FDA BRIEF, Weeks of Dec 21st and Dec 28th, 2015 – Drug and Device Digest



FDA Voice



FDA 2015: A Look Back (and Ahead) – Part 1: Medical Product Innovation

By: Stephen M. Ostroff, M.D.

 Reflection of  FDA’s  2015 accomplishments by  Acting Commissioner

Medical Product Approvals

  • > 40 approvals including 4 new treatments for multiple myeloma, 2 new drugs for heart failure, and several drugs for  rare or “orphan” diseases
  • Several important vaccines, including meningococcal disease, seasonal influenza vaccine for elderly, anthrax
  • Several innovative devices  including brain cancer, congenital heart disease
  • Speed and efficiency in both drug and device approvals

Amplifying the Patient Voice

  • Patient-Focused Drug Development initiative
  • Voice of the Patient report (drug)
  • Patient Preference Initiative (device)
  • Draft guidance, Patient Engagement Advisory Committee


  • First biosimilar approved
  • Several Guidances

Next Generation Sequencing Tests and Strengthening Clinical Trials

  • Growing ability to apply technologies of next generation sequencing and precision medicine
  • Precision Medicine Initiative, precisionFDA web platform
  • Refine clinical trial design and statistical methods of analysis to create more efficient studies with smaller patient populations, more focused therapies, and better outcomes


FDA Invites Patient Organizations to Take a Place at the Podium

By: Theresa M. Mullin, Ph.D.

Reflection on Patient-Focused Drug Development (PFDD) program by is Director of FDA’s Office of Strategic Programs

  • More first-hand knowledge from those most affected by the diseases
  • Better understand context for regulatory decision making
  • Committed to hold meetings for at least 20 disease areas & 24 disease-focused meetings 2017
  • Encourage patient organizations in conducting an externally-led PFDD meeting and keeping FDA informed



FDA approved


ardea    ZURAMPIC  (lesinurad)


Indication: In combination with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase (XO)  inhibitor alone

 Unmet need:

  • Gout is a painful form of arthritis caused by uric acid buildup
  • Need for new treatment option for controlling hyperuricemia for the long-term treatment of gout

Reg pathway: NDA Standard Review

Mechanism of Action: Inhibits transporter proteins functions involved in uric acid reabsorption in the kidney and reduces serum uric acid levels


  • 3 multicenter, randomized, double-blind, placebo-controlled studies, Patients with hyperuricemia and gout
  • Zurampic + XO inh (allopurinol or febuxostat) vs XO inh
  • N=511, 510, 516, Duration :  12 mo.
  • Superior lowering of serum uric acid to less than 6 mg/dL at 6 mo.


  • Boxed Warning : Risk for acute kidney (renal) failure
  • Common Adverse Reaction : Headache, influenza, increased blood creatinine, and gastroesophageal reflux disease
  • Postmarketing Study : Renal and Cardiovascular safety



UPTRAVI (selexipag)


Indication : Treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH

Unmet Need:

  • PAH is high blood pressure in arteries connecting heart to lungs; can lead to limitations on exercise ability and shortness of breath
  • Need for additional treatment option for PAH patients

Reg Pathway : NDA – Standard review, Orphan Drug Designation

Mechanism of  Action:  Oral prostacyclin receptor agonist


  • Single multi-center, double-blind parallel group, N=1156, Uptravi vs Placebo, 1.4 yrs
  • Primary endpoint : Time to first occurrence of : death, hospitalization for PAH, PAH worsening,  initiation of parenteral prostanoid therapy or chronic oxygen therapy, other disease progression
  • 40% reduction (99% CI: p-value < 0.0001) of primary endpoint events vs placebo  – primarily due to reduction in hospitalization for PAH and reduction  disease progression events


  • Common Adverse Reaction : Headache, diarrhea, jaw pain, nausea, muscle pain (myalgia), vomiting, pain in an extremity, and flushing



FENIX  Continence Restoration System

Torax Medical Inc, Shoreview, Minnesota

Indication for Use: Treat fecal incontinence in patients who are not candidates for, or have previously failed, medical or other surgical options

Unmet Need:

  • Fecal incontinence caused by damage anal sphincter muscles; frequently underreported
  • Need for viable surgical option other non-invasive methods have failed

Reg Pathway: PMA, Humanitarian Device Exemption (HDE) process


  • 3 components: Implant, Anal Sphincter Sizing Tool, Introducer Tool
    • Implant : Titanium beads with magnetic cores; minimizes involuntary opening of anal canal
    • Sizing Tool : Associates anal sphincter size to appropriate implant
    • Introducer Tool : Guides sizing tool and implant into position


  • Study (n=35), evaluations before and after procedure and at 6 wks, 3 mo, 6 mo, 12 mo
  • Bowel diary to track fecal incontinence events & validated questionnaire (Fecal Incontinence Quality of Life Scales)
  • 50% reduction after 12 mo: 9 %  (fecal incontinence episodes), 54.3 % (fecal incontinence days), 37.1 % (urgent episodes)
  • Improvements in Quality of Life measures : depression, self-perception, embarrassment


  • Adverse Events : Pain, infection, impaction or defecatory disorder, device erosion, device removal/re-operation, and bleeding
  • Patients required register with MedicAlert Foundation


fda guidances.JPG


emerging signals

  • Need for FDA to notify the public about emerging signals that the Agency is monitoring or analyzing
  • Proposes criteria, timeframes, communication, follow-up for emerging signals that may impact benefit/risk
  • Emerging Signals : New adverse event, increase in severity/frequency,  new product-product interactions, device malfunctions, patient injuries,  reduction in benefit
  • FDA will assess of need for communication : Within 30 days of receipt of information
  • If yes, FDA will communicate using standardized format and provide updates


  • Electroconvulsive Therapy (ECT) Devices for Severe Major Depressive Episode associated with Major Depressive Disorder or Bipolar Disorder reclassified  into class II from class III
  • Guidance provides recommendations for complying with the special controls and for 510(k) information for special controls


  • Specific emerging technology review assigned to a group within CDER (Emerging Technology Team – ETT) to collaborate with sponsor to implement emerging manufacturing technology
  • IND, NDA, BLA, ANDA implementation– specific discussion meetings to present proposal and align on requirements


CDRH Fiscal Year 2016 (FY 2016) Proposed Guidance Development and Focused Retrospective Review of Final Guidance


A List

Final Guidance Topics

  • General Wellness Products
  • Medical Device Accessories
  • Benefit-Risk Factors to Consider when Reviewing IDE Submissions
  • UDI Direct Marking
  • Adaptive Design for Medical Device Clinical Studies
  • Incorporating Patient Preferences into Medical Devices Premarket Approvals, Humanitarian Device Exemptions, and De Novo Classifications
  • Applying Human Factors & Usability Engineering to Optimize Medical Device Design
  • Policy for Regulatory Oversight of Laboratory Developed Tests (LDTs)
  • Submission and Review of Sterility Information for Devices Labeled as Sterile
  • Use of ISO 10993-1, Biological Evaluation of Medical Devices Part I: Evaluation and Testing
  • Postmarket Surveillance Studies
  • Medical Device Reporting (MDR) for Manufacturers

Draft Guidance Topics

  • Medical Device Decision Support Software
  • Use of Symbols in Labeling
  • 510(k) Modifications
  • Software Modifications
  • 510(k) Third Party Review Program
  • Companion Diagnostics Co-Development
  • Use of Real-World Observational Patient Data to Support Decision Making for Medical Devices
  • UDI Convenience Kit
  • Public Notification of Emerging Postmarket Medical Device Signals

There is also a B List


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