FDA BRIEF: Week of March 27, 2017

FDA approved

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ZEJULA (niraparib) capsules

Tesaro, Waltham, MA, USA 

INDICATION: Maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy


  • >2,000 women will be diagnosed in 2017;  >14,000 will die
  • Maintenance therapy important for patients with positive response
  • ZEJULA offers new treatment option to delay growth regardless of genetic mutation


  • Fast Track, Priority Review and Breakthrough Therapy designation
  • Orphan Drug designation for treating recurrent epithelial ovarian cancer.
  • Application approved approximately three months ahead of the goal date
  • Postmarketing Requirement:  PK trial in patients with moderate hepatic impairment

MECHANISM OF ACTION: Inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes, PARP-1 and PARP-2, which play a role in DNA repair


  • Single double-blind, placebo-controlled trial, n=553, patients with platinumsensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients with deleterious or suspected deleterious germline BRCA mutations (gBRCAm) were assigned to the germline BRCA mutated (gBRCAmut) cohort (n=203), and those without germline BRCA mutations were assigned to the non-gBRCAmut cohort (n=350)., ZEJULA vs. placebo
  • Primary efficacy outcome: PFS (progression-free survival)  determined by RECIST
  • gBRCAmut cohort: 21 mo. vs  5.5 mo. (p<0.0001)
  •  non-gBRCAmut cohort: 9.3 mo. vs 3.9 mo. (p<0.0001)


  • Common adverse reactions:  Thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue, decreased appetite, urinary tract infection, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, and hypertension.


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DUPIXENT (dupilumab) injection

Regeneron Pharmaceuticals,  Tarrytown, NY, USA

INDICATION:  Treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. DUPIXENT can be used with or without topical corticosteroids


  • Atopic dermatitis most common of the many types of eczema; onset in childhood and can last through adulthood
  • New and innovative therapy for skin disease not controlled by topical therapies


  • Priority Review, Breakthrough Therapy designation
  • Postmarketing requirements: Pediatric studies, Registry-based observational study on maternal, fetal, and infant outcomes,  Retrospective cohort study on pregnancy outcomes

MECHANISM OF ACTION: Human monoclonal IgG4 antibody, inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), inhibits cytokine-induced responses, including the release of proinflammatory cytokines, chemokines and IgE


  • 3 randomized, double-blind, placebo-controlled trials, n=2,119 , patients with moderate-to-severe atopic dermatitis, DUPIXENT or placebo for 16 weeks
  • Primary endpoint: Change from baseline and at least a 2-point improvement
  • Other endpoints: Eczema Area and Severity Index, itch reduction,  improvement in pruritus
  • Greater response of clear or almost clear skin,  itch reduction
  • Serious allergic reactions and eye problems- conjunctivitis, keratitis
  • Most common side effects: Injection site reactions; cold sores, eye and eyelid inflammation

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OCREVUS (ocrelizumab) intravenous infusion

Genentech, Member of Roche Group, San Francisco, CA, USA

INDICATION: Treatment of adult patients with relapsing or primary progressive forms of multiple sclerosis (PPMS)


  • MS most common causes of neurological disability in young adults and occurs more frequently in women than men
  • Approximately 15 percent of patients with MS have PPMS
  • OCREVUS first approved drug for PPMS


  •  Breakthrough Therapy Designation, Fast Track Designation, Priority Review
  • Postmarketing requirements: Pediatric study, Longitudinal observational study in adult patients for breast cancer incidence,  prospective pregnancy exposure registry, pre-and postnatal development study in primates

MECHANISM OF ACTION:  Binding to CD20, resulting in antibody-dependent cellular cytolysis and complement-mediated lysis


  • 2 studies, n= 1,656, treated for 96 weeks; OCREVUS vs. Rebif (interferon beta-1a)
  • Primary outcome: Annualized relapse rate (ARR)
  • Additional outcomes: Confirmed disability progression, new gadolinium (Gd)-enhancing lesions,  new or enlarging MRI T2 hyperintense lesions
  • Significantly lowered ARR and tdisability progression
  • 1 randomized, double-blind, placebo-controlled clinical trial in PPMS,n=488
  •  Primary outcome: Onset of disability progression
  • Onset of disability progression significantly longer for OCREVUS vs. placebo
  • Should not be used in patients with hepatitis B infection
  • Must be dispensed with patient Medication Guide
  • Can cause serious  infusion-related reactions, which can be serious
  • May increase the risk for malignancies, particularly breast cancer
  • Most common side effect:  Upper respiratory tract infection, skin infection, and lower respiratory tract infection



Brain Sentinel Monitoring and Alerting System

Brain Sentinel, San Antonio, TX, USA

INDICATION FOR USE: Adjunct to seizure monitoring in adults in the home or healthcare facilities during periods of rest.

The device is to be used on the belly of the biceps muscle to analyze surface electromyographs (sEMG) signals that may be associated with generalized tonic-clonic (GTC) seizures and to provide an alarm to alert caregivers of unilateral, appendicular, tonic extension that could be associated with a GTC seizure.

The System records and stores sEMG data for subsequent review by a trained healthcare professional

REG PATHWAY: De Novo request

  • Regulation Number: 21 CFR 882.1580
  • Regulation Name: Non-EEG physiological signal based seizure monitoring system
  • Regulatory Classification: Class II
  • Product Code: POS

GENERIC DEVICE DESCRIPTION: Non-invasive prescription device that collects physiological signals other than EEG to identify physiological signals that may be associated with a seizure


  • Adverse tissue reaction: Biocompatibility evaluation
  • Equipment malfunction leading to injury to users (shock, burn): Electrical safety, thermal, and mechanical testing, Electromagnetic compatibility testing, Labeling
  • Interference with or from other electrical devices: Electromagnetic compatibility testing
  • Incorrect alerts, including missing a seizure or false alarm: Clinical performance testing, Non-clinical performance testing, Software verification, validation and hazard analysis, Labeling, Training



CDER Oncology Fellowships

Students participating in the Commissioner's Fellowship Program

Oncology Genomics Fellowship – CDER

Oncology Bioinformatics Fellowship – CDER

Join a multi-disciplinary team to pursue next generation sequencing and molecular biology translational research in order to understand complex regulatory and scientific questions in oncology. Multiple projects collaborating with outside academic or government institutions will be pursued. As many of the projects will be performed using next generation sequencing technology, experience in this technique will be key.

Oncology Genomics Fellowship – CDER

Oncology Bioinformatics Fellowship – CDER

FDA News: FDA in India, TB Biorepository, Regulatory Science Progress Report, CDRH Accomplishments

FDA BRIEF: Week of March 27, 2017

Mary Lou Valdez with India Office Staff

FDA In India- Championing a Culture of Quality

By: Mary Lou Valdez is FDA’s Associate Commissioner for International Programs

India and FDA:

  • 7th largest supplier of food, 2nd largest supplier of pharmaceuticals and biologics to US
  • Agency’s office in New Delhi conducts inspections and trains Indian medical products and foods facilities
  • Collaboration with Indian regulatory counterparts – Indian Export Inspection Council (EIC), Food Safety Standards Agency of India (FSSAI), Drugs Controller General of India (DCGI), and Joint Secretary of the Ministry of Health and Family Welfare
  • Participation in Global Food Safety Partnership (GFSP) Governing Council meeting and the Indian Pharmaceutical Alliance (IPA) Forum

Common Theme:

  • Collaboration to enhance regulatory effectiveness and advance risk-based, science-based approaches to regulation
  • Allow India to engage with International Council for Harmonisation (ICH) and the Pharmaceutical Inspection Cooperation Scheme (PIC/S)


Liquid nitrogen tanks

Tuberculosis Biorepository Aims To Bolster TB Drug Development by Facilitating Research on Biomarkers

By: Leonard Sacks, M.D., Associate Director for Clinical Methodology, Office of Medical Policy, CDER 

TB Biorepository:

Biorepository websitedisclaimer icon.


FY 2015-2016: Regulatory Science Progress Report


  • Advancing the science of medical product development and evaluation: Non-clinical predictive models, drug carcinogenic effects, computational phantoms for devices, genetic and transplantation approaches to create predictive animal models 
  • Improving Clinical Evaluation:  Foster biomarker development and adoption, guide treatment decisions and predict disease progression 
  • Advancing product manufacturing and quality:  Computational capability for studying continuous manufacturing, advanced process control system, predicting critical properties of human stem cell preparations
  • Ensuring the safety and effectiveness of marketed medical products: National electronic system for active medical product surveillance, Sentinel system,  National Evaluation System for health Technology (NEST) 
  • Advancing regulatory science to promote global health: Responses to Ebola, Zika, pandemic influenza virus 
  • Infrastructure and organizational changes to advance regulatory science:  Enhanced IT for regulatory application reviews, organizational and programmatic changes to address regulatory science issues, enhance scientific interactions with stakeholders, industry engagement with guidance documents, workshops


cdrh report.JPGEstablish a National Evaluation System for Medical Devices:

  • Establish the National Evaluation System for health Technology (NEST)
  • Develop a framework for the incorporation of real-world evidence into regulatory decision making

Partner with Patients:

  • Patient Engagement Advisory Commitee
  • Education and Training

Promote a Culture of Quality and Organizational Excellence:

  • Quality Management Framework
  • Education and Training
  • Case for Quality
  • Voluntary Programs



FDA Classifications, Authorizations, Approvals: ILLUMINA, GENE-RADAR, XADAGO, BAVENCIO

FDA BRIEF: Week of March 20, 2017



Illumina MiSeqDx Platform

Illumnia Inc, San Diego, CA, USA

INTENDED USE: The MiSeqDx Platform is a sequencing instrument that measures fluorescence signals of labeled nucleotides through the use of instrument specific reagents and flow cells (MiSeqDx Universal Kit 1.0), imaging hardware, and data analysis software. The MiSeqDx Platform is intended for targeted sequencing of human genomic DNA from peripheral whole blood samples. The MiSeqDx Platform is not intended for whole genome or de novo sequencing.

REG PATHWAY: De Novo request

  • Regulation Number: 21 CFR 862.2265
  • Regulation Name: High throughput genomic sequence analyzer for clinical use
  • Regulatory Classification: Class II
  • Product Code: PFF

GENERIC DEVICE TYPE:  High throughput genomic sequence analyzer for clinical use.

Analytical instrument system intended to generate, measure and sort signals in order to analyze nucleic acid sequences in a clinical sample.

The device may include a signal reader unit; reagent handling, dedicated instrument control, and other hardware components; raw data storage mechanisms; data acquisition software; and software to process detected signals.


  • Inaccurate test results due to unavailability of necessary components of the instrument : General controls and special control
  • Inaccurate results due to unknown performance of the instrument system :General controls and special control
  • Special Controls: Labeling, Performance Characteristics


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Gene-RADAR® Zika Virus Test

Nanobiosym Diagnostics, Cambridge, MA, USA


Real-time RT-PCR based assay intended for the qualitative detection of RNA from the Zika virus in serum samples from individuals meeting Centers for Disease Control and Prevention (CDC) Zika Virus clinical criteria (i.e., clinical signs and symptoms associated with Zika virus infection) and/or CDC Zika virus epidemiological criteria (i.e., history of residence in or travel to a geographic region with active Zika transmission at the time of travel, or other epidemiological criteria for which Zika virus testing may be indicated).

Testing is limited to CLIA certified laboratories. Results are for the identification of Zika virus RNA. Zika virus RNA is generally detectable in serum during the acute phase of infection (approximately 14 days following onset of symptoms, if present). Positive results are indicative of current infection.

REG PATHWAY: Emergency Use Authorization

  • Serious or life-threatening disease or condition to humans infected with the virus
  • Based on totality of scientific evidence,  Gene-RADAR® Zika Virus Test, when used with the specified instrument(s) and in accordance with the Scope of Authorization, may be effective in detecting Zika virus and diagnosing Zika virus infection
  • There is no adequate, approved, and available alternative to the emergency use of the Gene-RADAR® Zika Virus Test for detecting Zika virus and diagnosing Zika virus infection.


  • Real-time PCR based test
  • Designed to detect RNA from the Zika virus, extracted from patient serum samples utilizing a QIAamp® Viral RNA Mini Kit (Qiagen), and amplified and detected on the Gene-RADAR® Platform.



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XADAGO (safinamide) tablets

Newron Pharmaceuticals, Italy

INDICATION:  Adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease (PD) experiencing “off” episodes.


  • 50,000 Americans  diagnosed with Parkinson’s disease
  • Neurological disorder, typically in people>60,  over age 60, occur when dopamine producing brain cells become impaired or die
  • Impacts daily activities such as eating, writing, and shaving
  • “Off” episode when patient’s medications are not working well, causing an increase in Parkinson’s symptoms, such as tremor and difficulty walking
  • No cure; Need for additional treatment options


MECHANISM OF ACTION:  Inhibitor of monoamine oxidase B (MAO-B) and catabolism of dopamine; increase dopaminergic activity in brain


  • 2 double-blind, placebo-controlled, multi-national, 24-week, PD patients with ‘off’ time during treatment with carbidopa/levodopa and other PD medications, n=645, 549, XADAGO vs. placebo
  • Primary endpoint: Change from baseline in total daily “ON” Time without troublesome dyskinesia; based on 18-hour diaries
  • Secondary endpoint: “OFF” Time during the diary period, Reduction in Uniform Parkinson’s Disease Rating Scale (UPDRS) Part III (motor examination)
  • Significant increased “ON” Time vs. placebo without troublesome dyskinesia
  • Significant reduction in “OFF” Time and reduction in UPDRS


  • Contraindications: Concomitant use with MAO inhibitors, opioids, dextromethorphan,  Severe hepatic impairment (Child-Pugh C: 10-15)
  •  Most common adverse reactions: Uncontrolled involuntary movement, falls, nausea, and trouble sleeping or falling asleep (insomnia)



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BAVENCIO (avelumab) injection

EMD Serono, Rockland,MA, USA

INDICATION: Treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC).

UNMET NEED: First FDA-approved product to treat this type of cancer.

REG PATHWAY: BLA, Orphan Drug Status, Breakthrough Therapy Designation, Priority Review

  • Approved under accelerated approval based on tumor response and duration of response
  • Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
  • Multicenter clinical trial confirming the clinical benefit of avelumab in patients with metastatic Merkel cell carcinoma (MCC) who have not received prior systemic therapies for metastatic MCC

MECHANISM OF ACTION: Programmed death ligand-1 (PD-L1) blocking antibody.


  • Single open-label, single-arm, multi-center study, patients with histologically confirmed metastatic MCC, n=88, BAVENCIO every 2 weeks until disease progression or unacceptable toxicity.
  • Primary Endpoint: Overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST)
  • Secondary endpoint : Duration of Response (DOR)


  • Most common adverse reactions: Fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, and peripheral edema
  • Serious adverse reactions: Acute kidney injury, anemia, abdominal pain, ileus, asthenia, and cellulitis



FDA News: Pediatric Trial participation, RMAT Designation, FDA-ARGOS, CDRH Experiential Learning Program

FDA BRIEF: Week of March 20, 2017

nurse and father tending to child in hospital bed (600x400)

Would Your Child Benefit from a Clinical Trial?

Pediatric clinical trials:

  • yield important information on a drug’s safety, dosing, and/or effectiveness
  • forms the basis for FDA approval & guides product label

Only about 50% of FDA approved drugs been labeled for pediatric use 

  • routine use of treatments that have been tested only in adults
  • pediatric responses  may not be predictable from adult data
  • also varies due to metabolism changes across across age groups e.g. newborn vs. adolescent


This is Not a Test: RMAT Designation Goes Live

By: Peter Marks, M.D., Ph.D.,  Director, CBER
Peter Marks

Regenerative Medicine Advanced Therapy (RMAT) Designation

  • new program to foster development and approval of regenerative medicine
  • per provisions included in 21st Century Cures Act

RMAT designation

  • certain cell therapies, therapeutic tissue engineering products
  • preliminary supportive clinical evidence to treat serious/life-threatening diseases
  • eligible for increased, earlier FDA interactions, priority review, accelerated approval
  • fulfillment of post-approval  accelerated approval  requirements: clinical evidence, clinical studies, patient registries, real world evidence,larger confirmatory datasets, post-approval monitoring




FDA – ARGOS (dAtabase for Regulatory Grade micrObial Sequences)

  • to promote advancement of Infectious Disease Next Generation Sequencing (ID-NGS)
  • in collaboration with the Department of Defense, the Institute for Genome Sciences at the University of Maryland and the National Center for Biotechnology Information
  • publicly available public health resource  for quality controlled and curated genomic sequence data
  • could be used as tool for in-silico (computer simulation) performance validation
  • invites additional collaborators from scientific community – biothreat organisms, emerging pathogens, clinically significant bacterial, viral, fungal, and parasitic genomes
  • goal to collect geographically and historically diverse sequence information for a minimum of 5 isolates per species




Innovative learning opportunity for FDA review staff

  • opportunity to understand the policies, laboratory and manufacturing practices, challenges addressing patient perspective/input, quality system management, device development life cycle
  • NOT intended for FDA to inspect, assess, judge, or perform a regulatory function (e.g., compliance inspection)
  • encourages participation from companies, academia, clinical facilities, medical device incubators and accelerators, health insurers, health technology assessment groups
  • Application Process based on CDRH Areas of Interest : Submission Period: March 23, 2017- April 30, 2017




FDA BRIEF: Week of March 13, 2017

FDA approved

Image result for kisqaliKISQALI (ribociclib) tablets

Novartis Pharmaceuticals Corporation,  East Hanover, NJ, USA

INDICATION:  In combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)- negative advanced or metastatic breast cancer.

UNMET NEED: Effective new treatment option for the continuing unmet need of the HR+/HER2- advanced breast cancer population.


  • Priority Review, Breakthrough Therapy Designation
  • Post-marketing Requirements: Clinical trial to assess the efficacy and safety of an alternative dosing, clinical pharmacokinetic trial in severe renal impairment

MECHANISM OF ACTION: Inhibitor of cyclin-dependent kinase (CDK) 4 and 6 that are activated and play crucial role in cell  cycle progression and cellular proliferation.


  • Single  randomized, double-blind, multicenter study  (n=668), postmenopausal women with HR-positive, HER2-negative, advanced breast cancer with no prior therap, 21 days, 7 days off, KISQALI plus letrozole vs. placebo plus letrozole
  • Primary Endpoint: Investigator-assessed progression-free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  • Pre-planned interim analysis PFS: 27.8% vs. 44.9%, p< 0.0001



  • Most common adverse reactions: Neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain
  • Most common grade 3 or 4 adverse reactions: Neutropenia, leukopenia, abnormal liver function tests, lymphopenia, and vomiting
  • Warning and Precaution: Prolongation of QT interval


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KEYTRUDA (pembrolizumab) injection

SUPPLEMENTARY INDICATION:  treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy [see Clinical Studies (14.4)].

REG PATHWAY:  Supplemental  BLA

  • Orphan Drug Designation, Breakthrough Therapy Designation, Priority Review, Accelerated Approval
  • Accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.


  • Single multicenter, non-randomized, open-label study, n=210,  patients with relapsed or refractory cHL, KEYTRUDA  every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months
  • Major efficacy outcome measures: Overall Response Rate (ORR), Complete Response Rate (CRR), duration of response,  assessed by blinded independent central review
  • ORR  69% (95% CI: 62, 75); median follow-up 9.4 months
  • Median response duration: 11.1 months
  • Efficacy in pediatric patients extrapolated from results observed in adults.


  • Most common adverse reactions: Fatigue, pyrexia, cough, musculoskeletal pain, diarrhea, rash and hypertransaminasemia
  • Additional common adverse reactions: Dyspnea, arthralgia, vomiting, nausea, pruritus, hypothyroidism, upper respiratory tract infections, headache, peripheral neuropathy, hyperbilirubinemia and increased creatinine
  • Other immune-mediated adverse reactions: hyperthyroidism, pneumonitis, uveitis, myositis, myelitis and myocarditis
  • Safety profile in the pediatric patients similar to adults



FDA News: FDA Commissioner Nomination, Listing of Class II Exempt, Office of Patient Affairs

FDA BRIEF: Week of March 13, 2017


Dr. Dr. Scott Gottlieb nominated as next FDA Commissioner

  • Former FDA deputy commissioners for medical and scientific affairs from 2005 to 2007
  • Practicing physician and governmental health policy adviser
  • Resident fellow at American Enterprise Institute, Clinical Assistant Professor at New York University, Health Information Technology adviser for the Department of Health and Human Services
  • To be confirmed by the Senate
American Enterprise Institute

Class II.JPG

Class II devices that the FDA is proposing to exempt or partially exempt from the premarket notification [510(k)] requirements.

List of 1,003 class II devices that will be exempt or partially exempt from 510(k)

  • In accordance with streamlined procedures established by the 21st Century Cures Act
  • Identified devices are sufficiently well understood and do not present risks
  • No premarket notification review for reasonable assurance of safety and effectiveness

Not exempt from other regulatory controls

  • Suitable for the intended use
  • Adequately packaged and properly labeled
  • cGMP requirements for manufacture
  • Have establishment registration and device listing forms on FDA file



FDA Office of Patient Affairs

Office of Patient Affairs to enhance mechanisms for patient engagement 

  • Provide a more transparent, accessible, and robust experience for patient communities
  • Based on public feedback solicited per Food and Drug Administration Safety and Innovation Act (FDASIA)


  • Offering a single, central entry point to the Agency for the patient community
  • Providing triage and navigation services for inbound inquiries from patient stakeholders
  • Hosting and maintaining robust data management systems that would incorporate and formalize knowledge shared with FDA by patient stakeholders and FDA’s relationships with patient communities
  • Developing a scalable and forward-looking platform for communicating with patient stakeholders, particularly online channels



FDA Approvals, Classifications: NOCTIVA, AEROFORM, CINtec

FDA BRIEF: Week of March 6, 2017

FDA approved

Image result for noctiva

NOCTIVA (desmopressin acetate) nasal spray

Marketed by Milford, Pennsylvania-based Renaissance Lakewood, LLC for Serenity Pharmaceuticals, LLC., USA

INDICATION:  Treatment of nocturia due to nocturnal polyuria in adults who awaken at least 2 times per night to void. Nocturnal polyuria was defined in the NOCTIVA clinical trials as night-time urine production exceeding one-third of the 24-hour urine production

UNMET NEED:  First therapeutic option to help reduce the number of times needed to  wake up at night to urinate

REG PATHWAY: NDA, Division of Bone, Reproductive and Urologic Products, ODE III, CDER

  • not approved for all causes of night-time urination
  • health care providers need to confirm urine overproduction at night with a 24-hour urine collection
  • Post-Marketing Requirement for PK study
  • No REMS

MECHANISM OF ACTION: Synthetic analog of vasopressin; selective agonist at V2 receptors on renal cells in the collecting ducts, increasing water re-absorption in the kidneys, and reducing urine production


  • Two 12-week randomized, doubleblind, trials, 6 mo.  history of nocturic episodes, n=1,045, NOCTIVA vs, placebo
  • Co-primary endpoints: (1) Change in mean nocturic episodes/night from baseline (2) % patients achieving at least  50% reduction in episodes  from baseline
  • Small reduction in average number of night-time urinations with NOCTIVA but more patients achieved 50% reduction in episodes


  • Boxed warning and Medication Guide for hyponatremia
  • Most common side effects: Nasal discomfort, cold symptoms (nasopharyngitis), nasal congestion, sneezing, high or increased blood pressure, back pain, nose bleeds, bronchitis and dizziness.



AEROFORM Tissue Expander System

AirXpanders, Palo Alto, CA, USA

INDICATION FOR USE: For soft tissue expansion in breast reconstruction following mastectomy, for the treatment of underdeveloped breasts, and for the treatment of soft tissue deformities in the breast. Intended for temporary subcutaneous or submuscular implantation and is not intended for use beyond six months.

REG PATHWAY: De Novo Request

  • Regulation Number: 21 CFR 878.3510
  • Regulation Name: Carbon dioxide gas controlled tissue expander
  • Regulatory Classification: Class II
  • Product Code: PQN

GENERIC DEVICE TYPE: Carbon dioxide gas controlled tissue expander.

  • Prescription device intended for temporary subcutaneous or submuscular implantation to stretch the skin for surgical applications, specifically to develop surgical flaps and additional tissue coverage.
  • Made of an inflatable elastomer shell and is filled with carbon dioxide gas.
  • Utilizes a remote controller to administer doses of carbon dioxide gas from an implanted canister inside the device.


  • Pain from Overexpansion with Carbon Dioxide: Labeling, Software verification, validation and hazard analysis
  • Tissue Damage from Overexpansion with Carbon Dioxide: In-vivo performance testing, Labeling, Software verification, validation and hazard analysis
  • Prolonged Treatment Time: In-vivo performance testing, Non-clinical performance testing, Labeling, Software verification, validation and hazard analysis
  • Re-operation:  In-vivo performance testing, Non-clinical performance testing
  • Underexpansion, Overexpansion, or No Expansion: Electromagnetic compatibility, electrical safety, and wireless compatibility testing, Labeling, Software verification, validation and hazard analysis, Human factors testing, Patient training
  • Adverse Tissue Reaction: Biocompatibility evaluation
  • Infection: Sterilization validation, Shelf life testing


Positive CINtec® Histology immunostaining of a cervical biopsy specimen

CINtec Histology Kit

Ventana Medical Systems, Inc., Tucson, AZ, USA

INDICATION FOR USE: Qualitative immunohistochemistry (IHC) test using mouse monoclonal anti-p16 antibody clone E6H4, and is intended for use in the light microscopic assessment of the p16INK4a protein in formalin-fixed, paraffin-embedded (FFPE) cervical punch biopsy tissues using OptiView DAB IHC Detection Kit on a VENTANA BenchMark ULTRA instrument. The test is indicated as an adjunct to examination of hematoxylin and eosin (H&E) stained slide(s), to improve consistency in the diagnosis of cervical intraepithelial neoplasia (CIN). Diagnosis of CIN presence or level should be based on H&E stained slide(s) and other clinical and laboratory test information

REG PATHWAY: De Novo Request

  • Regulation Number: 21 CFR 864.1865
  • Regulation Name: A cervical intraepithelial neoplasia (CIN) test system
  • Regulatory Classification: Class II
  • Product Code: PRB

GENERIC DEVICE DESCRIPTION:  Cervical intraepithelial neoplasia (CIN) test system

  • Used to detect biomarker associated with CIN in human tissues
  • Adjunct test and not to be used as a stand-alone devic
  • Results must be interpreted in the context of the patient’s clinical history including, but not limited to, prior and current cervical biopsy results, Papanicolaou (Pap) test results, human papillomavirus (HPV) test results, and morphology on hematoxylin and eosin (H&E) stained sections
  • Not intended to detect the presence of HPV.


  • Inaccurate test results, such as false positive or false negative results: General and Special Controls
  • Failure to correctly interpret test results can lead to false positive or false negative results: General and Special Controls

FDA News: 1Q MDUFA III Performance, CDER Priorities and Accomplishments, TVAM Concerns

FDA BRIEF: Week of March 6, 2017

Image result for MDUFA III image



Metrics for Draft Guidances, PMA, 510(k), IDE posted






CDER – Moving forward in 2017

Main 2017 Priorities

  • Improving and implementing Informatics Process Management
  • Implementing recent provisions of the 21st Century Cures Act
  • Providing technical assistance to reauthorization of various User Fee bills
  • Executing action plan for combating opioid epidemic
  • Modernizing assessment of manufacturing facilities and mutual reliance initiative with EU
  • Controlling harm from pharmacy compounding


Significant 2016 Achievements

  • Good performance of GDUFA
  • Substantive steps in biosimilar regulation
  • User Fee negotiations
  • Integrating sentinel system with OSE and Safety Surveillance
  • Implementing provisions of various statutes: Sunscreen Innovation Act, Patient-Focused Meetings, Patient-Focused Drug Development meetings in rare disorders


Alert the health care professionals and patients about  Transvascular Autonomic Modulation (TVAM) – an experimental procedure 


  • Threading catheter into  venous system, e.g. jugular vein, where balloon attached to inflate to widen vein walls

FDA Unapproved Claim:

  • At least one physician, Dr. Michael Arata‘ – uses TAVM in venous system to treat signs and symptoms of autonomic dysfunction in neurological disorders
  • FDA approval for use only in arteries
  • No FDA review of data supporting safety and effectiveness for intended use in veins

Risk to patients:

  • No clear scientific evidence to support effectiveness – impacting symptom, changing course of health condition, improving quality of life
  • Associated with serious complications: Rupture of balloon, death, blood clots, cranial nerve damage, abdominal bleeding


FDA BRIEF: Week of February 27, 2017

FDA approved


XERMELO (telotristat ethyl) tablets, for oral use

Lexicon Pharmaceuticals, Woodlands, TX, USA

INDICATION: Treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy


  • Carcinoid syndrome seen with carcinoid tumors – rare, slow-growing
  • Tumors release excess serotonin, resulting in diarrhea leading to weight loss, malnutrition, dehydration, electrolyte imbalance
  • Need for another treatment option


  • NDA : Fast Track Designation, Priority Review, Orphan Drug Designation
  • Post-Marketing Requirements: 2-year rat carcinogenicity study, In-vitro interaction studies, hepatic impairment study

MECHANISM OF ACTION: Active metabolite, telotristat, inhibits tryptophan hydroxylase, mediator of serotonin biosynthesis


  • 12-week double-blind, placebo-controlled, randomized, multicenter trial, patients with metastatic neuroendocrine tumor and carcinoid syndrome diarrhea (n=90), XERMELO vs placebo
  • Primary efficacy endpoint: Change from baseline in daily bowel movements over 12 weeks
  • 33%  Xermelo patients vs. 4% placebo patients  with reduction of at lest 2 bowel movements


  • Most common side effects: Nausea, headache, increased levels of the liver enzyme gamma-glutamyl transferase, depression, accumulation of fluid causing swelling (peripheral edema), flatulence, decreased appetite and feve
  • May cause constipation


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PHENOTEST BC Kit and Pheno System

Accelerate Diagnostics Inc., Tucson, AZ, USA


Multiplexed in vitro diagnostic test utilizing both qualitative nucleic acid fluorescence in situ hybridization (FISH) identification and quantitative, antimicrobial susceptibility testing (AST) methods and is intended for use with the Accelerate Pheno system.

The Accelerate PhenoTest BC kit is capable of simultaneous detection and identification of multiple microbial targets followed by susceptibility testing of the appropriate detected bacterial organisms.

The Accelerate PhenoTest BC kit is performed directly on blood culture samples identified as positive by a continuous monitoring blood culture system. Results are intended to be interpreted in conjunction with Gram stain results.


  • First test to identify organisms causing bloodstream infections and identify antibiotics likely to respond (antibiotic sensitivity)
  • Reduces time taken to provide information,  expedite antibiotic treatment

REG PATHWAY: De Novo request

  • Regulation Number: 21 CFR 866.1650
  • Regulation Name: A cellular analysis system for multiplexed antimicrobial susceptibility testing
  • Regulatory Classification: Class II
  • Product Code: PRH, NSU, PEO, PAM, PEN, LON


  •  Multiplex qualitative and/or quantitative in vitro device intended for the identification and determination of the antimicrobial susceptibility results of organisms detected in samples from patients with suspected microbial infections
  • Intended to aid in the determination of antimicrobial susceptibility or resistance when used in conjunction with other laboratory findings


  • False positive /False negative results, failure to perform appropriate AST testing, Organism determined to be resistant when susceptible, Organism determined to be susceptible when resistant: General controls and special controls
  • Errors in Interpretation: General controls and special controls
  • Failure to correctly operate the test system: General controls and special controls
  • Special Controls: Premarket notification submission requirements, labeling, results interpretation, principles of operation



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ODACTRA™ House Dust Mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus) Allergen Extract Tablet for Sublingual Use

Merck, Whitehouse, Station, NJ, USA

INDICATION: Allergen extract indicated as immunotherapy for house dust mite (HDM)-induced allergic rhinitis, with or without conjunctivitis, confirmed by in vitro testing for IgE antibodies to Dermatophagoides farinae or Dermatophagoides pteronyssinus house dust mites, or skin testing to licensed house dust mite allergen extracts. ODACTRA is approved for use in adults 18 through 65 years of age.


  • House dust mite allergies commonly found in house dust;  found in bedding, upholstered furniture and carpeting
  • Cough, runny nose, nasal itching, nasal congestion, sneezing, itchy and watery eyes
  • Can negatively impact quality of life
  • Alternative treatment to allergy shots to help address symptoms


MECHANISM OF ACTION:  Contain house dust mite allergen extract from Dermatophagoides farinae and Dermatophagoides pteronyssinus;  precise mechanisms of action of allergen immunotherapy have not been fully established


  • 2  double-blind, placebo-controlled, randomized clinical field efficacy studies  and one environmental exposure chamber (EEC) study, n = 2,500, ODATRA vs. placebo
  • Primary Endpoint: Difference in  average Total Combined Rhinitis Score ( TCRS) during last 8 weeks of treatment; other endpoints average rhinitis daily symptom scores(DSS) and rhinitis daily medication scores (DMS)
  • 16 to 18 %  reduction in symptoms and need for additional medications vs, placebo


  • Most commonly reported adverse reactions: Nausea, itching in the ears and mouth, and swelling of the lips and tongue
  • Boxed warning: Severe  allergic reactions


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levita magnetics

LEVITA Magnetic Surgical System

Levita Magnetics International Corp, San Mateo, CA, USA

INDICATION FOR USE: Designed to grasp and retract the body and the fundus of the gallbladder in laparoscopic cholecystectomy procedures to facilitate access and visualization of the surgical site. The device is indicated for use in patients within a BMI range of 20 to 34 kg/m2

REG PATHWAY: De Novo request

  • Regulation Number: 21 CFR 878.4815
  • Regulation Name: Magnetic Surgical Instrument System
  • Regulatory Classification: Class II
  • Product Code: PNL


Prescription device used in laparoscopic surgical procedures consisting of several components, such as surgical instruments, and a magnetic controller

Magnetic controller is provided separately from the surgical instrument and is used outside the patient

External magnetic controller is magnetically coupled with the internal surgical instrument(s) at the surgical site to grasp, hold, retract, mobilize or manipulate soft tissue and organs.


  • Tissue Damage: In vivo Performance Testing,Human Factors Testing and Analysis, Training, Labeling
  • Need for Extended or Additional Surgery:In vivo Performance Testing, Non-clinical Performance Testing,Human Factors Testing and Analysis, Training, Labeling
  • Abdominal Wall Injury: In vivo Performance Testing, Human Factors Testing and Analysis, Labeling
  • Electromagnetic Field Incompatibility or Interference: Non-clinical Performance Testing, Human Factors Testing and Analysis, Training, Labeling
  • Adverse Tissue Reaction: Biocompatibility testing
  • Infection: Sterilization Validation, Reprocessing Validation, Shelf Life Validation, Labeling


FDA News: Prescription Drug Advertising, Women’s Heart Health Research, Neurovascular Catheters, FDA Vault, US-EU Mutual Recognition

FDA BRIEF: Week of February 27, 2017

Photo of Kathryn Aikin, Office of Prescription Drug Promotion, Understanding the Influence of Prescription Drug Advertising

Understanding the Influence of Prescription Drug Advertising

By: Kathryn Aikin, Ph.D., Senior Social Science Analyst and Research Team Lead, Office of Prescription Drug Promotion, Office of Medical Policy, CDER.

CDER’s Office of Prescription Drug Promotion (OPDP)

  • Ensures prescription drug marketing is truthful, balanced, accurately communicated
  • Upholds Guidance for Industry on Consumer-directed Broadcast Advertisements, 1999
  • Communication of important risk information and consumer sources  for  prescribing and risk information for the drug

OPDP Research 

  • Evaluate Direct-to-Consumer (DTC) Ads: Provide science-based information, commitment to public health, social science data  to inform regulatory actions
  • Social Science Research : Focus questions, methods, findings, effects of DTC ads, print ads, broadcast ads, animation etc.


womens health alert - fda office of womens health

FDA’s Commitment to Women’s Heart Health Research

By: Marsha B. Henderson, MCRP, Assistant Commissioner for Women’s Health

Marsha Henderson

Research on cardiovascular diseases in women and drug effects women’s heart health

  • Connection between certain drugs and Torsade de Pointes (TdP) and QT prologation
  • Evaluation of better ways to screen drugs for their potential to cause TdP
  • Understanding mechanism of sex differences
  • Developing FDA Guidance on QT prolongation assessment, Thorough QT (TQT) study
  • Improving predictive accuracy of drug’s potential for heart rhythm problem early in development

FDA QT Story GraphicREAD

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Neurovascular Thrombus Retrieval Catheters and Neurovascular Guide Catheters

 Used During Neurological Interventional Procedures

  • 510(k) premarket review and cleared indications are significantly different with differences in device design
  • Differences in FDA Review and Intended Use
Thrombus Retrieval Catheters Guide Catheters
Product Code: NRY  Product Code: DQY
Indications: Typically cleared with the indication for restoring blood flow or removal of thrombus within a blood vessel in the brain during an acute ischemic stroke within 8 hours of symptom onset in patients who are ineligible for or fail intravenous tissue plasminogen activator (IV t-PA) therapy. Indications: Typically cleared with the indication of introducing interventional devices into the neurovasculature or as a conduit for retrievers.
Performance Data: Typically, clearance of neurovascular thrombus retrieval catheters for this type of indication is based on non-clinical (e.g., bench and animal) performance data and, when necessary, clinical performance data. CDRH reviews these data to evaluate the ability of the device to safely navigate into the tortuous neurovasculature in close proximity to the thrombus and remove the thrombus to revascularize the blood vessel. Performance Data: Typically, clearance of neurovascular guide catheters for this type of indication is based on bench performance data to support the use of the catheter for the introduction of other interventional devices. Review of animal or clinical data is usually not required. In addition, neurovascular guide catheters are not reviewed for use in aspiration within the vessel for removing thrombus.


Opening the FDA’s History Vault

By Suzanne Junod, Ph.D., and John Swann, Ph.D.,  FDA Historians

Video Link

Suzanne Junod and John Swann

  •  > 10,000 artifacts on nation’s oldest public health agencies
  • Inform, explain, and educate for future decision making
  • Includes deceptive and dangerous foods, medicines, and so-called medical product -sample of Elixir Sulfanilamide, can of Bon Vivant vichyssoise soup, Dalkon Shield intrauterine device, Relaxicisor
  • Tells story of the origins of  laws and regulations
  • Adoption of new technology
  • Hiring of women to be human “computers”
  • Monthly video series


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Mutual Recognition promises new framework for pharmaceutical inspections for United States and European Union

Pharmaceutical Annex to the 1998 U.S.-EU Mutual Recognition Agreement

  • U.S. and EU regulators able to utilize each other’s GMP  inspections of pharmaceutical manufacturing facilities
  • Avoid the duplication of drug inspections, lower inspection costs
  • Enable regulators to devote more resources to higher risk other parts of the world



FDA – Office of Translational Sciences

Whats new in regulatory science

Office of Translational Sciences (OTS) – CDER

Promotes and Protects Public Health by:

  • scientific collaboration and innovation in drug regulatory review
  • validity of clinical trial design and analysis
  • quantitative and statistical approaches to decision making
  • alignment of CDER research with CDER goals
  • establishing technology transfer agreements
  • knowledge management databases
  • bioequivalence inspections


Office of Biostatistics

Office of Computational Science

Office of Clinical Pharmacology

Office of Study and Integrity and Surveillance


FDA Patient Representative Program

FDA Patient Representative Programpatient

Managed by Office of Health and Constituent Affairs, Office of Commissioner

FDA Patient Representatives

  • knowledgeable and experienced in over 300 diseases and conditions
  • participate in FDA Advisory Committees and panels, review division meetings
  • provide direct input to inform decision-making for drugs, biologics, and devices


Role of the FDA Patient RepresentativeCriteria for Becoming a FDA Patient RepresentativeConflict of InterestFrequently Asked Questions