Market Authorizations: HIZENTRA, ADCETRIS, ILUMYA, ACUMEN Software


HIZENTRA, Immune Globulin Subcutaneous (Human), 20% Liquid

CSL Behring

SUPPLEMENTAL INDICATION: Treatment of adult patients with chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment.
Limitations of Use: HIZENTRA maintenance therapy in CIDP has been systematically studied for 6 months and for a further 12 months in a follow-up study. Maintenance therapy beyond these periods should be individualized based upon the patient’s response and need for continued therapy


  • Serious nature of CIDP
  • Clinically clinically meaningful benefits in neurologic function


  • Multicenter, double-blind, randomized, placebo-controlled, parallel-group,  2 different weekly doses of HIZENTRA vs. placebo, n=172
  • Main endpoint: % subjects who had CIDP relapse or withdrawn from study
  • Superiority over placebo: 32.8% for 0.4 g/kg HIZENTRA and 38.6% for 0.2 g/kg HIZENTRA, p<0.001 or p=0.007, respectively


  • Compare favorably to the known and observed risks of Hizentra, which include local infusion site reactions, hypersensitivity reactions, aseptic meningitis, headache, etc., and the remote theoretical risk of adventitious infectious agent transmission


  • First approved in 2010 for  primary humoral immunodeficiency (PI)


  • Medicare, Medicaid, and most insurers cover Hizentra for PI
  • Covered as Medicare Part B benefit with claims considered for payment by the four regional Durable Medical Equipment Medicare Administrative Contractors (DME MACs). Medicaid coverage policy varies by state, payer and provider contract
  • Coverage for supplemental indication: TBD



 ADCETRIS (brentuximab vedotin)

Seattle Genetics, Inc.

INDICATION: Treatment of adult patients with previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with chemotherapy


  • 8,260 people in US diagnosed with Hodgkin lymphoma in 2016; 1,070 patients with non-Hodgkin lymphoma died from disease in 2017
  • Improvement in initial treatment regimens of advanced Hodgkin lymphoma
  • Advancements in treatment that give prescribers and patients different options for care

MECHANISM OF ACTION: Combines antibody and drug, allowing the antibody to direct the drug to a target on lymphoma cells known as CD30.


  • Open label, 2 arm trial, Clinical trial comparing Adcetris plus chemotherapy vs. chemotherapy-only regimen common for cHL treatment, n=1,334 patients
  • Primary endpoint: Modified progression-free survival (mPFS)
  • Patients treated with Acteris + chemotherapy were 23% less likely to experience progression, death, or initiation of new therapy


  • Boxed Warning: Risk of John Cunningham virus infection resulting in progressive multifocal leukoencephalopathy, or PML
  • Serious risks: Perpheral neuropathy; anaphylaxis or infusion-site reactions; hematologic, pulmonary and hepato-toxicities; serious or opportunistic infections; tumor lysis syndrome; serious dermatologic reactions and gastrointestinal complications
  • Common side effects: Neutropenia, anemia, peripheral neuropathy, nausea, fatigue, constipation, diarrhea, vomiting and fever (pyrexia)


  • Previously approved in 2011 to treat cHL after relapse, cHL after stem cell transplant when a patient is at a high risk of relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after failure of other treatment, and primary cutaneous ALCL after failure of other treatment
  • This application granted Priority Review and Breakthrough Therapy designations


  • Payor coverage when determined to be medically necessary by meeting predefined medical criteria and guidelines


CaptureILUMYA ( (tildrakizumab-asmn) injection, for subcutaneous use

Merck and Sun Pharma

INDICATION:  Treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy

MECHANISM OF ACTION: Humanized IgG1/k monoclonal antibody that selectively binds to the p19 subunit of IL-23 and inhibits release of proinflammatory cytokines and chemokines


  • Two multicenter, randomized, double-blind, placebo-controlled trials, n= 926, ILUMYA vs. placebo. Subjects had Physician Global Assessment (PGA) score of ≥3 moderate) on a 5-point scale of overall disease severity, Psoriasis Area and Severity Index (PASI) score ≥12, and a minimum body surface area (BSA) involvement of 10%
  • Improvement in psoriasis-related parameters


  • May increase the risk of infection
  • Adverse reactions: Upper respiratory infections, injection site reactions, diarrhea


  • Required pediatric assessments
  • Postmarket requirements:  Registry-based observational exposure cohort study on maternal, fetal, and infant outcomes of women,  retrospective cohort study using claims or electronic medical record to assess major congenital malformations,  spontaneous abortions, stillbirths etc, observational study of long-term safety



ACUMEN Hypotension Prediction Index (HPI) Feature Software

Edwards Lifesciences

INDICATION FOR USE: Provides the clinician with physiological insight into a patient’s likelihood of future hypotensive events (defined as mean arterial pressure < 65 mmHg for at least one minute in duration) and the associated hemodynamics.

The Acumen HPI feature is intended for use in operating room (OR) patients receiving advanced hemodynamic monitoring. The Acumen HPI feature is considered to be additional quantitative information regarding the patient’s physiological condition for reference only and no therapeutic decisions should be made based solely on HPI parameter.

GENERIC DEVICE TYPE: Adjunctive predictive cardiovascular indicator

  • Prescription device that uses software algorithms to analyze cardiovascular vital signs and predict future cardiovascular status or events. This device is intended for adjunctive use with other physical vital sign parameters and patient information and is not intended to independently direct therapy.


  • Delayed or incorrect treatment due to erroneous device output resulting from software malfunction or algorithm error : Software verification, validation, and hazard analysis, Non-clinical performance testing, Clinical performance testing,  Labeling
  • Delayed or incorrect treatment due to user misinterpretation or over-reliance on indicator: Usability assessment, Labeling


  • Software description and the results of verification and validation testing based on a comprehensive hazard analysis and risk assessment
  • Scientific justification for the validity of predictive cardiovascular indicator algorithm(s);  verification of algorithm calculations and validation using an independent data set
  • Human factors and usability engineering assessment to evaluate risk of misinterpretation of device output
  • Clinical data assessment
  • Labeling


  • Regulation Number: 21 CFR 870.2210
  • Regulation Name: Adjunctive predictive cardiovascular indicator
  • Regulatory Class: Class II
  • Product Code: QAQ

REIMBURSEMENT: Will initiate a targeted launch of this first-of-its-kind technology


Image credit: CSL Behring, Seattle Genetics, Merck/Sun, Edwards

FDA News: Breast Implants Risk, Prevent Illegal Products entering US, Lead Testing Issues

Capture.JPGFDA updates public information about known risk of lymphoma from breast implants

FDA identified possible association between breast implants and anaplastic large cell lymphoma (ALCL) in 2011

  • Gathering information to better characterize and quantify risk
  • Updating total number of known cases of BIA-ALCL and lifetime risk of developing BIA-ALCL

Reporting 414 total cases of BIA-ALCL

  • Lifetime risk of developing BIA-ALCL for patients with textured breast implants ranges from 1 in 3,817 to 1 in 30,000.

Does not change the agency’s recommendations regarding breast implants

  • Choosing breast implant is personal decision
  • Decision on individual needs and with the most complete information about risks and benefits


Capture.JPGFDA Using Innovative Methods to Prevent Illegal Products with Hidden Drug Ingredients from Entering US 

FDA closely monitor’s products arriving at the nation’s international mail facilities

  • Increasingly challenging task given high volume (>275 million packages/yr)
  • Deploy advanced screening technologies to screen packages more efficiently and reliably

Successful six-month pilot with portable screening device – ion mobility spectrometer

  • Compares chemical signature of unknown substance against chemical signatures of known compounds in less than 30 seconds
  • 65% samples tested positive for undeclared pharmaceutical ingredients – results confirmed in FDA laboratory
  • Developing opioid screening method for the device


Capture.JPG FDA’s findings from ongoing investigation into lead testing issues

Warning in 2017 about inaccurate lead tests by Magellan Diagnostics

  • Aggressively investigated problem
  • Becton Dickinson (BD) & Company, the manufacturer of blood sample collection tubes also investogated

Assessment of accuracy of Magellan’s LeadCare when used with blood collected into BD tubes

  • Significant chance of false results with tubes with rubber stoppers containing  thiuram
  • Can release sulfur-containing gases that dissolve into blood samples and bind tightly to lead particles

BD recalls EDTA Blood Collection Tubes Due to Chemical Interference with Certain Tests


Image credits: FDA, BD



FDA working with manufacturers to withdraw Zinbryta from market

 Zinbryta approved in 2016

  • Relapsing forms of multiple sclerosis

Biogen and partner AbbVie voluntarily withdrawing  marketing application globally

  • Reported cases of encephalitis and meningoencephalitis
  • Nature/complexity of adverse events affects and limited number of patients being treated prevents adequate characterization of evolving benefit/risk profile
  • Withdrawal in the best interest of patients

Working closely with FDA and global regulatory authorities on  withdrawal timelines 

  • European Medicines Agency announced recall following 12 reports of serious inflammatory brain disorders worldwide



Bayer’s voluntary recall of Alka-Seltzer Plus products due to labeling errors

Recall due to labeling errors

  • Ingredients listed on carton front sticker may be different from back AND product in carton
  • May lead consumers to ingest ingredient to which they are allergic to or  ciuld have serious health consequences




Warning Letter: OPTERNATIVE Eye Examination Mobile Medical App 

Product is ‘device’

  • Intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body

Violation of the Federal Food, Drug, and Cosmetic Act 

  • FDA review of website
  • ADULTERATION: No approved application for premarket approval
  • MISBRANDING: No FDA notification of intent to commercialize

2016 FDA meeting on regulatory requirements

  • Meeting with Office of Compliance and Office of Device Evaluation
  • Requirement of premarket submission to evaluate safety and effectiveness

If failure of prompt action to correct violations

  • FDA initiated action without further notice
  • Seizure, injunction, civil money penalties


Image credits: FDA, Biogen, Opternative


Market Authorizations: MASTERS heart valve for newborns, 23andMe PGS for BRCA1/BRCA2, TROGARZO, IMUGEN Fluorescent Immunoassay, SKINPEN



SJM Masters Series Mechanical Heart Valve with Hemodynamic Plus (HP) Sewing Cuff

St. Jude’s Medical (Abbott)

INDICATION FOR USE: Use as a replacement valve in newborn pediatric patients with a diseased, damaged, or malfunctioning mitral or aortic heart valve


  • Smallest mechanical valve size approved in the world
  • > 35,000 babies in U.S. born with congenital heart defects, requiring heart valve surgery, replacement heart valve surgery
  • Limited replacement heart valve options because of patients’ small size
  • Masters Series 15-mm HP valve represents important treatment option


  • Rotatable, bileaflet (two-leaflet) valve designed for implantation in the aortic or mitral position
  • Bileaflet design consists of two semi-circular discs
  • Open and close in response to blood pressure changes during the heartbeat
  • Similar to a patient’s own valve


  • Single-arm study (N=20) Age 1.5 weeks to 27 months, serious heart failure
  • Probability of survival post-implant:  69.3%
  • Probability of not experiencing a valve-related adverse event: 66.8%
  • Adverse events in 1 year followup: Blood clots in the device, bleeding in the brain
  • Anticoagulation therapy may be necessary after procedure, to prevent clotting on the device


  • PMA initially approved in 1995 for use in adult patients
  • Also approved for use in replacing previously implanted aortic or mitral prosthetic heart valves
  • New approval expands range of valve sizes available


  • Considerations: Hospital Coding And Reimbursement (ICD-9, ICD-10), Inpatient Reimbursement (MS-DRG), Hospital Billing (FDA approved indication, diagnosis, condition, procedure)
  • Sponsor Coding information

Fact Sheet


Capture.JPG23andMe PGS Genetic Health Risk Report for BRCA1/BRCA2 



Personal Genome Service (PGS) uses qualitative genotyping to detect select cxlinically relevant variants in genomic DNA isolated from human saliva collected from individuals ≥18 years with the Oragene Dx model OGD500.001 for the purpose of reporting and interpreting genetic health risks, including 23andMe PGS Genetic Health Risk Report for BRCA1/BRCA2 (Selected Variants).

The 23andMe PGS Genetic Health Risk Report for BRCA1/BRCA2 (Selected Variants) is indicated for reporting of the 185delAG and 5382insC variants in the BRCA1 gene and 6174delT variant in the BRCA2 gene.

The report describes if a woman is at increased risk of developing breast and ovarian cancer, and if a man is at increased risk of developing breast cancer or may be at  increased risk of developing prostate cancer. The three variants included in this report are most common in people of Ashkenazi Jewish descent and do not represent majority of BRCA1/BRCA2 variants in the general population.

The test report does not describe a person’s overall risk of developing any type of cancer, and the absence of a variant tested does not rule out the presence of other variants that may be cancer-related. This test is not a substitute for visits to a healthcare provider for recommended screenings or appropriate follow-up and should not be used to determine
any treatments.


  • Provides information on increased breast, ovarian or prostate cancer risk to those who might not otherwise get genetic screening
  • Step forward in the availability of Direct-To-Consumer genetic tests

GENERIC DEVICE TYPE:  Cancer Predisposition Risk Assessment System for BRCA1/BRCA2 Select Variants

Qualitative in vitro molecular diagnostic system used for detecting variants in genomic deoxyribonucleic acid (DNA) isolated from human specimens that will allow users to access information about their genetic predisposition for some cancers.

The test could help to inform conversations with a healthcare professional. Assessment system is for over-the-counter use.


  • Sufficient data to show that the test is accurate (i.e., can correctly identify the three genetic variants in saliva samples), and can provide reproducible results
  • Accuracy> 99% concordance to Sanger sequencing
  • Precision> 99% reproducibility and repeatability
  • User comprehension studies, using representative GHR test reports
  • Instructions, reports easy to follow and understood by consumer
  • Test report provides information describing what results mean, interpret results and additional information


  • 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 


  • Regulation Number: 21 CFR 866.6090
  • Regulation Name: Cancer Predisposition Risk Assessment System for BRCA1/BRCA2 Select Variants
  • Regulatory Class: Class II
  • Product Code: QAZ


  • N/A. Non-prescription product


CaptureTROGARZO™ (ibalizumab-uiyk) injection

TaiMed Biologics USA Corp.

INDICATION:  In combination with other antiretroviral(s), is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen.


  • Multidrug resistant HIV patients have limited treatment options
  • High risk of HIV-related complications and progression to death
  • First drug in new class of antiretroviral medications to provide significant benefit to patients who have run out of treatment options; improve outcomes

DESCRIPTION: Recombinant humanized monoclonal antibody, blocks HIV-1 from infecting CD4+ T cells by binding to domain 2 of CD4 and interfering with post-attachment steps required for entry


  • Single arm, multicenter clinical trial, n=40 heavily treatment-experienced
    HIV-infected subjects with multidrug resistant HIV-1,  viral load >1,000 copies/mL
  • 3 discreet periods: Control, functional monotherapy period, maintenance period
  • Primary efficacy endpoint: Proportion of subjects achieving a ≥ 0.5 log10 decrease in viral load in functional monotherapy period vs control period
  • 83% (monotherapy period) vs. 3% (control period)
  • 55% had a ≥ 1 log10 reduction in viral load, 48% had a ≥ 2 log10 reduction
  • 43% achieved HIV RNA suppression


  • Seriousness of disease, need to individualize other drugs in treatment regimen, and safety data from other trials considered in evaluating Trogarzo development program
  • 292 patients with HIV-1 infection exposed to Trogarzo IV infusion
  • Most common adverse reactions: Diarrhea, dizziness, nausea and rash. Severe side effects included rash and changes in the immune system (immune reconstitution syndrome)


  • Fast Track, Priority Review and Breakthrough Therapy designations
  • Also received Orphan Drug
  • Several postmarketing requirements




Imugen Babesia microtiArrayed Fluorescent Immunoassay (AFIA)

Oxford Immunotec


Donor screening test to detect antibodies to Babesia microti in plasma samples from individual human donors, including volunteer donors of whole blood and blood components, as well as other living donors.

Also intended for use to screen organ and tissue donors when specimens are obtained while the donor’s heart is still beating


  • Babesiosis caused by Babesia parasites transmitted by Ixodes scapularis ticks (blacklegged or deer ticks)
  • 1,000 -2,000 cases reported each year
  • Babesia can also be transmitted by transfusion of blood
  • First approval of Babesia detection tests for use in screening donors


  • Priority review
  • Currently is no FDA guidance for the testing of donor samples for Babesia; planning to issue guidance

CBER Infectious disease tests


SkinPen Precision System

Bellus Medical, LLC

INDICATION FOR USE:  Microneedling device and accessories intended to be used as a treatment to improve the appearance of facial acne scars in adults aged 22 years or older

GENERIC DEVICE TYPE: Microneedling device for aesthetic use

Device using one or more needles to mechanically puncture and injure skin tissue for aesthetic use. This classification does not include devices intended for transdermal delivery of topical products such as cosmetics, drugs, or biologics.


  • Adverse tissue reaction: Biocompatibility evaluation, Labeling
  • Cross-contamination and infection: Sterilization validation, Reprocessing validation, Non-clinical performance testing, Shelf life testing, Labeling
  • Electrical shock or electromagnetic interference with other devices:  Electromagnetic compatibility testing, Electrical safety testing, Labeling
  • Damage to underlying tissue including nerves and blood vessels, scarring, and
    hyper/hypopigmentation due to (i) Exceeding safe penetration depth (ii) Mechanical failure (iii) Software malfunction: Non-clinical performance testing, Technological characteristics, Shelf life testing, Labeling, Software verification, validation, and hazard analysis


  • Regulation Number: 21 CFR 878.4430
  • Regulation Name: Microneedling device for aesthetic use
  • Regulatory Class: Class II
  • Product Code: QAI


  • CMS does not cover products for aesthetic use; not deemed to be medically necessary


Image Credits: Abbott, 23andMe, Taimed, Oxford Immunotec, Bellus Medical

FDA News: Predicting Stem Cell Activity, Essure Post-Market Review, CDER Regulatory Science Videos



 Predicting Stem Cell Activity to Ensure Safe and Effective Therapies

Human multipotent stromal cells (MSCs) being prepared for use as therapies to treat human diseases or medical conditions- but have serious limitations:

  • As of January 2018, no MSC-based clinical trials have resulted in FDA-approved treatments
  • Significant challenge in ensuring MSCs will work together to perform the same desired function when they are administered to patients

FDA scientists developing ways to improve predictability

  • FDA’s MSC Consortium  trying to develop methods to predict with more certainty how manufactured or isolated MSCs will behave in patients
  • Predict MSC behavior stimulated by growth factors
  • Powerful imaging technologies to monitor and analyze changes in size and shape of many thousands of cells in a matter of hours
  • Applicable to development and FDA approval of potential stem-cell based products


Capture.JPGFDA activities related to the ongoing post-market review of Essure and FDA’s commitment to keep women informed

Active role in providing Essure consumers with up-to-date, evidence-based information to help  informed medical decisions

  • Met with consumers affected by Essure, a method of permanent birth control
  •  >750,000 women worldwide have received implant
  • Some developed significant medical problems e.g.  abdominal pain, abnormal uterine bleeding, device migration

FDA Steps

  • Monitor product safety and effectiveness since approval in 2002
  • Convened medical experts panel n the fall of 2015 to provide advice on understanding concerns
  • Ordered manufacturer, Bayer, to conduct postmarketing study to better evaluate safety profile
  • Boxed Warning and Patient Decision Checklist added to labeling
  • Ongoing activities posted on  Essure website

FDA continues to believe that Essure may be appropriate for some women

  • Based on current information
  • Recognize serious problems associated with use
  • Consider regulatory options that appropriately balance benefits and risks based on new information
  • Continue to communicate publicly, share learnings, help women make informed decisions

Patient Decision Checklist



 CDER: Regulatory Science

CDER has launched new video series on major challenges in drug evaluation and development and how to address

Image credit: FDA

FDA News: Brain Implants, Rare Disease Day, Flu Vaccine Effectiveness, Duodenoscope Surveillance

FDA BRIEF: Week of February 26, 2018

Capture.JPGBrain Implant for Some Blind People Shows Benefits of FDA’s Breakthrough Device Program

FDA’s Breakthrough Devices Program is beginning to show important results

  • Second Sight Medical Products Inc.’s Orion Cortical Visual Prosthesis System
  • Early FDA interactions for flexible study design, review team support, and senior management engagement
  • Involved specialists across disciplines such as ophthalmology and neurology
  • Solved any potential stumbling blocks – e.g. measuring benefits/risks

Novel technology with novel way to evaluate benefits/risks of device

  • Mimics perception of light through miniature video camera worn by patient
  • Transmits signals to implant in their visual cortex
  • CDRH approved clinical trial involves five patients at two sites;  first patient received the implant on Jan. 30, 2018


Capture.JPGTaking new steps to  meet the challenges of rare diseases – FDA markets 11th Rare Disease Day

One out of every 10 Americans lives with at least one of more than 7,000 rare diseases

  • U.S. observes last day of February as Rare Disease Day
  • Raise awareness about rare diseases and their impact on patient’s lives
  • What more FDA can do to advance needs of patients and families

FDA incentives, approvals, trends

  • Orphan Drug Act financial and other incentives (1983)
  • Humanitarian Device Exemption regulatory path for devices (1990)
  • >650 therapies, 72 devices approved
  • Increasing emphasis on personalized medicine, including genetically targeted drug development

Modernization and new initiatives

  • Orphan Drug Designation Modernization Plan for more efficient process
  • Orphan Products Council to further address scientific and regulatory challenges
  • New Memorandum of Understanding with National Organization for Rare Disorders (NORD) to conduct outreach
  • Public meeting om changing landscape of orphan drug development

New Website



FDA’s ongoing efforts to help improve effectiveness of influenza vaccines

Working to determine the root causes

  • Collaborating with CMS to use large database with details of flu vaccine administered to four million individuals
  • Better understand less than optimal effectiveness with both cell-based and egg-based vaccines
  • Potential differences in outcomes between high-dose vs. normal dose

Looking ahead to 2018-2019 flu season

  • FDA advisory committee meeting March 1, 2018. to select strains, WHO recommendations
  • Apply learnings from this flu season


Capture.JPGDuodenoscope surveillance sampling and culturing

Duodenoscopes used to treat patients undergoing endoscopic retrograde cholangiopancreatography (ECRP)

  • Life-saving, least invasive way treating cancerous tumors, gallstones
  • > 500,000 ERCPs performed each year in US
  • Scopes are reused; if not thoroughly cleaned and disinfected, high risk of patient-to-patient infection.

FDA, CDC and ASM announced availability of voluntary, standardized duodenoscope surveillance sampling, culturing protocols

  • For hospitals and health care facilities
  • To further reduce risk of infection and increase safety of these medical devices


Image credit: FDA, CDC


Novel Materials and Manufacturing Research Program


Medical device materials undergo physical and chemical changes during total product life cycle (TPLC). Some examples:

  • chemical reactions, separation/purification, temperature excursions
  • microstructure changes, molding/extrusion, weaving
  • 3D printing

Novel Materials and Manufacturing Research Program elucidates 

  • TPLC findings
  • Relationship to Safety and Effectiveness (S&E) of device
  • How seemingly minor manufacturing changes can lead to S&E changes


Image credit: FDA

Market Authorizations: IMFINZI, VERZENIO


 IMFINZI (durvalumab) injection


EXPANDED INDICATION: Treatment of patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy


  • Lung cancer is the leading cause of cancer death in the United States, with an estimated 222,500 new diagnoses and 155,870 deaths in 2017
  • First treatment approved for stage III unresectable NSCLC
  • An approved therapy to keep the cancer from progressing for a longer time after chemoradiation


  • Randomized trial, n=713 patients whose cancer had not progressed after completing chemotherapy and radiation, IMFINZI vs. placebo
  • Major efficacy outcome: Progression-free survival (PFS) assessed by a BICR RECIST 1.1 and overall survival (OS)
  • PFS: 45% vs. 66%, p<0.0001



  • Common side effects:  Cough, fatigue, pneumonitis/radiation pneumonitis, upper respiratory tract infections, dyspnea, rash
  • Serious risks: Immune-mediated side effects, such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis


  • Priority Review, Breakthrough status
  • Postmarketing commitments: Overall Survival data, efficacy outcomes in subgroups defined by ADA binding and neutralizing status vs. control
  • Granted accelerated approval in 2017 for the treatment of locally advanced or metastatic bladder cancer


  • HCPCS Code: C9492, special coverage
  • CPT codes for infusion administration and home infusion


Capture.JPGVERZENIO (abemaciclib) tablets

Eli Lilly

EXPANDED 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

ADDRESSING UNMET NEED: Initial therapy for HR-positive, HER2-negative metastatic breast cancer


  • Randomized (2:1), double-blinded, placebo-controlled, multicenter clinical trial in postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, n=493, VERZENIO vs placebo on top of physician’s choice of letrozole or anastrozole
  • Primary endpoint: Progression-free survival (PFS) (RECIST 1.1): 28.2 mo. vs. 4.8 mo.,  p<0.0001


  • Most common adverse reactions:  Diarrhea, neutropenia, fatigue, infections, nausea, abdominal pain, anemia, vomiting, alopecia, decreased appetite, leukopenia



  • No Medicare coverage
  • Obtained through specialty pharmacies


Image credit: AstraZeneca, Eli Lilly 

FDA Guidances: Product Recalls, Device Clinical Data from ex-US studies, 510(k) Refusal to File Policies

CapturePublic Warning and Notification of Recalls

Recall: Removal of marketed product that considered to be in violation of FDA laws; Agency would initiate legal action. NOT the same as market withdrawal

Recall Determination:  FDA assessment FDA that ongoing or completed removal or correction of a marketed violative product constitutes a recall

Recall Classification: I, II, or III, assigned by FDA on basis of the health hazard

  • Class I: Could cause serious health problems or death
  • Class II: Might cause a temporary health problem
  • Class III: Unlikely to cause any adverse health reaction, violate FDA labeling or manufacturing laws

Public Warning:  Alert public that product being recalled presents a serious health hazard; for Class I recalls

Public Notification of Recalls: Weekly FDA Enforcement Report

FDA 101: Product Recalls



Acceptance of Clinical Data to Support Medical Device Applications and Submissions

FDA regulations on data acceptance from clinical investigations conducted outside US

  • Conform with good clinical practices (GCP)
  • Applies to clinical data submitted to support IDE, 510(k), De Novo, PMA, PDP, HDE

Conformity with GCP

  • Statements regarding conduct of clinical investigations
  • Special considerations for in vitro diagnostic (IVD) device investigations using leftover, de-identified biospecimens

Supporting Information, Waivers, Records



Refuse to Accept Policy for 510(k)

Minimum threshold of acceptability and acceptance for substantive review of 510(k)  

  • Submission is administratively complete, includes information necessary reach determination regarding substantial equivalence
  • Same intended use as predicate device
  • Same technological characteristics as predicate device – or- different technological characteristics
  • Appropriate clinical or scientific data to demonstrate safety and effectiveness
  • Does not raise different questions of safety and effectiveness than the predicate
  • Pre-Submission Interaction encouraged

Refuse to Accept Principles

  • Not based on substantive review of information
  • Justification for any alternative approach
  • Consideration of device-specific and cross-cutting guidances

Checklist provided


Image credit: FDA