http://blogs.fda.gov/FDAvoice/index.php
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- Draft guidance, Patient Engagement Advisory Committee
Biosimilars
- 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
ZURAMPIC (lesinurad)
TABLETS
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
Efficacy:
- 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.
Safety:
- 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)
TABLETS
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
Efficacy:
- 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
Safety:
- 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
Description:
- 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
Effectiveness:
- 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
Safety:
- Adverse Events : Pain, infection, impaction or defecatory disorder, device erosion, device removal/re-operation, and bleeding
- Patients required register with MedicAlert Foundation
http://www.fda.gov/RegulatoryInformation/Guidances/default.htm
- 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