FDA Launches precisionFDA to Harness the Power of Scientific Collaboration
By: Taha A. Kass-Hout, M.D., M.S. and Elaine Johanson
- Collaboration between industry, academia, government
- Online, cloud-based portal on “reading” DNA – next-generation sequencing (or NGS)
- Look for meaningful DNA differences for disease risk, treatment response, tailor personalized treatment
- Leverages experience with establishing openFDA – easy access to public datasets
2016 CDER PRIORITIES: Janet Woodcock M.D., Director, CDER, FDA
|PDUFA 6 agreements
Advertising /Promotion regulations
Prescription Opioid Epidemic
|Sentinel Network and Drug Safety
Drug Supply Chain, Imports
Drug Label Improvement, Pregnancy & Lactation Rule
Biomarkers, Accelerated Approval, Qualification
Qualitative Benefit/Risk assessment
Electronic Health Data, Clinical Evidence
Patient-focused Drug Development
CV safety studies for Diabetes and Obesity
Pediatric Evaluation for non- PREA/BPCA drugs
Bayesian Statistics, Adaptive Designs, Modeling
PFUFA and meeting goals
FOI and reducing backlog
Advisors and Consultants and AC meetings
- Supporting Regulatory Operations and strengthening Electronic Submissions Gateway (ESG)
- Electronic Regulatory Submissions
- Data Standards
- Metrics and Measures
- Communications and Technical Interactions
- Timely and Effective (with causality assessment) reporting
- Key elements of a systematic approach to safety surveillance
- Safety Assessment Committee
- Safety Surveillance Plan describing policies and procedures
- Recommendations for :
- Committee Organization
- Safety Assessment practices
- Prospective development of Safety Surveillance Plans
Indication : Reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adults undergoing surgery.
- Neuromuscular blocking drugs (e.g. rocuronium bromide, vecuronium bromide) cause temporary paralysis by interfering with nerve impulse transmission to muscle
- Used to paralyze vocal cords for tracheal intubation, used as general anesthesia during surgery, used to prevent automatic breathing when a patient is on a ventilator
- Need for treatment option to help patients recover sooner from intubations and ventilations during surgery
Reg Pathway: NDA submitted in 2007, Complete Response Letter, Approval of responses to Action Letter
Mechanism of Action: As a modified gamma cyclodextrin, forms a complex with the neuromuscular blocking agents rocuronium and vecuronium and reduces availability to bind to receptors in neuromuscular junction.
- 3 Multicenter, randomized, parallel-group studies vs neostigmine or succinylcholine (n=456), post-surgical patients with moderate and deep blockage
- Primary Endpoint : Time from start of administration to recovery of twitch responses to train-of-four (TOF) ratio of 0.9 (correlates with recovery from neuromuscular blockade)
- Study 1 Moderate Blockade (vs neostigmine) : Faster recovery, 1.4 min vs 21.5 min
- Study 2 Deep Blockade (vs neostigmine) : Wider range of recovery; median times comparable
- Study 3 (blockade by succinylcholine vs blockade by rocuronium followed by Bridion) : Faster Recovery, 4.4 min vs 7.2 min
- Possibility of a hypersensitivity reaction or anaphylaxis – intervene as appropriate.
- Marked bradycardia some leading to cardiac arrest – monitor closely and treat appropriately
- Most common adverse reactions: Vomiting, low blood pressure (hypotension), pain, headache and nausea.
- May reduce effect of hormonal contraceptives
Basaglar (insulin glargine )
Indication: Improve glycemic control in adult and pediatric patients with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus.
- 21 million people in US diagnosed with diabetes; increases risk of heart disease, blindness, nerve and kidney damage
- Need to expand availability of treatment options for long-acting insulin products
Reg Pathway: FIRST “follow-on” insulin glargine product . 505(b)(2) application : Comprised of reference to FDA’s approval of Lantus (insulin glargine injection) and additional clinical studies. Tentative approval in 2014.
Mechanism of Action: Lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production.
- Comparability to other insulin glargine products: 2,327 adults and 349 pediatric patients with type 1 diabetes mellitus and 1,563 adult patients with type 2 diabetes mellitus. Basaglar similar to other products.
- The Basaglar-specific data : 2 clinical trials enrolling 534 and 744 patients with type 1 and 2 diabetes mellitus, respectively.
- Insulin Class effect : Severe, life-threatening, generalized allergic reactions, including anaphylaxis, or generalized skin reactions, angioedema, bronchospasm, hypotension and shock
- Common adverse reactions: Hypoglycemia, allergic reactions, injection site reactions, pitting at the injection site (lipodystrophy), itching, rash, edema (fluid retention) and weight gain.
LifeVest Wearable Cardioverter Defibrillator
Zoll Lifecor Corporation, Pittsburgh, Pennsylvania.
Intended Use : Wearable cardioverter defibrillator to monitor and treat cardiac arrhythmias in children (restrictions must have a chest circumference of 26 inches and weigh at least 18.75kg). Has been previously approved for use in adults (> 18 years of age).
Unmet need :
- A life-threatening abnormal heart rhythm- ventricular fibrillation (V-fib) or ventricular tachycardia (V-tach), most common cause of sudden cardiac arrest and death
- Rapid treatment with a defibrillator can save lives
- For children – Need for defibrillator worn by patients with constant monitoring of arrhythmias and provision of appropriate response
Reg Pathway: PMA supplement, based on published studies and Registry of 248 patients
- 2 main components: (i) electrode belt and garment surrounding chest,(ii) monitor around waist
- Responds automatically if it senses the need to deliver a shock, restoring a life-sustaining heartbeat.
Checkme Pro portable health monitor
Viatom Technology, Taiwan, 510K
- One-lead ECG recording, pulse oximetry, temperature measurement, and movement sensing
- Provides QRS duration, ST segment, and rhythm analysis for basic cardiac monitoring
- Track SpO2 up to 10 hours during sleep
- Records can be reviewed by Physician
GRUVE anterior cervical plate system
Lifespine, Huntley, IL, 510K
- Surgical treatment of spine disorders
- Allows extreme bone screw angulation, large graft windows, in addition to a tactile and visual confirmation of the locking mechanism during final screw placement
NxTag Respiratory Pathogen Panel
Luminex, Austin TX, 510K
- Simultaneous detection of 20 respiratory pathogens in a single closed-tube system, including atypical bacteriaChlamydophila pneumoniae and Mycoplasma pneumonia
- Minimal hands-on time with no upstream reagent preparation, simplified workflow
- Synct software for data analysis and reporting