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Content Currents


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: August 15, 2014


CDER List of Guidance Documents

CDER Guidances: New/Revised/Withdrawn through 6/30/14

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lead to the List of Guidance Documents (CDER) updated on July 7, 2014, and to CDER Guidances that are new, revised, or withdrawn through the second calendar quarter of 2014.

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

CDRH FY 2014 Proposed Guidance Development

On August 13, 2014, FDA announced the availability of the guidance entitled “Unique Device Identification System: Small Entity Compliance Guide.”  This guidance is intended primarily to provide information to the medical device industry, including small businesses, concerning FDA’s September 24, 2013, final rule establishing a unique device identification system; see 78 FR 58786 et seq. It provides an overview of the UDI Rule’s regulatory requirements and discusses the actions a small entity should take to meet those requirements. Other guidance documents, such as the guidance document titled Global Unique Device Identification Database (GUDID) and issued on June 25, 2014, discuss in greater detail the technical implementation of the UDI Rule.  [Federal Register]

On August 14, 2014, FDA announced a correction to the final rule “Postmarketing Safety Reports for Human Drug and Biological Products; Electronic Submission Requirements”    that appeared in the June 10, 2014 Federal Register. The document amended FDA’s postmarketing safety reporting regulations for human drug and biological products to require that persons subject to mandatory reporting requirements submit safety reports in an electronic format that FDA can process, review, and archive. The document was published with incorrect information regarding the availability of the International Conference on Harmonization’s (ICH) data elements for postmarketing safety reports. The document also published with an incorrect statement regarding the impact of the final rule on small entities. This document corrects those errors. [Federal Register]

On August 14, 2014, FDA announced the availability of a guidance entitled “Immunogenicity Assessment for Therapeutic Protein Products.” This guidance is intended to assist manufacturers and clinical investigators in developing a risk-based approach in both the nonclinical and clinical phases of product development that will allow them to evaluate and reduce the likelihood that the immunogenicity of the product will cause harm to patients. This guidance finalizes the draft guidance issued in February 2013. [Federal Register]

On August 14, 2014, FDA issued a revised draft guidance entitled “Clinical Pharmacology Labeling for Human Prescription Drug and Biological Products—Considerations, Content, and Format.”  This draft guidance is one of a series of guidance documents intended to assist applicants in complying with FDA regulations on the content and format of labeling for human prescription drug and biological products. The guidance describes the recommended information to include in the Clinical Pharmacology section of labeling that pertains to the safe and effective use of human prescription drug and biological products. Comments may be submitted until October 14, 2014.  [Federal Register]

On August 14, 2014, FDA announced the reopening of the comment period for the draft guidance entitled “Best Practices in Developing Proprietary Names for Drugs” which was published in the Federal Register on May 29, 2014.  FDA is reopening the comment period in response to several requests for additional time and to allow interested persons more time to submit comments.  Comments should be submitted by September 15, 2014. [Federal Register]

On August 14, 2014, FDA announced the availability of the draft guidance entitled “De Novo Classification Process (Evaluation of Automatic Class III Designation).”   FDA is issuing this draft guidance to provide proposed updated recommendations for efficient interaction with FDA, including what information to submit when seeking a path to market for a novel device via the de novo process. This draft guidance has been revised and is being reissued for comment because the Food and Drug Administration Safety and Innovation Act (FDASIA), which became law on July 9, 2012, amended the FD&C Act to provide for the submission of de novos without a preceding premarket notification (510(k)) submission.  Comments should be submitted by October 14, 2014.  [Federal Register]


Updated List of CDER Key Officials Posted

FDA Expecting Ten Biosimilar Applications by End of FY15
The agency says it expects to receive three biosimilar marketing applications in fiscal year 2014 and another seven in FY 2015, as well as much more in program revenue.  At least one 351(k) application has been filed so far. The additional applications should boost user fee revenue for the fledgling program, which in FY 2013 did not spend any of its collections.

The possibility of having three pending marketing applications at the same time and another handful coming after Oct. 1 (the start of FY 2015) may eliminate concerns that interest in FDA’s abbreviated approval pathway had stalled. But it also will place more pressure on the agency to complete some important policies, including a draft guidance on naming biosimilar products. (The draft guidance is reported to have been sent to HHS for clearance prior to release for stakeholder comment.) More at link above.  (Pink Sheet, paid subscription required.)

Stem cell therapy: FDA regulatory science aims to facilitate development of safe and effective regenerative medicine products
In an August 12, 2014 FDA Voice blog, Dr. Steve Bauer, Chief of the Cellular and Tissues Therapy Branch in the Office of Cellular, Tissue, and Gene Therapy, CBER, writes:

“There is tremendous interest in the development of regenerative medicine, including numerous proposed products that rely on stem cells. Stem cells have the ability to generate more stem cells or to turn into more mature cell types such as nerve- or bone-producing cells. These properties make stem cells potentially well suited for use in regenerative medicine.

Because stem cells can change based on their surroundings…ensuring the safety of effective regenerative medicine products can be challenging.  FDA’s Center for Biologics Evaluation and Research has assembled seven of its laboratories into a consortium to develop tests and techniques that will help answer (these types of) questions as these products move through the development process.”

The consortium has published scientific articles on a number of stem cell topics. See more at title link above. (FDA.gov)

FDA's JumpStart Program: Supporting Innovation
As part of the HHS Innovates program, HHS Secretary Sylvia Mathews Burwell and Deputy Secretary Bill Corr acknowledge excellence in the field with the Secretary’s Pick Award, an honor that identifies and celebrates internal innovation by HHS employees.

The winner of one of three Secretary’s Pick Awards was the FDA’s Office of Computational Science (OCS), part of the Office of Translational Sciences (OTS) in the agency’s Center for Drug Evaluation and Research (CDER). OCS received the award for its work in developing CDER’s JumpStart program, an innovative initiative dedicated to enhancing the efficiency of CDER’s new drug development and review process. The JumpStart program provides CDER’s new drug review teams with clinical trial data analyses early in the review process when they assess quality, data composition, exploratory analyses, and tools for the analyses. It gives the reviewers a “jump start” on their review providing the information on the quality of the submission as well as analyses to support an effective and efficient evaluation of the medical product submission. More at link above.  (FDA.gov)

FDA Pilot Program for Qualification of Medical Device Development Tools
On August 14, FDA launched the Medical Device Development Tools (MDDT) Pilot Program.

The MDDT pilot program allows any tool developer, medical device manufacturer, or others involved in medical device development such as research organizations and academia to voluntarily submit a proposal for their tool to be considered by the FDA for qualification. Qualification means that the FDA has evaluated the tool and concurs with available supporting evidence that the tool produces scientifically-plausible measurements and works as intended within the specified context of use. The FDA intends to qualify some tools submitted through the pilot program.  More at link above.  (FDA.gov)

FDA Discusses Interim Disclosure in CV Outcomes Trials
FDA met with industry and patient representatives Monday to discuss how to preserve trial integrity in two-stage cardiovascular outcomes studies that use a prespecified interim analysis to support approval and full results to fulfill postmarketing requirements.

Participants agreed that disclosing whether interim analyses meet the standard of approval would not jeopardize the remainder of the trial. But they said disclosing preliminary data about the hazard ratio, confidence interval or other safety signals could lead to slower enrollment, biased trial practices or uninterpretable results. More at link above.  (BioCentury) (See also Pink Sheet, paid subscription required: Pink Sheet)

FDA Encourages Continuous Manufacturing and Offers Assistance
FDA officials are encouraging the pharmaceutical industry to switch from batch to continuous manufacturing, and they’re promising to help with the transition.

The center is establishing an Emerging Technologies Team as part of its massive drug quality reorganization in October to help remove any real or perceived regulatory roadblocks against adoption of continuous manufacturing and other new technologies.

The main challenge facing the team appears to be a perception within industry that FDA won’t allow continuous manufacturing. Another issue is that there remains a lot of uncertainty around continuous manufacturing, both in the agency and in industry, that they will need to work together to resolve. More at link above.  (Pink Sheet, paid subscription required)


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

Public Meeting. Nonprescription Drugs Advisory Committee Meeting.  September 3, 2014. White Oak Campus, Silver Spring, MD.   The committee will discuss the standards used to demonstrate that over-the-counter (OTC) topical antiseptics used in healthcare settings are generally recognized as safe and effective.  [Federal Register]

Public Workshop. Hemostatic Medical Devices for Trauma Use. September 3-4, 2014.  White Oak Campus, Silver Spring, MD.  The purpose of this workshop is to discuss factors that contribute to hemostatic medical device performance and reliability and types of studies used to assess bleeding and validate methods to evaluate the severity of bleeding, and to define regulatory pathways for novel products. [Federal Register]

New:  Public Workshop. Clinical Development of Drugs for the Prevention of Infections Caused by Staphylococcus aureus in the Health Care Setting. September 5, 2014.  White Oak Campus, Silver Spring, MD.  This public workshop is intended to provide information for and gain perspective from health care providers, patients and patient advocacy organizations, academia, and industry on various aspects of clinical development of drugs to prevent Staphylococcus aureus infections including the design of clinical trials. [Federal Register]

Public Meeting. Advancing the Use of Biomarkers and Pharmacogenomics. September 5, 2014. Washington, DC.  The purpose of the public meeting is to initiate constructive discussion and information sharing on the advancement of biomarker science in the context of therapeutic product development among relevant stakeholders. [Federal Register]

Public Meeting in Collaboration with the National Cancer Institute. Methodological Considerations in Evaluation of Cancer as an Adverse Outcome Associated with Use of non-Oncological Drugs and Biological Products in the Post-approval Setting.  September 10 - 11, 2014.  Silver Spring, MD.  The purpose of the public meeting is to engage in constructive dialogue and information sharing among regulators, researchers, the pharmaceutical industry, public health agencies, health care providers, and the general public concerning challenges in designing and implementing post-approval studies to evaluate the risk of cancer associated with use of non-oncological drugs and biological products. The input from this meeting and public docket will be used to inform the Agency on best study design and methodological options to consider when evaluating cancer risk in the post-approval setting.  [Federal Register]

Public Advisory Committee Meeting. Cardiovascular and Renal Drugs Advisory Committee. September 10, 2014. White Oak Campus, Silver Spring, MD.  The committee will be asked to discuss the potential clinical utility of fixed-combination prescription drugs composed of an anti-hypertensive drug, aspirin, and a statin administered to reduce the risk of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke in patients with a history of cardiovascular disease. The committee will be asked to discuss the patient population that could benefit from such a product, whether that population would be likely to take such a drug long term, and how this could be assured. [Federal Register]

Meeting. Third Annual Patient Network Meeting; Under the Microscope: Pediatric Drug Development. September 10, 2014. Washington, DC.  The meeting will serve as a forum for FDA’s stakeholders (patients, caregivers, patient advocates, healthcare professional groups, the general public, academia, and industry) to learn about regulations that encourage pediatric product development; to discuss ways to advance pediatric product development, how health disparities impact pediatric product development, the importance of transparency in pediatric clinical trials, and how analysis of information from failed pediatric clinical trials might improve future designs for pediatric trials; and to identify ways patient input can benefit clinical trial design for pediatric trials. [Federal Register]

Meeting. International Medical Device Regulators Forum (IMDRF), September 15-19, 2014.  Embassy Row Hilton, Washington, DC.  A week of global meetings to discuss worldwide medical device regulation and harmonization efforts.  [FDA.gov]

Public Advisory Committee Meeting. Cellular, Tissue and Gene Therapies Advisory Committee. September 17, 2014. Hyattsville, MD.  In open session, the committee will hear updates of research programs in the Laboratory of Biochemistry, Division of Therapeutic Proteins, the Laboratory of Molecular Oncology and the Laboratory of Molecular and Developmental Immunology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, FDA. Another portion of the meeting will be closed to the public.  [Federal Register]

Public Advisory Committee Meeting. Joint Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. September 18, 2014. White Oak Campus, Silver Spring, MD.  The committees will discuss the appropriate indicated population for testosterone replacement therapy and the potential for adverse cardiovascular outcomes associated with this use. [Federal Register]

Public Workshop. Pediatric Clinical Investigator Training Workshop. September 22, 2014.  Bethesda, MD.  The purpose of this workshop is to provide investigators with training and expertise in designing and conducting clinical trials in pediatric patients that will lead to appropriate labeling. [Federal Register]

Public Meeting. Patient-Focused Drug Development for Hemophilia A, Hemophilia B, von Willebrand Disease, and Other Heritable Bleeding Disorders. September 22, 2014. White Oak Campus, Silver Spring, MD.  The public meeting is intended to allow FDA to obtain patient perspectives on the impact of Hemophilia A, Hemophilia B, von Willebrand Disease, and other heritable bleeding disorders on daily life as well as patient perspectives on the available therapies for these disorders. [Federal Register]

Public Workshop. Next-Generation Sequencing Technology, Data Formats Standardization and Promotion of Interoperability Protocols.  September 24-25, 2014. National Institute of Health Campus, Bethesda, MD. The purpose of the workshop is to engage NGS stakeholders in a forum to discuss the current use of the technology and the development of data standards of NGS-related information. [Federal Register]

Public Meeting. Patient-Focused Drug Development for Idiopathic Pulmonary Fibrosis. September 26, 2014. White Oak Campus, Silver Spring, MD.  The public meeting is intended to allow FDA to obtain patient perspectives on the impact of idiopathic pulmonary fibrosis on daily life as well as patient views on treatment approaches for idiopathic pulmonary fibrosis. [Federal Register]

Public Workshop. Additive Manufacturing of Medical Devices: An Interactive Discussion on the Technical Considerations of 3–D Printing. October 8-9, 2014. White Oak Campus, Silver Spring, MD.  The purpose of this workshop is to provide a forum for FDA, medical device manufactures, additive manufacturing companies, and academia to discuss technical challenges and solutions of 3–D printing. The Agency would like input regarding technical assessments that should be considered for additively manufactured devices to provide a transparent evaluation process for future submissions. [Federal Register]

Public Meeting.  Patient-Focused Drug Development and Scientific Workshop on Female Sexual Dysfunction.   October 27-28, 2014.  White Oak Campus, Silver Spring, MD.  FDA is conducting a Patient-Focused Drug Development public meeting and scientific workshop on Female Sexual Dysfunction (FSD).  [Federal Register]

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


Antibiotic Disincentives? Medicare Decisions Underscore Limits of Add-On Payments
Recent decisions by CMS to deny or decline to renew extra Medicare reimbursement for two novel antibiotics are a disappointment for drug developers looking to the program to reward innovation.

CMS has denied Durata Therapeutics Inc.’s recently launched I.V. antibiotic Dalvance (dalbavancin) a boost in reimbursement under the Medicare new technology add-on payment (NTAP) program and declined to extend existing NTAP benefits another year for oral antibiotic Dificid (fidaxomicin), marketed by Cubist Pharmaceuticals Inc. The decisions were announced in the annual Medicare hospital inpatient prospective payment system final rule for 2015, released Aug. 4.  More at link above.  (Pink Sheet, paid subscription required)

IOM Releases Report on Contemporary Issues for Protecting Patients in Cancer Research
In the nearly 40 years since implementation of federal regulations governing the protection of human participants in research, the number of clinical studies has grown exponentially and the studies themselves have become much more complex. In addition, growing emphasis on targeted cancer therapies requires greater collaboration and sharing of research data—including use of electronic records—and thus has also increased concerns about the potential for inappropriate or unauthorized use of data. These changes and challenges raise new ethical and practical questions for the oversight of clinical studies, and for protecting patients and their health information in an efficient manner that does not compromise the progress of biomedical research.

On February 24 and 25, 2014, the National Cancer Policy Forum of the Institute of Medicine convened a workshop to frame and discuss contemporary issues in human subjects protections as they pertain to cancer research, with the goal of identifying potential relevant policy actions. This document summarizes the workshop. More at link above.  (IOM)

Drug Repurposing and Repositioning: an IOM report
Drug development can be time-consuming and expensive. Recent estimates suggest that, on average, it takes 10 years and at least $1 billion to bring a drug to market. Given the time and expense of developing drugs de novo, pharmaceutical companies have become increasingly interested in finding new uses for existing drugs - a process referred to as drug repurposing or repositioning.

Given the widespread interest in drug repurposing, the Roundtable on Translating Genomic-Based Research for Health of the Institute of Medicine hosted a workshop on June 24, 2013, in Washington, DC, to assess the current landscape of drug repurposing activities in industry, academia, and government.  This report examines enabling tools and technology for drug repurposing; evaluates the business models and economic incentives for pursuing a repurposing approach; and discusses how genomic and genetic research could be positioned to better enable a drug repurposing paradigm. (IOM)

Bioengineers create functional 3D brain-like tissue
Bioengineers at the Tissue Engineering Resource Center at Tufts University, Boston, which is funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), have created three-dimensional brain-like tissue that functions like and has structural features similar to tissue in the rat brain and that can be kept alive in the lab for more than two months.

As a first demonstration of its potential, researchers used the brain-like tissue to study chemical and electrical changes that occur immediately following traumatic brain injury and, in a separate experiment, changes that occur in response to a drug. The tissue could provide a superior model for studying normal brain function as well as injury and disease, and could assist in the development of new treatments for brain dysfunction. More at link above.  (NIH.gov)

WHO Endorses Investigational Ebola Compounds
The World Health Organization said in a statement that using investigational Ebola compounds that have not yet been evaluated for safety and efficacy in humans is ethical as long as certain conditions are met. An advisory committee said those conditions include transparency about informed consent and freedom of choice; confidentiality; patient respect; preservation of dignity; and community involvement. The group advised there was a "moral obligation to collect and share all data generated, including from treatments provided for 'compassionate use.'"

The group agreed that interventions should be evaluated in clinical trials to definitively prove their safety and efficacy or provide evidence to stop their use. The panel also noted the need for ethical discussion about obtaining data after use, how to prioritize use, and fair distribution. Distribution was cited as an important topic for discussion because it is unlikely that any of the new interventions would be able to meet the short-term demand.

WHO did not specifically name any Ebola treatments. The organization said it would release a full report of the advisory meeting by Aug. 17.  (BioCentury)

WHO to pick who gets Canada's Ebola vaccine
Canada will donate doses of its experimental Ebola vaccine to the international community and the World Health Organization will help determine who receives it, a federal official says.

The Canadian government expects to donate 800 to 1,000 doses of the experimental Ebola vaccine developed at the National Microbiology Laboratory.  The number of doses available depends on whether the vaccine is used in its traditional form to prevent infection, or as a treatment, said Kobinger. Studies in animals suggest Canada's experimental vaccine can also be used to treat Ebola infection.

More at link above.  (CBC News)

PCORI Approves Drug-focused Research Grants Topic for First PCORnet Study
The Patient-Centered Outcomes Research Institute board has approved a drug-related topic and grant amount for the first comparative-effectiveness clinical trial to be conducted in the electronic data research network being developed by PCORI.

Known as PCORnet, the network is designed to pull together large numbers of insurance claims and medical records to facilitate observational research as well as pragmatic clinical trials.

At its meeting in late July, the PCORI board also approved $54.8 million in funding to support 33 comparative-effectiveness research projects, including five that involve drug-related topics. More at link above.  (Pink Sheet, paid subscription required.)

Europe to boost cooperation with international partners on generics
The European Union’s decentralised procedure is being used as a model to accelerate the assessment of applications for generic medicines as part of the International Generic Drug Regulators Pilot (IGDRP).

The European Union (EU) is leading an international pilot project through which, upon request from a generic pharmaceutical company, it will share the assessment reports generated as part of the decentralised procedure in real time with collaborating regulatory agencies outside the EU.

The first phase of the pilot project will involve the EU, Australia, Canada, Chinese Taipei and Switzerland.

Other members of the IGDRP may decide to take part in the pilot programme at a later stage. These include Brazil, China, Japan, Korea, Mexico, New Zealand, Russia, Singapore and South Africa. The European Directorate for the Quality of Medicines & Healthcare (EDQM) and the World Health Organization (WHO) participate as observers.  (EMA)

China Human Genetic Resources Administration Office Asserts Authority to Approve Clinical Studies Sponsored by Foreign Companies in China Involving Human Sample Collection
The China Human Genetic Resources Administration Office (CHGRAO) recently indicated informally that clinical studies sponsored by foreign companies in China, either by themselves or through local CROs, should be approved by CHGRAO to the extent the studies involve collection of samples containing human genetic resources. Such approvals should be in place before the clinical study agreements are signed with the Chinese hospitals. More at link above. (Sidley Austin News Release)

Draft of China's First Traditional Chinese Medicine Law Released for Public Comment
In a bid to grow traditional Chinese medicines (TCMs) to become a strong and internationally recognized sector, China is now establishing a formal legal framework for a type of treatment that has been around for centuries.

The State Council, China’s Cabinet, on July 24 released the draft regulation – the China Traditional Medicine Administration Law – for public comments after rounds of discussions and a more than decade wait.

“We need to improve standards, and upgrade our service, trade and policy making,” said Wang Guoqiang, the head of Administration for Chinese Traditional Medicine, who is also the Deputy Commissioner of the national Health and Family Planning Commission. “Several key aspects include legal framework, standardization, efficacy and product R&D,” he added. More at link above.  (Pink Sheet, paid subscription required)


GMP False Claims Case Falters but Pharma Isn't in Clear Yet
A U.S. appellate court ruling that FDA current good manufacturing practice violations are not per se violations of the False Claims Act is likely just the start of the debate on whether drug manufacturing troubles can be targets for FCA enforcement.

In affirming the U.S District Court for the District of Maryland’s dismissal of the case brought by a former employee at Omnicare Inc.’s Heartland drug repackaging operation for failure to state a claim, the Fourth Circuit said that the Medicare and Medicaid statutes do not require cGMP compliance or any other FDA safety regulation compliance as a condition of reimbursement.

The appeals court also said the CMS statutes don’t expressly prohibit reimbursement for adulterated drugs. More at link above.  (Pink Sheet, paid subscription required)

Alabama Supreme Court: Innovator Company Liable for Harm Caused by a Generic Version of Its Drug
Should brand-name drug makers be held liable if consumers are harmed by a medicine made by a generic rival?  The Alabama Supreme Court believes the answer is yes. And the court has upheld its own controversial ruling that Pfizer can be sued by an Alabama man who claimed he was injured by a generic version of its Reglan heartburn medicine. Why? The brand-name drug maker purportedly failed to warn his physician about the risks.

The decision is potentially significant, because this is one of the few cases in which a court has found that a brand-name drug maker can be sued, even though a consumer had taken only the generic version. Consequently, the ruling may be considered by other courts deciding similar cases and prompt still more such lawsuits.  More at link above. (Pharmalot in Wall Street Journal)


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.