to support abbreviated new drug applications (ANDAs). In the Federal Register of June 11, 2010, FDA announced the availability of a guidance for industry entitled ‘‘Bioequivalence Recommendations for Specific Products’’ that explained the process that would be used to make product- specific BE recommendations available to the public on FDA’s Web site. The BE recommendations identified in this notice were developed using the process described in that guidance. To ensure that the Agency considers your comment of this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by August 31, 2015. [Federal Register]

On July 1, 2015, FDA announced the availability of a guidance for industry and FDA staff entitled “Intent to Exempt Certain Unclassified, Class II, and Class I Reserved Medical Devices From Premarket Notification Requirements.”  This guidance describes FDA’s intent to exempt certain unclassified medical devices (that FDA intends to classify into class I or II), certain class II medical devices, and certain class I medical devices from premarket notification requirements. FDA believes the devices identified in this guidance document are sufficiently well understood and do not require premarket notification to assure their safety and effectiveness. [Federal Register]

On July 6, 2015, FDA announced the availability of a guidance for industry entitled “The Drug Supply Chain Security Act Implementation: Product Tracing Requirements for Dispensers—Compliance Policy.” This guidance announces FDA’s intention with regard to enforcement of certain product tracing requirements of the Federal Food, Drug, and Cosmetic Act (FD&C Act) added by the Drug Supply Chain Security Act (DSCSA). FDA does not intend to take action against dispensers who, prior to November 1, 2015, accept ownership of product without receiving product tracing information, prior to or at the time of a transaction or do not capture and maintain the product tracing information, as required by the FD&C Act. The guidance is effective July 1, 2015.  FDA is implementing this guidance without prior public comment because it has determined that prior public participation is not feasible or appropriate. [Federal Register]

On July 7, 2015, FDA announced the availability of a draft guidance for industry entitled “Qualification of Biomarker—Plasma Fibrinogen in Studies Examining Exacerbations and/or All-Cause Mortality for Patients With Chronic Obstructive Pulmonary Disease.”  This draft guidance provides a qualified context of use (COU) for plasma fibrinogen in interventional clinical trials of chronic obstructive pulmonary disease (COPD) subjects at high risk for exacerbations and/or all-cause mortality. This draft guidance also describes the experimental conditions and constraints for which this biomarker is qualified through the Center for Drug Evaluation and Research (CDER) Biomarker Qualification Program. This biomarker can be used by drug developers for the qualified COU  in submissions of investigational new drug applications (INDs), new drug applications (NDAs), and biologics license applications (BLAs) without the relevant CDER review group reconsidering and reconfirming the suitability of the biomarker. To ensure that the Agency considers your comment of this draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by September 8, 2015. [Federal Register]

On July 9, 2015, FDA announced the availability of a draft guidance for industry and FDA staff entitled “Heparin-Containing Medical Devices and Combination Products: Recommendations for Labeling and Safety Testing.”  This draft guidance describes FDA’s intent to address the safety concerns by clarifying new expectations for labeling with regard to the soon-to-be revised heparin United States Pharmacopeia (USP) monographs as well as outline safety testing recommendations. Comments should be submitted by October 7, 2015, to ensure that the Agency considers them before it begins work on the final version of the guidance. [Federal Register]

On July 9, 2015, FDA announced the availability of a guidance for industry, researchers, patient groups, and FDA staff entitled “Meetings With the Office of Orphan Products Development.” This guidance provides recommendations to industry, researchers, patient groups, and other stakeholders (collectively referred to as ‘‘stakeholders’’) interested in requesting a meeting with FDA’s Office of Orphan Products Development (OOPD) on issues related to orphan drug designation requests, humanitarian use device (HUD) designation requests, rare pediatric disease designation requests, funding opportunities through the Orphan Products Grants Program and the Pediatric Device Consortia Grants Program, and orphan product patient- related topics of concern. This guidance document is intended to assist these groups with requesting, preparing, scheduling, conducting, and documenting meetings with OOPD.  [Federal Register]

Other Actions:

On June 29, 2015, FDA announced a notice and request for public comment entitled ‘‘Use of Ozone-Depleting Substances; Request for Comment Concerning Essential-Use Designations.” (FDA or Agency) is seeking public comment on whether the uses of ozone-depleting substances (ODSs), including chlorofluorocarbons (CFCs), in certain FDA-regulated products currently designated essential are no longer essential under the Clean Air Act due to the availability of alternatives that do not use CFCs or because the products are no longer being marketed. Essential-use products are exempt from FDA’s ban on the use of CFC propellants in FDA-regulated products and the Environmental Protection Agency’s (EPA’s) ban on the use of CFCs in pressurized dispensers. FDA is seeking public comment because it is responsible for determining which FDA-regulated products that release CFCs or other ODSs are essential uses under the Clean Air Act. Comments may be submitted until August 28, 2015. [Federal Register]

On July 2, 2015, FDA announced ‘‘Patient-Focused Drug Development; Announcement of Disease Areas for Meetings Conducted in Fiscal Years 2016–2017.” This effort provides a more systematic approach under PDUFA V for obtaining the patients’ perspective on disease severity and currently available treatments for a set of disease areas. FDA selected these disease areas based on a careful consideration of the public comments received after publication of a preliminary list of disease areas in the Federal Register on October 8, 2014. Following publication of the notice, almost 2,700 comments addressing over 50 disease areas were submitted by patients, patient advocates and advocacy groups, caregivers, healthcare providers, professional societies, scientific and academic experts, pharmaceutical companies, and others. The following diseases will be the focus of meetings scheduled in FYs 2016–2017: Alopecia areata, Autism, Hereditary angioedema, Non-tuberculous mycobacterial infections, Patients who have received an organ transplant, Psoriasis, Neuropathic pain associated with peripheral neuropathy, and Sarcopenia.  [Federal Register]

On July 2, 2015, FDA proposed the ‘‘Removal of Review and Reclassification Procedures for Biological Products Licensed Prior to July 1, 1972.” FDA is taking this action because the two regulations are obsolete and no longer necessary in light of other statutory and regulatory authorities established since 1972, which allow FDA to evaluate and monitor the safety and effectiveness of all biological products. In addition, other statutory and regulatory authorities authorize FDA to revoke a license for products because they are not safe and effective, or are misbranded. FDA is taking this action as part of its retrospective review of its regulations to promote improvement and innovation.  Comments on the proposed rule may be submitted through September 30, 2015. [Federal Register]

On July 2, 2015, FDA announced the ‘‘Revocation of General Safety Test Regulations That Are Duplicative of Requirements in Biologics License Applications.” (FDA) is amending the biologics regulations by removing the general safety test (GST) requirements for biological products. FDA is finalizing this action because the existing codified GST regulations are duplicative of requirements that are also specified in biologics license applications (BLAs), or are no longer necessary or appropriate to help ensure the safety, purity, and potency of licensed biological products. FDA is taking this action as part of its retrospective review of its regulations to promote improvement and innovation, in response to the Executive order. This rule is effective August 3, 2015. [Federal Register]

On July 2, 2015, FDA announced its intention to take enforcement action against ‘‘Unapproved and Misbranded Otic Prescription Drug Products.” The enforcement action will be taken against unapproved and misbranded otic drug products labeled for prescription use and containing benzocaine; benzocaine and antipyrine; benzocaine, antipyrine, and zinc acetate; benzocaine, chloroxylenol, and hydrocortisone; chloroxylenol and pramoxine; or chloroxylenol, pramoxine, and hydrocortisone; and against persons who manufacture or cause the manufacture or distribution of such products in interstate commerce. These unapproved and misbranded prescription drug products are marketed without evidence of safety and effectiveness; may present safety concerns; and pose a direct challenge to the new drug approval system and, in some cases, the over-the-counter (OTC) drug monograph system. The rule is effective July 2, 2015. [Federal Register]

On July 8, 2015, FDA announced the issuance of the final rule ‘‘Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products.” The rule requires all applicants of covered approved drugs or biological products— including certain applicants of blood or blood components for transfusion and all manufacturers of covered drugs marketed without an approved application—to notify FDA electronically of a permanent discontinuance or an interruption in manufacturing of the product that is likely to lead to a meaningful disruption in supply (or a significant disruption in supply for blood or blood components) of the product in the United States. The rule is effective September 8, 2015. [Federal Register]


SECTION 2 EMA CONSULTATIONS, GUIDELINES, & NEWS

Improving safety of medicines across Europe
EMA publication of safety reports for nationally authorised medicines will support timely and harmonised implementation of safety measures in EU Member States

EMA has started to publish the outcomes of single assessments of periodic safety update reports (PSURs) for active substances contained only in nationally authorised medicines. This initiative aims to support the harmonised implementation of safety measures for medicines with the same active substance across European Union (EU) Member States.

All pharmaceutical companies holding marketing authorisations for medicines at national level are advised to regularly monitor the published information to check for outcomes relevant to their products. More at link above. (EMA.eu)

Update on publication of clinical data
The European Medicines Agency (EMA) on June 29, 2015, published the video recording of its webinar held on 24 June to provide an update on the implementation of its policy on the publication of clinical data, as well as the slides of all the presentations given. (See EMA website.)

EMA's policy on publication of clinical data entered into force on 1 January 2015 and applies to clinical reports contained in all marketing-authorisation applications submitted on or after this date. The first reports will be published as soon as a decision on the application has been taken, currently foreseen for mid-2016.

To help stakeholders anticipate the requirements and prepare for the publication of clinical reports, the Agency explained the work processes which are foreseen. The topics covered by the webinar included an explanation of the principles for the submission of redacted clinical reports, the redaction consultation process, as well as guidance on redacting commercially confidential information in clinical reports and on the anonymisation of clinical reports for the purpose of publication.

A face-to-face meeting was held on 6 July 2015 at the EMA to allow more detailed discussions on the draft guidance on anonymisation of clinical reports for publication and on redacting commercially confidential information in clinical reports. Stakeholder organisations have been contacted to nominate experts as participants in this meeting. The guidance is expected to be finalised and published after the summer. More at link above. (EMA.eu)

Draft reflection paper on viral safety of plasma-derived medicinal products with respect to hepatitis E virus
EMA has published a draft reflection paper as titled above. Hepatitis E virus (HEV) infection is widespread and blood/plasma donors are often asymptomatic. Therefore, there is a risk for viraemic blood donations. This raises questions about the safety of plasma-derived medicinal products. This reflection paper considers transfusion-associated infections and clinical experience with HEV-infections, HEV detection and epidemiology of HEV in blood/plasma donations, if serum antibodies against HEV significantly neutralise, studies on inactivation/removal of HEV during manufacture of plasma-derived products, and risk assessment for plasma-derived medical products. The consultation period will close on September 30, 2015.  Detailed information is available at the link above. (EMA.eu)

Draft guideline on manufacture of the finished dosage form

This guideline replaces the note for guidance on the manufacture of the finished dosage form (CPMP/QWP/486/95). The note for guidance has been updated to reflect changes to the format and content of the Common Technical Document (CTD) Module 3 dossier. It also addresses current manufacturing practices in terms of complex supply chains and worldwide manufacture. In addition, the content and principles of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q8 guideline (ref. 1) is also taken into account.  The comment period will close on January 1, 2016.  More at link above. (EMA.eu)


SECTION 3 FDA NOTES & RELATED NEWS

Celebrating the 3rd Anniversary of the FDA Safety and Innovation Act
On July 9, FDA celebrated the third anniversary of the signing of the landmark Food and Drug Administration Safety and Innovation Act (FDASIA).

FDASIA gave FDA authority to collect user fees from industry over five years, beginning in 2012, to fund reviews of innovator drugs, medical devices, generic drugs, and biosimilar biological products. It also promotes innovation to speed patient access to safe and effective products, increases stakeholder involvement in FDA processes, and enhances the safety of the drug supply chain. Just as important, FDASIA improves the agency’s ability to help prevent drug shortages.

In his July 9 FDA Voice blog, Dr. Stephen Ostroff, Acting Commissioner of FDA, wrote: “FDA has made great strides to implement this important law since President Obama signed it, issuing more than 35 draft and final guidances, more than 10 proposed and final rules, three strategic plans, 14 reports to Congress, 18 public reports, and 13 public meetings designed to solicit input from a vast assortment of stakeholders.

“All told, we have completed more than 70% of the law’s deliverables and we continue to maintain our commitment to a transparent and accessible implementation plan that allows the public to follow our progress.”

In addition to updates on FDA’s recent FDASIA-related efforts to reduce drug shortages, implement the Patient-Focused Drug Development program, close gaps in data quality and access, and protect the drug supply chain, Ostroff focused on progress on breakthrough therapy development.  “As of last month, 315 requests for this special designation have been received and 93 drugs and biologics have been granted breakthrough status. Expedited development is underway for the majority of these breakthrough designated products, while 26 breakthrough therapy drug/indication combinations have already been approved and are now on the market for use by patients. This program, which, along with fast track, accelerated approval, and priority review, was the topic of FDA’s final guidance on our expedited review programs, also has helped facilitate earlier and continuing consultation and advice by FDA for industry researchers and product developers.

“In large part, as a result of these expedited programs, we saw the approval of a record number of new drugs in 2014 for the treatment of both rare diseases and more common conditions like various forms of cancer and hepatitis C. We also saw the approval of a record number of biologics, including new vaccines for meningococcus type B.” More at link above. (FDA.gov)

CDER Breakthrough Therapy Program: What Happens Post-Designation? (PDF - 688KB)
The Office of New Drugs (OND, CDER) presented at DIA2015 on the process of breakthrough therapy development and marketing application review once a Breakthrough designation is awarded. The full presentation was recently posted on the FDA website (see link above). (FDA.gov)

PatientsLikeMe Teams With FDA To Explore Patient-Reported Adverse Events
During last month's DIA Annual meeting in Washington, D.C., online patient community PatientsLikeMe announced a research collaboration with the Food and Drug Administration to determine how patient-reported data can give new insights into drug safety.

PatientsLikeMe has 350,000 members with 2,500 conditions who report on their real-world experiences online.  Patients, family members, or others interested may search for a particular patients, conditions, and treatments. For example, view the page for Rheumatoid Arthritis/Crohn’s treatment Remicade to see all of the patient-entered information; similar information is available for almost any drug.

In all, PatientsLikeMe has collected more than 110,000 adverse event reports on 1,000 different medications, data that the FDA will now be able to access and analyze as a supplement to traditional sources, including FAERS. Using the example of Remicade again, users have reported around 70 side effects at this point- from fatigue, to headache, to nausea.

“Right now the FDA uses a voluntary reporting system consisting of individual case safety reports, the majority of which are submitted by healthcare professionals and patients to drug product manufacturers, who then are required to report them to the FDA,” states Sally Okun, Vice President, Advocacy, Policy & Patients Safety at PatientsLikeMe. “Our data are different in that the information is generated by patients themselves, and provide real-time insights about what it’s (sic) like to use medical products over time, like tolerability of the drug and factors that may influence taking the drug as prescribed.” More at link above. (Policy & Medicine)

FDA Social Media Updates
The Office of External Affairs (OEA) began an initiative in FY14 with CDER to improve consumer engagement by enhancing its social media responses, specifically to drug related inquiries more quickly and proactively. This initiative began as a 90 day pilot program, but due to its success, the program has become fully operational. The pilot program involved several CDER employees working together with OEA employees to respond to drug related inquiries posted on FDA’s Facebook page. As a result of this collaboration, FDA was able to respond to inquiries within two business days. CDER found this method to be an extremely effective way to communicate with consumers and permanently assigned one CDER employee to be responsible for responding to these inquiries going forward. The employee now has direct access to post responses and manage the drug related content on behalf of CDER on FDA’s Facebook page. Further, it was recognized that some of the same topics were frequently asked, and therefore, CDER developed a frequently asked questions and answers file to respond to consumers even faster. Now, CDER is able to respond to drug related inquiries within one business day. OEA has now begun working with the Office of Foods and Veterinary Medicine, largely with the Center for Food Safety and Applied Nutrition, on a pilot program and anticipates working with other Centers to develop similar programs and increase FDA’s overall response rate to social media inquiries. For more information on OEA’s social media measures, please see the title link above. (FDA.gov)


SECTION 4 AGENCY AND ADVISORY COMMITTEE MEETINGS

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

Public Meeting.  Medical Device User Fee Act Reauthorization.  July 13, 2015.  White Oak Campus, Silver Spring, MD.  FDA will hold a public meeting to gather initial input on reauthorization of the Medical Device User Fee program, as required by section 738A of the Federal Food, Drug, and Cosmetic Act. [Federal Register]

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]

Public Workshop. New Methods To Predict the Immunogenicity of Therapeutic Coagulation Proteins. September 17-18, 2015.  Bethesda, MD.  The purpose of this workshop is to discuss recent scientific progress in identifying the genetic determinants for an unwanted immune response to therapeutic coagulation proteins (immunogenicity), and to identify and discuss potential new methods to predict such immunogenicity. [Federal Register]

Public Meeting. Patient-Focused Drug Development for Huntington’s and Parkinson’s Diseases. September 22, 2015.  White Oak Campus, Silver Spring, MD.  The public meeting is intended to provide FDA with patients’ perspectives on the impact on daily life of Huntington’s disease and Parkinson’s disease and patient views on treatment approaches. Although these are both neurological diseases, since they are quite distinct, FDA will structure this public meeting into two distinct sessions (Huntington’s from 9 am – 12:30 pm; Parkinson’s from 1:30 – 5:00 pm). [FDA.gov]

Public Meeting. Patient-Focused Drug Development for Alpha-1 Antitrypsin Deficiency. September 29, 2015.  White Oak Campus, Silver Spring, MD.  The public meeting is intended to provide FDA with patients’ perspectives on the impact on daily life of AATD. FDA also is seeking patients’ perspectives on the available therapies for this disorder. [Federal Register]

Public Workshop. Acute Ischemic Stroke Medical Devices Trials. October 6, 2015.  Bethesda, MD.  The purpose of this workshop is to obtain public input and feedback on scientific, clinical, and regulatory considerations associated with acute ischemic stroke medical devices. Ideas generated during this workshop may facilitate further development of guidance regarding the content of premarket submissions for acute ischemic stroke emerging technologies and help to speed development and approval of future submissions. [Federal Register]

Public Meeting and Request for Comment. Non-Microbial Biomarkers of Infection for In Vitro Diagnostic Device Use. October 16, 2015.  White Oak Campus, Silver Spring, MD.  The purpose of this workshop is to receive input from stakeholders and discuss approaches to the study of non- microbial biomarkers for differentiating viral from bacterial infections and for diagnosis and assessment of sepsis. Comments and suggestions generated through this workshop will facilitate further development of regulatory science for establishing appropriate comparator methods and clinically relevant performance standards for non- microbial based in vitro diagnostics for infection.  A docket is also established for public comments, which are due by November 13, 2015. [Federal Register]


SECTION 5 OTHER ORGANIZATIONS & AUTHORITIES

Global Health Risk Framework: A Workshop on Research and Development of Medical Products
The U.S. Institute of Medicine (IOM) of the National Academies of Sciences, Engineering, and Medicine will serve as the secretariat for an independent global commission that will conduct a study to recommend an effective global architecture for recognizing and mitigating the threat of epidemic infectious diseases. The commission will receive input from four IOM workshops on governance for global health, financing response to pandemic threats, resilient health systems, and research and development of medical products, which will be coordinated.

This workshop will inform the Commission prior to the final release of its report by providing a forum for relevant stakeholders to describe and provide input on the core needs and strategies to facilitate development of medical products to prevent, diagnose, treat, and protect from emerging global infectious diseases. The focus of the workshop will be on global systems and policy needs to foster communication, partnerships, and other strategies to advance medical product development.

The workshop will focus on strategies to facilitate the development of medical products– including therapeutics, vaccines, diagnostics, and personal protective equipment. Key areas for consideration include: product development, clinical development, optimization for development, regulatory review standards and systems, manufacturing, legal issues, and indicators relevant to medical product research and development.

The workshop is co-hosted by Hong Kong University and will be held on August 19-21, 2015. Participants will be invited from around the world to engage in dialogue and identify potential avenues for collaboration. More at link above. (Institute of Medicine)

Financial Incentives to Encourage Development of Therapies That Address Unmet Medical Needs for Nervous System Disorders: Workshop Summary
Our brains control a vast array of processes that are central to life, health, and identity, but malfunctions in the central nervous system (CNS) instigate a wide range of devastating symptoms. The associated illnesses include developmental, psychiatric, and neurodegenerative illnesses, many of which are chronic and cause serious and long-lasting disabilities. Together, they are extremely prevalent and have an enormous impact from cradle to grave.

Several national initiatives have been launched to better understand the brain (e.g., Brain Research through Advancing Innovative Neurotechnologies [BRAIN] Initiative), yet large pharmaceutical companies are divesting from their neuroscience research programs. Despite the tremendous market potential, CNS drugs are relatively unattractive because of perceived high risk. The underlying science remains a challenge, and clinical trials can be lengthy and expensive, resulting in high development costs. Furthermore, demonstrating product safety and efficacy in the regulatory review process can be a costly and timely process. These factors, combined with a patent system that rewards treatments with short development times, collude to create a situation that makes it challenging to develop innovative therapies.

IOM convened a workshop in January 2015 to explore policy changes that might increase private sector investment in research and development innovation that fills unmet medical needs for CNS disorders. Workshop participants strategized about how to incentivize companies to fortify their CNS drug development programs, shrinking obstacles that currently deter ventures. Representatives from academia, government agencies, patient groups, and industry gathered to share information and viewpoints, and to brainstorm about budget-neutral policy changes that could help widen the pipeline toward drugs that address unmet needs for CNS disorders. Report access at link above. (IOM)

Progress of the Precision Medicine Initiative at Six Months
On July 8, 2015, to mark six months of progress to advance the PMI, the White House hosted a Champions of Change event honoring extraordinary patients, researchers, innovators, and advocates who are making a difference in people’s lives and driving precision medicine forward. These individuals are harnessing the power of data to improve our understanding of health and disease in order to improve patient care.

In addition to celebrating these Champions, the Administration released a set of draft guiding principles to protect privacy and build public trust as the PMI develops. These principles will guide the development of a research cohort of one million or more participants who voluntarily contribute their health data to help us answer the many as yet unsolved mysteries of health and disease. These principles are being made available today as a working draft, with the intent of soliciting the broadest possible input and feedback from stakeholders, experts, and the public.

And importantly, federal agencies and private-sector groups are also stepping up to the President’s call to action by making important commitments to:

  • Make health data more portable
  • Ensure patients can easily access and share their own health information, including contributing it for research
  • Rigorously protect patient privacy and choice and safeguard data security
  • Support research platforms connecting researchers and participants as partners.

More at title link above. (White House Office of Science & Technology Policy)

Obama Nominates Slavitt to Run CMS
Bloomberg News (7/10, Tracer) reports that President Obama has asked the Senate to confirm Andy Slavitt as administrator of the Centers for Medicare and Medicaid Services. Slavitt, already the acting administrator of CMS, “joined the government in 2014, after working as an executive vice president at UnitedHealth Group Inc.’s Optum unit, which helped fix the main Obamacare website, healthcare.gov.” Senate Finance Committee Chairman Orrin Hatch (R-UT) said Slavitt will need to answer “tough questions” about his work at UnitedHealth and his “conflicted history in the medical services industry.”

The Hill (7/10, Sullivan) predicts Slavitt’s nomination will spark “partisan fireworks” over the ACA at confirmation hearings. Indeed, Senate Majority Leader Mitch McConnell (R-KY) said in a statement, “While Andy Slavitt’s nomination will receive thorough consideration in the Senate, it has long been clear that no one can successfully manage a law as unworkable as Obamacare. The sole focus of CMS should be to look out for our nation’s seniors and the many vulnerable Americans who use these programs, without the distraction of Obamacare.”

Families USA, meanwhile, applauded Slavitt’s nomination, saying in a statement that he “played a remarkably successful role in overseeing the second open enrollment period under the Affordable Care Act and played a heroic role in the successful re-launch of HealthCare.gov,” Reuters (7/10) reports. The article notes Slavitt has been CMS acting administrator since March, following the departure of Marilyn Tavenner.

Also covering the story are the Washington Examiner (7/10), Modern Healthcare (7/9, Subscription Publication), and the Daily Caller (7/10, Tapscott).  (Via DIA Daily, a DIA membership benefit)

CMS proposes Part B reimbursement rule for biosimilars
CMS proposed a rule under which all biosimilars for a given reference product covered under Medicare Part B would be issued the same Healthcare Common Procedure Coding System (HCPCS) code, and would therefore be reimbursed at the same rate.

CMS also proposed that newly approved biosimilars be reimbursed at 106% of their wholesale acquisition cost (WAC) until Medicare has enough data to compute an average sales price (ASP). Under the current CMS policy on Part B drugs, physicians are reimbursed the ASP for the biosimilar plus 6% of the ASP for the reference product.

The not-for-profit Biosimilars Forum issued a statement opposing the proposal, arguing that each biosimilar should be issued a unique HCPCS code. The group noted the possibility that biosimilars for the same reference product may not necessarily share all indications or interchangeability status. A coalition of 11 companies launched the Biosimilars Forum in May to increase patient access to biosimilars in the U.S.

Comments on CMS's proposal are due Sept. 8. CMS expects to issue a final rule by Nov. 1. (BioCentury)

Hospitals Slam GAO Finding that 340B Drug Discounts Fuel Prescribing
Hospitals say the U.S. Government Accountability Office used faulty methodology when it determined that hospitals that serve large numbers of low-income patients abuse a federal drug discount by overprescribing medications. HHS raised similar concerns about the findings. Hospitals that serve a disproportionate number of low-income patients have access to discounted outpatient drug prices through the 340B Drug Pricing Program, which is administered by HHS.

The GAO report released Monday found that in both 2008 and 2012, per-beneficiary Medicare Part B drug spending, including oncology drug spending, was substantially higher at hospitals utilizing the 340B discount than at other hospitals.

This indicates that, on average, beneficiaries at 340B disproportionate share hospitals (DSH) were either prescribed more drugs or more expensive drugs than beneficiaries at the other hospitals in GAO's analysis,” the watchdog agency said. For example, in 2012, average per-beneficiary spending at 340B DSH hospitals was $144, compared to approximately $60 at non-340B hospitals.

Provider trade groups questioned how the GAO came up with its results. They said the report doesn't take into account that 340B hospitals may see sicker patients than other hospitals, and noted that the GAO may have unfairly ignored other reasons for higher spending, including the fact that patients of non-340B hospitals more frequently receive drugs in non-hospital settings.

“None of this stopped GAO from reaching unsupported conclusions and policy recommendations based on its faulty analysis,” Dr. Bruce Siegel, CEO of America's Essential Hospitals, a trade group for safety net hospitals, said in a statement. “We're surprised not only by the lack of evidence and data for GAO's conclusions and recommendations, but also by its suggestion that physicians in our nation's essential hospitals would ignore patient needs to enrich hospitals.”

American Hospital Association Senior Vice President Tom Nickels made similar criticisms of the methodology in a newsletter to members. "Simply put, the GAO report misses the mark,” he said.  More at link above. (Modern Healthcare)

Biosimilars Council Joins Pharmacies and Payers in Urging Same Names for Biologics and Biosimilars
The Biosimilars Council, a division of the Generic Pharmaceutical Association (GPhA), strongly urges the Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA) to avoid any departure from the currently accepted international nonproprietary naming (INN) system. In a letter sent today to HHS and FDA, the Biosimilars Council joined a diverse group of healthcare stakeholders to raise shared concerns that adopting distinguishable names for biosimilars and biologics would erect barriers to patient access to new, more affordable medicines and could jeopardize their safety.

The letter states:

“We share the FDA's deep commitment to patient safety, and as such, we believe that biologics and biosimilars should be required to have the same International Nonproprietary Name (INN). Requiring different INNs for biologics and biosimilars could lead to patient and prescriber confusion, increasing the possibility of medication errors, and would also effectively separate the biosimilar from existing safety information about the underlying molecule.”

Further, these groups believe that the current mechanisms in place (e.g., NDC code, lot number, brand name, manufacturer, etc.) are more than sufficient to allow for the tracking of important safety information related to new biosimilar products:

“We are concerned that any unnecessary changes may interfere with current pharmacy safety alert systems used by both retail and community pharmacists. In addition, because adverse events and product recalls for small-molecule and biologic drugs already are successfully identified using the national drug code (NDC code) and lot number, there is no compelling evidence that biosimilars should be handled differently.”  More at link above. (Generic Pharmaceutical Association)

PhRMA Foundation Names Cannon New President
The Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation on Tuesday (7/8/15) named Eileen Cannon president.

“On behalf of our member companies and staff, I’d like to congratulate Eileen on her well-deserved promotion to president of the PhRMA Foundation,” stated John Castellani, president and CEO, PhRMA. “Over the past 15 years, Eileen’s leadership has been instrumental in helping to connect promising young researchers to resources that not only help launch their careers, but also help to advance critical new science that contributes to the drug discovery process for patients.”

This year, the foundation is celebrating its 50th anniversary and its tradition of fostering the development of highly-trained, top-quality scientists to help address the growing needs of stakeholders in the biopharmaceutical sector, including scientific and academic institutions, government and the biopharmaceutical industry. Having funded the research of more than 2,200 young scientists, the Foundation continues its contribution to the future of care for patients.

Cannon has played a central role in the foundation’s expansion during her tenure. Over the last several years, she has helped implement new initiatives in regulatory science, comparative effectiveness research, translational medicine and safe and effective prescribing.

Cannon’s leadership has also contributed to the development of new partnerships with national scientific organizations and government agencies, such as the National Institute of Health and the Foundation of the National Institute of Health. This collaboration has led to the creation of education initiatives that are critical to biopharmaceutical research and development, practicing physicians and patients. (DSN.com)
 
Ebola Panel Urges More Power, More Money for WHO
The World Health Organization needs more money, more flexibility, and more power to cope with future outbreaks like the Ebola epidemic, according to an independent panel.

Calling the Ebola epidemic "a defining moment for the health of the global community," the panel urged "significant changes" to the WHO, its bureaucracy, and its relationships with member states.

The needed changes include:

  • Increasing the amount of dues the member states pay by at least 5% next year
  • Establishing an intermediate level of alert between business-as-usual and a full-on international emergency
  • Setting up "disincentives" to prevent states from ignoring the International Health Regulations (IHR), as many have done during the Ebola epidemic
  • Adding incentives for countries to declare emergencies instead of downplaying them for fear of trade and travel barriers

More at link above. (MedPage Today)

Innovative Medicines Initiative Releases Personalised Medicine Strategic Research & Innovation Agenda
Personalised Medicine (PM) approaches, particularly for diagnosis and treatment of cancer and rare diseases, are already being implemented. However, development and implementation of PM approaches for other diseases and many aspects of healthcare delivery is still far from being a reality. Thus further PM implementation will need a paradigm shift for all citizens, researchers and national healthcare systems.

Taking into account that PM can only be successfully implemented when handled as a truly cross-sectoral topic, this document integrates the perspective of experts across the entire healthcare value chain. This SRIA is based on an analysis of important recent strategic reports as well as interviews and consultations with experts and representatives of all relevant sectors important to the implementation of PM.

Based on recent and future developments, the SRIA contains 35 recommendations (each is numbered, and the relevant recommendations for each challenge area are shown in parentheses below and Annex A) clustered under five challenges. The SRIA also presents nine prioritised recommendations, which have the highest potential impact and outcome in facilitating the introduction of PM for the benefit of patients, citizens and society as a whole. Report at link above. (Innovative Medicines Initiative)

IMI launches €95 million Call for proposals with focus on Alzheimer’s disease, diabetes, patient involvement
The Innovative Medicines Initiative (IMI) announced July 9 it is launching its 5th Call for proposals under the IMI 2 programme.  IMI 2 – Call 5 has a total budget of €95 million and features 6 topics. Of these, four focus on different aspects of Alzheimer’s disease, one focuses on diabetic kidney disease, and one addresses patient input on assessments of the benefits and risks of medicines.

Four topics focus on Alzheimer’s disease, an area where there is an urgent need for new treatments.

The topic on diabetes is designed to address the need for biological markers of diabetic kidney disease (DKD). DKD is a common complication of diabetes; the biological markers will add to our understanding of DKD and will advance the development and evaluation of new treatments for DKD.

In line with IMI’s goal of boosting patient involvement in research, the Call also features a topic that will explore when and how best to gain patients’ input on the benefits and risks of medicines, at all stages of the drug development life cycle, to inform decision-making processes. More at link above. (Innovative Medicines Initiative)

DoP (India) extends voluntary implementation of UCPMP by pharma cos to August
The Department of Pharmaceuticals (DoP) has extended the voluntarily implementation of Uniform Code of Pharmaceuticals Marketing Practices (UCPMP) by two months till August 31, 2015. Earlier, the department had implemented UCPMP voluntarily for a period of six months with effect from January 1, 2015 which came to an end on June 30, 2015.

Meanwhile, after implementing the UCPMP voluntarily, the DoP had started meeting the stakeholders from the pharma and medical device industry to review and take a final call on mandatorily implementing the norms for ethical marketing practices in these sectors, so as to curb the unethical practices adopted by several companies to market their products among medical practitioners.

But, as the discussions with the stakeholders remained inconclusive, the department decided to extend the voluntarily implementation of uniform code by two months.

Earlier in November last year, after several years of dilly-dallying on the issue, the DoP had issued the much awaited UCPMP which should be voluntarily adopted and complied with by the pharma industry for a period of six months with effect from January 1, 2015 and it would be reviewed thereafter on the basis of the inputs received by the department. More at link above. (PharmaBiz)

With Provision for Jail Term, Clinical Trial Norms Get "Shot in the Arm"
The government is planning to add more teeth to clinical trial rules so that violations attract stringent punishment, including imprisonment, besides hefty fines in even cases where the patient is not directly impacted during the experiments with new medicines.

The changes are part of the Drugs and Cosmetics Amendment Bill, 2015, which is likely to be tabled in Parliament during the upcoming monsoon session, official sources said.

Following the rising number of deaths during clinical trials leading to strict directives from the Supreme Court, the health ministry framed specific guidelines and protocol for companies conducting clinical trials to test new products. Accordingly, the government plans to introduce stringent laws for those violating these protocols, the sources said.

The proposed changes include a provision for a year of imprisonment if violation of rules leads to any kind of adverse impact on the patient enrolled in a clinical trial. The new law would also make it mandatory for the companies conducting a trial to pay fine of up to Rs 3 lakh in case of any error or violation of the protocol even if the patient is not directly impacted, the sources said. More at link above. (Economic Times, India)


SECTION 6 LEGAL AND COMPLIANCE

House Approves 21st Century Cures Act
The U.S. House of Representatives today approved H.R. 6, the 21st Century Cures Act, by a vote of 344-77. The nonpartisan legislation will help to bring our health care system into the 21st Century, investing in science and medical innovation, incorporating the patient perspective, and modernizing clinical trials, to deliver better, faster cures to more patients and loved ones in need.

The bill’s authors, House Energy and Commerce Committee Chairman Fred Upton (R-MI), Oversight and Investigations Subcommittee Ranking Member 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) commented:

“Today, we took a big leap on the path to cures, but we still have much work left to do. The 344 votes today should be a springboard for action. On to the Senate.”  More at link above. (Energy & Commerce)

Over 700 Groups Stand Behind #Cures2015
H.R. 6 is a nonpartisan bill originating from the Energy and Commerce Committee’s 21st Century Cures initiative, launched over a year ago by Chairman Fred Upton (R-MI) and Rep. Diana DeGette (D-CO). In addition to resounding support from leading health care experts and thought leaders across the country from both sides of the aisle, this legislation has the backing of over 700 groups encompassing patient advocacy groups, rare disease groups, cancer centers, technology groups, top universities, biopharmaceutical companies, medical device companies, and others from across the country. A list of those groups can be found at the link above.  (Energy & Commerce Committee release)

House passes 21st Century Cures baton to Senate
The U.S. House of Representatives voted 344-77 to pass the 21st Century Cures Act (H.R. 6) on Friday. The focus of the bill's supporters, including the Biotechnology Industry Organization (BIO), Pharmaceutical Research and Manufacturers of America (PhRMA), and many patient advocacy and medical groups, now shifts to the Senate, where the Health, Education, Labor and Pensions (HELP) Committee is working on companion legislation.

Prior to passing the bill, the House voted 281-141 to defeat an amendment offered by Rep. Dave Brat (R-Va.) that would have made the bill's NIH and FDA funding increases discretionary. H.R. 6 retains two mandatory five-year funds, an $8.75 billion NIH Innovation Fund and a $550 million FDA Cures Fund.

HELP Committee Chairman Lamar Alexander (R-Tenn.) has said he plans to introduce a medical innovation bill by YE15. Alexander is starting from scratch, and is expected to produce a slimmer bill than H.R. 6. If the Senate passes Alexander's bill, negotiations to reconcile it with H.R. 6 would take place in parallel with discussions about reauthorization of PDUFA. FDA provisions from the bills, as well as other FDA reform proposals and innovation incentives, could be integrated into PDUFA legislation. More at link above. (BioCentury)

Payments to Nurse Practitioners and PAs not Covered Under Physician Payment Sunshine Act
Nurse practitioners and physician assistants are playing an ever-larger role in the health care system, but the Physician Payment Sunshine Act does not require drug and device makers to publicly report payments to these health care providers, even though they are allowed to write prescriptions in most states, ProPublica reports. An analysis of prescribing patterns in Medicare Part D shows that these two groups of providers wrote about 10% of the nearly 1.4 billion prescriptions in the program in 2013.  More at link above. (WSJ Pharmalot)


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.