DIA
Drug Information Association Logo

Content Currents

DIA

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: June 26, 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final guidances for which CDRH would appreciate external feedback on whether these final guidances should be revised or withdrawn.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 June 17, 2015, FDA announced that a collection of information entitled “Impact of Ad Exposure Frequency on Perception and Mental Processing of Risk and Benefit information in Direct-to-Consumer Prescription Drug Ads” has been submitted to the Office of Management and Budget (OMB). Perceptual and cognitive effects of increased ad exposure frequency have been studied extensively using non-drug ads. To our knowledge, the literature concerning ad exposure frequency has not been extended to include specific attention to prescription drug ads. The Office of Prescription Drug Promotion (OPDP) plans to examine the effects of variation in ad exposure frequency on perception and mental processing of risk and benefit information in DTC prescription drug ads through empirical research.  Fax written comments on the collection of information by July 17, 2015. [Federal Register]

On June 23, 2015, FDA announced that a collection of information entitled “Postmarketing Adverse Drug Experience Reporting and Recordkeeping Biological Products” has been submitted to the Office of Management and Budget (OMB) for review and clearance. This Federal Register notice outlines the reporting and recordkeeping requirements that FDA proposes to enable it to take necessary actions to protect the public health from adverse experiences related to drugs on the market. (In keeping with 21 CFR 310.305 and 314.80.)  Fax written comments on the collection of information to OMB by July 22, 2015. [Federal Register]

On June 25, 2015, FDA announced an opportunity for public comment on a proposed collection of information entitled “Hearing, Aging, and Direct-to-Consumer Television Advertisements.” This notice solicits comments on research entitled, ‘‘Hearing, Aging, and Direct-to-Consumer Television Advertisements’’. This study will examine how changes to hearing across the lifespan affect the comprehension of direct-to-consumer (DTC) television advertisements for prescription drugs. Comments should be submitted by August 24, 2015. [Federal Register]

On June 25, 2015, FDA announced that a collection of information entitled “Guidance for Industry on Postmarketing Adverse Event Reporting for Nonprescription Human Drug Products Marketed Without an Approved Application” has been submitted to the Office of Management and Budget (OMB) for review and clearance. Respondents to this collection of information are manufacturers, packers, and distributors whose name (under section 502(b)(1) (21 U.S.C. 352(b)(1)) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act)) appears on the label of a nonprescription drug marketed in the United States. FDA is requesting public comment on estimates of annual submissions from these respondents, as required by the Dietary Supplement and Nonprescription Drug Consumer Protection Act (Pub. L. 109–462) and described in the guidance. The guidance document discusses what should be included in a serious adverse drug event report. Fax written comments on the collection of information to OMB by July 27, 2015. [Federal Register]

Guidances and Draft Guidances:

On June 17, 2015, FDA announced the availability of a guidance for industry entitled “Naming of Drug Products Containing Salt Drug Substances.” This guidance replaces the draft guidance of the same title that published on December 26, 2013. This guidance describes the United States Pharmacopeia’s (USP’s) ‘‘Monograph Naming Policy for Salt Drug Substances in Drug Products and Compounded Preparations,’’ which became official on May 1, 2013, and how the Center for Drug Evaluation and Research (CDER) is implementing it. [Federal Register]

On June 17, 2015, FDA announced the availability of a guidance for industry and FDA staff entitled “Content and Format of Abbreviated 510(k)s for Early Growth Response 1 Gene Fluorescence In-Situ Hybridization Test System for Specimen Characterization Devices.” I This guidance provides industry and Agency staff with recommendations for the suggested format and content of an abbreviated 510(k) submission for EGR1 gene FISH test system for specimen characterization devices. (An EGR1 gene FISH test system for specimen characterization is a device intended to detect the EGR1 probe target on chromosome 5q in bone marrow specimens from patients with acute myeloid leukemia or myelodysplastic syndrome. [Federal Register]

On June 18, 2015, FDA announced the availability of a draft guidance for investigational device exemption sponsors, sponsor-investigators, and FDA staff entitled “Factors To Consider When Making Benefit-Risk Determinations for Medical Device Investigational Device Exemptions.”  The purpose of this draft guidance is to provide greater clarity for FDA staff and IDE sponsors and sponsor-investigators regarding the principal factors that FDA considers when assessing the benefits and risks of IDE applications for human clinical study. The draft guidance also characterizes benefits in the context of investigational research, which includes direct benefits to the subjects and benefits to others (to the extent they are indirect benefits to subjects or reflect the importance of knowledge to be gained). 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 16, 2015. [Federal Register]

On June 19, 2015, FDA announced the availability of a guidance for industry entitled “Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules.”  FDA is concerned that differences in these physical characteristics between generic drugs and the originator drug could affect patient outcomes. This guidance discusses FDA recommendations for the size, shape, and other physical attributes of generic tablets and capsules intended to be swallowed intact. [Federal Register]

On June 25, 2015, FDA announced the availability of a guidance for industry entitled “Allowable Excess Volume and Labeled Vial Fill Size in Injectable Drug and Biological Products.”  FDA is concerned that injectable vial misuse, including unsafe handling and injection techniques, has led to an increase in vial contamination and an increased risk of bloodborne illness transmission between patients. This guidance clarifies the FDA requirements and regulations pertaining to allowable excess volume in injectable vials and describes when justification is needed for a proposed excess volume in an injectable drug or biological product. This guidance also discusses the importance of appropriate fill volume and recommends that labeled vial fill sizes be appropriate for the use and dosing of the drug and biological product. This guidance replaces the draft of the same name that was published on March 14, 2014. [Federal Register]

On June 26, 2015, FDA announced the availability of a draft guidance for industry and FDA staff entitled “Unique Device Identification: Direct Marking of Devices.” When finalized, this draft document will assist industry, particularly labelers, as defined under 21 CFR 801.3, and FDA staff in understanding FDA’s requirements for direct marking of devices for unique device identification purposes. Under 21 CFR 801.45, “[a] device that must bear a unique device identifier (UDI) on its label must also bear a permanent marking providing the UDI on the device itself if the device is intended to be used more than once and intended to be reprocessed before each use.” This draft guidance defines some terms used in the Agency’s regulations pertaining to the UDI direct marking requirements, including how FDA interprets the term “reprocessed” as used in 21 CFR 801.45.  Comments should be submitted by September 24, 2015. [Federal Register]

Other Actions:

On June 19, 2015, FDA announced the release of the ‘‘Health Level Seven (HL7) Individual Case Safety Reporting (ICSR) Files Implementation Package,” with the system requirements to enable manufacturers that chose the HL7 ICSR submission option to prepare for and test eMDR submissions.  On August 14, 2015, the eMDR final rule goes into effect, requiring manufacturers to submit medical device reports (MDRs) to the FDA electronically rather than in paper form. Electronic submission expedites report processing and reduces the burden of data entry on the FDA, manufacturers, and importers. There are two options available to all reporters for submitting eMDRs: eSubmitter or Health Level 7 Individual Case Safety Reports (HL7 ICSR). Manufacturers should consider registering for an ESG account and submit a test submission as soon as possible to ensure that they are electronic submission compliant by August 14, 2015, regardless of which transmission method they choose. Manufacturers may begin testing their submissions as early as June 29, 2015. Information on the FDA ESG and steps to obtain a production account, please visit the Electronic Submissions Gateway page. For more information about how to prepare for eMDR, please visit the FDA eMDR page.  [FDA.gov]

On June 26, 2015, FDA announced its interest in supporting demonstration projects related to  ‘‘Source Data Capture From Electronic Health Records: Using Standardized Clinical Research Data.” The purpose of the demonstration projects is to test the capability and evaluate performance of using an end- to-end Electronic Health Record (EHR)- to-Electronic Data Capture (EDC) single- point data capture approach, using established data and implementation standards in a regulated clinical research environment. A demonstration project should ideally test the use of a standards-based technology solution to enable the collection of related healthcare and clinical research information within a single system and workflow. Stakeholders may include regulated industry, EHR and EDC vendors, academic medical centers, and other interested parties. Requests for participation should be submitted by August 10, 2015. [Federal Register]


SECTION 2 EMA CONSULTATIONS, GUIDELINES, & NEWS

Early dialogue to support development of medicines for children
The European Medicines Agency (EMA) has launched an initiative that offers free-of-charge early paediatric interaction meetings with medicines developers to stimulate early dialogue on the development of their medicines for use in children. A one-year pilot phase started on June 16, 2015.

The new initiative aims to encourage discussions on the paediatric needs that could be addressed with a specific medicine well before the submission of a paediatric investigation plan (PIP). In the European Union, pharmaceutical companies are obliged to develop all new medicines also for use in children. The paediatric development is detailed in a PIP that needs to be agreed with EMA’s Paediatric Committee (PDCO).

Early discussion between developers, EMA and its PDCO on the overall paediatric development strategy is expected to help medicines developers optimise the development plan for their medicine and ultimately speed up access to the medicine for children.

Following receipt of a request for an early paediatric interaction meeting, an EMA paediatric coordinator and a PDCO representative will be appointed as well as additional participants from other EMA departments or national competent authorities as required. A date for a teleconference with the applicant will then be arranged.

EMA can only consider a limited number of applications during the pilot phase and the Agency will give priority to medicines that address major public health needs.

Medicines developers that wish to participate in the pilot phase are invited to provide information on their medicine using a specific form and send it to paediatrics@ema.europa.eu.  More at link above. (EMA.eu)

Draft questions and answers on sodium in the context of the revision of the guideline on 'Excipients in the label and package leaflet of medicinal products for human use'
Following the European Commission (EC) decision to revise the annex of the guideline on ‘Excipients in the label and package leaflet of medicinal products for human use’ (CPMP/463/00 Rev. 1), a multidisciplinary group of experts involving the Safety Working Party (lead), the Quality Working Party, the Paediatric Committee, the Pharmacovigilance Risk Assessment Committee, the Coordination Group for Mutual Recognition and Decentralised Procedures - Human, the Vaccines Working Party, the Biologics Working Party and the Blood Products Working Party, was created in 2011. The objective of this group is to update the labelling of selected excipients listed in the annex of the above mentioned EC guideline, as well as to add new excipients to the list, based on a review of their safety. The main safety aspects to be addressed were summarized in a concept paper published in March 2012.

Sodium salts used as excipients are most commonly used to increase solubility, but they can also be used for disintegration, chelation, lubrication, binding, emulsifying and stabilizing. They may be also added for colouring or for antimicrobial properties.

Increasing long-term intake of dietary sodium has been shown to increase BP across all study populations and age ranges. Prolonged high BP has been associated with stroke, myocardial infarction, heart failure and kidney disease and has also been linked to dementia and premature death.

It is important that patients, parents, carers, pharmacists, prescribers and other healthcare professionals are able to easily identify how much sodium is present in medicines, especially given that many medicines affected by this issue are available OTC with minimal chance for a healthcare professional to offer any advice on sodium and potential risks.

A proposal for updated information in the package leaflet on sodium is presented in this document. The consultation period will close on September 30, 2015. More at link above. (EMA.eu)

Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 June 2015
Ten new medicines, including two enzyme replacement therapies for the treatment of rare genetic diseases, have been recommended for approval at the June 2015 meeting of the Committee for Medicinal Products for Human Use (CHMP).  Detailed information is available at the link above. (EMA.eu)


SECTION 3 FDA NOTES & RELATED NEWS

FDA takes action to protect consumers from potentially dangerous counterfeit medicines and devices sold online
FDA, in partnership with international regulatory and law enforcement agencies, took action during the week of June 15, against more than 1,050 websites that illegally sell potentially dangerous, unapproved prescription medicines and medical devices to consumers. These actions include the issuance of regulatory warnings to the operators of offending websites and seizure of illegal medicines and medical devices worldwide.

The action occurred as part of the Eighth Annual International Internet Week of Action (IIWA), a global cooperative effort, led by INTERPOL, to combat the unlawful sale and distribution of illegal and potentially counterfeit medical products on the Internet.

As part of this year’s international effort – Operation Pangea VIII – the FDA sent Warning Letters to the operators of nearly 400 websites offering unapproved or misbranded prescription medicines to U.S. patients and to nine firms distributing unapproved or uncleared medical devices online. FDA inspectors, in collaboration with other federal agencies, screened and seized illegal drug products and medical devices received through International Mail Facilities (IMFs) in Chicago, Miami and New York during the IIWA.

The goal of Pangea VIII – which involves law enforcement, customs and regulatory authorities from 115 countries – was to identify the makers and distributors of illegal prescription drug products and medical devices and to remove these products from the supply chain. Preliminary findings from drug products screened at IMFs show that certain drug products from abroad, such as antidepressants, hormone replacement therapies, sleep aids and other drugs to treat erectile dysfunction, high cholesterol and seizures were en route to U.S. consumers. More at link above. (FDA.gov)

FDA Enforcement Update From CDRH, CDER, and CBER: Advertising and Promotion
Keeping track of the Food and Drug Administration’s enforcement of advertising and promotion of drugs, devices, and biologics is a challenging task that requires constant monitoring. At this year’s 2015 DIA Annual Meeting in Washington, DC, FDA representatives from the Center for Devices and Radiological Health (CDRH), the Center for Drug Evaluation and Research (CDER), and the Center for Biologics Evaluation and Research (CBER) provided a good summary of enforcement activity and priority areas that manufacturers should take note of.  

CDRH Update: Promotion and Advertising of Devices: Deborah Wolf spoke from her perspective as Regulatory Counsel within the Division of Premarketing and Labeling Compliance (DPLC) of CDRH’s Office of Compliance. The DPLC enforces premarket clearance and approval requirements, as well as labeling and promotion and advertising requirements for medical devices. Wolf focused on a number of particular products and promotional activities that have drawn DPLC’s ire.

CDER Update: Promotion and Advertising of Drugs: Thomas Abrams of CDER’s Office of Prescription Drug Promotion split his presentation into two sections—first providing a high level overview of the seven guidance documents OPDP has released since 2014, and second, highlighting one case that implicated a number of priority areas for the agency.

Indeed, OPDP has been busy issuing a number of guidances related to social media, how manufacturers may distribute scientific and medical publications on unapproved new uses, new recommendations for disclosing risk information in consumer advertisements, and most recently, OPDP’s document outlining firms’ responsibilities to submit promotional materials in electronic formats. Abrams made clear that the agency was working to align its guidance with First Amendment considerations, but did not specify a date for a promised guidance on manufacturer communications regarding unapproved uses.

CBER Update: Promotion and Advertising of Biologics: Lisa Stockbridge, Ph.D, the Branch Chief at CBER’s Advertising and Promotional Labeling branch began by noting that CDER and CBER share guidance documents, and thus promotional guidances for drugs are applicable to biologics as well. CBER products include blood and blood components; vaccines; allergenic extracts; human tissue and cellular products; gene therapy products; and biological devices and test kits.

Stockbridge noted that common issues within CBER were similar to the drug side, including where companies expand the indication of their products, comparison/superiority claims without adequate support; and absence of risk.  More at link above. (Policy and Medicine)


SECTION 4 AGENCY AND ADVISORY COMMITTEE MEETINGS

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

Public Meeting and Request for Comment. Exploring Naloxone Uptake and Use. July 1-2, 2015.  White Oak Campus, Silver Spring, MD.  FDA CDER, in collaboration with the National Institutes on Drug Abuse, the Centers for Disease Control and Prevention, the Substance Abuse and Mental Health Services Administration, and the Health Resources and Services Administration, will hold a public meeting to discuss increasing the use of naloxone to reduce the incidence of opioid drug overdose fatalities. During the meeting, academic and government experts, industry representatives, and patient advocates will discuss which populations are at-risk for opioid drug overdose and how we can work together to encourage the use of naloxone to reduce the risk of overdose from opioid drugs.   A docket is also established for public comments. [Federal Register]

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 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 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

NIH 3D Print Exchange Recipient of HHS Innovation Award
Department of Health and Human Services Secretary Sylvia M. Burwell announced (6/25/15) the seven winners of the 2015 HHS Innovates Awards. This annual award program, in its eighth round, recognizes creative solutions developed by HHS employees in response to some of the nation’s most challenging problems in health, health care and government. Among the awarded projects was the The NIH 3D Print Exchange, an online portal to increase accessibility and exchange of 3D printing files to further scientific research. The goal of this tool, developed by the National Institutes of Health, is to empower researchers, physicians, and the public with high-quality, informative models that inspire new discoveries that transform science and health care.  The exchange includes over 5,000 3D models that are freely available to the public.  More at link above. (HHS.gov)

NIH provides interim corrective action plan for Clinical Center Pharmaceutical Development Section
NIH) has submitted interim corrective action plans to the U.S. Food and Drug Administration (FDA) to address problems with sterile manufacturing processes identified in its Pharmaceutical Development Section (PDS) and deficiencies of lesser significance in its pharmacy announced on June 4, 2015.

As part of the plan, NIH will hire a contracting firm experienced in Current Good Manufacturing Practice (CGMP) regulations and procedures. The firm will provide a full evaluation of the PDS operations and make recommendations for improvement and for addressing all FDA concerns. NIH will also establish an external group of advisors with expertise in CGMP-facility management, clinical research, engineering and regulatory requirements to consider the recommendations of the contractor and oversee the implementation of the corrective actions. The plan outlines an aggressive timeline to achieve key milestones by the end of September 2015. More at link above. (NIH release)

Alzforum Adds Listing for Clinical Trial Registries
Clinical trials for Alzheimer’s and other neurodegenerative diseases are expensive and slow, in part because they cannot find enough participants. Of the 5 million people with Alzheimer’s in the United States alone, many never learn about trial opportunities, and for rare dementias the pool of potential volunteers is small to begin with. Online registries that allow people to be contacted about trial opportunities in their area have sprung up to speed recruitment.

Alzforum has put 10 major registries in neurodegeneration into a convenient listing (see link above). These registries support research by compiling data, empowering patients, and providing a pool of potential participants for studies and clinical trials. Most registries include people with or without a diagnosis. Several registries invite enrollment by cognitively healthy people who are concerned about their dementia risk. More at link above. (Alzheimers Forum)

Advisory Panel Grapples with Combination Therapy Questions for Alzheimer's Disease
Of the 199 windows on the wavy walls of the Lou Ruvo Center for Brain Health in Las Vegas, no two are on the same plane. A specialized plaster coating on the walls ensures that the acoustics ring true amid this architectural free-for-all. The setting uncannily echoed the vibe at Opportunities and Challenges in Combination Therapy for Alzheimer’s Disease, an advisory panel meeting that took place at the Frank Gehry-designed building on May 28. Twenty-one clinicians, computational modelers, regulators, and leaders from foundations and pharma gathered to chart a path for using repurposed drugs in combination trials for Alzheimer’s. In 13 presentations and a two-hour discussion, they debated how drugs should be selected and whether combo trials were even ready for prime time. In the end, the panel concluded that combination therapy, in one form or another, may be needed to truly make a mark on AD. Leaders from the Alzheimer’s Association and the Alzheimer’s Drug Discovery Foundation (ADDF) agreed to request proposals for combination therapies on repurposed drugs, with details to come.  More at link above. (Alzforum)

American Society of Clinical Oncology Statement: A Conceptual Framework to Assess the Value of Cancer Treatment Options
The American Society of Clinical Oncology (ASCO) has published a framework for comparing the relative clinical benefit, toxicity, and cost of treatment in the medical oncology setting.

At the clinical level, the goal of the ASCO framework is to provide a standardized approach to assist physicians and patients in assessing the value of a new drug treatment for cancer as compared with one or several prevailing standards of care. From this framework, it is possible to provide medical oncologists with the information and physician-guided tools necessary to assess the relative value of cancer therapies as an element of shared decision making with their patients. At the societal level, the assumption underlying this effort is that the cost of a given intervention should bear a relationship to the beneficial impact it has for the patients who receive that treatment.

The framework has benefitted from input from representatives of four major stakeholder constituencies, including oncologists, patients, payers, and manufacturers. The framework should not be viewed as final in concept, and it is not yet suitable for use during a routine clinical encounter. It is designed to be used with the highest quality evidence available, but its development reveals significant gaps in the evidence base that, ideally, will be filled to more fully address the need for comparative information on the relative value of treatments assessed.

It is presented now to demonstrate an initial approach to the challenge and to stimulate further discussion toward the goal of developing a clinically useful tool.  According to the authors, “We seek feedback from all stakeholders, and we plan to use this feedback to further refine the framework and ensure its eventual usefulness to the oncology provider community.”

ASCO views this as an iterative process and encourages comments from all interested parties regarding the elements we have included in the value framework and its utility in facilitating discussion between providers and patients on the value of available treatment options. Comments may be submitted through August 21, 2015.  Full article at title link above. (ASCO.org)

Comparative Effectiveness Research Through a Collaborative Electronic Reporting Consortium
This article, published June 22, 2015 in the journal Pediatrics, describes the creation and details of a network of EHR networks devised to use clinical data in EHRs for conducting CER, led by the American Academy of Pediatrics Pediatric Research in Office Settings (PROS).

The United States currently lacks a system to use routinely collected electronic health record (EHR) clinical data to conduct comparative effectiveness research (CER) on pediatric drug therapeutics and other child health topics. To address this issue, PROS has linked data from its own EHR-based "ePROS" network with data from independent practices and health systems across the United States.

Beginning with 4 of proof-of-concept retrospective CER studies on psychotropic and asthma medication use and side effects with a planned full-scale prospective CER study on treatment of pediatric hypertension, the Comparative Effectiveness Research Through Collaborative Electronic Reporting (CER2) collaborators are developing a platform to advance the methodology of pediatric pharmacoepidemiology. CER2 will provide a resource for future CER studies in pediatric drug therapeutics and other child health topics.

This article outlines the vision for and present composition of this network, governance, and challenges and opportunities for using the network to advance child health and health care. The goal of this network is to engage child health researchers from around the United States in participating in collaborative research using the CER2 database. More at link above. (PubMed.gov)

TransCelerate BPM Technology Project to Cut Cost of Clinical Trial Drug Delivery

Ten of the world's largest drugs manufacturers are taking part in a TransCelerate project which aims to create a secure supply chain for medicines used in clinical trials and potentially cut the costs of delivering these drugs by at least 10%.

The software allows pharmaceutical companies to buy drugs directly from each other, rather than relying on distributors, which may not have the right drugs available when they are needed for the trial.  Sourcing the right drugs from open market distributors and wholesalers has not always been straightforward, according to Terry Walsh, who is running the project at TransCelerate, a not-for profit company funded by the pharmaceuticals industry.

The pharmaceutical suppliers undertook an 18-month pilot project, using spreadsheets and email to test the idea. The test went well, but it showed that the companies needed to have more sophisticated technology than Microsoft Outlook and Excel. The TransCelerate team hired Accenture to build the transaction system at its development centre in Boston in 2014.

Although the aim of the new system is to allow pharmaceutical companies to place orders securely, the technology is also saving the companies money, Walsh revealed. “There are definitely savings. It's 10%, or maybe 12%. When you have an R&D budget of $8bn, you are saving hundreds of thousands,” he said.

TransCelerate is looking at ways to develop the transaction engine, so that it will automatically feed critical information, such as the name of the drug and the dates they are required, into each pharmaceutical company’s IT systems. More at link above. (Computer Weekly)

U.S. is Still Most Attractive Country for Biopharma Investment: BRICs, Canada Lag Behind
In a new study from Pugatch Consilium consultancy, the U.S. and European economies continue to top the global charts in terms of attractiveness for biopharmaceutical investment. Notwithstanding low costs and considerable potential, emerging markets still come in at the bottom. Canada is also found to be surprisingly low on the list compared to developed economies, mainly due to challenging intellectual property policies.

The study, Measuring the Global Biomedical Pulse: The Biopharmaceutical Investment & Competitiveness (BCI) Survey (commissioned by PhRMA), finds that economies with policy environments that support investment and innovation rank as the most attractive in the eyes of top level executives operating on the ground, while economies with weak biopharmaceutical policies are considered to be much less competitive.

The BCI, a global survey-based index of economies’ biomedical competiveness, polls 350 biopharmaceutical executives of top-ranking multinational companies operating in 16 economies – who serve as ambassadors to their companies of the investment attractiveness of each market. By gauging their confidence in a given market and translating it into a quantitative score, the BCI enables a unique and highly relevant snapshot of economies’ biomedical competitiveness. Top performers in the BCI – the U.S., UK, Switzerland and Ireland – all score above 80% of the total possible score and place at the top of the sample in most of the seven major categories of the survey, which range from the ability to leverage R&D and manufacturing capabilities to the regulatory, IP and market environment. All four boast excellent and effective scientific research systems, regulatory and intellectual property (IP) frameworks that meet the highest international standards and relatively supportive market access environments. More at link above. (PhRMA.org)

Google unveils smart wristband for health tracking, but it's not for consumers
Google unveiled on Tuesday (6/23/15) a new sensor-packed wristband, meant to collect information on vital signs for medical professionals. The device will measure pulse, heart rhythm and skin temperature, as well as things like light exposure and noise levels.

The device was developed by Google X, the search giant's experimental-research division. But unlike other smartwatches that are powered by Google's Android Wear software and also have health tracking features, the new device isn't targeted at consumers. Instead, the aim is for patients to wear the band during clinical trials and drug tests, so the data can be used by medical researchers and physicians.

Google said the device is still in a very experimental phase. The company is working with academic researchers and drugmakers to make sure the device and its sensors are actually accurate and helpful to medical professionals. Google said that process could take years, but once the device is ready, the company will work with partners to build and distribute the wristband to a larger audience. More at link above. (Cnet.com)

London Mayor Johnson Starts Talks On $16 Billion Biotech Fund
London Mayor Boris Johnson is proposing a 10 billion-pound ($16 billion) fund to encourage growth of emerging health-care companies in the U.K. in an effort to catch up to biotechnology clusters in the U.S.

The so-called mega fund, to be discussed Thursday with banks and drugmakers Eli Lilly & Co. and Pfizer Inc., may be created by a mix of debt and equity finance, the mayor’s office said in a statement. A program jointly established by the European Union and the European Investment Bank to make more than 24 billion euros ($27 billion) available over the next seven years may also be tapped. (BioSpace)

NICE publishes updated guidance to help GPs and patients with earlier diagnosis of cancers
One in 2 people will be diagnosed with cancer in their lifetime. The disease is responsible for more than a quarter of all deaths in the UK; for many terminal cancer cases this will be due to a late diagnosis.

The National Institute for Health and Care Excellence (NICE) has updated and redesigned its guideline to support GPs and other primary care professionals to recognise the signs and symptoms of cancer and refer people for the right tests faster. It has also produced information to help the general public recognise the most common possible signs of cancer so that people can visit their doctor sooner.

Professor Mark Baker, clinical practice director at NICE, said: “The best way to successfully treat cancer is to make an early diagnosis. The sooner the disease is identified, the more likely treatment is to be effective. Earlier diagnoses have the potential to save thousands of lives each year.  More at link above. (NICE release)

CDSCO to upgrade manpower to enhance GMP compliance and quality of drugs
The Central Drug Standards Control Organization (CDSCO) of India would soon appoint 147 drug inspectors by the end of 2015 to ensure quality of drugs on par with global standards in line with current Good Manufacturing Practices (cGMP). The process for the appointments has already started, says a senior CDSCO official.

A total of additional 1195 posts have been sanctioned for the upgradation of manpower and labs under the 12th five year plan. Central government has allocated Rs.900 crore for enhancing manpower and capacities of minilabs at port offices and mobile labs at CDSCO level.

According to informed sources, “CDSCO expects to double the manpower and enhance the lab infrastructure both at the centre and states by the end of 2017. CDSCO has also conducted 17 training programmes to train drug inspectors on carrying out GMP inspections in the year 2013-14 to ensure quality of drugs supplied to over 200 countries from India”. More at link above. (Pharmabiz.com, via DIA Global Smartbrief, a DIA member benefit)

India to open drugs database to global regulators
Drug regulators and retailers across the world will soon be able to access a large database that India is building on domestic pharmaceutical manufacturers. India has decided to throw open the database to global stakeholders following concerns over spurious drugs emanating from the country.

The government had earlier introduced barcoding on export consignments of medicines to help trace their point of origin.

Now it has mandated all drug exporters to adhere to labelling of prescribed manufacturing data on various levels of packaging from October 1 while temporarily exempting barcode labelling on primary packaging.

A senior commerce ministry official said a pilot project will begin at the end of this month for uploading data provided by some select medicine exporters. More at link above. (Economic Times, India)

Australia Recommends Automatic Substitution of Biosimilars at Pharmacy Level
Australia’s Pharmaceutical Benefits Advisory Committee (PBAC) has recommended that biosimilars are suitable for substitution at the pharmacy level.

The Generics and Biosimilars Initiative (GaBi) website reports that medicines deemed substitutable at the pharmacy level by the PBAC include a notation in the official Pharmaceutical Benefits Schedule known as an ‘a’ flag. The PBAC advised that absence of data to suggest significant differences in clinical effectiveness or safety compared with the originator and availability of data for treatment-naïve patients initiating on the biosimilar would be among the relevant considerations in establishing that a biosimilar could be ‘a’ flagged with the originator biological.

Washington DC's Alliance for Safe Biologic Medicines (ASBM) condemned the PBAC recommendations, which position Australia as the first and only nation to allow pharmacy-level substitution of biologic medicines without physician involvement. More at link above. (Pharma Exec, via DIA Global Smartbrief, a DIA member benefit)


SECTION 6 LEGAL AND COMPLIANCE

Senate makes bipartisan call for landmark 60 percent increase in Alzheimer's research funding
The House Appropriations Committee today (6/24/15) approved the Labor, Health and Human Services, Education and Related Agencies (Labor-HHS) bill, including an additional $300 million for Alzheimer’s disease research. Yesterday, the Senate Labor, Health and Human Services (Labor-HHS) Appropriations Subcommittee approved a 60 percent increase — approximately $350 million — for Alzheimer's research.

If this increase becomes law, it will be the largest annual increase in federal Alzheimer's research funding to date and a significant step toward accomplishing the first goal of the National Plan to Address Alzheimer's Disease.

The National Plan to Address Alzheimer's Disease, which was mandated by the National Alzheimer's Project Act signed into law in 2011, has a primary goal to prevent and effectively treat Alzheimer's by 2025. Currently, Alzheimer's disease receives $586 million a year in federal funding for research. Leading scientists have said it will take a ramp up to $2 billion a year to reach this goal of the national Alzheimer's plan. More at link above. (Alz.org)

Harvard, MIT, Stanford, UPenn, and Vanderbilt Among Impressive Group In Support of Cures
The 21st Century Cures Act continues to enjoy growing support from individuals and groups all across the country.

Seventy-five research, life sciences, and patient advocacy organizations recently joined the wave of support voicing their approval of the legislation in a letter. “The scientific breakthroughs that take place across this nation with funding from NIH have raised life expectancy and improved the quality of life for countless Americans. … The blueprint for funding included in this bill has the potential to provide NIH with the resources needed to improve how we prevent and treat many of society’s most vexing diseases, including the thousands for which we currently do not have effective treatments.”

Last week, sixty-five cancer centers shared their praise for the landmark legislation. The number has recently been updated to sixty-seven cancer institutes, and the long list of supporters continues to grow. (Energy & Commerce Committee release)

What You Need to Know About the CBO’s 20-Page Analysis of the 21st Century Cures Act
H.R. 6, the 21st Century Cures Act, is a nonpartisan, multiyear effort to unleash the next generation of cures, therapies, and scientific discoveries for patients. The bill was approved by the Energy and Commerce Committee by a vote of 51-0, has nearly 200 co-sponsors to date, enjoys support from hundreds of organizations, and is expected to be considered by the full House of Representatives in the coming weeks.

Yesterday (6/24/15) the Congressional Budget Office released its analysis of the legislation. So you don’t have to struggle through the CBO’s 20-page breakdown, here are the three things you need to know:

  • H.R. 6 will be fully paid for and leads to billions in additional savings in the Medicare and Medicaid program outside the budget window.
  • H.R. 6 will provide an additional $10 billion for the National Institutes of Health and $550 million for the Food and Drug Administration in mandatory spending. The CBO currently estimates nearly $12 billion in savings would be generated by H.R. 6, and it is those savings that would be invested as mandatory resources to help the NIH and FDA implement the policies of H.R. 6. At the FDA, this means resources to help incorporate the patient perspective. At the NIH, this means resources to unleash the incredible advances in science. 
  • H.R. 6 reauthorizes the NIH for three years at levels consistent with appropriations levels today. The CBO analysis adds up the total funding the NIH is slated to receive under this bill, keeping it on track with current-law spending, and tallies that as discretionary spending. The level of current law spending outlined by the CBO will occur with or without H.R. 6.   
More at link above. (Energy & Commerce Committee) (DIA Note: Access the CBO report at CBO Cost Estimate: HR6 21st Century Cures Act)

Affordable Care Act survives Supreme Court challenge
The Supreme Court on Thursday upheld a key part of the Affordable Care Act that provides health insurance subsidies to all qualifying Americans, awarding a major victory to President Obama and validating his most prized domestic achievement.

In the 6-to-3 decision, Chief Justice John G. Roberts Jr. delivered a sympathetic affirmation of what has become known as Obamacare, and his legal reasoning seemed to insulate the 2010 law against the legion of opponents who want to undermine the program before it takes hold in American life.

In considering the health-care law, the justices were asked to interpret a passage that said the tax credits are authorized for those who buy insurance on marketplaces that are “established by the state.”

But federal exchanges were authorized for states that did not set up their own, and the Obama administration argued that millions of people served by a federal marketplace were entitled to the subsidies, too.

The court agreed that that was the only way the law would work and that, although the legislation’s wording was problematic, Congress’s intent was clear. “Congress passed the Affordable Care Act to improve health insurance markets, not to destroy them. If at all possible we must interpret the Act in a way that is consistent with the former, and avoids the latter,” Roberts wrote. More at link above. (Washington Post)

House Hearing on Public Health Legislation: Stem Cell Therapeutic and Research Reauthorization Act 2015
On 6/25/15, the House Subcommittee on Health convened a hearing to discuss three bipartisan bills to improve health care for newborns, infants, and children. Among the bills discussed was HR 2820, the Stem Cell Therapeutic and Research Reauthorization Act, introduced by Reps. Chris Smith (R-NJ) and Doris Matsui (D-CA). It reauthorizes the Stem Cell Therapeutic and Research Act of 2005, which provides federal support for cord blood donation and research essential to increasing patient access to transplant.

Also discussed was HR 1462, the Protecting Our Infants Act of 2015, authored by Reps. Katherine Clark (D-MA) and Steve Stivers (R-OH), which aims to combat the rise of prenatal opioid abuse and neonatal abstinence syndrome. In recent years, there has been a steady rise in the number of overdose deaths involving heroin. According to the Centers for Disease Control and Prevention, the death rate for heroin overdose doubled from 2010 to 2012. This bill will address the growing problem and help protect newborns and infants.  More at link above, including a link to the posting site for the Majority Memorandum, legislative text, witness list, and witness testimony as they become available.  (Energy & Commerce)

House Committee Votes to Eliminate AHRQ
The House Appropriations Committee voted in favor of a bill that would eliminate the Department of Health & Human Services’ (HHS) Agency for Health Research on Quality (AHRQ), a research agency that has long been disliked by some members of Congress.

The appropriations bill, which the House committee approved on Wednesday by a vote of 30-21, must be approved by the full House as well as the Senate. In total, the draft bill includes $153 billion in discretionary funding, which is a reduction of $3.7 billion below the fiscal year 2015 enacted level and $14.6 billion below the President’s budget request.

Specifically, AHRQ’s 2015 budget was $440 million; one of AHRQ’s areas of focus is health IT research, and its 2016 budget request called for a total of $20 million in research grant support. Just last week, AHRQ announced plans to fund three Centers of Excellence to study how high-performing healthcare systems promote evidence-based practices in delivering care. The three grants, which are set to begin in September, will provide approximately $52 million over five years to study how complex delivery systems disseminate evidence-based findings and provide lessons learned to inform the dissemination of findings in other settings. However, effective Oct. 1, 2015, the agency would be eliminated outright if this bill were to pass.

Also of note, the legislation would additionally cut the funding of two other healthcare research agencies: the Patient-Centered Outcomes Research Institute (PCORI) and the Centers for Medicare and Medicaid Innovation. Additionally, the draft bill would keep funding for the Office of the National Coordinator for Health IT (ONC) the same as last year at $60.4 million, while the Obama administration had requested an increase to $91.8 million. It would also increase funding for the National Institutes of Health (NIH) by 3.6 percent. More at link above. (Healthcare Informatics)

REMS reform, round 2: Will the FAST Generics Act speed past the finish line this year?
On June 18, Representatives Steve Stivers (R-OH) and Peter Welch (D-VT) introduced the Fair Access for Safe and Timely (FAST) Generics Act of 2015, just nine months after the same bill stalled in Congress. According to a press release from Rep. Stivers’ office, the broad goals of the bill are “to increase consumer access to generic drugs, boost market competition and ultimately save consumers money.”

At issue is what the Generic Pharmaceutical Association (GPhA) and many other trade organizations and allied advocates, including two super-sized pharmacy benefit managers (PBMs), Express Scripts and Prime Therapeutics, refer to as the “abuse” of the Risk Evaluation and Mitigation Strategy (REMS), a policy intended to protect patient safety through a variety of mechanisms.

When the FDA implemented REMS in 2007 as part of the FDA Amendments Act of 2007, they included a provision known as the ETASU clause (Elements to Assure Safe Use), which effectively allows a drug company to carefully control the distribution of a drug---and in the process deny distribution of a drug sample to a would-be generic competitor.

Proponents of the FAST Generics Act argue that by misusing the ETASU clause, brand companies have found a loophole through which to further their corporate interests at the expense of the public.

The FAST Generics Act of 2014 was introduced in the House of Representatives by Stivers and Welch in September 2014, but ultimately, the bill went nowhere after being referred to the Subcommittee on Healthcare Reform. So what’s different this time? While the provisions of the bill are exactly the same, the REMS reform issue has gained considerable momentum in the last nine months as awareness and activism around the issue have increased.

The FAST Generics Act positions the Department of Health and Human Services (DHHS) as the intermediary between the generic and the brand manufacturers. Under the proposed scenario, generics companies would seek authorization from the DHHS and then submit a request to a brand manufacturer, along with the authorization. They would also have injunctive relief and be able to seek damages from three parties if unfairly denied access to product samples. More at link above. (BioPharma DIVE)

California Bill Gives Terminally Ill Patients "Right to Try" Experimental Drugs
The San Jose (CA) Mercury News (6/22, Seipel) reports that the California Legislature has passed bills that “would allow terminally ill patients who have exhausted all other options the opportunity to try experimental drugs, products or devices that have not been approved by the US Food and Drug Administration.”

Senate Bill 149 by Sen. Jeff Stone, R-Temecula, and Assembly Bill 159 by Assemblyman Ian Calderon, D-Whittier, are similar to legislation passed by 21 states since last year -- 16 this year alone.

The article points out that “both California bills have sailed through their respective chambers and will likely be combined into a single bill...lawmakers say.” However, “Gov. Jerry Brown [D] has not yet indicated whether he will sign the legislation into law.”  More at link above. (Courtesy, DIA Daily, subscription a member benefit)

Massachusetts Governor Orders Review of All State Regulations; Opportunity For Healthcare Industry Comment
Earlier this year, the Governor of Massachusetts, Charles Baker, signed an executive order initiating a “comprehensive review’ for all regulations enforced by the Executive Department. Only those regulations which are mandated by law or essential to the health, safety, environment, or welfare of the Commonwealth’s residents will be retained or modified, the order states. The measure is aimed at reducing “burdensome regulations to increase efficiency and competitiveness.”

Massachusetts agencies must show that their regulations meet a set of standards delineated by the Order. Perhaps most notably is the prong that the regulation not “exceed federal requirements."  This is an important announcement for life sciences companies—Massachusetts has long been one of the more complicated and challenging states to do business in based on several regulatory requirements that require time and resources above and beyond an already complex legal landscape.

“[C]onfusing, unnecessary, inconsistent and redundant government regulations inconvenience individuals, encumber cities and towns, stress resources of non-profit organizations, including our health care and educational institutions, inhibit business growth and the creation of jobs, and place Massachusetts for profit enterprises at a competitive disadvantage relative to their out-of-state and foreign competitors,” states the Order.

This will be an important measure to follow and stakeholders should take advantage of the opportunity to participate in this regulatory review process. More at link above. Policy and Medicine.


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.