Issue Number 2 | March 2014
Jones Day to Host FDLI Drug Law and Regulation Conference
We are pleased to announce that Christopher M. Mikson, M.D., Of Counsel at Jones Day, is a key presenter
at the Food and Drug Law Institute's industry standard two-day "Introduction to Drug Law and Regulation: The
Legal Framework for Drug Regulation." Chris will present an overview of the law surrounding biologics and
biosimilars, including relevant statutes and current developments. The course will be held at Jones Day's
Washington Office on April 2–3. Don't miss your opportunity to attend this important program that, for more
than 20 years, has taught thousands to think like a seasoned drug professional. Register today through FDLI.
Draft Guidance Promises Major Changes in New Chemical Entity Exclusivity Provisions
In recognition of the increasingly important role fixed-combination products play in treating cancer,
cardiovascular, and infectious diseases, FDA issued draft guidance in February that significantly departs from
its historical interpretation of the five-year New Chemical Entity ("NCE") exclusivity provision. Historically, FDA
has interpreted these provisions such that a fixed-combination was ineligible for five-year NCE exclusivity if it
contained a previously approved active moiety, even if the product also contained a new active moiety (i.e., an
active moiety that the Agency had not previously approved). The new draft guidance focuses on FDA's
evolving interpretation of the term "drug" in the eligibility clause of the five-year NCE exclusivity statutory
provisions to improve incentives for producing new drugs in fixed-combinations, a practice that is often safer
and more effective. For more on this topic, read the Jones Day Alert and Law 360 article.
President Proposes 8 Percent Increase for FDA's Budget
Earlier this month, President Obama released his proposed budget for fiscal year 2015. The President's budget
requests $4.7 billion in resources for FDA, an 8.1 percent increase over the agency's 2014 budget. Specifically,
the budget includes a $61 million increase for medical product safety programs, including premarket reviews.
The budget allots $25 million for strengthening oversight of the pharmacy compounding industry and includes
another $25 million for promoting products to prevent or protect against bioterrorism, the same as in fiscal year
Senator Proposes Bill to Reverse Approval of Hydrocodone Drug
On March 13, Sen. Joe Manchin (D-WV) introduced a bill to overturn FDA's marketing approval of Zohydro ER,
an opioid drug made from pure hydrocodone. According to The Wall Street Journal, the drug has been
criticized by more than 24 state attorneys general and several federal legislators concerned about abuse and
potential overdose deaths. A similar bill was introduced in the House of Representatives by Rep. Stephen
Lynch (D-MA), Rep. Hal Rogers (R-KY), and 11 other cosponsors. FDA approved the drug last year over the
objections of a medical advisory panel. FDA Commissioner Margaret Hamburg continues to defend the drug's
approval for select pain treatments.
Group of Generic Drug Manufacturers Opposes Labeling Proposal
Late last year, FDA announced a proposed rule to revise and clarify procedures for application holders of an
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approved drug or biologic to update the product labeling with newly acquired information in advance of FDA's
review of the change, commonly referred to as the Changes Being Effected procedure. The proposed rule
would require ANDA holders to revise their labeling under the same procedure as brand-name pharmaceutical
manufacturers. Generic manufacturers also would have to inform the brand-name manufacturers about any
In a public comment filed this month, a group of small generic drug companies argue that FDA lacks authority
under the Food, Drug, and Cosmetic Act to enact the rule because it would establish an exception to the
"sameness" requirement, which requires that generic drug labeling match the labeling of the reference listed
drug ("RLD"). The comment contends that the only legitimate exceptions to this rule are expressly provided for
in statute and that FDA's proposed rule purports to create an exception by allowing generic drug labeling to
differ from RLD labeling "on a temporary basis." Additionally, generic manufacturers argue this exception
threatens patient safety and would force generic drug manufacturers to engage in costly, duplicative safety
reviews that FDA already performs.
The comment period for the proposed rule closed on March 13.
For further details and background, view our Jones Day Commentary.
New "openFDA" Project Revamps Public Data on Drug Side Effects
A recently announced FDA project known as openFDA aims to make public information on adverse events,
product recalls, and product labeling more accessible and useful through new database applications and
structured file downloads. Every day, FDA receives thousands of reports from practitioners and patients about
drug side effects. FDA publishes this data in quarterly bulk files, but as Businessweek reports, the sheer
volume of submissions, duplicate records, and frequently misspelled drug names makes these files difficult to
use. While some private companies already organize this information into handy reports, openFDA would
streamline the initial data release for practical use by researchers, providers, and the general public.
FDA and European Medicines Agency Strengthen Collaboration in Medicine Safety
In late February, FDA announced a new "cluster" program with the European Medicines Agency ("EMA")
focusing on pharmacovigilance, or medicine safety. The monthly teleconferences will promote a more
coordinated exchange of information on the safety of medicines. FDA already clusters with EMA on other
topics, including biosimilars, cancer-treating medicines, orphan medicines, and blood-based products, and it
maintains similar partnerships with regulators in countries such as Canada and Japan. These clusters
recognize that any action taken in one country has global repercussions on public health.
FDA Commissioner Hamburg testifies at Senate hearing about mechanisms to streamline CDRH review of
medical device applications.
FDA announces April 1 public hearing on action plan for gathering and analyzing demographic subgroup data
for approval of medical products.
FDA initiates the Secure Supply Chain Pilot Program to enhance security of imported drugs.
FDA considers fertility method involving mitochondrial combination.
Federal advisory committee recommends DNA test replace traditional pap smear as primary screening tool for
FDA Issued Rules or Guidance on the Following Topics:
Administrative Procedures for CLIA Categorization—On March 12, FDA issued guidance on "Administrative
Procedures for CLIA Categorization." The guidance describes the administrative procedures related to Clinical
Laboratory Improvement Amendments of 1988 requirements for each category of medical device regulatory
review, including premarket review by the Center for Devices and Radiological Health, premarket review by
other FDA centers, exempt from premarket notification, and waiver.
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Placental/Umbilical Biologics—In the March 5 Federal Register, FDA issued "Guidance for Industry: Biologics
License Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended
for Hematopoietic and Immunologic Reconstitution in Patients With Disorders Affecting the Hematopoietic
System," dated March 2014. This finalizes the draft guidance dated June 2013.
Annual Reporting of CMC Changes—In the March 3 Federal Register, FDA issued guidance for industry
entitled "CMC Postapproval Manufacturing Changes To Be Documented in Annual Reports." This guidance
provides recommendations to holders of new drug applications ("NDAs") and ANDAs regarding chemistry,
manufacturing, and controls changes to be documented in annual reports.
Regulations for New Animal Drugs and ANADAs—In the February 27 Federal Register, FDA amended animal
drug regulations to reflect: approval actions for new animal drug applications ("NADAs") and abbreviated new
animal drug applications ("ANADAs") during December 2013; withdrawal of approval of 69 NADAs and 22
ANADAs for use of arsanilic acid, carbarsone, or roxarsone Type A medicated articles to manufacture
combination drug Type B and Type C medicated feeds; and a change of sponsor for 54 NADAs and 1 ANADA
for topical, intramammary, and certain other dosage form new animal drug products.
Electronic Transmission of ICSR Data—In the February 21 Federal Register, FDA issued guidance entitled
"E2B(R3) Electronic Transmission of Individual Case Safety Reports (ICSRs): Implementation Guide—Data
Elements and Message Specification." This guidance revises standards for the submission of ICSRs in human
drugs and improve the inherent quality of data.
Feedback on Medical Device Submissions—In the February 18 Federal Register, FDA issued guidance entitled
"Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with
FDA Staff." This guidance provides an overview of the ways to obtain FDA feedback regarding potential or
planned medical device submissions reviewed in the CDRH and the Center for Biologics Evaluation and
Research, including the Pre-Submission program (formerly the pre-Investigational Device Exemption program).
FDA Issued Proposed Orders or Draft Guidance on the Following Topics:
Enforcement Policy for Fecal Microbiota Uses—In the February 26 Federal Register, FDA issued draft
guidance entitled "Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal
Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies,"
dated March 2014. When finalized, this guidance will supersede the July 2013 guidance document on this
subject. Comments due March 28.
Regulations for New Chemical Exclusivity Determinations—In the February 24 Federal Register, FDA issued
draft guidance entitled "New Chemical Entity Exclusivity Determinations for Certain Fixed-Combination Drug
Products." If the guidance is finalized, a drug product will be eligible for five-year NCE exclusivity if it contains a
drug substance that meets the definition of "new chemical entity," regardless of whether that drug substance is
approved alone or in certain fixed-combinations. Comments due April 25.
Antiviral Product Development—In the February 28 Federal Register, FDA issued draft guidance entitled
"Attachment to Guidance on Antiviral Product Development—Conducting and Submitting Virology Studies to
the Agency: Guidance for Submitting HIV-1 Resistance Data." The draft aims to assist sponsors in submitting
HIV clinical virology data to support clinical trials of treatment products. Comments due April 29.
Publications About "Unapproved New Uses"—In the March 3 Federal Register, FDA issued draft guidance
entitled "Distributing Scientific and Medical Publications on Unapproved New Uses—Recommended
Practices." The draft guidance provides FDA's recommended practices for drug and medical device
manufacturers to follow when distributing scientific or medical articles or clinical guidelines that discuss
unapproved new uses for approved drugs or devices marketed in the United States. Comments due May 2.
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis—In the March 11 Federal Register, FDA issued draft
guidance entitled "Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Developing Drug Products for
Treatment." The purpose of this draft guidance is to assist sponsors in the development of drug products for
the treatment of chronic fatigue syndrome/myalgic encephalomyelitis. Comments due May 12.
Methods Validation for Drugs and Biologics—In the February 19 Federal Register, FDA announced revisions to
its draft guidance on "Analytical Procedures and Methods Validation for Drugs and Biologics." These revisions
supersede the 2000 draft guidance and the 1987 guidance for industry on "Submitting Samples and Analytical
Data for Methods Validation." Comments due May 20.
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Reclassification of Shortwave Diathermy ("SWD") Device—In the February 21 Federal Register, FDA issued a
proposed order to reclassify the SWD for all other uses, a preamendments class III device, into class II (special
controls), and to rename the device "nonthermal shortwave therapy (SWT)." FDA withdrew a prior proposal
that would have required the filing of a premarket approval application or a notice of completion of a product
development protocol for the device. Comments due May 21.
Injectable Drug and Biological Products—In the March 14 Federal Register, FDA issued draft guidance entitled
"Allowable Excess Volume and Labeled Vial Fill Size in Injectable Drug and Biological Products." This
guidance clarifies FDA requirements and regulations pertaining to allowable excess volume in injectable vials
and reinforces the importance of appropriate packaging sizes for injectable drug and biological products.
Comments due June 12.
FDA published the following Federal Register Notices Regarding Agency Information Collection
Approval for collection of information on Over-the-Counter Human Drugs; Labeling Requirements.
Approval for collection of information on Medical Devices; Third Party Review Under the Food and Drug
Administration Modernization Act (FDAMA).
Approval for collection of information on Human Tissue Intended for Transplantation.
Opportunity for comment on proposed collection of information on paperwork burden of recordkeeping by
institutional review boards reviewing clinical research studies (comments due April 3).
Opportunity for comment on proposed collection of information on paperwork burden of donor screening
recommendations for serological test systems for the detection of antibodies to Trypanosoma cruzi (comments
due April 4).
Opportunity for comment on proposed collection of information on guidance regarding citizen petitions and
petitions for stay of agency action (comments due April 10).
Opportunity for comment on proposed collection of information on paperwork burden of importer's entry notices
for FDA-regulated products (comments due April 14).
Opportunity for comment on proposed collection of information on required disclosures for direct-to-consumer
prescription drug TV advertisements (comments due April 21).
Opportunity for comment on proposed collection of information on paperwork burden of animal drug sponsors
filling out the Animal Generic Drug User Fee Act (AGDUFA) cover sheet (comments due April 21).
Opportunity for comment on proposed collection of information on reporting requirements for prescription drug
advertisements (comments due April 28).
Opportunity for comment on proposed collection of information on User Fee Waivers, Reductions, and Refunds
for Drug and Biological Products (comments due May 5).
Upcoming Meetings, Workshops, and Conferences
Training program on Regulatory Science and Sustainable Implementation of National and International Medical
Device Registries in collaboration with the Medical Device Epidemiology Network, March 24 in San Francisco,
Regulatory capacity-building training program on Medical Devices Regulatory Capacity Building Training
Program for AHWP, ASEAN, Latin American and Other Medical Devices Regulators in collaboration with the
World Health Organization, March 27–28 in San Francisco, CA.
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Public FDA/AAO Workshop on Developing Novel Endpoints for Premium Intraocular Lenses, March 28 in Silver
Public Workshop on Advancing Regulatory Science for High Throughput Sequencing Devices for Microbial
Identification and Detection of Antimicrobial Resistance Markers, April 1 in Silver Spring, MD.
Public Workshop on Methods for Thrombogenicity Testing, April 14 in Silver Spring, MD.
Drugs & Biologics
Conference on Predicting Serious Drug-Induced Liver Injury (DILI) in Patients: Who Gets It? Who Doesn't?
Why?, March 19–20 in Hyattsville, MD. Additional information and registration available here.
Conference on Leadership in a Global Supply Chain in collaboration with PharmaLink and Xavier University,
March 19–20 in Cincinnati, OH.
Public Hearing on Over-the-Counter Drug Monograph System, March 25–26 in Silver Spring, MD.
Rescheduled Public Meeting on Fibromyalgia Patient-Focused Drug Development, March 26 in Silver Spring,
Conference on Generic Drug User Fee Amendment (GDUFA) and You, March 27–28 in Lake Buena Vista, FL.
Public Workshop on Synergizing Efforts in Standards Development for Cellular Therapies and Regenerative
Medicine Products, March 31 in Silver Spring, MD.
Public Hearing on Action Plan for the Collection, Analysis, and Availability of Demographic Subgroup Data in
Applications for Approval of Food and Drug Administration-Regulated Medical Products, April 1 in Silver
Spring, MD. Comments are due May 16.
Comments are due April 10 regarding the recent Public Workshop on Application of Physiologically Based
Pharmacokinetic Modeling To Support Dose Selection.
Public Meeting on Pulmonary Arterial Hypertension Patient-Focused Drug Development, May 13 in Silver
Public Meeting on Patient-Focused Drug Development for pulmonary arterial hypertension (part of PDUFA V's
performance commitments), along with an opportunity for public comment. The meeting will be held May 13 in
Silver Spring, MD. Comments are due July 14.
Public Meeting on Study Approaches and Methods To Evaluate the Safety of Drugs and Biological Products
During Pregnancy in the Post-Approval Setting, along with an opportunity for public comment. The meeting will
be held May 28–29 in Silver Spring, MD. Comments are due June 30.
Advisory Committee Meetings
March 20: Gastroenterology and Urology Devices Panel of the Medical Devices Advisory Committee Meeting
March 20: Vaccines and Related Biological Products Advisory Committee Announcement
March 26–27: Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee Meeting
March 31: Anti-Infective Drugs Advisory Committee Announcement
April 1: Endocrinologic and Metabolic Drugs Advisory Committee Meeting Announcement
May 5: Risk Communication Advisory Committee Meeting Announcement
May 6: Risk Communication Advisory Committee Meeting Announcement
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Note for Advisory Committees: FDA Launches Membership Nomination Portal
Earlier this year, FDA launched an online, interactive system that allows interested individuals to submit
nominations for membership to any of the agency's 33 advisory committees. The portal will also enable
nominees to submit their application from FDA's website.
For more comprehensive listings of FDA meetings, please visit these FDA web pages:
Workshops & Conferences (Medical Devices)
Meetings, Conferences, & Workshops (Drugs)
Workshops, Meetings & Conferences (Biologics)
FDA Advisory Committee Calendar
Recent Product Recalls
Recent drug recalls have included an antidepressant drug due to one bottle containing a foreign tablet, several
injection and enzyme replacement therapy products due to particulate matter or potential for other
contamination, and an eye drop product manufactured in Vietnam due to sterility issues at the production
Recent medical device recalls have been for reasons of operational difficulties of device controls, incorrect
statements in the instructions for use, and a physical defect leading the product not to function properly.
No biologic products have been posted to FDA's website in the last 60 days.
Click here for a complete listing of FDA Recalls.
Recent Warning Letters
FDA has recently issued warning letters to pharmaceutical manufacturers for Current Good Manufacturing
Practices violations. At least one letter was issued to a drug manufacturer in India and accompanied by an
import ban on the company's drugs. FDA additionally issued warning letters to two compounding pharmacies
for producing unapproved drugs, as well as significant violations related to the sterile manufacture of the drugs.
FDA also cited the lack of valid individual prescriptions for each of the drugs produced, which is typical when
FDA suspects that a compounding pharmacy is actually acting as a drug manufacturer and should therefore be
subject to regulation as such. Lastly, we continue to see warning letters to medical device manufacturers for
marketing a device without marketing clearance or approval.
Click here for FDA's Warning Letters Home page (scroll down for listing of recently posted Warning Letters).
The Office of Prescription Drug Promotion ("OPDP") issued a warning letter to a drug manufacturer, alleging
that the company's Facebook page contained false and misleading representations about a drug's efficacy and
for failing to communicate risk information.
Click here for a complete listing of 2014 OPDP Warning Letters.
Recent Drug and Device Approvals
FDA allows marketing of first medical device to prevent migraine headaches (March 11).
FDA approves Myalept to treat rare metabolic disease (February 25).
FDA approves Northera to treat neurogenic orthostatic hypotension (February 18).
For additional information on drug and device approvals and clearances, please visit FDA's web pages on Drug
Approvals and Databases (includes biologics) and Device Approvals, Denials, and Clearances.
Jones Day | Pharmaceutical & Medical Device Regulatory Update | Issue 2 Page 6 of 7
Colleen M. Heisey
Christopher M. Mikson
Emily K. Strunk
Matthew R. Bowles assisted in the preparation of this Update.
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