FDA BRIEF: Week of April 17, 2017

FDA approved


RENFLEXIS (infliximab-abda) intravenous infusion

Samsung Bioepis Co., Incheon, Republic of Korea


  • Crohn’s Disease
  • Pediatric Crohn’s Disease
  • Ulcerative Colitis
  • Rheumatoid Arthritis
  • Ankylosing Spondylitis
  • Psoriatic Arthritis
  • Plaque Psoriasis

REG PATHWAY: Biosimilar to REMICADE (infliximab)

  • Biological product approved based on showing high similarity to  reference product (infliximab)
  • No clinically meaningful differences in safety and effectiveness from reference
  • Only minor differences in clinically inactive components






Philips Medical Systems, Nederland B.V.


Automated digital slide creation, viewing, and management system. The PIPS is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue.

The PIPS is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens.

The PIPS comprises the Image Management System (IMS), the Ultra Fast Scanner (UFS) and Display. The PIPS is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy.

It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS.


  • First authorized whole slide imaging system
  • Enables pathologists to read tissue slides digitally in order to make diagnoses
  • Streamlined slide storage and retrieval system

REG PATHWAY: De Novo request

  • Regulation Number: 21 CFR 864.3700
  • Regulation Name: Whole Slide Imaging System
  • Regulatory Classification: Class II
  • Product Code: PSY

GENERIC DEVICE TYPE: Whole Slide Imaging System

Automated digital slide creation, viewing, and management system intended as an aid to the pathologist to review and interpret digital images of surgical pathology slides. The system generates digital images that would otherwise be appropriate for manual visualization by conventional light microscopy.


  • Inaccurate or missing results leading to, for example, incorrect diagnosis: General and Special Controls
  • Delayed results: General and Special Controls



GAMMACORE Non-invasive Vagus Nerve Stimulator

electroCore, LLC, Basking Ridge, NJ, USA

INDICATION FOR USE:  To provide noninvasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore device is indicated for the acute treatment of pain associated with episodic cluster headache in adult patients.

REG. PATHWAY: De Novo Request

  • Regulation Number: 21 CFR 882.8592
  • Regulation Name: External vagal nerve stimulator for headache
  • Regulatory Classification: Class II
  • Product Code: PKR

GENERIC DEVICE TYPE: External vagal nerve stimulator for headache

Prescription device used to apply an electrical current to a patient’s vagus nerve through electrodes placed on the skin for the treatment of headache.


  • Adverse tissue reaction resulting from patient contacting components:  Biocompatibility evaluation, Labeling
  • Electrical shock injury from device failure: Electrical safety, thermal, and mechanical testing, Software verification, validation, and hazard analysis, Labeling
  • Stimulation side effects such as Seizure, Cardiac side effects, Worsening of headache: Labeling
  • Ineffective therapeutic response due to device failure: Non-clinical performance testing, Software verification, validation and hazard analysis, Labeling
  • User error: Labeling



FDA Research on Health Disparities

Health Disparities refer to differences in the health status of different groups of people

  • May affect disease frequency, severity, mortality among certain groups
  • Exist for conditions, including HIV/AIDS, hepatitis, diabetes, cancer, heart disease
  • Racial and ethnic minorities may be more likely to have disparities

Office of Minority Health (OMH) Research and Collaboration program strengthening the FDA’s ability to identify and address these disparities

  • Fund scientific research in academia
  • Advance student fellowships on understanding of health
  • Focus on consumer communication, FDA-academia collaboration on how to improve the health literacy and cultural competence



FDA BRIEF: Week of April 10, 2017

FDA approved

INGREZZA (valbenazine) capsules

Neurocrine Biosciences, San Diego, CA

INDICATION:  Treatment of adults with tardive dyskinesia


  • Neurological disorder characterized by repetitive involuntary movements
  • Can be disabling and can further stigmatize patients with mental illness
  • Serious side effect seen in patients antipsychotic medications
  • First drug for the treatment


  • Fast Track, Priority Review and Breakthrough Therapy designations.
  • Postmarketing Requirements: In vitro studies, PK studies,  clinical dependence and withdrawal symptom assessment study

MECHANISM OF ACTION: Reversible inhibition of vesicular monoamine transporter 2 (VMAT2) that regulates monoamine uptake from cytoplasm to synaptic vesicle for storage and release


  • Randomized, double-blind, placebo-controlled trial, n=234,  patients with moderate to severe tardive dyskinesia, INGREZZA vs. placebo, 6 weeks, then on INGREZZA for 48 weeks
  • Primary efficacy measure: Abnormal Involuntary Movement Scale (AIMS) change from baseline
  • AIMS change  statistically significantly different from placebo; consistent across multiple subgroups


  • Serious side effects: Sleepiness, QT prolongation.





FDA News: Organs-on-Chips, Autism Therapy, America’s got Regulatory Talent, Class I Exempt Device Listing

FDA BRIEF: Week of April 10, 2017

‘Organs-on-Chips’ Technology: FDA Testing Groundbreaking Science

By: Suzanne Fitzpatrick, Ph.D., Senior Advisor for Toxicology, CFSAN

Emulate Chip

Creating human organ systems in miniature on micro-engineered chips

  • Flexible polymer organ-chips contain tiny channels lined with living human cells and are capable of reproducing blood and air flow just as in the human body
  • First developed to evaluate the effectiveness of drugs
  • Potentially useful technology to ensure food

Public-Private Collaboration

  • Universities- Harvard, MIT
  • Emulate founded by researchers at the Wyss Institute for Biologically Inspired Engineering, Harvard University


 Autism: Beware of Potentially Dangerous Therapies and Products

There is no cure for autism

  • Products or treatments claiming to “cure” autism do not work as claimed
  • Same true of products claiming to “treat” autism or autism-related symptoms
  • Some may carry significant health risks
  • Examples: Chelation Therapies,  Hyperbaric Oxygen Therapy, Detoxifying Clay Baths, various products, including raw camel milk and essential oils

FDA guidance on products with improper claims about intended use

  • Be suspicious of products that claim to treat a wide range of diseases
  • Personal testimonials are no substitute for scientific evidence
  • Few diseases or conditions can be treated quickly, so be suspicious of any therapy claimed as a “quick fix.”
  • So-called “miracle cures,” which claim scientific breakthroughs or contain secret ingredients, may be a hoax


 America’s Got Talent – Regulatory Science Style

By: Stephen Ostroff, M.D., Acting FDA Commissioner

America's Got Regulatory Science EventStudents compete by presenting their proposed solutions to a current challenge in regulatory science

  • University of Maryland’s Center of Excellence in Regulatory Science and Innovation (CERSI)
  • University of Rochester’s Clinical and Translational Science Institute (CTSI)

The students identify the needs by consulting eight priority areas identified in FDA’s Strategic Plan for Regulatory Science

  • Judged quality and novelty
  • Proposed solution’s potential significance and feasibility
  • Winning teams come to FDA to formally present ideas and have discussions with Agency scientists


List of Class I Exempt Devices

List of class I devices that are now exempt from premarket notification requirements

  • In accordance with procedures established by the 21st Century Cures Act
  • Will decrease regulatory burdens on the medical device industry
  • Will eliminate private costs and expenditures required to comply with certain Federal regulation



FDA News: Drug Development Future, IBS Treatments, Cosmetics vs. Drugs/Devices

FDA BRIEF: Week of April 3, 2017


Future of Drug Development

Future Drivers:

  • International regulatory convergence
  • Advanced manufacturing
  • Rise of biosimilars
  • New science and technology
  • Digital revolution
  • Drug costs



Irritable Bowel Syndrome Treatments Aren’t One-Size-Fits-All

Irritable bowel syndrome (IBS) often misunderstood and underdiagnosed condition

  • Affects about 15.3 million people in US
  • Difficult to diagnose in children- 14% of high school students and 6% of middle school students have IBS
  • No approved medications to cure IBS
  • No approved medications for treating IBS symptoms in children
  • Treatments vary from patient to patient and include changes in diet, nutrition, exercise
  • Drugs are a last option


A girl giving her friend a manicure


Cosmetics vs Drugs and Medical Devices: Q&A

Are all “personal care products” regulated as cosmetics?

  • Products intended to cleanse or beautify are generally regulated as cosmetics
  • Products intended to treat or prevent disease, or affect the structure or function of the body, are drugs : dandruff or acne products, sunscreen products, antiperspirants, and diaper ointments
  • Some are both cosmetics and drugsanti-dandruff shampoos and antiperspirant-deodorants, moisturizers and makeup with SPF
  • Some may belong to other categories: medical devices (hair removal and microdermabrasion devices), dietary supplements (vitamin, mineral tablets,  capsules), consumer products (manicure sets).

Are some drugs or “cosmeceuticals”?

  • Law does not recognize any such category




FDA BRIEF: Week of April 10, 2017

FDA approved

TAGRISSO™ (osimertinib) logo

TAGRISSO (osimertinib) Tablet

AstraZeneca Pharmaceuticals, Wilmington, DE, USA

INDICATION: Treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.


  • Accelerated NDA approval in November 2015 for this indication
  • Fast Track, Breakthrough Therapy Designation, Orphan Drug Designation for  treatment of EGFR mutation-positive NSCLC


  • Single randomized, multicenter open-label, patients with metastatic EGFR T790M mutation-positive NSCLC (identified by the cobas® EGFR mutation test), n=279, TAGRISSO vs.  platinum-based doublet chemotherapy  until intolerance to therapy, disease progression, or investigator determination of no benefit
  • Major efficacy outcome measure: Progression-free survival (PFS) per RECIST v1.1; Other- Objective Response Rate (ORR), Duration of Response (DOR)
  • Median PFS in months (95% CI):  10.1 (8.3, 12.3) vs. 4.4 (4.2, 5.6), p<0.001
  • Confirmed ORR: 65% (95% CI: 59%, 70%) vs. 29% (95% CI: 21%, 37%)
  • Median DOR:  11 months (95% CI: 8.6, 12.6) vs. 4.2 months (95% CI: 3.9, 5.9)
  • Confirmed CNS ORR: 57% (95% CI: 37%, 75%) vs. 25% (95% CI: 7%, 52%)


  • Most serious adverse reactions: Interstitial lung disease/pneumonitis, QTc interval prolongation, cardiomyopathy, keratitis
  • Most common adverse reactions: Diarrhea, rash, dry skin, nail toxicity, and fatigue


Image result for austedo images

AUSTEDO (deutetrabenazine) tablets

Teva Pharmaceuticals, North Wales, PA, USA

INDICATION: Treatment of chorea associated with Huntington’s disease

REG PATHWAY: NDA, Orphan Drug Designation

  • First approval of deuterated drug

MECHANISM OF ACTION: Major circulating metabolites  are reversible inhibitors of a vesicular monoamine transporter 2(VMAT2), resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.


  • Single randomized, double-blind, multi-center trial, ambulatory patients with manifest chorea associated with Huntington’s disease, n=90, AUSTEDO vs placebo for 12 weeks
  • Primary efficacy endpoint: Total Maximal Chorea Score, an item of the Unified Huntington’s Disease Rating Scale (UHDRS)
  • Score Improvement: 4.4 units vs. 1.9 units (p<0.0001); at Week 13 follow-up visit (1 week after discontinuation of the study medication), Scores of patients who had received AUSTEDO returned to baseline


  • Boxed Warning: Depression and Suicidality
  • Adverse Reactions: Neuroleptic Malignant Syndrome,  Akathisia, Agitation, and Restlessness, Parkinsonism, Sedation and Somnolence, QTc Prolongation, Hyperprolactinemia, Binding to Melanin-Containing Tissues


Product picture


Qiagen, Manchester, UK


For qualitative in vitro diagnostic test for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from EDTA whole blood. The ipsogen JAK2 RGQ PCR Kit is a real time PCR test performed on the QIAGEN Rotor-Gene Q MDx instrument.

The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, in conjunction with other clinicopathological factors.

This test does not detect less common mutations associated with Polycythemia Vera including mutations in exon 12 and is not intended for stand-alone diagnosis of Polycythemia Vera

REG PATHWAY: De Novo Request

  • Regulation Number: 21 CFR 866.6070
  • Regulation Name: Mutation detection test for myeloproliferative neoplasms
  • Regulatory Classification: Class II
  • Product Code: PSU

GENERIC DEVICE TYPE: Mutation detection test for myeloproliferative neoplasms

In vitro diagnostic device intended for the detection of the JAK2 V617F/G1849T allele in genomic DNA extracted from whole blood. The test is intended for use as an adjunct to evaluation of suspected Polycythemia Vera, in conjunction with other clinicopathological factors.


  • False Negative and False Positive Results; Special Controls


Image result for 23andMe Personal Genome Service (PGS) Test

23andMe Personal Genome Service (PGS) Test

23andMe, Inc, Mountain View, CA, USA

INDICATION FOR USE: Uses qualitative genotyping to detect the following clinically relevant variants in genomic DNA isolated from human saliva collected from individuals ≥18 years with the Oragene Dx model OGD-500.001 for the purpose of reporting and interpreting Genetic Health Risks (GHR) but does not describe a person’s overall risk for developing disease or condition.

PGS Genetic Health Risk Report for:

  • Hereditary Thrombophilia is indicated for reporting of the Factor V Leiden variant in the F5 gene, and the Prothrombin G20210A variant in the F2 gene
  • Alpha-1 Antitrypsin Deficiency is indicated for reporting of the PI*Z and PI*S variants in the SERPINA1 gene
  • Late-onset Alzheimer’s Disease is indicated for reporting of the ε4 variant in the APOE gene
  • Parkinson’s Disease is indicated for reporting of the G2019S variant in the LRRK2 gene and the N370S variant in the GBA gene
  • Gaucher Disease Type 1 is indicated for reporting of the N370S, 84GG, and V394L variants in the GBA gene
  • Factor XI Deficiency is indicated for reporting of the variants F283L, E117X, IVS14+1G>A in the F11 gene
  • Celiac Disease is indicated for reporting of a variant associated with the HLA-DQ2.5 haplotype
  • Glucose-6-Phosphate-Dehydrogenase Deficiency is indicated for reporting of the Val68Met variant in the G6PD gene
  • Early-Onset Primary Dystonia (DYT1/TOR1A-Related) is indicated for reporting of the deltaE302/303 variant in the DYT1 gene
  • Hereditary Hemochromatosis is indicated for reporting of the C282Y and H63D variants in the HFE gene

REG PATHWAY: De Novo Request

  • Regulation Number: 21 CFR 866.5950
  • Regulation Name: Genetic Health Risk Assessment System
  • Regulatory Classification: Class II
  • Product Code: PTA

Exemption of additional 23andMe GHR tests from premarket review

Exemption of GHR tests from other makers after first premarket notification.

GENERIC DEVICE TYPE: Genetic Health Risk Assessment System

  • Qualitative in vitro molecular diagnostic system used for detecting variants in genomic DNA isolated from human specimens that will provide information to users about their genetic risk of developing a disease to inform lifestyle choices and/or conversations with a healthcare professional.
  • This assessment system is for over-the-counter use.
  • This device does not determine the person’s overall risk of developing a disease


  • Incorrect understanding of the device and test system: General controls and special controls
  • Incorrect test results (false positives, false negatives): General controls and special controls
  • Incorrect interpretation of test results General controls and special controls





VIBERZI Drug Safety Podcast

FDA Logo, hands holding pills

Viberzi (eluxadoline) Safety Podcast

FDA review shows increased risk of serious pancreatitis in patients without a gallbladder

  • Prescribed to treat irritable bowel syndrome with diarrhea (IBS-D)
  • Patients, without a gallbladder, have increased risk of developing serious pancreatitis that could result in hospitalization or death
  • Pancreatitis caused by spasm of certain digestive system muscle in the small intestine
  • FDA working with manufacturer, Allergan, to address safety concerns