Fraudulent COVID-19 Products

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Beware of Fraudulent Coronavirus Tests, Vaccines and Treatments

Americans sheltering at home to help “flatten the curve”  might be tempted to buy/use fraudulent products to help diagnose, treat, cure, and even prevent COVID-19

  • Vaccine and drug manufacturers  are working to develop new vaccines and treatments as quickly as possible
  • However, some companies are attempting to profit from pandemic by selling unproven and illegally marketed products that make false claims, such as being effective against the coronavirus

There Are No Vaccines or Medicines for COVID-19, Yet

Protect Yourself and Your Family From Coronavirus Fraud

LEARN


Image credit: FDA

COVID-19 FDA Guidances

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COVID-19-Related FDA Guidance Documents

  • Providing timely recommendations, regulatory information, guidance, and technical assistance necessary to support rapid response efforts
  • Anticipates to immediately implement  guidances
  • Will consider comments received and update as appropriate

Current List includes:

  • Manufacture of Alcohol for Alcohol-Based Hand Sanitizer Products
  • REMS Requirements
  • Ventilators and Accessories and Other Respiratory Devices
  • Non-Invasive Remote Monitoring Devices Used to Support Patient Monitoring
  •  Preparation of Certain Alcohol-Based Hand Sanitizer Products
  • Postmarketing Adverse Event Reporting
  • Conduct of Clinical Trials of Medical Products
  • Food Supplier Verification Onsite Audit Requirements
  • Diagnostic Tests
  • Temporary Compounding of Certain Alcohol-Based Hand Sanitizer Products

LEARN


 

COVID-19 Emergency Use Authorizations, Diagnostic Testing policy, N95 Respirators and Surgical Masks

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COVID-19 Emergency Use Authorizations (EUA) for Medical Devices and Diagnostics

EUA being granted as there is significant potential for public health emergency that can affect national security or the health and security 

  1. Personal Protective equipment
  2. Diagnostic tests

Personal Protective Equipment

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  • Disposable filtering facepiece respirators (FFRs) approved by the National Institute for Occupational Safety and Health (NIOSH)
  • FFRs that were NIOSH-approved but have since passed the manufacturers’ recommended shelf-life, for use in healthcare settings by healthcare personnel (HCP) to prevent wearer exposure to pathogenic biological airborne particulates

Diagnostic Tests

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  • Qualitative Real-Time RT-PCR test for qualitative detection of nucleic acid from SARS-CoV-2 in upper and lower respiratory specimens from individuals suspected of COVID-19 by their healthcare provider
  • Positive test result  indicates RNA detected, patient is infected and presumed to be contagious; patient management should follow current CDC guidelines
  • Negative test result means RNA was not present in specimen; does not rule out COVID-19 and should not be used as the sole basis for treatment or patient management decisions

READ


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Policy for Diagnostic Tests for COVID-19 during the Public Health Emergency 

Two policies for accelerating the development of certain laboratory tests for COVID-19

  1. EUA submission to FDA
  2. No EUA submission
    • When test is developed under State authorities and State takes responsibility for testing by laboratories
    • CLIA certified and meet requirements

Laboratories offering testing under Policy

  • AdventHealth
  • ARUP Laboratories
  • Assurance Scientific
  • Baylor Scott and White Medical Center – Temple
  • BioReference Laboratories
  • The Children’s Hospital of Philadelphia
  • Diatherix Eurofins
  • Emory Medical Laboratory, Emory Healthcare
  • Gravity Diagnostics
  • Henry Ford Health System
  • HMH Hackensack University Medical Center
  • Hospital of the University of Pennsylvania
  • Houston Methodist Hospital
  • Integrity Laboratories
  • Johns Hopkins Medical Microbiology Laboratory at Johns Hopkins Hospital
  • Montefiore Medical Center
  • New York Presbyterian Hospital -Weill Cornell Medicine (NYPH-WCM)
  • Next Bio-Research Services LLC
  • NYU Langone Medical Center
  • Quest Diagnostics Infectious Disease, Inc.
  • Stanford Health Care Clinical Laboratory
  • Texas Children’s Hospital Department of Pathology
  • TGen North, Clinical Laboratory
  • UCSF-Health
  • University of Washington
  • Viracor Eurofins Clinical Diagnostics

Other FAQs


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N95 Respirators and Surgical Masks (Face Masks)

FDA regulates surgical masks and surgical N95 respirators differently based on their intended use

  • Surgical mask : Loose-fitting, disposable device that creates physical barrier between mouth and nose of wearer and potential contaminants in the immediate environment. Edges of mask are not designed to form seal around nose and mouth
  • N95 respirator: Respiratory protective device designed to achieve very close facial fit and very efficient filtration of airborne particles; edges designed to form seal around the nose and mouth.

N95 Respirators not for public use 

READ


Image credit: FDA, CDC

Increased availability of NIOSH approved respirators to healthcare personnel

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FDA and CDC take action to increase access to respirators, including N95s, for health care personnel

FDA-CDC collaboration to prioritize access to needed medical products through Emergency Use Authorization (EUA) 

  • Certain industrial respirators during the COVID-19 outbreak in health care settings
  • Respirators approved by NIOSH, but not currently meeting the FDA’s requirements, that may be effective in preventing health care personnel from airborne COVID-19 exposure

EUA does NOT apply to the general American public

  • Should not wear these respirators to protect against COVID-19
  • No added health benefit

FDA information

CDC information


Image credit: FDA

COVID-19 News: New expedited diagnostic testing policy, New York SARS-CoV-2 diagnostic authorization, Medical product shortages, Misinformation about natural products

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Policy for COVID-19 Diagnostics Testing in Laboratories Certified to Perform High Complexity Testing under CLIA prior to Emergency Use Authorization 

Policy for novel COVID-19 molecular diagnostics tests developed and used in CLIA laboratories prior to FDA issuance of emergency use authorizations (EUA) 

  • Public health emergency circumstances requiring rapid diagnostic testing to control emergence
  • Rapid COVID-19 detection with accelerated policy enabling CLIA laboratories for more rapid testing capacity
  • Immediately in Effect guidance
  • Accelerated Emergency Use Authorization Template

READ

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New York SARS-CoV-2 Realtime Reverse Transcriptase (RT)-PCR Diagnostic Panel 

Wadsworth Center, New York State Department of Public Health 

INDICATION: Presumptive qualitative detection of nucleic acid from SARS-CoV-2 in  nasopharyngeal/oropharyngeal swabs and sputa collected from individuals who meet CDC COVID-19 clinical and/or epidemiological criteria

DIAGNOSTIC PANEL:

  • Human Specimen Control (HSC): A human cell culture preparation used as an extraction control and positive control for the RNase P primer and probe set that is extracted and tested concurrently with each specimen extraction run
  • SARS-CoV-2 Positive Control (SARS-CoV-2 Pos): Run with each batch of specimens. Monitors improper assay setup, reagent failures of rRT-PCR reagents and reaction conditions
  • No Template Control (NTC): Nuclease-free water included in each run. Monitors for reagent and system contamination
  • RNase P (RP) control in clinical samples: The RP primer and probe set is included in each run to test for human RNase P, which controls for specimen quality and demonstrates that nucleic acid was generated by the extraction process

REGULATORY PATHWAY: Emergency Use Authorization

  • SARS-CoV-2 can cause a serious or life-threatening disease or condition
  • Based on the totality of scientific evidence, reasonable to believe diagnostic panel may be effective in diagnosing COVID-19
  • There is no adequate, approved, and available alternative

Letter of Authorization

Fact Sheet


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COVID-19 Supply Chain Update

Outbreak would likely impact the medical product supply chain, including potential disruptions to supply or shortages of critical medical products in the U.S

  • Alert from a manufacturer about drug shortage due to disruption in China manufacturing
  • In contact with >180 manufacturers of human drugs
  • In contact with 63 manufacturers of essential medical devices
  • Preparing for increasing demand in personal protective equipment—surgical gowns, gloves, masks, respirator protective devices etc
  • Not aware of any cellular or gene therapies that are made in China
  •  No reports of transmission by food or food packaging

Proposals  to prevent or mitigate medical product shortages

  • Lengthen expiration dates
  • Require risk management plans
  • Improve data sharing and require more accurate supply chain information
  • Establish reporting requirements for device manufacturers

READ


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Image credits: FDA, NIH

Clinical Trial of Remdesivir to Treat COVID-19

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NIH (NIAID) Clinical Trial of Remdesivir to Treat COVID-19 Begins

Randomized, controlled clinical trial to evaluate the safety and efficacy of the investigational antiviral REMDESIVIR in hospitalized adults diagnosed with COVID-19 

  • Remdesivir is an investigational broad-spectrum antiviral treatment with previous testing for treatment for Eboila, MERS and SARS
  • Enrolling hospitalized adults with COVID-19 in Nebraska, Remdesivir vs placebo
  • Participants must have laboratory-confirmed SARS-CoV-2 infection and evidence of lung involvement with need for supplemental oxygen, abnormal chest X-rays, requiring mechanical ventilation
  • Will compare (vs. placebo) participant outcomes on day 15  on seven-point scale (fully recovered – death)

LEARN


Image credit: FDA and NIAID

News & Views: COVID-19 updates, Rare Disease efforts, Fraudulent DTC genetic tests & review, Stopping illicit medical products from India, Updated Insulin regulatory pathway, Directory for approved drugs (since 1985)

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FDA’s Actions in Response to 2019 Novel Coronavirus at Home and Abroad

Active partner in Novel Coronavirus (COVID-19) response, working closely with  Department of Health and Human Services, as well as with international counterparts

  • Active Supply Chain Surveillance: Closely monitor domestic and global supply chain
  • Inspections and Monitoring Compliance of FDA Products Manufactured Overseas: Risk-based surveillance testing of imported products, including those from China
  • Safety of Consumer Products: Close monitoring of fraudulent products and false product claims related to COVID-19
  • Efforts to Diagnose, Treat and Prevent: Expedite development and availability of medical products needed to diagnose, treat and prevent disease
  • Next Steps: Collaborating with interagency partners, international partners, medical product developers and manufacturers to help advance response efforts combat this virus

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Rare Disease Day 2020: FDA Continues Important Work on Treatments for Rare Diseases

Commemorating  Rare Disease Day by efforts to get treatments to patients with rare diseases across the thousands of identified rare diseases

  • Public meeting with stakeholders to address challenges and opportunities surrounding rare disease product development
  • New request for applications (RFA) for the Orphan Products Grants Program
  • Additional information on orphan “exclusivity protected uses.”
  • Enhanced rare disease patient website

WATCH

READ 


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Collaborative Review of Scientific Evidence to Support Associations Between Genetic Information and Specific Medications

Concerns with DTC genetic tests making claims about genetic test results to manage medication treatment that are NOT supported FDA-approved drug labeling or other scientific evidence

  • Steps to help ensure that claims are grounded in sound science to avoid inappropriate management of patients’ medications
  •  New web-based resource including table describing some of the gene-drug interactions for altered drug metabolism, differential therapeutic effects, differences in risks of adverse events
  • Continue to review various professional guidelines e.g. Clinical Pharmacogenetics Implementation Consortium
  • Continue participation in community-based collaborative approach for ongoing evaluation of the evolving science

Table of Pharmacogenetic AssociationsREAD


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FDA Takes Action with Indian Government to Protect Consumers From Illicit Medical Products

Operation Broadsword targeted packages entering the U.S. through International Mail Facility from Jan. 28 through Jan. 30

  • Investigators from both governments examined > 800 shipments, ~50 different FDA-regulated products, many transshipped through third-party countries to conceal point of origin and avoid detection
  • Stopped approximately 500 shipments of illicit, and potentially dangerous, unapproved prescription drugs and combination medical devices from reaching American consumers
  • FDA provided consumer information :  BeSafeRx: Know Your Online Pharmacy.  and encouraged to report any unlawful sale of medical products online to FDA.

READ


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Smooth Regulatory Transition of Insulin and Other Biological Products  to Increase Patient Access and Potentially Lower Prices on Insulin

Steps to ensure a smooth transition to new regulatory pathway

  • Final Rule for Biosimilars Action Plan
  • Incorporates changes made by the Biologics Price Competition and Innovation Act of 2009 (BPCI Act) and the Further Consolidated Appropriations Act, 2020
  • Intended to balance innovation and competition and facilitate the development and approval of biosimilar and interchangeable product

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Compilation of CDER New Molecular Entity (NME) Drug and New Biologic Approvals

New resource to assist external and agency researchers collecting historical information about FDA’s drug approvals 

  • Provide researchers with curated data regarding drug products approved by CDER since 1985 through 2019
  • Facilitate data accessibility, transparency, and accuracy when researchers seek information about an approved drug
  • Derived from FDA internal databases and document records, and reflects the state of each application at the time of initial regulatory approval
  • CDER will manage the compilation and will update it periodically with the latest drug approval data

Compilation of CDER NME and New Biologic Approvals 1985-2019

Compilation of CDER New Molecular Entity (NME) Drug and New Biologic Approvals – Data Dictionary


Image credit: FDA

Potential Nitrosamines in Medication

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What to Know and Do About Possible Nitrosamines in Medication

Ongoing investigation of several potentially cancer-causing substances, called nitrosamines, recently found in blood pressure, heartburn, acid reflux medications

  •  Some drugs – including angiotensin II receptor blockers (ARBs), ranitidine, and nizatidine – have been recalled because of nitrosamine impurities
  • Patients need to talk to their health care professional, as risks of stopping medicine may outweigh the potential risk of exposure to nitrosamines
  • Nitrosamines not expected to cause harm when ingested at low levels

LEARN


Image credit: FDA

Market Authorizations: 2019-nCoV diagnostic, ERVEBO Ebola vaccine, TEPEZZA for thyroid eye disease

Capture2019-nCoV Real-Time RT-PCR Diagnostic Panel

CDC

INTENDED USE: For the presumptive qualitative detection of nucleic acid from the 2019-nCoV in upper and lower respiratory specimens (such as nasopharyngeal or oropharyngeal swabs, sputum, lower respiratory tract aspirates, bronchoalveolar lavage, and nasopharyngeal wash/aspirate or nasal aspirate) collected from individuals who meet CDC criteria for 2019-nCoV testing. Testing is limited to qualified laboratories
designated by CDC and, in the United States, certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), to perform high complexity tests.

PREPARATION & TESTING:

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DESCRIPTION:

  • Reverse transcriptase polymerase chain reaction (PCR) test that provides presumptive detection of 2019-nCoV from respiratory secretions, such as nasal or oral swabs
  • Positive test result indicates likely infection with 2019-nCoV and infected patients should work with their health care provider to manage their symptoms and determine how to best protect the people around them
  • Negative results do not preclude 2019-nCoV infection and should not be used as the sole basis for treatment or other patient management decisions; negative results must be combined with clinical observations, patient history and epidemiological information

REGULATORY PATHWAY: Emergency Use Authorization to address public health  emergency

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ERVEBO ebola vaccine for intramuscular injection

Merck

INDICATION: Prevention of disease caused by Zaire ebolavirus in individuals 18
years of age and older

ADDRESSING UNMET NEED: First FDA-approved vaccine for the prevention of Ebola virus disease (EVD), caused by Zaire ebolavirus

MECHANISM OF ACTION: Immunization results in an immune response and protection from disease caused by Zaire ebolavirus

EFFECTIVENESS:

  • Guinea study, during 2014-2016 outbreak, n= 3,537 contacts and contacts of contacts with laboratory-confirmed EVD, “immediate” or 21-day “delayed” vaccination
  • ERVEBO 100% effective in preventing Ebola cases with symptom onset greater than 10 days after vaccination
  • No EVD cases in “immediate” cluster group vs 10 cases in 21-day “delayed” cluster group
  • Liberia study- n= 477, Sierra Leone study – n=500, Canada, Spain, US study – n=900
  • Antibody responses in Canada, Spain and U.S. study were similar to those among individuals in the studies conducted in Liberia and Sierra Leone.

SAFETY:

  • Most commonly reported side effects were pain, swelling and redness at the injection site, as well as headache, fever, joint and muscle aches and fatigue.

REGULATORY PATHWAY: BLA

  • Priority Review and Tropical Disease Priority Review Voucher, Breakthrough Therapy designation
  •  Because of public health importance, FDA worked closely with Merck and completed its BLA evaluation in less than six months

LABEL 


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TEPEZZA (teprotumumab-trbw) injection, for intravenous use

Horizon Therapeutics

INDICATION: Treatment of Thyroid Eye Disease

ADDRESSING UNMET NEED:

  • First drug approved for the treatment of thyroid eye disease-
  • Rare condition where muscles and fatty tissues behind eye become inflamed, causing eyes to be pushed forward and bulge outwards (proptosis)

MECHANISM OF ACTION: Not been fully characterized- binds to IGF-1R and blocks  activation and signaling

EFFICACY:

  • Two studies, n=170 patients with active thyroid eye disease, TEPEZZA or placebo
  • Primary endpoint: >2 millimeter reduction in proptosis- 71% (Study 1) and 83% (Study 2) vs. 20% and 10%

SAFETY:

  • Most common adverse reactions: Muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing loss, dry skin, dysgeusia, headache
  • Should not be used if pregnant, counseling on pregnancy prevention during treatment and for 6 months following last dose

REGULATORY PATHWAY: BLA

  • Priority Review, in addition to Fast Track and Breakthrough Therapy Designation 
  • Orphan Drug designation, with support from FDA Orphan Products Grants Program
  • Postmarketing commitments: Additional studies to characterize efficacy, safety, quality

LABEL


Image credits: FDA, Merck, Horizon Therapeutics

 

 

 

 

 

 

 

News and Views: Coronavirus medical countermeasures, 2019 New Therapies, Gene Therapy innovation, Deter anti-competitive business for biologics, Heart Health education for women, HIV Drugs mobile database, Warning for nicotine toothpicks

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Advance Development of Novel Coronavirus Medical Countermeasures (MCM)

FDA collaborating with interagency partners, product developers, international partners and global regulators to
  • Expedite development and availability of MCM to diagnose, treat, mitigate, prevent
  • Utilize pathways, including Emergency Use Authorization (EUA) to more rapidly make MCM available
  • Provide regulatory advice, guidance, and technical assistance to  sponsors developing investigational MCMs
  • Provide review and feedback on development proposals including design and set-up of clinical trials
  • Protect safety of nation’s blood supply and human cells, tissues,cellular/tissue-based products for transplantation
  • Enable access to investigational MCM through EUA or expanded access mechanisms
  • Protect consumers against fraudulent products by monitoring fraudulent products and false product claims and taking appropriate action

READ , 2019-nCOV website 


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2019 CDER New Drug Approvals Report

Annual report entitled Advancing Health Through Innovation: New Drug Therapy Approvals

  • Variety of novel drugs for advancing patient care – never approved in US
  • Overview of other notable approvals — new uses of uses for approved drugs
  • Treat new population of patients, such as children
  • Innovative ways to enhance efficiency and expedite review and approval

Innovation and Access areas

  • Rare Diseases
  • Neurological and Psychiatric disorder
  • Infectious diseases
  • Heart, Lung, Circulatory, Endocrine diseases
  • Autoimmune conditions
  • Women’s and Men’s specific health issues
  • Cancers and blood disorders
  • Biosimilars

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Strong Support of Innovation in Development of Gene Therapy Products

FDA efforts  to support innovators developing new gene therapy products, which insert new genetic material into a patient’s cells

  • 4 products approved
  • > 900 investigational new drug (IND) applications for ongoing clinical studies
  • will serve to improve therapeutic choices

Publication of guidances issued to provide recommendations for product developers

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New Efforts to Further Deter Anti-Competitive Business Practices, Support Competitive Market for Biological Products to Help Americans

FDA and FTC to collaborate to curtail and discourage anti-competitive behavior to faciliate robust competition and bring down cost for biologics

  1. Promote greater competition in biologic markets
  2. Deter behavior that impedes access to samples needed for the development of biologics, including biosimilars
  3. Take appropriate action against false or misleading communications
  4. Review patent settlement agreements involving biologics, including biosimilars, for antitrust violations

READ 


CaptureHeart Health Education for Women

FDA Office of Women’s Heath (OWH) initiatives is support of American Heart Month
  • Heart health educational video ‘Getting a Beat : On what women know about heart health
  • New KNOWH the Difference initiative, which focuses on sharing important knowledge and news on women’s health (KNOWH)
  • OWH research and extramural funding opportunities
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Mobile-Friendly Database with Information on Life-Saving HIV Drugs

Interactive database  on critical information about antiretrovirals (ARVs) eligible for purchase under the President’s Emergency Plan for AIDS Relief (PEPFAR) program

  • Empower public and health care providers by enhancing the amount and availability of information and data provided on each drug
  • Health care providers, consumers, procurer access to FDA-reviewed product labeling and essential scientific information for safe and effective use of drug
  • Information on pediatric drugs, where manufactured, shelf-life, storage requirements
  • Ability to export reports, collect metrics, readily access on mobile platforms

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FDA Warns Maker of Nicotine-Containing Toothpicks of Several Violations, Including Illegal Sales 

  • Warning letter to Smart Toothpicks LLC,  Tempe, Arizona, for selling dissolvable tobacco products, including Peppermint Ice Nicotine Toothpicks
  • Three specific violations:
    • selling a tobacco product to a minor through the company’s website
    • selling unauthorized modified risk tobacco products
    • failing to include required nicotine warning statements on both packaging and advertising
  • Written response to this letter within 15 working days on corrective actions
    • discontinue violative labeling, advertising, sale, and/or distribution
    • plan for maintaining compliance with the FD&C Act

Action is part of the agency’s Youth Tobacco Prevention Plan, to prevent and reduce youth tobacco use 

READ


Image credits: FDA

e-cigarettes: Enforcement policy on unauthorized flavored cartridges

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Enforcement policy on unauthorized flavored cartridge-based e-cigarettes that appeal to children, including fruit and mint

FDA intends to prioritize enforcement against these illegally marketed ENDS products by focusing on the following groups of products that do not have premarket authorization

  • Any flavored, cartridge-based ENDS product (other than a tobacco- or menthol-flavored ENDS product)
  • All other ENDS products for which the manufacturer has failed to take (or is failing to take) adequate measures to prevent minors’ access
  • Any ENDS product that is targeted to minors or likely to promote use of ENDS by minors.

Companies that do not cease manufacture, distribution and sale of unauthorized flavored cartridge-based e-cigarettes (other than tobacco or menthol) within 30 days risk FDA enforcement actions

LEARN


Image credit: FDA

Device Authorizations: COBAS MRSA diagnostic, WOUNDCHECK for bacterial status, GSP Neonatal Creatine Kinase for Duchenne, CONTROL-IQ for diabetes

CaptureCOBAS vivoDx MRSA diagnostic test 

Roche Molecular Systems Inc.

INDICATION FOR USE: Automated qualitative in vitro diagnostic test for the direct detection of live methicillin-resistant Staphylococcus aureus (MRSA) cells in nasal swab samples from patients who are at risk for nasal colonization by MRSA.
The test utilizes selective agents and bioparticles (Smarticles technology) to introduce a luciferase gene into targeted bacteria to create an amplified luminescent signal in only viable (live) MRSA cells. The cobas vivoDx MRSA test is intended to aid in the prevention and control of MRSA infections in healthcare settings. It is not intended to diagnose MRSA infections, nor to guide, or monitor treatment. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

ADDRESSING UNMET NEED: New tool in the fight to prevent and control MRSA in high-risk settings

DESCRIPTION: System for detection of microorganisms and antimicrobial resistance using reporter expression

  • New bacteriophage technology based on bioluminescence to detect MRSA from nasal swab samples in 5 hours vs  compared to 24-48 hours for conventional culture

PERFORMANCE TESTING: Test correctly identified MRSA in  90% of samples where MRSA was present and 98.6% of samples with no MRSA

RISKS: Failure to use the device correctly, False positive or negative results, Failure to interpret results correctly

MITIGATIONS: Labeling, Design verification and validation, Other special controls

REGULATORY PATHWAY: De Novo premarket review pathway

CLASSIFICATION ORDER


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WOUNDCHEK Bacterial Status

Woundcheck Laboratories

INDICATION FOR USE: in vitro diagnostic chromatographic test for qualitative detection of bacterial protease activity directly from wound fluid samples collected with a swab. The WCBS test is intended for use in adult patients as an aid in assessing the risk for nonhealing of chronic venous, diabetic foot, and pressure ulcers associated with wounds where there are no signs of wound infection and where patients are asymptomatic for clinical signs of infection. The test is intended for use with chronic wounds that are between 21 days and < 6 months of age and chronic wounds that are ≥ 6 months of age that are < 1cm2 in size.

DEVICE TYPE: To detect bacterial protease activity in chronic wound fluid

  • Lateral flow prescription device that may include a sterile swab
  • Intended for use in patients as an aid in assessing the risk for non-healing of chronic venous, diabetic foot, and pressure ulcers associated with wounds where there are no signs of wound infection and where patients are asymptomatic for clinical signs of infection.

RISKS: Failure to use the device correctly, False positive or negative results, Failure to interpret results correctly

MITIGATIONS: Labeling, Design verification and validation, Other special controls

REGULATORY PATHWAY: De Novo premarket review pathway

CLASSIFICATION ORDER 


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GSP Neonatal Creatine Kinase – MM kit

PerkinElmer

ADDRESSING UNMET NEED: First test to aid in newborn screening for Duchenne Muscular Dystrophy (DMD), a rare genetic disorder that causes progressive muscle deterioration and weakness

DESCRIPTION: Muscular dystrophy newborn screening test

  • Intended to measure creatine kinase levels obtained from dried blood spot specimens on filter paper from newborns (prick of a newborn’s heel 24 to 48 hours after birth) as an aid in screening newborns for muscular dystrophy
  • Kit works by measuring the concentration of a type of protein called CK-MM, which is part of a group of proteins called creatine kinase
  • Creatine kinase is found in muscle tissue and CK-MM enters the blood stream in increased amounts when there is muscle damage

PERFORMANCE: 

  • Clinical study, n=3,041 newborns, dried blood samples tested for DMD associated protein levels
  • Kit able to accurately identify the four screened newborns that had DMD-causing genetic mutations
  • Additional testing of 30 samples from newborns with clinically confirmed cases of DMD; all correctly identified

RISKS: False positive and False negative results

MITIGATIONS: Labeling, Design verification and validation, Special controls

REGULATORY PATHWAY: De Novo premarket review pathway

CLASSIFICATION ORDER


CaptureControl-IQ Technology

Tandem Diabetes Care

INDICATION FOR USE: Intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically increase, decrease, and suspend delivery of basal insulin based on iCGM readings and predicted glucose values. It can also deliver correction boluses when the glucose value is predicted to exceed a predefined threshold.
Control-IQ technology is intended for the management of Type 1 diabetes mellitus in persons 14 years of age and greater.
Control-IQ technology is intended for single patient use and requires a prescription.
Control-IQ technology is indicated for use with NovoLog or Humalog U-100 insulin.

DESCRIPTION: Interoperable automated glycemic controller

  • Intended to automatically calculate drug doses based on inputs such as glucose and other relevant physiological parameters, and to command the delivery of such drug doses from a connected infusion pump
  • Designed to reliably and securely communicate with digitally connected devices to allow drug delivery commands to be sent, received, executed, and confirmed. Interoperable automated glycemic controllers are intended to be used in
    conjunction with digitally connected devices for the purpose of maintaining glycemic control.

RISKS:

  • Inability of the controller to handle different pharmacokinetic and pharmacodynamic characteristics of the drugs
  • Lack of compatibility of connected devices
  • Connected devices having inadequate performance to allow safe use of  controller
  • Failure to report device malfunctions or adverse events to manufacturer
  • Latent flaws in software
  • Failure to provide appropriate treatment due to loss of communication with
    connected devices
  • Risk due to insecure transmission of data
  • Failure to correctly determine the root cause of device malfunctions
  • Data transmission interference/electromagnetic disturbance

MITIGATIONS: Device performance, drug compatibility information in labeling
User training, Validation of processes, and procedures as well as limitations with connected and interoperable devices, Assigning post-market responsibilities. Software validation testing, Electrical safety verification and validation, electromagnetic compatibility,radio frequency wireless testing, user training

REGULATORY PATHWAY: De Novo premarket review pathway

CLASSIFICATION PATHWAY


Image credits:  Roche, Woundcheck Labs, PerkinElmer, Tandem

News & Views: 24th FDA Commissioner, Drug importation from Canada, Center of Excellence for drug compounding, Acute pain opioid prescribing, Generic drug pricing, Operation Vapor Lock, Naloxone and opioid overdose, 2019-2020 Flu season

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Stephen Hahn, MD, confirmed as the 24th FDA Commissioner

  • Radiation Oncologist with Residency at the National Cancer Institute
  • Professor at University of Pennsylvania
  • Chief Medical Executive at MD Anderson Cancer Center

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Steps to lower U.S. prescription drug prices

Allow importation of certain prescription drugs shipped from Canada

  • Purpose of proposed rule is to lower prices and reduce out of pocket costs
  • Foreign seller, licensed by Health Canada and registered with FDA, to purchase directly from manufacturer
  • US importer, subject to the supply chain security requirements, to buy directly from foreign seller
  • Importer arranges for statutorily prescribed testing for authenticity, degradation, and other requirements by a qualifying US laboratory
  • Post-importation requirements including adverse event, medication error, field alert to manufacturer and to FDA

NPRM


CaptureImproving quality of compounded drugs

Novel approaches to reduce risks with production practices of outsourcing facilities 

  • Establishing Compounding Quality Center of Excellence to enhance collaboration among and provide educational programs for outsourcing facilities
  • Three main areas of focus: in-person, online education and trainings, conference to exchange ideas and best practices, market research help inform FDA on key issues

READ


Capture.JPGCapture.JPGNational Academies of Sciences, Engineering, and Medicine (NASEM) report on framing opioid prescribing guidelines for acute pain

FDA contracted NASEM for evidence-based guidelines for opioid analgesic prescribing for acute pain. NASEM recommendations are:

  • Develop an analytic framework (e.g., Figure above ) to develop and assess evidence base for clinical practice guidelines (CPG)
  • Outpatient opioid prescribing CPGs should explicitly state patient populations  (e.g., adults versus children) and contextual aspects (e.g. setting, prescriber type, prior treatments)
  • To determine optimal opioid prescribing strategies, examine not only intermediate outcomes (e.g. pills prescribed, unused, long-term opioid use), but also the short- and long-term health outcomes (e.g. mortality, overdose, opioid use disorder, pain, and function)
  • Well-designed observational and quality improvement initiatives helpful for evaluating the effects of opioid prescribing strategies on health outcomes
  • CPGs should be implemented by governmental (federal, state, and local) and nongovernmental entities
  • Prioritized surgical and medical indications listed for CPG development
  • State the role of opioid alternatives as first-line therapies, specify any other interventions, including nonopioid interventions, used to relieve pain

READ


Capture.JPGGreater Generic Competition and Lower Generic Drug Prices

  • New analysis showing greater competition among generic drug makers associated with lower generic drug prices
  • With six or more competitors,  price reductions of >95% compared to brand prices before generic entry
  • FDA helping bring greater efficiency and transparency to generic drug review process to encourage competition

READ


Capture.JPGOperation Vapor Lock seized sale of  illicit THC vaping cartridges 

FDA and DEA have seized 44 websites advertising the sale of illicit THC vaping cartridges 

  • Website advertising under various brand names with information indicating sale items would be considered a controlled substance under federal law
  • Some websites solely to fraudulently obtain payments without intending to mail product

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Capture.JPGHaving Naloxone on Hand Can Save a Life During an Opioid Overdose

Naloxone is a life-saving drug that, when sprayed into the nose or injected, quickly reverses the powerful effects of opioids during an overdose

  • Expanded availability by allowing consumers to get directly from pharmacist, by putting a “standing order”
  • Need to recognize opioid overdose and use Naloxone
  • Will not harm if no opioids in system
  • Discuss Naloxone when getting opioid prescription

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Capture.JPG2019-2020 Influenza season

Flu vaccine lots that have been released by FDA and are available for distribution by the manufacturers

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Image credit: FDA

Medicines and Driving

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Some Medicines and Driving don’t Mix

  • Some prescription and nonprescription medicines have side effects and cause reactions that may make it unsafe to drive (e.g.opioid pain relievers, anti-anxiety, anti-seizure drugs, antipsychotic, antidepressants, codeine)
  • Cannabidiol (CBD) products and driving can be dangerous
  • Some sleep medicines can impair even the next morning
  • Allergy medicines can affect ability to drive

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Image credit: FDA

Drug Authorizations: OXBRYTA and ADAKVEO for sickle cell, XCOPRI for partial-onset seizures, CALQUENCE for leukemia/lymphoma, GIVLAARI for acute hepatic porphyria

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OXBRYTA (voxelotor) tablets

Global Blood Therapeutics

INDICATION FOR USE: Treatment of sickle cell disease (SCD) in adults and pediatric patients 12 years of age and older.

ADDRESSING UNMET NEED: Treatment option for 100,000 people in the U.S., and the more than 20 million globally, who live with this debilitating blood disorder

MECHANISM OF ACTION: Hemoglobin S (HbS) polymerization inhibitor that binds to HbS with a 1:1 stoichiometry and exhibits preferential partitioning to red blood cells (RBCs) – increasing the affinity of Hb for oxygen

EFFICACY:

  • Randomized, double-blind, placebo-controlled, multicenter trial, n=274 patients with sickle cell disease, OXBRYTA vs. placebo
  • Endpoint: Hb response rate defined as a Hb increase of >1 g/dL from baseline to Week 24
  • 51.1% (OXBRYTA) vs. 6.5% (placebo),  (p < 0.001); no outlier subgroups observed

SAFETY:

  • Common side effects: Headache, diarrhea, abdominal pain, nausea, fatigue, rash and pyrexia

REGULATORY PATHWAY: NDA

  •  Accelerated Approval, Fast Track designation. Orphan Drug designation
  • Accelerated approval requirements: Phase 3, randomized, doubleblind, placebo-controlled trial in pediatric patients (age 2 years to < 15 years) with Sickle Cell Disease , long-term (5 years) followup

LABEL


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ADAKVEO (crizanlizumab-tmca) injection

Novartis

INDICATION FOR USE: Reduce the frequency of vasoocclusive crises (VOCs) in adults and pediatric patients aged 16 years and older with sickle cell disease.

ADDRESSING UNMET NEED: First targeted therapy approved for sickle cell disease, specifically inhibiting selectin, a substance that contributes to cells sticking together and leads to vaso-occlusive crisis- a painful condition

MECHANISM OF ACTION: Humanized IgG2 kappa monoclonal antibody that binds to P-selectin and blocks interactions between endothelial cells, platelets, red blood cells, and leukocytes.

EFFICACY:

  • 52-week, randomized, multicenter, placebo-controlled, double-blind study, n=198 patients with sickle cell disease, any genotype, ADAKVEO vs placebo
  • Endpoint: Annual rate of vaso-occlusive crisis (VOC) to a healthcare visit
  • Median annual rate of 1.63 visits (ADAKVEO) vs. 2.98 visits (placebo)
  • 36%  on Adakveo did not experience VOC during the study, delayed the time of first VOC experience

SAFETY:

  • Common side effects: Back pain, nausea, pyrexia, arthralgia
  • Need to monitor patients for infusion-related reactions,  interference with automated platelet counts or platelet clumping

REGULATORY PATHWAY: BLA

  •  Priority Review and Breakthrough Therapy designation, Orphan Drug designation
  • Postapproval requirements: Further evaluation of immune mediated safety

LABEL


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XCOPRI® (cenobamate tablets)

SK Lifesciences

INDICATION FOR USE: Treatment of partial-onset seizures in adult patients

ADDRESSING UNMET NEED: New option to treat adults with partial-onset seizures, which is an often difficult-to-control condition that can have a significant impact on patient quality of life

MECHANISM OF ACTION: Precise mechanism unknown; demonstrated to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents

EFFICACY:

  • Two multicenter, randomized, double-blind, placebo-controlled studies, N=655 adult patients
  • Endpoint: % change from baseline in seizure frequency per 28 days in the treatment period
  • 55.6%  reduction (XCOPRI 200 mg) vs 21.5% reduction (placebo), p< 0.0001

SAFETY:

  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS),  shortening of the QT interval and ventricular fibrillation – dose needs to be titrated
  • Increased risk of suicidal thoughts or behavior and other neurological adverse reactions
  • Most common side effects: Somnolence (sleepiness), dizziness, fatigue, diplopia (double vision), headaches

REGULATORY PATHWAY: NDA

  • Contains cenobamate – (Controlled substance schedule to be determined after review by the Drug Enforcement Administration
  • Required pediatric assessments

LABEL


CaptureCapture.JPGCALQUENCE® (acalabrutinib) capsules

AstraZeneca

INDICATION FOR USE: treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)

EFFICACY & SAFETY:

  • Two randomized, actively controlled trials in patients with CLL
  • Endpoint:  Progression-free survival (PFS) as assessed by independent review; significantly improved in both acalabrutinib arms, p<0.0001
  • Most common adverse reactions: Anemia, neutropenia, thrombocytopenia, headache, upper respiratory tract infection, diarrhea

REGULATORY PATHWAY: Supplemental NDA

  • First approved in 2017 
  • This review conducted under Project Orbis, framework for concurrent submission and review by FDA, the Australian Therapeutic Goods Administration, and Health Canada
  • FDA review used the Real-Time Oncology Review (RTOR) and Assessment Aid pilot programs, to sreamline data submission, Priority Review and Breakthrough Therapy designation

LABEL


CaptureGIVLAARI (givosiran) injection

Alnylam Pharmaceuticals

INDICATION FOR USE: Treatment of adults with acute hepatic porphyria (AHP)

MECHANISM OF ACTION: Double-stranded small interfering RNA that causes degradation of aminolevulinate synthase 1 (ALAS1) mRNA in hepatocytes;  leads to reduced circulating levels of neurotoxic intermediates aminolevulinic acid
(ALA) and porphobilinogen (PBG), factors associated with attacks and other disease manifestations of AHP

EFFICACY: 

  • Randomized, double‑blind, placebo‑controlled, multinational trial, n=94 patients with AHP, GIVLAARI vs placebo
  • Endpoint: Rate of porphyria attacks requiring hospitalizations, urgent healthcare visit, or intravenous hemin administration at home
  • 1.9 (95% CI:1.3,2.8) with GIVLAARI vs, 6.5 (95% CI:4.5, 9.3) with placebo
  • 70% (95% CI: 60%, 80%) fewer porphyria attacks with GIVLAARI

SAFETY:

  • Most common adverse reactions: Nausea and injection site reactions
  • Warnings for anaphylactic reactions, hepatic and renal toxicities, and injection site reactions

REGULATORY PATHWAY: NDA

  • Priority Review, Orphan product, Breakthrough Therapy designations
  • Postmarketing commitments: Trial in pediatric patients age greater than or equal to 12 years to less than 17 years with AHP

LABEL


Image credit: Global Blood Therapeutics, Novartis, SK Lifesciences, AstraZeneca, Alnylam

 

 

CURE ID crowdsourcing App for novel uses of existing medicines

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 CURE ID app for health care professionals to report novel uses of existing medicines for patients with difficult-to-treat infectious diseases

Allow clinical community to report experiences treating difficult-to-treat infectious diseases with novel uses of existing FDA-approved drugs

  • Focus on infectious diseases lacking adequate treatments, neglected tropical diseases, emerging infectious drug-resistant threats
  • Collects simple case report form from caregivers about experience using an approved product for an unapproved use
  • Organizes and analyzes data fast for promising new uses for existing drugs
  • Collaboration between FDA and the National Center for Advancing Translational Sciences (NCATS), NIH

https://cure.ncats.io

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Image credit: FDA

Device Authorizations: MYRIAD myChoice CDx diagnostic, PENTAX duodenoscope, MISIGHT contact lens, TULA system for otitis media

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MYRIAD myChoice® CDx

Myriad Genetic Laboratories, Inc.

INDICATION FOR USE: Next generation sequencing-based in vitro diagnostic test that assesses the qualitative detection and classification of single nucleotide variants, insertions and deletions, and large rearrangement variants in protein coding regions and intron/exon boundaries of the BRCA1 and BRCA2 genes and the determination of genomic Instability Score (GIS) which is an algorithmic measurement of Loss of Heterozygosity (LOH), Telomeric Allelic Imbalance (TAI), and Large-scale State Transitions (LST) using DNA isolated from formalin-fixed p raffin embedded (FFPE) tumor tissue specimens.

The results of the test are used as an aid in identifying ovarian cancer patients with positive homologous recombination deficiency (HRD) status for treatment with the targeted therapy  in accordance with the approved therapeutic product labeling.

ADDRESSING UNMET NEED: First diagnostic for testing of FFPE ovarian tumor tissue for the selection of patients who are eligible for treatment with niraparib (Zejula)

DEVICE DESCRIPTION:

  • Single-site assay; includes reagents, software, instruments and procedures for testing DNA extracted from formalin-fixed, paraffin-embedded (FFPE) tumor samples
  • Employs single DNA extraction method from FFPE specimens, 30-200 ng of which undergoes multiple steps including fragmentation, end repair and adenylation, adapter ligation, library construction/amplification, hybridization and capture, sequencing and data analysis

EFFECTIVENESS & SAFETY:

  • Clinical test as an aid to clinicians in identifying ovarian cancer patients who may be eligible for treatment with Zejula (niraparib)
  • Primary endpoint: Overall Response Rate (ORR), key secondary endpoints were ORR in all patients and Median DOR (duration of response) in all patients
  • In patients with tBRCAm tumors (n=63), ORR was 28.6% and median DOR 9.2 mo.
  • Statistically significant overall response rate with clinically meaningful DOR seen in  patients with deleterious or suspected deleterious BRCA mutation, positive GIS status,  patients who had received prior chemotherapy
  • Overall, the response rate is better than what would be expected of available therapy and represents an improvement in a surrogate endpoint that is reasonably likely to predict clinical benefit
  • Risks are associated with potential mismanagement of patients resulting from false results of the test or a failure to receive results

REGULATORY PATHWAY: PMA

  • Device Generic Name: Next Gen Sequencing oncology panel, somatic or germline variant detection system
  • Device Procode: PQP

Patient Labeling: Test Request Form


CapturePENTAX Medical Video Duodenoscope ED34-i10T2

Pentax

INDICATION FOR USE: To provide visualization and access to the upper gastrointestinal (GI) tract to treat bile duct disorders and other upper GI problems

ADDRESSING UNMET NEED: First duodenoscope with disposable elevator piece, reducing the number of parts needing disinfection. Represents a major step toward lowering the risk of infection among patients who undergo procedures with these devices

DEVICE DESCRIPTION:

  • Intended to be used with endoscopic devices, introduced in patient’s mouth
  • Provides visualization via a video monitor of and therapeutic access to the biliary tract (liver, gall bladder and bile ducts) through the upper gastrointestinal tract
  • Risks: Ootential for injuries, including, but not limited to, burns, electric shock, perforation, infection and bleeding

REGULATORY PATHWAY: 510(k)


CaptureMISIGHT (omafilcon A) contact lens

Cooper Vision

INDICATION FOR USE: Single use Soft Contact Lenses for the correction of myopic  ametropia and for slowing the progression of myopia in children with non-diseased eyes, who at the initiation of treatment are 8-12 years of age and have a refraction of -0.75  to -4.00 diopters (spherical equivalent) with ≤ 0.75 diopters of astigmatism.

The lens is to be discarded after each removal

ADDRESSING UNMET NEED:  First contact lens indicated to slow the progression of myopia (nearsightedness) in children, which ultimately could mean a reduced risk of developing other eye problems

EFFECTIVENESS & SAFETY:

  • Three-year randomized, controlled clinical trial , n=135 children ages 8 to 12, MiSight vs. conventional soft contact lens
  • Progression in myopia with MiSight lenses less than conventional lenses, less change in the axial length of eyeball at each annual checkup
  • No serious ocular adverse events in either arm of the study
  • Additionally, real world data from a retrospective analysis of n-782 medical records from seven community clinics. Ulcer rate comparable to adults who wear contact lenses daily
  •  Required postmarket study to further evaluate the safety and effectiveness

REGULATORY PATHWAY: PMA

  • Classification name:  Daily Wear Soft Contact Lens To Reduce The Progression Of Myopia
  • Product Code: QIT

LABELING


Capture.JPGTULA System

Tusker Medical

INDICATION FOR USE: Tubes Under Local Anesthesia (TULA) System for delivery of tympanostomy tubes, that can be inserted into the eardrum to treat recurrent otitis media.

ADDRESSING UNMET NEED: An option for the treatment of recurrent ear infections that does not require general anesthesia. Has the potential to expand patient access to treatment that can be administered in  physician’s office with local anesthesia and minimal discomfort

DEVICE DESCRIPTION:

  • Consists of an Iontophoresis System, a local anesthetic, and a Tube Delivery System
  • Iontophoresis System is designed to provide child-friendly bilateral local anesthesia of the tympanic membrane, enabling a viable alternative to general anesthesia
  • Once the tympanic membrane is numb, the Tube Delivery System is used to insert the tympanostomy tube
  • With a single button push, the Tube Delivery System automatically creates the myringotomy and inserts the tube in less than 500 milliseconds
  • Parents are present during the TULA office-based procedure, and younger children may sit on their parent’s lap, if desired.

EFFECTIVENESS $ SAFETY:

  • Study with 222 pediatric patients to assess the effectiveness of the Tula System for the delivery of ear tubes
  • Procedural success rate was 86% and 89% in children younger than age 5 and between ages 5-12 years old, respectively
  • Most common adverse event: Inadequate anesthesia during the procedure.

REGULATORY PATHWAY: PMA

  • Breakthrough Device designation

Image Credit:Myriad Genetic Laboratories, Pentax, Cooper Vision, Tusker Medical

News & Views: Cybersecurity, Technology Modernization Action Plan, Implementing SUPPORT Act, Homeopathic products oversight, Breast implants safety, CBD warning for pregnancy, CDRH Patient Engagement, New youth e-cigarette education

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Medical Device Cybersecurity : Information for patients

New technologies can be implantable or wearable, used at home or in health care settings: Safer, timelier and more convenient

Anytime a medical device has software and relies on a wireless or wired connection, vigilance is required : Vulnerable to cyber threats and requires cybersecurity

Patients need to

  • Apply software updates
  • Register device with manufacturer
  • Be observant and vigilant
  • Involve  family or caregivers
  • If there is a serious event, seek medical attention.

Capture.JPGFDA’s Technology Modernization Action Plan (TMAP)

Technological foundation for development of FDA’s ongoing strategy around data

  • For stewardship, security, quality control, analysis, and real-time use of data
  • Will accelerate path to better therapeutic and diagnostic options

Proposal to

  • Modernize FDA’s technical infrastructure 
  • Develop technology products to support FDA’s regulatory mission
  • Communicate and collaborate with stakeholders to drive technological progress that is interoperable across the system

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Capture.JPGFDA first year accomplishments implementing SUPPORT Act authorities to address the opioids crisis

FDA’s implementation of the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act (SUPPORT Act)

  • Clarifying FDA regulation of non-addictive pain products
  • Evidence-based opioid analgesic prescribing guidelines and report
  • Strengthening FDA and U.S. Customs and Border Protection (CBP) coordination and capacity
  • Restricting entrance of illicit drugs
  • Safety-enhancing packaging and disposal
  • Clarifying FDA postmarket authorities
  • Study on abuse-deterrent opioid formulations access barriers under Medicare

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Capture.JPGEfforts to protect patients from potentially harmful drugs sold as homeopathic products

Homeopathic products are marketed without FDA review and may not meet standards for safety, effectiveness, quality and labeling

  • Issuance of draft guidance discussing risk-based enforcement approach to drug products labeled as homeopathic
  •  Withdrawing outdated Compliance Policy Guide (CPG) 400.400, entitled “Conditions Under Which Homeopathic Drugs May be Marketed”

Risk-based approach with appropriate regulatory and enforcement actions when  patients are being put at risk

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Capture.JPGEfforts to protect women’s health and enhance safety information available to patients considering breast implants

 Draft guidance  to ensure patients have complete information about the benefits and risks of breast implants

  • Boxed Warning in labeling: Not lifetime devices, chances of developing complications, associated with risk of developing breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)
  • Inclusion of patient decision checklist at end of patient informational booklet
  • Revision of rupture screening recommendations for silicone gel-filled implants
  • Inclusion of product  ingredient information  that is easily understood by patients

To help patients better understand breast implant benefits and risks in making health care decisions that fit patients’ needs and lifestyle 

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CaptureWarning against Using Cannabis, Including CBD, When Pregnant or Breastfeeding

FDA strongly advises against use of cannabidiol (CBD), tetrahydrocannabinol (THC), and marijuana in any form during pregnancy or while breastfeeding

Unapproved products and FDA does not know

  • safety and effectiveness to treat a particular disease
  • what, if any, dosage may be considered safe
  • interaction with other drugs or foods
  • whether they have dangerous side effects or other safety concerns

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CaptureCDRH Patient Engagement

Mission to engage with patients, understand their perspective, and proactively integrate the patients’ perspectives into the total product life cycle of medical devices 

  • Designing medical devices
  • Planning and conducting medical device clinical investigations
  • Informing CDRH’s thinking on current issues impacting a patient community
  • Helping to identify emerging signals
  • Communicating safety messages
  • Identifying specific populations’ perspectives on benefit-risk for a given treatment

Ways to engage

Contact: CDRH_PatientEngagement@fda.hhs.gov.

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CaptureWork  with Scholastic with launch of new youth e-cigarette prevention educational resources for middle and high schools

Education is an important complement to the FDA’s overarching youth tobacco prevention efforts

  • Continuing to educate youth, parents, and teachers about the dangers of e-cigarette use
  • Joined forces with Scholastic to develop and distribute educational resources to high school educators across the country
  • Expanding collaboration with Scholastic to include middle school educators
  • Help ensure that > one million middle and high school teachers have resources to start educational conversations about the harms of e-cigarette use with their students

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Image credit: FDA

Authorizations: ORAQUICK Ebola test, TRIKAFTA for cystic fibrosis, REYVOW for migraine, SCENESSE for erythropoietic protoporphyria

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ORAQUICK EBOLA RAPID ANTIGEN TEST 

OraSure Technologies, Inc

INDICATION FOR USE: In vitro diagnostic single-use immunoassay for the qualitative detection of antigens from viruses within the Ebolavirus genus but does not differentiate
between these viruses

ADDRESSING UNMET NEED: First rapid diagnostic test for the Ebola Virus Disease (EVD). The test provides a rapid, presumptive diagnosis that must be confirmed.

TYPE OF DEVICE: Device to detect antigens of biothreat microbial agents in human clinical specimens.

To detect antigens of biothreat microbial agents in human clinical specimens is  identified as an in vitro diagnostic device intended for the detection of antigens of microbial agents in specimens collected from patients with signs and symptoms of infection with biothreat microbial agents and who have been exposed to these agents or are suspected or at risk of exposure. The device can include antibodies for  immobilization and detection of the analyte. This device may also be used for cadaver testing to prevent human diseases for which cadavers constitute a source of human-to-human transmission.

EFFECTIVENESS AND SAFETY:  

  • Data from multiple clinical studies of blood samples and cadaveric oral fluid from the 2014 West African outbreak and analytical studies
  • Reasonable assurance of the safety and effectiveness when intended to identify antigens associated with Ebola virus in blood from symptomatic patients and oral fluid of cadavers – with high levels of Ebola virus
  • OraQuick Ebola Test is not intended to be used for general Ebola infection screening (e.g., airport screening) or testing of individuals at risk of exposure without observable signs of infection

REG PATHWAY: De Novo classification

  •  Emergency Use Authorization (EUA) pathway -Collaboration between FDA, WHO and Democratic Republic of Congo (DRC)
  • Breakthrough Device designation
  • Regulation Number: 21 CFR 866.4002
  • Regulation Name: Device to detect antigens of biothreat microbial agents in human clinical specimens
  • Regulatory Class: Class II
  • Product Code: QID

CLASSIFICATION ORDER


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 TRIKAFTA (elexacaftor/ivacaftor/tezacaftor) tablet

Vertex

INDICATION: Treatment of cystic fibrosis (CF) in patients aged 12 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one F508del mutation.

ADDRESSING UNMET NEED: First triple combination therapy available to treat patients with the most common cystic fibrosis mutation.

MECHANISM OF ACTION: Elexacaftor and tezacaftor bind to different sites on the CFTR protein to increase the amount of CFTR protein delivered to the cell surface. Ivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The combined effect of elexacaftor, tezacaftor and ivacaftor is increased quantity and function of F508del-CFTR at the cell surface, resulting in increased CFTR activity

EFFICACY:

  • 2 randomized, double-blind, active and placebo-controlled trials, patients with CF, 12 years and older
  • First trial – n=403 with F508del mutation and mutation on second allele  that is not responsive to ivacaftor or tezacaftor/ivacaftor alone
  • Second trial- n=107 patients with two identical F508del mutations
  • Primary analysis: Increases in % predicted forced expiratory volume in one second, (ppFEV1). Trikafta increased the ppFEV1 in both trials ( 13.8% from baseline vs.  placebo and 10% from baseline vs. tezacaftor/ivacaftor)

SAFETY:

  • Serious adverse drug reactions: Rash and influenza (flu) events
  • Most common adverse drug reactions: Headaches, upper respiratory tract infections, abdominal pains, diarrhea, rashes, increased liver enzymes (alanine aminotransferase and aspartate aminotransferase), nasal congestion, increased blood creatine phosphokinase, rhinorrhea, rhinitis, influenza, sinusitis and increased blood bilirubin
  • Warnings related to elevated liver function tests 

REG PATHWAY: NDA

  • Priority Review, Fast Track, Breakthrough Therapy, and orphan drug designation
  • Rare pediatric disease priority review voucher
  • Postmarketing requirements: Rat carcinogenicity studies, hepatic impairment study

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REYVOW (lasmiditan)

Eli LIlly

INDICATION: Acute treatment of migraine with or without aura in adults.

ADDRESSING UNMET NEED: New option for the acute treatment of migraine that affects one in seven Americans

MECHANISM OF ACTION: Binds with high affinity to the 5-HT1F receptor; presumably exerts its therapeutic effects ithrough agonist effects at the 5-HT1F receptor

EFFICACY:

  • 2 randomized, double-blind, placebo-controlled trials, n=3,177 adult patients with history of migraine with and without aura, REYVOW vs, placebo
  • Primary Endpoint: % patients whose pain resolved and whose most bothersome migraine symptom (nausea, light sensitivity, or sound sensitivity) resolved two hours after treatment; significantly greater among patients receiving Reyvow.

SAFETY:

  • Risk of driving impairment
  • Most common side effects: Dizziness, fatigue, a burning or prickling sensation in the skin (paresthesia), sedation

REG PATHWAY: NDA

  • Controlled Substance scheduling by DEA pending
  • Required pediatric assessments
  • Postmarketing requirement: Maternal, fetal, and infant outcomes during pregnancy exposure

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SCENESSE (afamelanotide) implant

Clinuvel

INDICATION: To increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP)

ADDRESSING UNMET NEED: First treatment to increase pain-free light exposure in patients with rare disorder phototoxic reactions from EPP

MECHANISM OF ACTION: Synthetic tridecapeptide and a structural analog of α-melanocyte stimulating hormone – melanocortin receptor agonist and binds predominantly to melanocortin 1 receptor.

EFFICACY:

  •  2 parallel group clinical trials (n-93, 74), patients with erythropoietic protoporphyria, SCENESSE vs placebo
  • First trial primary endpoint: Total number of hours over 180 days spent in direct sunlight between 10 a.m. and 6 p.m. on days with no pain; . 64 hrs vs. 41 hrs
  • Second trial primary endpoint: Total number of hours over 270 days spent outdoors between 10 am and 3 pm on days with no pain for which “most of the day” was spent in direct sunlight; 6 hrs vs. 0.75 hrs

SAFETY:

  • Most common side effects: implant site reaction, nausea, oropharyngeal pain, cough, fatigue, skin hyperpigmentation, dizziness, melanocytic nevus , respiratory tract infection, somnolence, non-acute porphyria, skin irritation

REG PATHWAY: NDA

  • Priority Review, Orphan Drug designation
  • Postmarketing requirements: Thorough QT clinical study, Registry based observational exposure cohort study on long-term safety,

LABEL


Image credits: OraSure, Vertex, Eli Lilly, Clinuvel

 

 

News & Views: CDRH women health plan, ASCA, ALS guidance, Patient engagement, Limited Imodium packaging, Improving naloxone access, Premarket Tobacco Product Applications, Project Orbis

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CDRH: Health of Women Strategic Plan

  • Explores unique issues related to the performance of medical devices in women
  • Improves analysis and communication of sex- and gender-specific data to better assure the safe and effective use of medical devices
  • Develops and implements health science programs, strategies and initiatives focused on women’s health issues across CDRH

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The Accreditation Scheme for  Conformity Assessment (ASCA): Pilot Program

Under ASCA Pilot’s conformity assessment scheme, recognized accreditation bodies accredit testing laboratories for the competence of testing and calibration laboratories

  • ASCA-accredited testing laboratories may determine conformance of device with eligible standards
  • Provide declaration of conformity  to support  premarket submission

Scope

  • Development of the ASCA pilot
  • Conformity assessment resources leveraged in ASCA Pilot
  • Roles and Responsibilities: Accreditation bodies, Testing laboratories, Manufacturers, FDA staff
  • Selected Device Standards
  • Accreditation body and Testing Laboratory Participation

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Amyotrophic Lateral Sclerosis Guidance

ALS is progressive neurodegenerative disease that primarily affects motor neurons in cerebral motor cortex, brainstem, spinal cord, leading to loss of voluntary movement

  • Guidance focuses on specific clinical drug development and trial design issues that are unique to the study of ALS

Considerations

  • Early Phase Clinical Development, Population,  Effectiveness and Safety Considerations.
  • Specific Effectiveness Trial : Trial design, effectiveness endpoints,  timing of assessments, statistical considerations., prognostic factors,  integrated assessment of function and survival, Accelerated Approval considerations, Benefit-Risk considerations.

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Patient Engagement in the Design and Conduct of Medical Device Clinical Investigations

FDA values experience and perspectives of patients and their family caregivers. Draft guidance scope:

  • Use patient engagement to elicit experience, perspectives from patient advisors to improve design and conduct of medical device clinical investigations
  • Benefits of engaging with patient advisors
  • Patient engagement activities not considered by FDA to constitute research
  • Collecting and submitting patient engagement information

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Limited packaging for loperamide (Imodium) to encourage safe use

Reports of serious heart problems and deaths with much higher than the recommended doses of loperamide

  • Primarily among people intentionally misusing or abusing the product

To foster safe use of the over-the counter (OTC) anti-diarrhea drug loperamide

  • Use blister packs or other single dose packaging and to limit the number of doses in a package

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Continued efforts to increase availability of all forms of naloxone to help reduce opioid overdose deaths

Addressing opioid overdose continues to be one of the most urgent public health priorities

  • Naloxone is a critical tool for individuals, families, first responders and communities to help reduce opioid overdose deaths
  • Three FDA-approved forms of naloxone – injectable, auto-injector and nasal spray – require a prescription, which can be a barrier

Steps to improve access to naloxone (Narcan)

  • Pharmacists given direct authority to prescribe and sell naloxone to consumers
  • Community distribution and use by individuals with or without medical training
  • Approveal of first generic version of Narcan
  • Encouraging development of OTC naloxone products.

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Proposed rule for premarket tobacco product applications as part of commitment to continuing strong oversight of e-cigarettes and other tobacco products

Premarket tobacco product applications (PMTAs) for oversight of e-cigarettes and other tobacco products. Provide sufficient information on 

  • Physical aspects of a tobacco product
  • Potential public health benefits and harms
  • Also review tobacco product’s components, ingredients, additives, constituents, toxicological profile and health impact, as well as how the product is manufactured, packaged and labeled
  • Establish requirements for manufacturers to maintain records related to the legal marketing status of their tobacco products

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FDA takes first action under new international collaboration with Australia and Canada designed to provide a framework for concurrent review of cancer therapies

Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE), provides  framework for concurrent submission and review of oncology products among international partners

  • May allow cancer patients receive earlier access to drkugs
  • Greater uniformity of new global standards of treatment leading to the optimal design of  global clinical trials

First Project Orbis action in conjunction with the Australian Therapeutic Goods Administration and Health Canada

  • Accelerated approval to Lenvima (lenvatinib) in combination with Keytruda (pembrolizumab) for treatment of advanced endometrial carcinoma
  • Also used ‘Real-Time Oncology Review’ (RTOR) pilot program, which can streamline the submission of data prior to the completion and submission of the entire clinical application

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Image credits: FDA, CDC

News & Views: AEDs, Office on New Drugs reorganization, New digital health policies, Office of Women’s Health, THC vapes warning

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Check Your AED: Is it FDA Approved?

Automated external defibrillators (AEDs) are portable, life-saving devices designed to treat sudden cardiac arrest,

  • Public access AEDs used by laypeople who have received minimal training
  • Professional use AEDs  used by first responders who receive additional AED training

Premarket approval (PMA) now required new and existing AEDs and necessary AED accessories batteries, pad electrodes, adapters and hardware keys for pediatric use)- deadline Feb 3, 2020

  • To ensure the quality and reliability
  • Needs sufficient valid scientific evidence to reasonably assure the device is safe and effective
  • Requires manufacturers to receive FDA approval before initiating design, manufacturing, or labeling changes to the device, imposes certain other annual reporting requirements.

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Reorganization of the Office of New Drugs with Corresponding Changes to the Office of Translational Sciences and the Office of Pharmaceutical Quality

To modernize the New Drugs Regulatory Program – a reorganization of the New Drugs Regulatory Program

Restructuring of the Office of New Drugs (OND) and corresponding changes in the Office of Translational Sciences (OTS) and Office of Pharmaceutical Quality (OPQ)

  • Create offices that align interrelated disease areas, and divisions with clearer and more focused areas of expertise
  • Enable greater efficiency, better understand the diseases, enhance scientific leadership

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New steps to advance digital health policies that encourage innovation and enable efficient and modern regulatory oversight

Guidances to continue to encourage innovative approaches to the development of digital health tools and advanced FDA oversight 

Clinical Decision Support Software, (revision)

  • Patients, families and health care professionals increasingly embracing digital health technologies to inform everyday decisions
  • Encourage developers to create, adapt and expand functionalities of software to support providers in diagnosing and treating diseases, while ensuring  no  unacceptable risk to patient
  • Focus our regulatory oversight on CDS functions intended to help health care professionals and patients inform their clinical management for serious or critical conditions- no independent evaluation of the basis of software’s recommendations

Changes to Existing Medical Software Policies Resulting from Section 3060 of the 21st Century Cures Act

  • Types of software that are no longer considered medical devices under the amended definition of device
  • Mobile apps that are intended only for maintaining or encouraging a healthy lifestyle – generally fall outside the scope FDA’s regulation

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Critical Focus on Women’s Health

Office of Women’s Health established in 1994  to advance health of women through science, policy, education, outreach, and inclusion of women in clinical trials

  • Investing in Women’s Health Through Engagement and Education 
  • Fostering Scientific Research and Filling Knowledge Gaps
  • Advancing Medical Therapies that Meet Women’s Needs

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FDA Warns Public to Stop Using Tetrahydrocannabinol (THC)-Containing Vaping Products and Any Vaping Products Obtained Off the Street

FDA strengthening warning to consumers to STOP using vaping products containing THC

  • More than 1,000 reports of lung injuries- including some resulting in deaths-following the use of vaping products
  • Most of the patients reported using THC-containing products, suggesting THC vaping products play a role in the outbreak

FDA Actions

  • Working closely with federal and state partners to identify the products or substances that may be causing the illnesses
  • FDA’s Forensic Chemistry Center using state-of-the-art technology to analyze hundreds of samples for the presence of a broad range of chemicals

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Image credit: FDA

Drug Authorizations: JYNNEOS smallpox vaccine, RYBELSUS for Type 2 Diabetes, ERLEADA for Metastatic Prostate Cancer, OFEV for Interstitial Lung Disease

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JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) suspension for subcutaneous injection

Bavarian Nordic A/S

INDICATION: Caccine indicated for prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection.

ADDRESSING UNMET NEED: Only currently FDA-approved vaccine for the prevention of monkeypox disease

  • Routine vaccination of the American public was stopped in 1972; thus a large proportion of the U.S., as well as the global population has no immunity
  • Reflects U.S. government’s commitment to preparedness for intentional release of this highly contagious virus

MECHANISM OF ACTION: Live vaccine produced from the strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), an attenuated, non-replicating orthopoxvirus; elicits humoral and cellular immune responses to orthopoxviruses

EFFICACY:

  • Clinical study, n=400 healthy adults, 18 -42 years, never been vaccinated for smallpox
  • Endpoint: Noninferior immune responses with Jynneos vs.  ACAM2000, an FDA-approved vaccine smallpox prevention
  • Supportive data from non-human primates – Jynneos protected from exposure to viruses related to the smallpox virus.
  • Monkeypox effectiveness:  Antibody responses in smallpox clinical study participants and in non-human primates

SAFETY:

  • N>7,800 individuals receiving at least one dos
  • Commonly reported side effects: Pain, redness, swelling, itching, firmness at the injection site, muscle pain, headache and fatigue

REG PATHWAY: BLA

  • Priority Review and material threat medical countermeasure (MCM) priority review voucher
  • Vaccine also part of the Strategic National Stockpile (SNS), the nation’s largest supply of potentially life-saving pharmaceuticals and medical supplies for use in a public health emergency

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RYBELSUS (semaglutide) oral tablets 

Novo Nordisk

INDICATION: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

ADDRESSING UNMET NEED: First glucagon-like peptide (GLP-1) receptor protein treatment approved that does not need to be injected

MECHANISM OF ACTION: Acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1

EFFICACY:

  • Several clinical trials, placebo-controlled and compared to other GLP-1 injection treatments, stand-alone therapy and in combination with other diabetes treatments, paitents with Type 2 diabetes
  • In the placebo-controlled studies: Aignificant reduction in blood sugar (hemoglobin A1c);  after 26 weeks, 69%  – 77% on Rybelsus decreased their HbA1c to < 7%, vs.  31% on placebo

SAFETY:

  • Boxed warning:  Increased risk of thyroid c-cell tumors including medullary thyroid carcinoma (MTC)
  • Warnings: Pancreatitis,  Diabetic retinopathy, hypoglycemia, acute kidney injury and hypersensitivity reactions
  • Most common side effects: Nausea, diarrhea, vomiting, decreased appetite, indigestion and constipation

REG PATHWAY: NDA

  • Required  pediatric assessments: 52-week, randomized, double-blind, placebo-controlled parallel group study in pediatric patients ages 10-17
  • Postmarketing requirement: Medullary thyroid carcinoma registry-based case series of at least 15 years duration

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ERLEADA (apalutamide) tablets

Janssen

INDICATION FOR USE:  For treatment of Metastatic castration-sensitive prostate cancer (mCSPC)

EFFICACY & SAFEY:

  • Randomized, double-blind, placebo-controlled, multi-center clinical trial, n= 1,052 patients with mCSPC, Erleada vs . placebo
  • Major efficacy outcome: Overall Survival (OR) and radiographic progression-free survival (rPFS) . Statistically significant improvements in OS (hazrad ratio 0.67),  p=0.0053;  rPFS (hazard ratio 0.48), p<0.0001
  • Most common adverse reactions:  Fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture

REG PATHWAY: sBLA

  • Initially approved for non-metastatic prostate canacer
  • Used OCE’s Real-Time Oncology Review (RTOR) pilot program and accompanying Assessment Aid
  • Granted priority review

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OFEV  (nintedanib) capsules

Boehringer Ingelheim

INDICATION: To slow the rate of decline in pulmonary function in patients with systemic sclerosisassociated interstitial lung disease (SSc-ILD).

ADDRESSING UNMET NEED:

  • ~ 100,000 US individuals have scleroderma, and ~ half of scleroderma patients have interstitial lung disease associated SSc-ILD
  • Slows rate of decline in pulmonary function in SSc-ILD

MECHANISM OF ACTION: IUnhibits multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs); blocks intracellular signaling which is crucial for proliferation, migration, transformation of fibroblasts related to IPF pathology

EFFICACY:

  • Randomized, double-blind, placebo-controlled trial, n=576 patients, 20-79 years with disease, treatment for 52 weeks – up to 100 weeks
  • Primary endpoint: .Forced vital capacity (FVC) – a measure of lung function, defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible
  • Less lung function decline with Ofev vs placebo

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SAFETY:

  • Most frequent serious adverse event: Pneumonia, diarrhea
  • Warnings: Moderate or severe hepatic impairment,  embryo-fetal toxicity

REG PATHWAY: sNDA

  • Originally approved in 2014 for idiopathic pulmonary fibrosis (IPF), which is another interstitial lung condition
  •  

    Received Priority Review designation, Orphan Drug designation

LABEL


Image credits: Bavarian Nordic, Novo Nordisk, Janssen, Boehringer Ingelheim

Vaping Illnesses

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Vaping Illnesses: Consumers can Help Protect Themselves by Avoiding Tetrahydrocannabinol (THC)-Containing Vaping Products

  • Consumers are likely aware of the recent reports of respiratory illnesses — including some resulting in deaths – following the use of vaping products
  • FDA remains deeply concerned about these incidents and is working closely with CDC, state and local public health partners to investigate
  • More information needed to better understand whether there’s relationship between specific products or substances and reported illnesses
  • CDC and the FDA encourage the public to submit detailed reports of any unexpected tobacco- or e-cigarette-related health or product issues to the FDA via the online Safety Reporting Portal.

LEARN


image credit: FDA

Biosimilars Basics

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New patient webpage o help increase awareness of and understanding of Biosimilars

  • Basic definitions: biological medications, biosimilar medications, and other terms to facilitate understanding the relationship between biosimilars and the original (reference) medications they are compared to
  • Increase awareness: FDA-approved biosimilar medications are safe and effective medications for treating many illnesses such as chronic skin and bowel diseases, arthritis, kidney conditions, and cancer
  • Provide details: How biosimilar medications can benefit patients

LEARN


Image credit: FDA

2019 FDA Science Forum

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2019 FDA Science Forum

2019 FDA Science Forum entitled Transforming Health: Innovation in FDA Science  with topic areas

  1. Precision Health: For individuals and special populations
  2. Advanced Technology: 3D printing and nanomaterials
  3. Product Accessibility, Integrity, and Security: Theory, modeling, methodology
  4. Predictive Tools: In vitro/in vivo assays and computational modeling
  5. Advancing Digital Health and Artificial Intelligence: Artificial intelligence and evaluating digital health devices
  6. Outbreak! Prevention through cybersecurity, promoting medical product security, rapid response to infectious disease outbreaks
  7. Addiction: Neurobiology, opioids, cannabinoids, nicotine
  8. Empowering Consumers, Patients, and Other Stakeholders: Science of patient input.

LEARN


Image credit: FDA

News & Views: Patient-Focused drug development, Benefit-Risk for weight loss devices, Humanitarian Device Exemption, Warning for umbilical cord blood products, Special 510(k) program, Warning to JUUL, Safer Technologies Program


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Patient-Focused Drug Development (PFDD) Guidance Series for Enhancing the Incorporation of the Patient’s Voice in Medical Product Development and Regulatory Decision Making

Series of four methodological guidance documents to collect and submit patient experience data and other relevant patients and caregivers information

  1. Collecting Comprehensive and Representative Input
  2. Methods to Identify What is Important to Patients
  3. Selecting, Developing or Modifying Fit-for-Purpose Clinical Outcome Assessments
  4. Incorporating Clinical Outcome Assessments into Endpoints for Regulatory Decision M​aking​

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Capture.JPGConsideration of Benefit-Risk Approaches for Weight-Loss Devices

Proposal for assessing tolerability of risk in light of varying degrees of effectiveness for devices intended for weight loss

Benefits: 

  • Weight loss: Amount of weight loss, proportion of patients experiencing weight loss, durability of weight loss
  • Changes in comorbidities: Clinically significant reduction in HbA1c18, hypertension, and/or hyperlipidemia

Risks: 

  • Adverse events: Severity, types, numbers, rates, duration 
  • Long-term effects of the device permanent implantation, anatomic changes, restriction of future treatment options, reversibility limitations
  • Clinical treatments/procedures related to the device: Expected concomitant medications or therapies, rate of early device removal, risks related to placement/removal procedures

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Humanitarian Device Exemption (HDE) and Humanitarian Use Devices (HUDs)

Devices intended to benefit US patients in the treatment or diagnosis of diseases or conditions that affect or are manifested in not more than 8,000 individuals per year

  • Will not expose patients to an unreasonable or significant risk of illness or
    injury, and probable benefit to health outweighs the risk
  • Would not be available to a person with the disease or condition in question
    without the HDE; No comparable device

Scope of guidance:

  • FDA Review Actions
  • Assessing Probable Benefit and Risk
  • Post-Approval Requirements
  • Special Considerations for Devices Marketed Under an HDE
  • Appendices to support the HDE Program: Filing Checklist, Probable Benefit-Risk Assessment Summaries

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Capture.JPGUnapproved Stem cell therapy – Warning to Stemell for selling unapproved umbilical cord blood and umbilical cord products that may put patients at risk

Warning to Stemell, Inc. (Stemell), CA, for products derived from umbilical cord blood and umbilical cord: StemL UCB-Plus and StemL UCT-Plus

  • Significant deviations from current good tissue practice (CGTP) and current good manufacturing practice (CGMP) requirements
  • Deficient donor eligibility practices and environmental monitoring
  • Creating potential significant safety concerns that put patients at risk

False claim that stem cell products don’t fall under the regulatory provisions for drugs and biological products

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Special 510(k) Program

Facilitate submission, review, clearance of change to manufacturer’s own legally marketed predicate device (“existing device”) authorized through 510(K) or De Novo

  • Performance data are unnecessary
  • If performance data are necessary, well-established methods are available
  • All performance data necessary to support SE can be reviewed in a summary or risk analysis format

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Warning to JUUL Labs for marketing unauthorized modified risk tobacco products, including in outreach to youth

For marketing unauthorized modified risk tobacco products

  • Engaging in labeling, advertising, and/or other activities directed to consumers
  • Presentation given to youth at a school.

Requesting more information, about several issues raised in a recent Congressional hearing regarding JUUL’s outreach and marketing practices

  • Targeted at students, tribes, health insurers and employers

Part of series of FDA actions for providing strong oversight of e-cigarettes and other electronic nicotine delivery systems (ENDS) 

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Safer Technologies Program (STeP) for Medical Devices

To spur innovation towards safer medical devices and was modeled after the Breakthrough Devices Program

  • For PMA, De Novo and 510(K) pathways; Devices and device-led combination products
  • Should be reasonably expected to significantly improve the benefit-risk profile
  • reduction in the occurrence of a known serious adverse event
  • reduction in the occurrence of a known device failure mode
  • reduction in the occurrence of a known use-related hazard or use error
  • improvement in the safety of another device or intervention.

Advantages

  • Interactive and timely communications with the FDA, review team support, senior management engagement
  • Prioritized review
  • May reduce the total time to develop a device and achieve marketing authorization, while still meeting the agency’s gold standard for safety and effectiveness

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Image credit: FDA

News & Views: New health warnings on cigarette packages, Investigation of respiratory illnesses with e-cigarette use, Duodenoscopes with enhanced safety, Uncertainty in device benefit-risk determinations, Benefit-Risk determinations in De Novo classifications, Drugs for male breast cancer, Expediting access to drugs

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New required health warnings with color images for cigarette packages and advertisements to promote greater public understanding of negative health consequences of smoking

Science-based approach to develop and evaluate the new proposed cigarette health warnings

  • Focus on serious health risks – such as bladder cancer, diabetes, erectile dysfunction and conditions that can cause blindness

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CaptureFederal and CDC collaboration to investigate respiratory illnesses reported after use of e-cigarette products

FDA and CDC collaborating to investigate incidents of severe respiratory disease associated with use of e-cigarette products

  • Updating the number of potential cases of respiratory illnesses after use of e-cigarette products
  • Sharing more details about CDC and FDA work
  • Providing public and health partners across the country with information to help mitigate risk of additional incidents

More information needed to better understand relationship between specific products and reported illnesses

  • THC and cannabinoids use reported in many cases
  • e-cigarette products should not be used by youth, young adults, pregnant women, and adults who do not currently use tobacco products

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Capture.JPGTransition to Duodenoscopes with Innovative Designs to Enhance Safety

  • Duodenoscopes used in more than 500,000 endoscopic retrograde cholangiopancreatography (ERCP) procedures each year
  • Have complex designs with reusable hard-to-clean components
  • Failure to correctly reprocess duodenoscope could result in patient-to-patient disease transmission
  • Recommendation to use duodenoscopes with innovative device designs that make reprocessing easier, more effective, or unnecessary. (e.g. Fujifilm Corporation, Duodenoscope model ED-580XT, Pentax Medical, Duodenoscope model ED34-i10T)

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Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device Premarket Approvals, De Novo Classifications, and Humanitarian Device Exemptions

In premarket decision-making for devices, there exists some uncertainty around benefits and risks – type, magnitude, duration, frequency, other aspects

Appropriate uncertainty in a benefit-risk determination would depend on totality of information covering several factors

  • Extent of probable benefits of the device – magnitude, probability, duration, frequency
  • Extent of probable risks of the device- severity, type, number, rates, probability,  duration
  • Extent of uncertainty of benefit-risk profile of  precedent devices
  • Patients’ perspective on appropriate uncertainty
  • Extent of the public health need
  • Feasibility of generating extensive premarket clinical evidence
  • Ability to reduce or resolve remaining uncertainty postmarket
  • Effectiveness of mitigations, such as labeling, and other tools
  • Type of decision being made (e.g., HDE vs PMA)
  • Probable benefits of earlier patient access to the device

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Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications

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Male Breast Cancer: Developing Drugs for Treatment

Breast cancer is rare in males (<0.1%),  diagnosed at an older age, with more advanced stage of disease, and more likely to have lymph node involvement 

  • Eligibility criteria for clinical trials of breast cancer drugs should allow for inclusion of both males and females
  • May be possible to extrapolate findings to male patients where no difference in efficacy or safety between males and females is anticipated

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Delivering Promising New Medicines Without Sacrificing Safety and Efficacy

Congress has established five programs to expedite patient access to drugs that treat serious or life-threatening conditions while maintaining FDA’s gold standard of safety and efficacy

To assist drug development

  • Fast Track designation:  Drug is intended to treat a serious disease and that laboratory, animal model, or human data show promise
  • Breakthrough Therapy designation:  Preliminary clinical evidence indicates that  drug may demonstrate substantial improvement over available therapy
  • Regenerative Medicine Advanced Therapy designation (RMAT): Preliminary clinical evidence indicates regenerative medicine therapy has potential to address unmet medical needs for such condition

To expedite FDA review timelines: 

  • Priority Review designation FDA aims to take action on a marketing application within six months, compared to 10 months under standard review. Only granted if  data submitted in the marketing application appear to show a significant improvement in safety or effectiveness for a serious condition

Different route for expediting:

  • Accelerated Approval: Approval of a drug that demonstrates an effect on a “surrogate endpoint” that is reasonably likely to predict clinical benefit

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Image credit: FDA

AUTHORIZATIONS: ROZLYTREK for cancers with specific genetic defect, PRETOMANID for multidrug resistant TB, TURALIO for tenosynovial giant cell tumor, NUBEQA for castration resistant prostate cancer

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ROZYLTREK (entrectinib)

Genentech, Inc.

INDICATION: 

  • ROS1-Positive Non-Small Cell Lung Cancer : Treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive.
  • NTRK Gene Fusion-Positive Solid Tumors: Treatment of adult and pediatric patients 12 years of age and older with solid tumors that:
    • have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation
    • are metastatic or where surgical resection is likely to result in severe morbidity, and
    • have either progressed following treatment or have no satisfactory alternative therapy.

Approved under 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.

ADDRESSING UNMET NEED:

  • “Tissue agnostic” cancer treatment based on a common biomarker across different types of tumors rather than  body location
  • Innovation in precision oncology drug development, targeted and effective treatments
  • Simultaneous approvals in adult and pediatric populations

MECHANISM OF ACTION: Inhibitor of the tropomyosin receptor tyrosine kinases (TRK), proto-oncogene tyrosine-protein kinase ROS1, naplastic lymphoma kinase (ALK), JAK2 and TNK2. Inhibits tumorigenic potential through deactivation of downstream signaling pathways leading to constrained cell proliferation

EFFICACY:

  • Four clinical trials studying, n= 54 with NTRK fusion-positive tumors
  • Overall Response Rate (tumor shrinkage) of 57%; 7.4% having complete disappearance of the tumor; 61% with tumor shrinkage persisting for nine months or longer.
  • Most common cancer locations: Lung, salivary gland, breast, thyroid, colon/rectum

For non-small cell lung cancer,  with ROS1-positive and metastatic

  • Clinical studies, n= 51 with ROS1-positive lung cancer
  • Overall response rate: 78%, 5.9% with complete disappearance of cancer, 55% had tumor shrinkage persist for 12 months or longer

SAFETY:

  • Most serious side effects: Congestive heart failure, central nervous system effects, skeletal fractures, hepatotoxicity, hyperuricemia, QT prolongation, vision disorders
  • Common side effects: Fatigue, constipation, dysgeusia, edema , dizziness, diarrhea, nausea, dysesthesia, dyspnea, myalgia, cognitive impairment, weight gain, cough, vomiting, fever, arthralgia, vision disorders

REGULATORY PATHWAY: NDA

  • Accelerated approval. .Priority ReviewBreakthrough Therapy and Orphan Drug designation
  • Postmarketing requirements: Clinical studies that further characterize clinical benefit, functional activation or inhibition of off-target receptors, transporters, and/or channels, integrated safety analyses and supporting data, effect of moderate and severe hepatic impairment

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Capture.JPGPRETOMANID Tablets

The Global Alliance for TB Drug Development (TB Alliance)

INDICATION: Limited Population: Part of a combination regimen with bedaquiline and linezolid for the treatment of adults with pulmonary extensively drug resistant (XDR) or treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB).  Approval of this indication is based on limited clinical safety and efficacy data.

Indicated for use in limited and specific population of patients

ADDRESSING UNMET NEED:

  • Multidrug-resistant TB and extensively drug-resistant TB are public health threats due to limited treatment options
  • estimated 490,000 new cases of multidrug-resistant TB worldwide, with a smaller portion of cases of extensively drug-resistant TB
  • New treatments are important to meet patient national and global health needs

MECHANISM OF ACTION: Nitroimidazooxazine antimycobacterial drug

EFFICACY:

  • Open-label study conducted in three centers in South Africa, n=109 with extensively drug-resistant, treatment intolerant or non-responsive multidrug-resistant pulmonary TB (of the lungs), taken orally in combination with bedaquiline and linezolid, 6 months
  • Endpoint: Incidence of bacteriologic failure (reinfection – culture conversion to positive status with different M. tuberculosis strain), bacteriological relapse (culture conversion to positive status with same M. tuberculosis strain), or clinical failure through follow-up until 6 months after the end of treatment
  • Successes (lack of failure) : 89%, significantly exceeded the historical success rates or treatment of extensively drug resistant TB

SAFETY:

  • Most common adverse reactions:  Peripheral neuropathy, acne, anemia, nausea, vomiting, headache, increased liver enzymes, dyspepsia, rash, increased pancreatic enzymes, hypoglycemia, diarrhea

REGULATORY PATHWAY:

  • Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD)pathway
  • Qualified Infectious Disease Product (QIDP) designation, Priority Review, Orphan Drug designation
  • Awarded Tropical Disease Priority Review Voucher 

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CaptureTURALIO (pexidartinib) capsules

Daiichi Sankyo

INDICATION: Treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery

ADDRESSING UNMET NEED: TGCT is a rare tumor that affects the synovium and tendon sheaths causing damage to surrounding tissue

MECHANISM OF ACTION: Tyrosine kinase inhibitor that targets colony stimulating factor 1 receptor (CSF1R); inhibition of proliferation of cell lines dependent on CSF1R and ligand-induced autophosphorylation of CSF1R

EFFICACY:

  • Multi-center international clinical trial, n=120 patients, TURALIO vs. placebo
  • Primary efficacy endpoint: Overall response rate (ORR) analyzed after 25 weeks
  • Statistically significant improvement in ORR: 38% on TURALIO vs 0% on placebo
  • Complete response rate: 15%, Partial response rate: 23%

SAFETY:

  • Boxed Warning: Risk of serious and potentially fatal liver injury. REMS program
  • Common side effects: Increased lactate dehydrogenase, increased aspartate aminotransferas, loss of hair color, increased alanine aminotransferase, increased cholesterol

REGULATORY PATHWAY: NDA

  •  Breakthrough Therapy designation,  Priority Review designation, Orphan Drug designation
  • Postapproval commitments: Further evaluate the risk of hepatoxicity
  • REMS to prevent potentially fatal liver toxicity: To include (i) Communication Plan and (ii)  Elements to  Assure Safe Use

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Capture.JPGNUBEQA (darolutamide) tablets

Bayer

INDICATION: Treatment of patients with non-metastatic castration resistant prostate  cancer (nmCRPC)

MECHANISM OF ACTION: Androgen receptor (AR) inhibitor

EFFICACY:

  • Multicenter, double-blind, placebo-controlled clinical trial, n=1,509 patients with non-metastatic castration resistant prostate cancer, NUBEQA vs. placebo, all  received gonadotropin-releasing hormone (GnRH) analog concurrently or had previous bilateral orchiectomy
  • Primary endpoint: Metastasis free survival (MFS)
  • 40.4 months with darolutamide vs. 18.4 months with placebo,  p<0.0001

SAFETY:

  • Most common adverse reactions: Fatigue, pain in extremity, and rash
  • Other: Ischemic heart disease, failure, seizures

REGULATORY PATHWAY: NDA

  • Fast track designation, Priority Review

LABEL


Image credits: Genentech, TB Alliance, Daiichi Sankyo, Bayer

 

 

 

 

Novotel

Recarbio

XPOVIO

News & Views: Novartis Data Accuracy Issues, e-cigarettes and seizures, Topical drugs bioequivalence, Drug safe importation

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Data accuracy issues with Zolgensma, manufactured by AveXis (Novartis)

  • On May 24, the FDA approved Zolgensma, a gene therapy product intended to treat children less than two years of age with spinal muscular atrophy (SMA)
  • On June 28, the agency was informed by AveXis Inc (Novartis subsidiary), about  data manipulation issue of data submitted in the BLA for the approval
  • Thus FDA approved Zolgensma without knowledge of data manipulation; the Agency continues to be supportive of the benefit-risk profile at this time
  • However, the Agency is concerned about the delay in notification by Novartis
  • Ensuring truthful, complete and accurate data in product applications is a critical component of industry responsibility
  • There will be further inspections and investigations and will take action including civil or criminal penalties

FDA 483 Inspection Report

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Capture.JPGSeizures following e-cigarette use as part of agency’s ongoing scientific investigation of potential safety issue

  • Continuing FDA scientific investigation on direct relationship between e-cigarettes and risk of seizure or other neurological symptoms
  • 127 reports on e-cigarette users experiencing seizures (between 2010-2019)
  • Some users reported other serious neurological symptoms e.g. fainting, tremors
  • FDA requesting use of Safety Reporting Portal   for any unexpected health or product issues experienced with e-cigarettes

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Capture.JPGEvaluating bioequivalence for topical drugs

  • FDA research initiative to facilitate generic topical dermatological drug product development
  • New method for monitoring amount of topical drug in dermis using dermal open-flow microperfusion (dOFM)
  • Thin, hollow porous tube inserted just under the skin surface, liquid similar to body fluid is injected, any applied drug absorbed through the skin’s outer layer enters  flowing liquid, which is then collected for analysis
  • Clinical study performed to confirm dOFM could reliably measure changing amounts of drug in skin after topical application of dermatological drug products

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 New Action Plan to Lay Foundation for Safe Importation of Certain Prescription Drugs

Two potential pathways for safe importation of certain drugs originally intended for foreign markets
  1. Pathway 1: Authorize importation of drugs from Canada with conditions to ensure  no additional risk to public’s health and safety
  2. Pathway 2: Import versions of FDA-approved drug products being sold in foreign countries that are the same as the U.S. versions; use a new National Drug Code
Safe Importation Action Plan – PDF*


Image credits: Novartis, FDA

News & Views: Software Precert program, Drug shortages and sterilization,CSF shunts & hearing aids, PrEP HIV program, Drug abuse labeling, EU inspection partnership, Weight management devices, Breast implant recall, Regulating E-Cigs

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Software Precertification (Pre-Cert) Program Update

Pre-Cert program introduced to streamline regulation of  digital health devices, specifically software as a medical device (SaMD)

Test phase: Excellence Appraisal and Streamlined Review components

  • Mock Excellence Appraisal summary
  • Streamlined Review packages by extracting elements from original submission
  • Mock review on whether regulatory decision could be made

Learnings

  • Regulatory decision could be made
  • Opportunities to simplify Excellence Appraisal and Streamlined Review process

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Capture.JPGPreventing Medical Device Shortages by Ensuring Safe and Effective Sterilization in Manufacturing

Sterilization issues during manufacturing is cause of device shortages; steps to prevent

  • Monitoring  device supply, planning for and preventing potential shortages
  • Engaging with Healthcare Infection Control Practices Advisory Committee (HICPAC)
  • New innovation challenges for ideas from stakeholders, academics, industry
    • new or alternative sterilization methods
    • alternatives to those that use ethylene oxide

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Programmable CSF Shunts and Magnetic Field Interference with Implanted Hearing Devices 

Magnetic interactions in patients implanted with both programmable  cerebrospinal fluid (CSF) shunt systems and hearing aids (cochlear implants, bone conduction hearing devices, or middle ear hearing devices)

  • May inadvertently change programmable CSF shunt valve settings
  • Altered mental status, headaches, lethargy, irritability, vomiting, changes in vision, and difficulty walking – could progress to seizures, hemorrhage, or even death

Recommendations

  • Educate patients and caregivers about potential risk
  • Check CSF shunt valve setting after placement or adjustment of other devices
  • Consider different placement of CSF shunt valve if patient has other implanted devices
  • Contact the applicable device manufacturer for further information

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Capture.JPGPrEP and additional steps to help reduce the risk of getting HIV

Pre-exposure prophylaxis (or PrEP)  is for people at very high risk of HIV infection

  • Daily doses of Truvada (tenofovir and emtricitabine) that are used in combination with other medicines to treat HIV
  • FDA is  eliminating risk evaluation and mitigation strategy (REMS) for Truvada to improve accessibility  and patient uptake

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Capture.JPGEnsuring Patient Safety and Drug Manufacturing Quality Through Partnership with European Union Regulators

Mutual Recognition Agreement (MRA) with EU to more effectively deploy inspectional resources across the globe

  • FDA has completed capability assessments of 28 EU member states
  • Created important efficiencies for risk-based site selection model for inspection
  • Considering to extend beyond human drug products to veterinary products, human vaccines, and plasma-derived drugs

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Drug Abuse and Dependence Section of Labeling for Human Prescription Drug and Biological Products 

The primary role of DRUG ABUSE AND DEPENDENCE section of labeling is to convey information about potential for abuse, misuse, addiction, physical dependence, and tolerance

Controlled Substance : Under the Controlled Substances Act, For Which Controlled Substance Scheduling Is Pending, Not Controlled Under the Controlled Substances Act 

Abuse: Information on Abuse, Misuse, Addiction

Dependence: Information on Physical Dependence and Withdrawal, Tolerance

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FDA resources on Weight-Loss and Weight-Management Devices

Therapies for weight-loss or weight-management range from healthy eating and exercise, to prescription medicine, medical devices and surgery.

FDA Webpage provides information about:

Capture.JPGAction to protect women from breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)

  • Requested Allergan, manufacturer of BIOCELL textured breast implant, to recall device due to the risk of BIA-ALCL
  • Allergan is moving forward with worldwide recall
  • safety communication for patients with breast implants, considering breast implants and their health care professionals

CaptureSteps to control E-Cigs

  • Restricting youth access to electronic nicotine delivery systems (ENDS, which includes products known as “e-cigarettes”)
  • Conducting retailer and manufacturer checks on restricting sales to youth
  • Increasing Requirements for ENDS Manufacturers for safety
  • Utilizing Premarket Review Requirements for market authorizations

Real Cost campaign

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Image credits: FDA, Allergan

Market Authorizations: IB-STIM for Irritable Bowel Syndrome, PIQRAY for advanced or metastatic breast cancer, ZOLGENSMA for spinal muscular atrophy

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Innovative Health Solutions

INDICATION FOR USE: Percutaneous electrical nerve field stimulator (PENFS) system intended to be used in patients 11-18 years of age with functional abdominal pain associated with irritable bowel syndrome (IBS). The IB-Stim is intended to be used for 120 hours per week up to 3 consecutive weeks, through application to branches of Cranial Nerves V, VII, IX and X, and the occipital nerves identified by transillumination, as an aid in the reduction of pain when combined with other therapies for IBS.

ADDRESSING UNMET NEED:

  • First medical device for reduction of functional abdominal pain in patients 11-18 years of age with irritable bowel syndrome (IBS) when combined with other therapies for IBS
  • Advancing the development of pediatric medical devices

DESCRIPTION:

  • Prescription-only device
  • Small single-use electrical nerve stimulator placed behind patient’s ear
  • Battery-powered chip that emits low-frequency electrical pulses to stimulate branches of certain cranial nerves continuously for five days
  • Stimulating nerve bundles in and around the ear is thought to provide pain relief
  • Patients can use the device for up to three consecutive weeks to reduce functional abdominal pain associated with IBS

EFFECTIVENESS & SAFETY:

  • Clinical study, n= 50 patients 11-18 years of age with IBS; IB-Stim vs placebo
  • Endpoint: Change from baseline to the end of the third week in worst abdominal pain, usual pain and Pain Frequency Severity Duration (PFSD) scores
  • Worst pain at baseline: Similar between the treatment and placebo groups
  • Greater change (improvement) in worst pain from baseline to week three in  IB-Stim group; effect also seen at weeks one and two
  • Greater change also demonstrated in composite PFSD scores from baseline to week three in the IB-Stim group compared to the placebo group.
  • 30% decrease in usual pain at the end of three weeks in 52% IB-Stim patients vs 30% placebo
  • Six patients reported mild ear discomfort and three patients reported adhesive allergy at the site of application
  • Contraindicated for patients with hemophilia, patients with cardiac pacemakers or those diagnosed with psoriasis vulgaris

REGULATORY PATHWAY: De Novo request


Capture.JPGPIQRAY (alpelisib) tablets

Novartis

INDICATION: In combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CAmutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen.

  • Also approved the companion diagnostic test: Therascreen PIK3CA RGQ PCR Kit to detect the PIK3CA mutation in a tissue and/or a liquid biopsy
  • Patients who are negative by the therascreen test using the liquid biopsy should undergo tumor biopsy for PIK3CA mutation testing.

ADDRESSING UNMET NEED: First PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer.

MECHANISM OF ACTION: Inhibitor of phosphatidylinositol-3-kinase (PI3K) with  activity predominantly against PI3Kα; inhibited the phosphorylation of PI3K downstream targets, induce an increase in estrogen receptor (ER) transcription in breast cancer cells

EFFICACY:

  • Randomized trial, n=572 postmenopausal women and men with HR-positive, HER2-negative, advanced or metastatic breast cancer
  • Addition of Piqray to fulvestrant significantly prolonged progression- free survival (median of 11 months vs. 5.7 months) in patients whose tumors had a PIK3CA mutation.

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SAFETY:

  • Common side effects: High blood sugar levels, increase in creatinine, diarrhea, rash, decrease in lymphocyte count in the blood, elevated liver enzymes, nausea, fatigue, low red blood cell count, increase in lipase (enzymes released by the pancreas), decreased appetite, stomatitis, vomiting, weight loss, low calcium levels, aPTT prolonged (blood clotting taking longer to occur than it should), hair loss
  • Monitor patients for severe hypersensitivity reactions (intolerance)

REGULATORY PATHWAY: NDA

  • First novel drug approved under the Real-Time Oncology Review pilot program
  • Use of updated Assessment Aid, a multidisciplinary FDA review template for review consistency and reduced review time
  • Priority Review designation
  • Postmarketing Commitments: Overall survival data, drug interaction studies

LABEL


Capture.JPGZOLGENSMA (onasemnogene abeparvovec-xioi) intravenous infusion

AveXis

INDICATION: Adeno-associated virus vector-based gene therapy indicated for the  treatment of pediatric patients less than 2 years of age with spinal muscular atrophy *SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene

Limitations for use:

  • Safety and effectiveness of repeat administration not been evaluated
  • Use in patients with advanced SMA not been evaluated

ADDRESSING UNMET NEED:  First gene therapy approved to treat children less than two years of age with spinal muscular atrophy (SMA), a leading genetic cause of infant mortality

MECHANISM OF ACTION: Recombinant AAV9-based gene therapy designed to deliver copy of gene encoding the human SMN protein. SMA is caused by a bi-allelic mutation in the SMN1 gene, which results in insufficient SMN protein expression. Intravenous administration of ZOLGENSMA results in cell transduction and expression of SMN protein has beennobserved in two human case studies

EFFICACY:

  • Ongoing clinical trial and a completed clinical trial, n=36, patients with infantile-onset SMA, 2 weeks -8 months old
  • 19/ 21 patients remaining, age:9.4 -18.5 months; 13/19 at least 14 months of age
  • Compared to natural history of patients with infantile-onset SMA, patients treated with Zolgensma demonstrated significant improvement in ability to reach developmental motor milestones (e.g., head control and the ability to sit without support)

SAFETY:

  • Boxed Warning: Acute liver injury
  • Most common side effects: Elevated liver enzymes and vomiting

REGULATORY PATHWAY: BLA

  • Fast Track, Breakthrough Therapy, and Priority Review designations
  • Orphan Drug designation and rare pediatric disease priority review voucher,

LABEL


Image credit:  Innovative Health Solutions, Novartis, AveXis

News & Views: Medical device reporting, Cannabidiol policy, Benefit-Risk framework for opioid analgesics, CDER modernization, New drug approval transparency, Heart Failure treatment, Complex Innovative Trial Design Program, Safety with paclitaxel-coated stents, Prostate tissue ablation devices

Capture.JPGCDRH efforts to increase transparency in medical device reporting 

CDRH is updating Medical Device Reporting (MDR) Program

  • End Alternative Summary Reporting (ASR) Program: Granted . exemption from individual medical device reports for well-known and well-established risks
  • Implement Voluntary Malfunction Summary Reporting (VMSR) Program   to efficiently detect potential safety signals
  • Modernize Manufacturer and User Facility Device (MAUDE) database
  • Actively engage in the National Evaluation System for health Technology (NEST)

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Capture.JPG Sound, Science-based Policy on Cannabidiol

Apply  rigorous, science-based approach to products containing cannabis or cannabis-derived compounds, including cannabidiol (CBD)

  • Many unanswered questions about the science, safety, and quality of many of these products
  • If product being marketed to have a therapeutic effect – regulated as a drug subject to FDA review and authorization
  • If marketed as food, including dietary supplements- overarching goal of protecting consumers and  currently illegal

FDA Public Meeting on May 31st for stakeholders to share feedback and experiences. Remaining open questions:

  • Daily safe dose of CBD and variability depending on form
  • Drug interactions
  • Impacts to special populations – children, elderly, pregnant, lactating women
  • Long-term exposure risks

READ


Capture.JPGBenefit-Risk framework for evaluating opioid analgesics

New draft guidance, “Opioid Analgesic Drugs: Considerations for Benefit-Risk Assessment Framework,”

  • Benefit-risk assessment framework to address opioid crisis with focus on  formal assessment of associated public health risks
  • Assess benefits and risks of proposed new opioid analgesics relative to already approved opioid and non-opioid analgesics
  • Provide information on mitigation of risks of overdose, abuse or addiction
  • Provide public health implications of product in terms of risks to non-patients, including members of the patient’s household, visiting relatives, friends, others
  • New REMS is safety profile different from already approved products

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Capture.JPGModernizing FDA’s New Drugs Regulatory Program

Initiative to modernize the New Drugs Regulatory Program to better serve patients and  staff in their work to carry out center’s mission

  • Scientific Leadership: Grow scientific expertise;  clarify regulatory pathways 
  • Integrated Assessment: Whether applications meet legal & regulatory requirements
  • Benefit-Risk Monitoring: Monitor pre- and post- approval 
  • Managing Talent: Attract, develop, and retain outstanding people
  • Operational Excellence: Standardize workflow, business processes, roles, responsibilities
  • Knowledge Management: Facilitate identification, capture, distribution, effective use of information

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Capture.JPGNew drug approval transparency efforts

Efforts to enhance transparency around our drug approval decisions

  • Focus on information to improve patient care and better inform health care professionals about the product
  • Posting portions of clinical study reports after a drug receives FDA approval
  • Requesting public comment about programs

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Capture.JPGTreatment for hear failure: Endpoints for drug development

Guidance pertains primarily to treating both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF)

  • Mortality data: Primary efficacy and safety
  • Endpoints related to how patients feel and function: Evidence of effectiveness
  • Hospitalization and outpatient intervention: All-cause vs. cause-specific
  • Biomarkers and surrogate endpoints: For clinical benefit
  • Acute heart failure: Symptom relief
  • Heart failure with preserved ejection fraction
  • Pediatric population

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Circulatory System Devices Panel recommendations on late mortality safety signal associated with paclitaxel-coated products

Panel met to discuss safety vs benefit of paclitaxel-coated balloons and paclitaxel-eluting stents used to treat peripheral arterial disease in the femoropopliteal arteries

  • Unanimously agreed that the aggregate data showed a mortality signal
  • Could not conclude that the late mortality signal represented a class effect
  • Missing data (vital status, repeat interventional treatments, paclitaxel exposure)  hindered interpretation of analyses
  • Could not identify patient subgroups that might be at particularly high (or low) mortality risk
  • Observed rates of both cardiovascular and non-cardiovascular death were higher in patients treated with paclitaxel-coated devices vs. uncoated devices
  • Precluded determination of relationship between paclitaxel dose and mortality
  • Preclinical animal data do not indicate a potential biological mechanism for the late mortality signal
  • Short-term benefits of paclitaxel-coated devices continue to outweigh the risks, and  devices should not be removed from market; Additional comments on post-market surveillance and labeling

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Capture.JPGComplex Innovative Trial Design (CID) Program

The CID Pilot Program is designed to:

  • Facilitate the use of CID approaches in late-stage drug development
  • Use of complex adaptive, Bayesian, and other novel clinical trial designs
  • Promote innovation by allowing FDA to publicly discuss the trial designs considered through the pilot program, including trial designs for medical products that have not yet been approved by FDA.

YouTube


Capture.JPGClinical investigations for prostate tissue ablation devices

Draft guidance to provide recommendations for high intensity ultrasound systems for prostate tissue ablation:

  • Complying with clinical testing special control under 21 CFR 876.4340(b)(8) for 510(k)s)
  • Collecting clinical data to support marketing submissions for new types of prostatic tissue ablation devices

Marketing authorization for a general indication for ablation of prostatic tissue

  • High intensity therapeutic ultrasound energy into prostate to thermally ablate  defined, targeted volume of tissue
  • Achieve same clinical effect of ablating targeted tissue volumes using different sources of energy
  • Does NOT address intended uses for the treatment of a specific disease (e.g., prostate cancer or benign prostatic hyperplasia)

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Image credit: FDA

FDA’s New History Exhibit

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Forward Into the Past With FDA’s New History Exhibit

First permanent exhibit documenting the FDA’s history at the White Oak headquarters in Silver Spring, MD.

  • Includes many of the noteworthy achievements in the FDA’s long history
  • FDA continues to understand and learn from its history, to inform its work
  • Experience the new exhibit to gain better understanding of how FDA has evolved over the years and how its history continues to pave the way for the future

YouTube

Flickr


Image credit: FDA on Flickr

 

 

 

Webpage: Patient-Reported Outcomes (PROs) in Medical Device Decision Making

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Patient-Reported Outcomes (PROs) in Medical Device Decision Making

This web page focuses on the use of patient-reported outcomes (PRO) as one type of patient input.

  • What Are Patient-Reported Outcomes
  • How CDRH Uses PROs in Regulatory Decision Making
  • CDRH Collaborations, Studies, Articles, and Workshops on Patient-Reported Outcomes
  • How to Incorporate Patient-Reported Outcome Measures (PROMs) in a Regulatory Submission

LEARN


Image credit: FDA

News & Views: Measles vaccine, Interchangeable biosimilars, Warning for vaping social influencers, Project Facilitate for expanded access, Enhancing diversity of clinical trials, Fixed-quantity packaging for opioids, Safety throughout drug’s lifecycle, Participation in Pre-Cert program, Better prescription drug advertising, Global drug quality

CaptureVaccination Is the Best Protection Against Measles

Measles, Mumps, and Rubella Virus Vaccine Live (M-M-R II, commonly called MMR)

  • For people ages 12 months and older
  • Two doses of the vaccine is about 97% effective at preventing measles

Measles, Mumps, Rubella and Varicella Virus Vaccine Live (ProQuad, commonly called MMRV)

  • For children ages 1 through 12 years.
  • Also prevents chickenpox

READ 


CapturePolicy advancements to help bring interchangeable biosimilars to market

Pathway for “interchangeable” biologics

  • Substituted without the involvement of the prescriber
  • Similar to how generic drugs are routinely substituted for brand name drugs

 Final guidance on the pathway for “interchangeable” biologics

  • Overview of important scientific considerations in demonstrating interchangeability
  • Biological product is biosimilar to reference product and produces same clinical result
  • Risk of safety or diminished efficacy of alternating or switching will not be greater than the risk of using the reference product without such alternation or switch

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Capture.JPGActions for violations by online posts on flavored e-liquids by social media influencers

FDA and FTC  warning letters to four firms that manufacture, sell, advertise flavored e-liquid products for social media influencers

  • Violations related to online posts by social media influencers on each company’s behalf, including failure to include the required nicotine warning statement
  • Enforcement action to address increased popularity of e-cigarettes among youth leading to health concerns, nicotine addiction, and more likely to transition to conventional cigarettes

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Capture.JPGProject Facilitate to assist physicians seeking access to unapproved therapies for patients with cancer

New pilot program to assist oncology health care professionals in requesting access to unapproved therapies for patients with cancer

  • New call center called Project Facilitate as a single point of contact
  • Help submit Expanded Access request for an individual patient, including follow-up of patient outcomes
  • Expanded Access is pathway for treatment by investigational treatment outside of clinical trials for immediately life-threatening or serious disease or condition
  • Expanded Access requests help weigh whether potential benefit of investigational treatment justifies the potential risks

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Draft Guidance for Industry on Enhancing the Diversity of Clinical Trial Populations

  • More inclusive trial practices, trial designs, and methodological approaches to broaden eligibility criteria
  • Increase enrollment of more diverse populations in clinical trials
  • Maximizes generalizability of trial results
  • Better understand therapy’s benefit-risk profile across the patient population likely to use the drug in clinical practice, without jeopardizing patient safety
  • Reflects FDA policy encouraging inclusion in clinical trials of participants representative of the broad population of patients including minorities

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CaptureFixed-quantity blister packaging for certain opioid pain medicines to help decrease unnecessary exposure to opioids

Misuse of prescription opioids by getting them from a friend or family member

 

  • >191 million opioid prescriptions dispensed to ~ 60 million patients, either as first-time prescriptions or refills; ~ 90% patients reported not finishing what was prescribed to them

Special opioid packaging for reducing unused doses available for misuse, abuse, inappropriate access, accidental poisoning or overdose- considertions

  • Actual opioid use compared to prescribed amounts for common surgical procedures and acute pain conditions

  • 5-, 10-, and 15-Count Blister Packages of Certain IR Opioid and IR Opioid/Acetaminophen Products

  • New Packaging/Disposal REMS Element

  • Safety-Enhancing Benefits of Fixed-Quantity Blister Packaging for Opioid Analgesics for Treatment of Acute Pain

  • National Academies of Sciences, Engineering, and Medicine (NASEM) to help advance guideline development

Remove the Risk” campaign

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Capture.JPGTracking and Acting on Safety Data Throughout a Drug’s Lifecycle

Agency tracks, analyzes and acts on the adverse event data collected over time to discover and communicate new risks associated with approved drugs 

  • Reports from patients, health care professionals and manufacturers about adverse events in  FDA Adverse Event Reporting System (FAERS)
  • Monitor FAERS database to identify safety signals, analyze and interpret data, combine with other scientific information for decision-making
  • If new risk confirmed, require addition to product’s label and may require a Risk Evaluation Mitigation Strategy (REMS) to ensure benefits outweigh risks
  • From 2002 through 2014, new safety issues discovered and added to labels for 278 drugs

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CaptureParticipation in 2019 Test Plan for Digital Health Software Precertification (Pre-Cert) Program

Agency seeking test cases from software organizations planning to submit a De Novo Request or 510(k) submission for software as a medical device (SaMD)  to meet the goals of the Test Plan

  • Small and large software development firms
  • Companies that develop a range of products, including both low- and high-risk SaMD
  • Companies that are not considered to be traditional medical device manufacturers but who intend to make SaMD

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Capture.JPGHelping to Better Communicate the Risks and Benefits in Prescription Drug Advertising

Direct-to-consumer advertising influence awareness of prescription drug treatments, influence patients and doctors

  • Using eye-tracking technology, researchers are examining elements of these ads that can affect the viewer’s ability to understand risks and benefits
  • With high-distraction ad – less able to recall or recognize risks described, spent less time on written statement of risks
  • Objective to help drug companies develop ads that better inform public

READ


CaptureAssuring Drug Quality Around the Globe

Programs to address the challenges to drug quality posed by globalization to protect patients and consumers

  • Tools to assure continued safety, effectiveness, quality post-approval
  • Same quality for both domestic and foreign manufactured products
  • Addressing quality inspections and issues

READ


Image credit: F DA 

 

Device Authorizations: MONARCH system for ADHD, XVIVO system for lung transplantation, COMANECI for intracranial aneurysms, NERIVIO MIGRA for migraine, ZIKV Detect 2.0 for Zika virus detection

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MONARCH external Trigeminal Nerve Stimulation (eTNS) System

NeuroSigma

INDICATION FOR USE: Treatment of pediatric Attention Deficit Hyperactivity Disorder (ADHD) as a monotherapy in patients ages 7 through 12 years old who are not currently taking prescription ADHD medications. The device is used for patient treatment by prescription only and is intended to be used in the home under the supervision of a caregiver during periods of sleep.

ADDRESSING UNMET NEED: Non-drug option for treatment of ADHD in pediatric patients through the use of mild nerve stimulation, a first of its kind

GENERIC DEVICE TYPE:Transcutaneous electrical nerve stimulator for Attention Deficit Hyperactivity Disorder

  • Prescription device that stimulates transcutaneously or percutaneously through electrodes placed on the forehead

DEVICE DESCRIPTION:

  • Cell-phone sized device generates low-level electrical pulse and connects via wire to a small patch that adheres to a patient’s forehead
  • Delivers low-level electrical stimulation to branches of trigeminal nerve, which sends therapeutic signals to the parts of the brain involved in ADHD
  • Neuroimaging studies show that eTNS increases activity in brain regions that are known to be important in regulating attention, emotion and behavior

EFFECTIVENESS & SAFETY:

  • Clinical trial, n=62 children with moderate to severe ADHD, eTNS vs. placebo
  • Primary endpoint: Improvement on clinician-administered ADHD Rating Scale, ADHD-RS
  • Subjects using eTNS device had statistically significant improvement in ADHD symptoms vs. placebo group
  • At end of week four, the average ADHD-RS score in eTNS decreased from 34.1 to 23.4 points, versusdecrease from 33.7 to 27.5 points in placebo
  • Most common side effects: Drowsiness, an increase in appetite, trouble sleeping, teeth clenching, headache and fatigue; no serious adverse events 

IDENTIFIED RISKS: Adverse tissue reaction, Injury or discomfort from electrical stimulation, including burns and nerve damage, Misuse that may result in device failure, user discomfort, or injury, Skin irritation or infection from use on broken skin 

REGULATORY PATHWAY: De Novo request

  • Regulation:21 CFR 882.5898
  • Regulation Name: Transcutaneous electrical nerve stimulator for Attention Deficit Hyperactivity Disorder
  • Regulatory Class: Class II
  • Product Code: QGL

CLASSIFICATION ORDER


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XVIVO PERFUSION SYSTEM 

Xvivo Perfusion Inc. 

INDICATION FOR USE: For use in flushing and temporary continuous normothermic machine perfusion of initially unacceptable excised donor lungs during which time the ex-vivo function of the lungs can be reassessed for transplantation.

ADDRESSING UNMET NEED: 

  • Lung transplantation is life-saving treatment for end-stage lung disease
  • Many patients die while waiting for suitable lungs for transplant
  • Only 15 percent of lungs from deceased donors suitable for transplantation
  • New device to temporarily ventilate, oxygenate, and perfuse preservation solution through lungs that were initially thought to be unacceptable for transplant

DESCRIPTION:

  • Consists of XPS Perfusion Cart Hardware, fluid path and non-fluid path disposables, XPS Cart Software, and STEEN Solution
  • STEEN Solution™ is clear, sterile, non-pyrogenic, non-toxic physiological salt solution containing human serum albumin (HSA) and dextran 40
  • Extracellular (low potassium) electrolyte solution with physiological colloid-osmotic pressure (COP) designed for use as a temporary continuous normothermic machine perfusion solution for ex vivo assessment of isolated lungs after removal from the donor

EFFECTIVENESS & SAFETY:

  • Study involving 332 sets of donor lungs allocated into three groups
  • Control group: Lungs initially deemed suitable for transplant that were provided to 116 recipients after standard preservation
  • Second group: Lungs initially deemed unsuitable for transplant and, after being perfused with the Xvivo Perfusion System, were implanted into 110 recipients
  • Third group: Perfused with the Xvivo Perfusion System and were still deemed not suitable after the perfusion, and therefore were not implanted into patients
  • One-year survival rate: 94% (Control) vs 86.4% (Second and third groups)
  • Difference in rates was not deemed to be clinically significant
  • Most common adverse events: Acute rejection, bronchial complications, respiratory failure and infections

REGULATORY PATHWAY: PMA

  • Classification: III
  • Procode: PHO
  • Originally granted marketing authorization in 2014 under humanitarian device exemption (HDE), limiting use to maximum of 8,000 patients per year
  • PMA pathway allows increased number of lungs to be available for transplant
  • Post-Approval requirements: Long-Term Post Approval Studies

LABEL


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COMANECI Embolization Assist Device

Rapid Medical

INDICATION FOR USE: For use in the neurovasculature as a temporary endovascular device used to assist in the coil embolization of wide-necked intracranial aneurysms with a neck width ≤ 10 mm. A wide-necked intracranial aneurysm defines the neck width as ≥ 4 mm or a dome-to-neck ratio < 2

GENERIC TYPE OF DEVICE: Temporary coil embolization assist device

  • Prescription device intended for temporary use in the neurovasculature to  mechanically assist in the embolization of intracranial aneurysms with embolic coils. The device is delivered into the neurovasculature with an endovascular approach. This device is not intended to be permanently implanted and is removed from the body when the procedure is completed.

RISKS AND MITIGATIONS:

  • Infection: Sterilization validation, Pyrogenicity testing, Shelf life testing, Labeling
  • Adverse tissue reaction: Biocompatibility evaluation
  • Tissue or vessel damage: Non-clinical performance testing, Clinical performance testing, Labeling
  • Thromboembolic event:  Non-clinical performance testing, Clinical performance testing, Labeling
  • Coils ensnarement: Non-clinical performance testing, Clinical performance testing, Labeling

REGULATORY PATHWAY: De Novo request

  • Regulation Number: 21 CFR 882.5955
  • Regulation Name: Temporary coil embolization assist device
  • Regulatory Class: Class II
  • Product Code: PUU

CLASSIFICATION ORDER


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NERIVIO MIGRA 

Theranica Bioelectronics ltd

INDICATION FOR USE: For acute treatment of migraine with or without aura in patients 18 years of age or older who do not have chronic migraine. It is a prescription use, self-administered device for use in the home environment at the onset of migraine headache or aura.

GENERIC DEVICE TYPE: Trunk and limb electrical stimulator to treat headache

  • Device intended to treat headache through the application of electrical stimulation anywhere on the body of the patient apart from the patient’s head or neck through electrodes placed on the skin. The stimulation may be provided transcutaneously or percutaneously

RISKS AND MITIGATIONS:

  • Adverse tissue reaction: Biocompatibility evaluation
  • Electrical, mechanical, or thermal hazards that may result in user discomfort or injury: Non-clinical performance testing, Electrical, mechanical, and thermal safety testing, Electromagnetic compatibility (EMC) testing, Software verification, validation, and hazard analysis, Labeling
  • Interference with other devices: Electromagnetic compatibility (EMC) testing, Labeling
  • Software malfunction leading to injury or discomfort: Software verification, validation, and hazard analysis
  • Hardware malfunction leading to injury or discomfort: Non-clinical performance testing, Shelf life testing, Labeling
  • Use error that may result in user discomfort, injury, or delay treatment for headaches: Labeling

REGULATORY PATHWAY: De Novo request

  • Regulation Number: 21 CFR 882.5899
  • Regulation Name: Trunk and limb electrical stimulator to treat headache
  • Regulatory Class: Class II
  • Product Code: QGT

CLASSIFICATION ORDER


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ZIKV Detect 2.0 IgM Capture ELISA

InBios

INDICATION FOR USE: Intended for the qualitative detection of Zika virus IgM
antibodies in human sera for the presumptive clinical laboratory diagnosis of Zika virus infection.
The assay is intended for use only in patients with clinical signs and symptoms consistent with Zika virus infection, and/or CDC Zika virus epidemiological criteria (e.g., 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). Assay results are for the presumptive detection of IgM antibodies to Zika virus (ZIKV). Positive results must be confirmed by following the latest CDC guidelines for the diagnosis of Zika virus infection.

ADDRESSING UNMET NEED:

  • 1st Commercial serology kit to receive FDA Marketing Authorization
  • Previous tests for detecting Zika virus IgM antibodies—including the ZIKV Detect 2.0 IgM Capture ELISA—had been authorized only for emergency use under the FDA’s Emergency Use Authorization (EUA) authority

GENERIC DEVICE TYPE: Zika virus serological reagents

  • In vitro diagnostic devices that consist of antigens or antibodies for the detection of Zika virus or Zika antibodies in human specimens from individuals who have signs
    and symptoms consistent with Zika virus infection and/or epidemiological risk factors. The detection aids in the diagnosis of current or recent Zika virus infection or serological status. Negative results obtained with this test do not preclude the possibility of Zika virus infection, past or present. Positive results should be interpreted with consideration of other clinical information and laboratory findings and should not be used as the sole basis for treatment or other patient management decisions.

RISKS AND MITIGATIONS:

  • Risk of false results: Device description, performance characteristics, validation procedures, labeling
  • Failure to correctly interpret test results: Device description, performance characteristics, Labeling
  • Failure to correctly operate the device: Device description, performance characteristics, validation procedures, Labeling

REGULATORY PATHWAY: De Novo request (previously authorized via EUA)

  • Regulation Number: 21 CFR 866.3935
  • Regulation Name: Zika Virus Serological Reagents
  • Regulatory Class: Class II
  • Product Code: QFO

CLASSIFICATION ORDER


Image credits: NeuroSigma, Xvivo, Rapid Medical, Theranica, InBios

Drug and Vaccine Authorizations: EVENITY for osteoporosis, DENGVAXIA for Dengue, MAVYRET for Hep C in children, BENLYSTA in SLE, TIBSOVO for AML, VYNDAQEL/VYNDAMAX for cardiomyopathy, RUZURGI for LEMS

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EVENITY (romosozumab-aqqg) injection, for subcutaneous use 

Amgen

INDICATION FOR USE: Treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy
Limitations of Use : Anabolic effect wanes after 12 monthly doses of therapy. Therefore, the duration of EVENITY use should be limited to 12 monthly doses. If osteoporosis therapy remains warranted, continued therapy with an anti-resorptive agent should be considered

ADDRESSING UNMET NEED:
  • > 10 million US women osteoporosis; weakened bones likely to fracture
  • Approval provides women with postmenopausal osteoporosis with high risk of fracture with a new treatment

MECHANISM OF ACTION: Monoclonal antibody that inhibits action of sclerostin, a regulatory factor in bone metabolism; increases bone formation and, to a lesser extent, decreases bone resorption

EFFICACY:
  • 2 randomized, double-blind studies, placebeo and alendronate controlled respectively, n>11,000 women with postmenopausal osteoporosis
  • Endpoints: Risk of a new fracture in spine (vertebral fracture): 73% lowered risk vs. placebo, maintained over the second year of trial when Evenity.  50% lowered risk vs. two years of alendronate alone
  • Evenity followed by alendronate reduced risk of fractures in other bones (nonvertebral fractures) vs. alendronate alone
SAFETY:
  • Boxed Warning: Potential risk for myocardial infarction, stroke and cardiovascular death
  • Common side effects: Joint pain, headache, injection site reactions
REGULATORY PATHWAY: BLA
  • Pediatric assessments: Waived; do not apply to population
  • Postmarketing requirements: Cardiovascular safety

LABEL


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DENGVAXIA (Dengue Tetravalent Vaccine, Live) Suspension for Subcutaneous Injection

Sanofi Pasteur

INDICATION FOR USE: indicated for the prevention of dengue disease caused by dengue virus serotypes 1, 2, 3 and 4. DENGVAXIA is approved for use in individuals 9 through 16 years of age with laboratory-confirmed previous dengue infection and living in endemic areas
Limitations of use: Not approved for use in individuals not previously infected by any dengue virus serotype or for whom this information is unknown; Safety and effectiveness have not been established in individuals living in dengue non-endemic areas who travel to dengue endemic areas

ADDRESSING UNMET NEED:

  • FDA committed to working with CDC and WHO to combat public health threats
  • Approval is important step toward reducing impact of virus in endemic US regions

MECHANISM OF ACTION: Elicits dengue-specific immune responses against four dengue virus serotypes

EFFICACY:

  • Three randomized, placebo-controlled studies, n=35,000 individuals in dengue-endemic areas, including Puerto Rico, Latin America and Asia Pacific region, 9-16 years of age
  • Endpoint: Symptomatic virologically-confirmed dengue (VCD); DENGVAXIA 76%  effective in preventing VCD in individuals who previously had laboratory- confirmed dengue disease

SAFETY: 

  • Most commonly reported side effects: Headache, muscle pain, joint pain, fatigue, injection site pain and low-grade fever

REGULATORY PATHWAY: BLA

  • Priority Review and a Tropical Disease Priority Review Voucher
  • Postmarketing Study Requirement/Commitments: Safety and effectiveness in children 2 to < 9 years of age

PACKAGE INSERT


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MAVYRET (glecaprevir and pibrentasvir) tablets

AbbVie

INDICATION FOR USE: Treatment of adult and pediatric patients 12 years and older or weighing at least 45 kg with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A)

ADDRESSING UNMET NEED:  First treatment for all genotypes of hepatitis C in pediatric patients

MECHANISM OF ACTION: Fixed-dose combination of glecaprevir and pibrentasvir, which are direct-acting antiviral agents against the hepatitis C virus

EFFICACY:

  • Open-label study, n=47  adolescent subjects 12 -< 18 years  with genotype 1, 2, 3 or 4 HCV infection without cirrhosis or with mild cirrhosis, 8 or 16 weeks.
  • 100% had no virus detected in blood 12 weeks after finishing treatment, suggesting  infection had been cured

SAFETY:

  • Adverse reactions observed were consistent with those observed in adults
  • Most commonly reported adverse reactions: Headache and fatigue

REGULATORY PATHWAY: Supplemental NDA

  • Initial US approval (NDA) in adult patients in 2017

LABEL


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BENLYSTA (belimumab) intravenous infusion

GlaxoSmithKline

INDICATION FOR USE: Treatment of patients aged 5 years and older with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy

ADDRESSING UNMET NEED:

  • First treatment for pediatric patients with Systemic Lupus Erythematosus (SLE)
    • Benlysta has been approved for use in adult patients since 2011

EFFICACY:

  • International, randomized, doubleblind, placebo-controlled, 52-week, n=93  pediatric patients with a clinical diagnosis of SLE
  • Primary efficacy endpoint: SLE Responder Index (SRI-4) at Week 52; numerically higher patients achieving a response in SRI-4 with BENLYSTA vs. placebo

SAFETY:

  • Warning for mortality, serious infections, hypersensitivity and depression
  • Most common side effects: Nausea, diarrhea and fever, infusion reactions

REGULATORY PATHWAY: sBLA, Priority review

LABEL


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TIBSOVO (ivosidenib) tablets

Agios Pharmaceuticals

RealTime IDH1 Assay

Abbott

INDICATION FOR USE: Treatment of newly-diagnosed acute myeloid leukemia (AML)  with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in adult patients who are ≥ 75 years old or who have comorbidities that preclude use of intensive induction chemotherapy

ADDRESSING UNMET NEED: First-line treatment for AML with IDH1 mutation

EFFICACY:

  • Open-label, single-arm, multicenter clinical trial, n=28 (newly-diagnosed AML with IDH1 mutation detected by Abbott RealTimeTM IDH1 Assay
  • Endpoints: Rate of complete remission (CR) or complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, conversion rate from transfusion dependence to transfusion independence
  • CR+CRh :42.9%, 41.2% achieved transfusion independence lasting at least 8 weeks

SAFETY:

  • Boxed Warning for Differentiation Syndrome which may be life-threatening or fatal
  • Adverse reactions: Diarrhea, fatigue, edema, decreased appetite, leukocytosis, nausea, arthralgia, abdominal pain, dyspnea, differentiation syndrome and myalgia

REGULATORY PATHWAY: sNDA

  • Used Real-Time Oncology Review pilot program
  • Priority Review and Orphan Product designation
  • Postmarketing requirement: Determine safe dose in mild, moderate and severe hepatic impairment

LABEL


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VYNDAQEL (tafamidis meglumine) and VYNDAMAX (tafamidis) capsules 

FoldRx (Pfizer subsidiary)

INDICATION FOR USE: Treatment of cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization

ADDRESSING UNMET NEED:

  • Transthyretin-mediated amyloidosis is rare, debilitating, often fatal disease
  • Approval an important advancement in treatment of cardiomyopathy caused by transthyretin-mediated amyloidosis

MECHANISM OF ACTION: Selective stabilizer of TTR;  slows dissociation into monomers, the rate-limiting step in the amyloidogenic process

EFFICACY:

  • Multicenter, international, randomized, double-blind, placebo-controlled study
    n=441 patients with wild type or hereditary ATTR-CM
  • Endpoints: All-cause mortality and frequency of cardiovascular-related hospitalizations
  • Significant reduction (p=0.0006) in all-cause mortality and frequency of
    cardiovascular-related hospitalizations with Vyndaqel / Vyndamax group

SAFETY:

  • No drug-associated side effects identified
  • May cause fetal harm when administered to pregnant woman

REGULATORY PATHWAY: NDA

  •  Fast Track, Priority Review and Breakthrough Therapy designations
  • Orphan Drug designation

LABEL


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RUZURGI (amifampridine) tablets 

Jacobus Pharmaceutical Company

INDICATION FOR USE: Treatment of Lambert-Eaton myasthenic syndrome (LEMS) in patients 6 to less than 17 years of age

ADDRESSING UNMET NEED:

  • LEMS is a rare autoimmune disorder affecting connection between nerves and muscles
  • First approved treatment for LEMS specifically in children

MECHANISM OF ACTION: Broad spectrum potassium channel blocker

EFFICACY:

  • Randomized, double-blind, placebo-controlled withdrawal study
  • Primary measure of efficacy: Change in Triple Timed Up and Go test (3TUG)  and self-assessment scale for LEMS-related weakness
  • Less impairment with Ruzurgi; greater perceived weakening with placebo

SAFETY: 

  • Most common side effects: Burning or prickling sensation (paresthesia), abdominal pain, indigestion, dizziness and nausea
  • Seizures in patients without a history of seizures

REGULATORY PATHWAY: NDA,  Priority Review and Fast Track designations, Orphan Drug designation

LABEL


Image credits: Amgen, Sanofi, AbbVie, Agios, GSK, Pfizer, Jacobus

News & Views: CDRH reorg implementation, Deep Learning and patient safety, Patient Preference Information, CMS reimbursement for novel devices, Biologics development, Addressing health disparities, Safer prescribing of psychoactives with opioids, Marketed Device safety measures, Warnings for insomnia drugs,

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Team-Based Approach to Medical Device and Radiological Product Evaluation and Quality

Operationalizing  Office of Product Evaluation and Quality (OPEQ)

  • Identifying, Resolving, and Communicating Safety Issues — Faster and Better
  • Informing New Product Approvals with Latest Safety Data
  • Advancing Safer and More Effective Innovative Technologies
  • Enhancing Evidence Generation Throughout the Total Product Life Cycle
  • Fostering Employee Engagement, Opportunity, and Success

CDRH Directory


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Capturing Patient Experience Through Deep Learning

  • FDA developing computational approaches to use deep learning, a form of artificial intelligence (AI), to extract  adverse events of drugs and therapeutic biologics (using standard MedDRA terms) automatically from NDAs
  • Patient narratives in NDAs used to train a neural network to make correct MedDRA coding decisions using diverse natural language processing (NLP)
  • Development of user-friendly tool to check MedDRA  coding accuracy of previous submissions, such as adverse event reports from drug developers

READ


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Using Patient Preference Information (PPI) in Medical Device Evaluation

PPI defined as

  • Qualitative/Quantitative assessments of relative patient desirability or acceptability of specified alternatives or choices among outcomes or other attributes
  • Clarify what benefits and risks are most important to patients
  • Impact premarket clinical study design, benefit-risk assessments, postmarket evaluation

Agency has identified  Priority List of Patient Preference-Sensitive Areas

Parameters for patient preference-sensitive areas

  • Better understand full impact of disease and treatment options on patients
  • Patients may value benefits-risks  differently from healthcare professionals
  • Population-level differences in patient perspectives not well understood
  • Significant public health impact

READ


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CMS comprehensive strategy to foster innovation for transformative medical devices 

Goal to get new innovations to  beneficiaries concurrent with FDA approval

  • Removing government barriers to innovation
  • Harmonizing CMS coverage, coding, and payment processes

Initiatives

  • CMS-FDA Parallel Review Program – FDA approval and CMS coverage on same day
  • Modernize payment policies for ‘Breakthrough Devices’ designation – waive  requirement for “substantial clinical improvement”
  • More frequent, semi-annual, opportunities to request HCPCS code
  • Consider commercial payments in determining payments for innovative Durable Medical Equipment (DME)
  • Reevaluiate guidelines for new hospital technology add-on payment (NTAP)
  • Enhance ease of billing for new technologies
  • New guidance on Local Coverage Decisions (LCD) – contractors not authorized to make coverage determinations to automatically non-cover any item or service

READ


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Efforts to Advance the Development of Biologics

Biologics, regulated by CBER, are either living cells or tissues, or are made from them, such as stem cells and genetically engineered immune cells

  • Drugs: Includes blood components/derivatives, vaccines, allergenics, and cellular/gene therapies
  • Devices: In vitro diagnostic tests for screening blood supply, for manufacturing blood and tissue products
  • Safety and efficacy linked to quality and consistency of manufacturing

Cellular and Gene Therapy Approvals in 2018

  • LUXTURNA for heritable disorder that causes blindness: retinal dystrophy associated with mutations in the RPE65 gene
  • YESCARTA, CAR-T cell therapy  to treat adults with certain types of relapsed or refractory diffuse large B cell non-Hodgkin lymphoma

Vaccine and Blood Product Approvals in 2018

  • HEPLISAV-B, Hepatitis B vaccine to prevent infection caused by all known subtypes of hepatitis B virus in adults 18 of age and older
  • SHINGRIX, vaccine for shingles prevention in adults 50 years of age and older
  • COBAS Zika Test and the PROCLIEX Zika Virus Assay for Zika detection in human plasma

READ


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Addressing Health Disparities Through Communication, Research, and Collaboration

Office of Minority Health and Health Equity (OMHHE) promotes and protects health of diverse populations and strives for health equity

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Preclinical Research to Achieve Safer Prescribing of Psychoactive Therapeutics for Patients Who Use Opioids

More than 30%  of deaths from opioids involve use of benzodiazepines, commonly used for anxiety or insomnia

  • Might worsen the respiratory effects of opioids in patients being treated for pain. To achieve this goal
  • Gaps in evidence needed for safer prescribing

FDA developing Preclinical Model to address gaps 

  • Rat study and predict interaction of psychoactive sedative drugs and opioids
  • Exposed to psychoactive drug with or without the opioid oxycodone
  • Determine respiratory effect and opioid-induced respiratory depression
  • Measurement of achieved blood concentrations over time to determine how to administer the drugs so that tested drug and opioid reach simultaneous peak levels

READ


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Marketed Device Safety Measures

SURGICAL MESH for transvaginal repair of pelvic organ prolapse – Sales stopped 

  • FDA ordered all manufacturers of surgical mesh intended for transvaginal repair of anterior compartment prolapse (cystocele) to stop selling-distributing immediately
  • Manufacturers- Boston Scientific and Coloplast- have not demonstrated reasonable assurance of safety and effectiveness for these high risk  devices these devices

READ

SURGICAL STAPLERS- New steps to reduce risks

  • Large number of adverse events reports  including opening of staple line, malformation of staples, misfiring, difficulty in firing, failure of stapler to fire staple, misapplied staples
  • Increasing regulatory requirements from Class I (low risk) to Class II (moderate risk)
  • Require labeling to provide adequate information for use, including hazards, contraindications, information for safe and effective use

READ

BREAST IMPLANTS- New efforts to protect health and ensure safety

  • Weighing risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)
  • Improve labeling to communicated risk of BIA-ALCL, greater risk of BIA-ALCL with textured implants, and risk of developing systemic symptoms to women and health care professionals professionals

READ


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Stronger warnings about rare but serious incidents related to certain prescription insomnia medicines

Rare, complex sleep behaviors specifically associated with use of eszopiclone (Lunesta), zaleplon (Sonata) and zolpidem (Ambien, Ambien CR, Edluar, Intermezzo, Zolpimist)

  • Serious injuries because of sleep behaviors, including sleepwalking, sleep driving, and engaging in other activities while not fully awake (e.g. using a stove)
  • Have also resulted in deaths

Labeling updates

  • Boxed Warning –most prominent warning
  • Contraindication-strongest warning
  • Avoid use in patients who have previously experienced an episode of complex sleep behavior with eszopiclone, zaleplon, and zolpidem

READ


Image credit: FDA

Remove the Risk- Opioid Disposal Campaign

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Remove the Risk- Opioid disposal awareness 

  • In 2017: 191 million opioid prescriptions to almost 60 million patients
  • 90% patients reported not finishing what was prescribed to them
  • Millions of unused prescription opioids in homes if not disposed of properly
  • In 2017: 47,600 people died from an overdose involving opioids

Remove the Risk PR campaign

  •  Targeting women ages 35-64, who are most likely to oversee household health care decisions
  • Information about safe disposal of these medicines.

LEARN


image: FDA

Drug Authorizations: ZULRESSO for postpartum depression, SUNOSI for daytime sleepiness, MAYZENT for multiple sclerosis, DOVATO for HIV, BALVERSA for metastatic bladder cancer

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ZULRESSO (brexanolone) intravenous injection 

Sage Therapeutics

INDICATION: Treatment of postpartum depression (PPD) in adults

ADDRESSING UNMET NEED:

  • First drug approved specifically for PPD
  • PPD is a serious condition that can be life-threatening

MECHANISM OF ACTION: Related to positive allosteric modulation of GABA receptors

EFFICACY:

  • Two multicenter, randomized, double-blind, women (18 to 45 years) with PPD, ZULRESSO vs placebo
  • Primary endpoint: Mean change from baseline in depressive symptoms as measured by HAM-D total score at the end of the infusion
  • Superiority to placebo in improvement of depressive symptoms,  improvement in depression was also observed at the end of the 30-day follow-up period.

SAFETY:

  • Boxed Warning: Patients at risk of excessive sedation or sudden loss of consciousness during administration; must be monitored for excessive sedation and sudden loss of consciousness and have continuous pulse oximetry monitoring
  • Most common adverse reactions: Sleepiness, dry mouth, loss of consciousness and flushing

REGULATORY PATHWAY: NDA

  • Priority Review and Breakthrough Therapy designations
  • Approved with a Risk Evaluation and Mitigation Strategy (REMS)- only available through restricted distribution program
  • Recommend scheduling of Zulresso under the Controlled Substances Act (CSA)- DEA scheduling pending
  • Required Pediatric Assessment: In adolescent females, 15 – <18 diagnosed with postpartum depression.

LABEL 


Capture.JPGSUNOSI (solriamfetol) tablets

Jazz Pharmaceuticals

INDICATION: To improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (OSA)

MECHNANISM OF ACTION: Could be mediated through its activity as a dopamine and norepinephrine reuptake inhibitor

EFFICACY:

Narcolepsy

  • 12-week, multi-center, randomized, double-blind, placebo-controlled,
    parallel-group study, n=239 patients with narcolepsy
  • Co-primary Endpoints:  Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS). Statistically significant improvements with SUNOSI

OSA:

  • 12-week multi-center, randomized, double-blind, placebo-controlled study, n=476 patients with OSA
  • Statistically significant improvements with SUNOSI on MWT and ESS

SAFETY:

  • Warnings and Precautions: Blood Pressure and Heart Rate Increases, Psychiatric Symptoms
  • Most common adverse reactions: Headache, nausea, decreased appetite, insomnia, anxiety.

REGULATORY PATHWAY: NDA

  • Recommended scheduling under Controlled Substances Act (CSA)- DEA scheduling pending
  • Postmarketing requirements: Prospective, registry study on maternal, fetal, infant outcomes, additional pregnancy study, lactation study

LABEL


Capture.JPGMAYZENT (siponimod) tablets 

Novartis

INIDCATION: Treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

ADDRESSING UNMET NEED:

  •  MS is among the most common causes of neurological disability in young adults and occurs more frequently in women than in men
  •  Can have a profound impact on person’s life
  • Approval provides  a  treatment option

MECHANISM OF ACTION: Sphingosine-1-phosphate (S1P) receptor modulator; binds with high affinity to S1P receptors-  reduces lymphocyte migration into CNS

EFFICACY:

  • Randomized, double-blind, parallel-group, placebo-controlled, time-to-event study, n=1651 in patients with secondary progressive multiple sclerosis (SPMS), MAYZENT vs placebo
  • Primary endpoint:  Time to three-month confirmed progression in disability
  • Progression of disability statistically significantly lower in Mayzent vs. placebo
  • Decreased number of relapses group with Mayzent

SAFETY:

  • Medication Guide:  May increase the risk of infections, may cause macular edema,  may cause transient decreases in heart rate and may cause a decline in lung function and liver fucntion
  • Most common adverse reactions: Headache, high blood pressure and liver function test increases

REGULATORY PATHWAY: NDA

  • Postmarketing requirements: Clinical Study to assess serious risk of pulmonary toxicity, Prospective pregnancy exposure registry, Pregnancy outcomes study

LABEL


Capture.JPGDovato (dolutegravir and lamivudine) tablet

ViiV Healthcare

INDICATION: complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults with no antiretroviral treatment history and with no
known substitutions associated with resistance to the individual components of DOVATO

ADDRESSING UNMET NEED:

  •  First FDA-approved two-drug, fixed-dose, complete regimen for HIV-infected adults who have never received treatment for HIV
  • Drug-sparing treatment available that uses fewer drugs is beneficial to patients who may have issues taking multiple medications over a long period of time

MECHANISM OF ACTION: Fixed-dose combination of the HIV-1 antiretroviral agents, dolutegravir and lamivudine

EFFICACY:

  • Two identical, randomized, double-blind, controlled clinical trials, n=1,433 HIV-infected adults with no prior antiretroviral treatment history
  • Primary efficacy endpoint: Proportion of subjects with plasma HIV-1 RNA <50 copies/mL at Week 48
  • Dovato had similar effect of HIV reducion vs drug regimen of dolutegravir, emtricitabine, and tenofovir

SAFETY:

  • Boxed Warning: Patients infected with both HIV and hepatitis B should add additional treatment for hepatitis B 
  • Known risk for neural tube defects with dolutegravir- avoid use at the time of conception through first trimester of pregnancy
  • Most common adverse reactions: Headache, diarrhea, nausea, insomnia and fatigue

REGULATORY PATHWAY:  NDA

  • Supportive of DHHS initiative Ending the HIV Epidemic: A Plan for America,
  • Aim to reduce new infections by 75% in the next 5 years and by 90% in the next 10  years, averting more than 250,000 HIV infections in that span

LABEL


Capture.JPGBALVERSA (erdafitinib) tablets

Janssen

therascreen FGFR RGQ RT-PCR Kit  

Qiagen

INDICATION: Treatment of adult patients with locally advanced or metastatic
urothelial carcinoma (mUC), that has:

  • susceptible FGFR3 or FGFR2 genetic alterations, and
  • progressed during or following at least one line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

Select patients for therapy based on an FDA-approved companion diagnostic for BALVERSA

ADDRESSING UNMET NEED: First personalized treatment targeting susceptible FGFR genetic alterations for patients with metastatic bladder cancer

MECHANISM OF ACTION: Kinase inhibitor that binds to and inhibits enzymatic activity of FGFR1, FGFR2, FGFR3 and FGFR4; inhibits FGFR phosphorylation and signaling and decreased cell viability in cell lines expressing FGFR genetic alterations

EFFICACY:

  • Multicenter, open-label, single-arm study, n=87 patients with locally advanced or metastatic bladder cancer, with FGFR3 or FGFR2 genetic alterations, that had progressed following treatment with chemotherapy
  • Major efficacy outcome measures: Objective response rate (ORR), Duration of response (DoR), determined by blinded independent review committee (BIRC) according to RECIST v1.1
  • ORR: 32.2%, with 2.3% having complete response and 30% having partial response
  • DOR: Approximately five-and-a-half months
  • Responses to Balversa were seen in patients who had previously not responded to anti PD-L1/PD-1 therapy

SAFETY:

  • Warnings and Precautions: Ocular disorders, Hyperphosphatemia
  • Common side effects: Increased phosphate level, mouth sores, feeling tired, change in kidney function, diarrhea, dry mouth, nails separating from the bed or poor formation of the nail, change in liver function, low salt (sodium) levels, decreased appetite, change in sense of taste, low red blood cells (anemia), dry skin, dry eyes and hair loss. Other side effects include redness, swelling, peeling or tenderness on the hands or feet (hand foot syndrome), constipation, stomach pain, nausea and muscle pain
  • Balversa because it may cause harm to a developing fetus or newborn baby

REGULATORY PATHWAY: NDA

  • Accelerated Approval, Breakthrough Therapy designation
  • Accelerated approval based on tumor response rate – Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials
  • Accelerated approval requirements: Demonstrating clinical benefit of erdafitinib in patients with locally advanced and metastatic urothelial carcinoma with susceptible FGFR 3 or FGFR 2 genetic alterations

LABEL


Image credit: Sage, Jazz, Novartis, ViiV, Janssen

 

Device Authorizations: TRILURON for osteoarthritis, LOADPRO for spine surgery, PLENITY for weight management, LEICA 400 filter for glioma

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TRILURON

Fidia Farmaceutici S.p.A.

INDICATION FOR USE: Treatment of pain in osteoarthritis (OA) of the knee in
patients who have failed to respond adequately to conservative nonpharmacologic therapy, and to simple analgesics, e.g., acetaminophen

DESCRIPTION:

  • Viscous solution consisting of a high molecular weight (500,000–730,000 daltons) fraction of purified sodium hyaluronate (Hyalectin®) in buffered
    physiological sodium chloride, having a pH of 6.8-7.
  • The sodium hyaluronate is extracted from rooster combs
  •  Hyaluronic acid is a natural complex sugar of the glycosaminoglycan family and is a long-chain polymer containing repeating disaccharide units of Naglucuronate-N-acetylglucosamine
  • Administered by intra-articular injection

EFFECTIVENESS AND SAFETY:

  • Retrospective analysis of data prospectively collected from two randomized, controlled trials to determine the effectiveness of TRILURON vs. Hyalgan (control device)
  • Both have identical chemical formulation and differ only in that a lower
    dose is injected (3 weekly injections for TRILURON™ compared to 5 weekly injections of Hyalgan)
  • Primary effectiveness endpoint: Mean change from baseline at 26 weeks in WOMAC Pain scores: TRILURON was non-inferior to Hyalgan
  • Primary evidence of safety of Hyalgan is directly applicable to TRILURON and has already been established

REG PATHWAY: PMA

  • Device Procode: MOZ

LABEL


Capture.JPGLOADPRO™ Intraoperative Rod Strain Sensor

Intellirod Spine, Inc

INDICATION FOR USE: Intraoperative surgical tool that allows surgeons to measure unidirectional rod microstrain on posterior rods in the sagittal plane when performing spine surgery.

Adjunct to surgeon tactile feedback and is not intended to replace a surgeon’s clinical judgment.

Single use, disposable tool to be used in conjunction with X-Spine Systems Fortex Pedicle Screw System for 5.5mm diameter titanium (ASTM F136) or cobalt chrome (ASTM F1537) rod configurations.

GENERIC DEVICE TYPE: Intraoperative orthopedic strain sensor

  • Adjunct tool intended to measure strain on an orthopedic implant in the intraoperative setting only
  • Not intended to provide diagnostic information or influence clinical decision-making.

RISKS & MITIGATIONS (SPECIAL CONTROLS):

  • Prolonged operative time due to device error or use error: Usability Testing, Non-clinical Performance Testing, Software verification, validation, and hazard analysis, Labeling 
  • Electrical shock or device failure due to interference from other devices: Electromagnetic compatibility testing, Electrical safety testing 
  • Infection: Sterilization validation, Reprocessing validation, Shelf life testing
    Labeling 
  • Adverse tissue reaction: Biocompatibility evaluation

REGULATORY PATHWAY: De Novo request 

  • Regulation Number: 21 CFR 888.3090
  • Regulation Name: Intraoperative orthopedic strain sensor
  • Regulatory Class: Class II
  • Product Code: QFP

CLASSIFICATION ORDER


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PLENITY device for weight management and/or weight loss

Gelesis, Inc.

INDICATION FOR USE: To aid in weight management in overweight and obese adults with a Body Mass Index (BMI) of 25 – 40 kg/m2, when used in conjunction with diet and exercise

GENERIC DEVICE TYPE: Ingested, transient, space occupying device for weight management and/or weight loss

  • Ingested material that transiently occupies space in the stomach
  • Device passes from the body via the natural gastrointestinal tract

RISKS & MITIGATIONS (SPECIAL CONTROLS):

  • Device related gastrointestinal adverse events, including:  Obstruction,  Dilation,  Diarrhea, Constipation, Dehydration: Clinical performance testing, Non-clinical performance testing, Labeling, Shelf life testing
  • Weight gain: Clinical performance testing, Labeling 
  • Interaction with medication: Clinical performance testing, Non-clinical performance testing, Labeling 
  • Adverse tissue reaction: Biocompatibility evaluation
  • Infection: Non-clinical performance testing. Shelf life testing

REGULATORY PATHWAY: De Novo request

  • Regulation Number: 21 CFR 876.5982
  • Regulation Name: Ingested, transient, space occupying device for weight management and/or weight loss
  • Regulatory Class: Class II
  • Product Code: QFQ

CLASSIFICATION ORDER


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Leica FL400 surgical microscope accessory filter

Leica

INDICATION FOR USE: Surgical microscope accessory filter set for viewing fluorescence of fluorophores comprising an excitation filter for blue spectral range 380 nm – 430 nm and an  observation filter comprising the long-wave blue, green, yellow and red spectrum in the spectral band greater than 444 nm.

Surgical microscope accessory used in fluorescent visualization of suspected grade III or IV gliomas during neurosurgery.

GENERIC DEVICE TYPE: Diagnostic neurosurgical microscope filter

  • Device intended for use during neurosurgery to visualize fluorescence and enhance visualization of tissue associated with a specific disease or condition

RISKS and MITIGATIONS (SPECIAL CONTROLS):

  •  False positive: visualization of fluorescence when in fact no target fluorophore is present: Non-clinical performance testing and Labeling
  • False negative: no visualization of fluorescence when in fact the target fluorophore is present:  Non-clinical performance testing and Labeling

REG PATHWAY: De Novo request for Accessory

  • Microscope cleared via 510(k) pathway
  • De novo request for filter as ‘accessory’
  • Regulation Number: 21 CFR 882.4950
  • Regulation Name: Diagnostic neurosurgical microscope filter
  • Regulatory Class: Class II
  • Product Code: QFX

CLASSIFICATION ORDER


Image credits: Fidia, Intellirod Spine, Gelesis, Leica

Enforcement Actions: INOVA Genomics unapproved tests, Duodenoscope contamination, Unapproved Concussion Apps, Reused/Unauthorized Test Strips

ENFORCEMENT ACTIONS

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Inova Genomics Laboratory Warning Letter

Marketing in the US without marketing clearances or approvals, in violation of the Federal Food, Drug, and Cosmetic Act
  • MediMap ADHD, MediMap Mind, MediMap Plus, MediMap Heart, MediMap Baby
  • Being marketed as genetic tests for predicting medication response, reducing negative side effects,  discovering the right drug and right dose for a patient…
  • MediMap tests are devices based on intended uses
  • Clinical validity  not established for their intended uses
  • Pose significant public health concerns- inaccurate test results could impact the decision-making of healthcare providers and patients, seriously detrimental to patient health

Not considered as a Lab Developed Test (LDT) that is exempt from FDA’s premarket review or labeling requirements

WARNING: Inova Genomics


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High Duodenoscope Contamination Rate

  • Postmarket surveillance studies by  all three manufacturers (Fujifilm Medical Systems USA, Inc, Olympus Medical Systems Corporation, Pentax of America)
  • Evaluate % duodenoscopes which remain contaminated after use of labeled reprocessing instructions
  • Preliminary results (3/2019) indicate higher than expected levels (0.4%)  of contamination
  • Root cause analyses are currently underway; importance of strictly adhering to manufacturer’s reprocessing and maintenance instructions

SAFETY: Duodenoscope Reprocessing


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Unapproved or uncleared Apps for concussion

Potential serious risks associated with use of unapproved or uncleared Apps 

  • Marketed to coaches or parents for use during sporting events
  • Could result in an incorrect diagnosis, potentially leading to person with serious head injury returning to their normal activities instead of getting medical care
  • FDA became aware of violative products being marketed to consumers – asked to  remove such claims
  • Will continue to monitor marketplace for devices making unsubstantiated claims and will take further action if necessary
  • Limited number of medical devices that have been FDA cleared or approved to aid in the diagnosis, treatment, or management of concussion – all require evaluation by health care professional

WARNING: Concussion Assessment


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Previously Owned Test Strips or Test Strips Not Authorized for US Sale

Marketing of pre-owned test strips or test strips not authorized for sale in the U.S.

  • Sold through online marketplaces- Amazon, eBay, Craigslist, or directly from seller
  • Pre-Owned Strips :  Unsafe, poor storage, tampering, infection risk from previous owner’s blood – Inaccurate test results
  • Test strips not authorized for US sale: Suboptimal quality, inaccurate results

WARNING: Glucose test strips


Image credit: FDA

 

News & Views: Acting Commissioner, FDA and CBP collaboration, Cannabis-derived product regulation, E-cigarette addiction treatment, Risk-Based Monitoring, Medical Counter Measures, Class I Accessories, Office of Minority Health and Health Equity

Transition of FDA Leadership: Dr. Ned Sharpless as Acting Commissioner

Farewell to Commissioner Gottlieb

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MEET


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FDA and CBP bolster collaboration to protect public health and safety

FDA and CBP agreement to maximize inspection and detection capabilities

  • Prevent illegal and harmful products entering International Mail Facilities and Ports of Entry
  • Sharing of FDA’s advanced screening technology to identify trends in future entries
  • Shared space and increased scientific presence at high-risk/high-volume facilities

READ


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Continued evaluation of potential regulatory pathways for cannabis-containing and cannabis-derived products

Products containing cannabis or cannabis derivatives marketed as human drugs, dietary supplements, conventional foods, animal foods/drugs, cosmetics

  • Public hearing on May 31 to share experiences and challenges and product safety
  • Formation of high-level internal agency working group on potential pathways for dietary supplements to be lawfully marketed
  • Webpage on FDA’s requirements for these products
  • Issuance of multiple warning letters to companies marketing CBD products with  unfounded claims aimed at vulnerable populations

READ


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Treatment strategies for nicotine addiction and teen use of e-cigarettes

To address troubling epidemic of youth e-cigarette use

  • Youth Tobacco Prevention Plan to ensure no tobacco products marketed to kids
  • Enforcement actions on illegal sales
  • Public education campaigns to warn youth
  • Advanced new policies aimed at preventing youth access to flavored tobacco products, including e-cigarettes and cigars
  • Workshop to examine science and treatment strategies for youth tobacco cessation

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Capture.JPGA Risk-Based Approach to Monitoring of Clinical Investigations

Scope: identifying critical data and processes necessary for human subject protection,investigation integrity, risk assessment, specific monitoring plan

  • Tailor monitoring plans to needs of investigation
  • Factors to consider in developing monitoring plan
  • Examples of monitoring methods and techniques
  • Risk-based monitoring important tool to identify and address issue

Monitoring Approach: include information regarding identified risks and how monitoring methods will address those risks

Monitoring Plan Content: A detailed list

Follow-Up and Communication of Monitoring Results: Significant issues identified through monitoring with appropriate Corrective and Preventive Actions

READ


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Medical CounterMeasures (MCMs) update

FDA responsible for safety and effectiveness of MCMs—drugs, therapeutic biologics,vaccines, devices, such as diagnostic tests

  • Smallpox preparedness: TPOXX for treatment of smallpox
  • Chemical nerve agent preparedness: Atropine autoinjector for treatment of poisoning by susceptible organophosphorous nerve agents and Seizalam (midazolam intramuscular injection) for the treatment of status epilepticus
  • Radiological/nuclear emergency preparedness: New indication for Leukine (sargramostim) to increase survival in acute exposure to radiation
  • Viral encephalitis preparedness: IXIARO Japanese Encephalitis Virus Vaccine
  • Zika protection: COBAS Zika to screen Zika virus in blood donations
  • Pandemic influenza preparedness: FLUARIX Influenza Virus Vaccine

READ


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Finalized List of Accessories Suitable for Class I

For  accessory to be eligible for class I distinct from another device if the accessory

  • is not for use in supporting or sustaining human life
  • does not represent potential unreasonable risk of illness or injury
  • general controls sufficient for reasonable assurance of safety and effectiveness
§ 876.1080 Gastroenterology-urology accessories to a biopsy instrument
§ 876.3500 Penile implant surgical accessories
§ 876.4630 Ureteral stent accessories
§ 876.5012 Biliary stent, drain, and dilator accessories
§ 876.5100 Suprapubic catheter accessories
§ 876.5290 Implanted mechanical/hydraulic urinary continence device surgical accessories
§ 878.5080 Air-handling apparatus accessory
§ 886.4355 Corneal inlay inserter handle

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CaptureFDA OMH has a new name: FDA Office of Minority Health and Health Equity (OMHHE)

Reorganization reflects commitment to modernizing structure to:

  • Advance mission to protect and promote public health
  • Meet challenges of rapid innovation across industries regulated by FDA
  • Better captures breadth of portfolio and continue to address needs of racial and ethnic minority populations and underserved communities

New organization chart


Image credit: FDA

 

Fact or Fiction: Smoking Cessation and Medications

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WATCH

Fact or Fiction: What to Know About Smoking Cessation and Medications

The best way to quit is “cold turkey.” FICTION!

All smoking cessation medications are the same. FICTION!

E-cigarettes are not an approved method to help people quit smoking. FACT!

Nicotine is not the primary cause of cancer from most tobacco products. FACT!

It is dangerous to use more than one nicotine replacement therapy product at the same time. FICTION!

Nicotine replacement therapy gum is different than regular gum. FACT!

Nicotine replacement therapy can be used only for the duration listed on the label. FICTION!

If you’ve tried nicotine replacement therapy in the past and it didn’t work, there is still reason to try it again. FACT!


Image credit: FDA

 

 

 

News & Views: Novel device materials, Modernize clinical trials, 2020 focus areas, New opioid REMS, Modernize mammography, Anthrax diagnostic reg pathway, AI/ML reg framework, Device inspections, Enforcement Actions

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Efforts to evaluate materials in medical devices to address potential safety questions

Materials used in today’s medical devices vary widely

  • Metal, plastic, silicone, an animal-derived product or some combination
  • Come into contact with tissue or other body parts for extended periods of time
  • Premarket review to determine potential adverse biological response
  • Post-marketing tools to monitor a device’s benefit-risk profile in real-world setting

Further enhance understanding of materials science 

  • Causes for exaggerated response in sensitive individuals
  • Advance development of safer materials
  • Case studies: Breast implants, Metals in devices, Animal materials in devices

CDRH’s OSEL conducting research on new advances in device materials

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 New strategies to modernize clinical trials to advance precision medicine, patient protections and more efficient product development

FDA opportunities for agile clinical research enterprise

However, sponsor reluctance to adopt innovative approaches

  • Rigid business model
  • Barriers between real world data and clinical research
  • Limited evidence sharing  across a learning health care system

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Focus Areas for Total Budget of $6.1 B

  • Reduce burden of addiction crisis
  • Foster competition by continued implementation of 21st Century Cures Act
  • Empower consumers/patients by promoting patient focused product development
  • Strengthen Science and Evidence-based decision making to enhance safety

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New steps to strengthen safety requirements aimed at mitigating risks associated with transmucosal immediate-release fentanyl products

To confront opioid  crisis, Risk Evaluation and Mitigation Strategy (REMS) programs to ensure benefits outweigh risks

  • Opioid Analgesics REMS program covers transmucosal immediate-release fentanyl (TIRF) medicines – 9 products on market
  • Indicated to manage breakthrough pain in adults with cancer who are routinely taking other opioid pain medicines to treat around-the-clock pain

Now modifying TIRF REMS – notifying manufacturers of following required changes

  • Document patient’s opioid tolerance concurrently with each prescription for outpatient use
  • Inpatient pharmacies to develop internal policies and procedures to verify opioid tolerance in hospitalized patients
  • Outpatient use requires evidence of safe use conditions, including concurrent documentation of opioid tolerance
  • New patient registry to monitor for serious adverse events including overdose (both fatal and non-fatal)

READ


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 Landmark policy changes to modernize mammography services and improve their quality

Proposed rule would require breast density reporting, enhance the FDA’s ability to enforce mammography facilities’ compliance with standards

  • FDA can directly notify patients and their health care professionals if facility did not meet quality standards
  • Only digital accessory components specifically FDA approved or cleared for mammography can be used
  • Strengthening record-keeping requirements to minimize information loss and improve access to and transfer of patient mammography records

READ


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Finalized requirements for tests to detect anthrax-causing bacteria

FDA plays a critical role in protecting our nation from bioterrorism threats such as anthrax

  • Final rule provides review pathway, testing criteria, how to address potential safety risks for lab workers

Regulatory pathway: In vitro diagnostic devices for Bacillus bacteria detection

  • Class II (moderate-risk) with special controls – requires premarket notification 510(k)
  • Provide information on testing criteria and performance evaluations
  • Restriction on distribution to laboratories that follow public health guidelines to address appropriate biosafety conditions, interpretation of test results, and coordination of findings with public health authorities, to reduce risks associated specimen handling

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Capture.JPGProposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML)-Based Software as a Medical Device (SaMD) 

Artificial intelligence and machine learning have the potential to fundamentally transform the delivery of health care

  • Earlier disease detection, more accurate diagnosis, identification of new observations or patterns on human physiology, development of personalized diagnostics and therapeutics
  • Greatest benefits of AI/ML in software is ability to learn from real-world use and experience (training) and improve performance (adaptation)
  • Deliver safe and effective software functionality that improves the quality of care that patients receive.

Use TPLC Model for regulatory framework to balance benefits and risks

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  • Quality systems and good ML practices (GMLP)
  • Premarket review for reasonable assurance of safety and effectiveness and continual management of  patient risks throughout lifecycle
  • Risk management approach for development, validation, execution of algorithm changes
  • Increased transparency to users and FDA using postmarket real-world performance reporting for maintaining continued assurance of safety and effectiveness

Framework to allow for modifications to AL/ML algorithms to be made from real-world learning and adaptation

  • Approved technoloigie use  “Locked” algorithms – don’t continually adapt or learn
  • Locked algorithms modified by manufacturer at intervals for “training” of algorithm using new data, followed by manual verification and validation of the updated algorithm.
  • Proposing Predetermined change control plan:  SaMD Pre-Specifications (SPS) and  Algorithm Change Protocol (ACP)

READ


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Review and Update of Device Establishment Inspection Processes and Standards

Scope 

  • Standardized methods of communication during inspection process
  • Practices for investigators and device establishments to facilitate continuity of inspections

Uniformity in investigators’ approaches to inspections inform firms’ inspection preparation

  • Pre-announcement Notice and Communication:  Telephone notification 5 days prior (domestic) or longer (foreign) – inspection is abbreviated, comprehensive, or pre-approval
  • Standard Inspection Timeframe: Generally 3 to 6 continuous business days
  • Communication During Inspections: Regular verbal communications during inspection, discuss all observations to minimize errors and misunderstandings

READ


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Enforcement Actions: Breast implant manufacturers, illegal online sales of opioids

Breast Implant Manufacturer

Warning letters for

  • Failure to comply with their requirements to conduct post-approval studies
  • To assess the long-term safety and risks of silicone gel-filled breast implants

Mentor Worldwide LLC and Sientra, Inc.

Illegal online sales of opioids

Warning letters for

  • Illegal marketing potentially dangerous, unapproved and misbranded opioid medications, including tramadol
  •  In addition to health risks, pose other risks to consumers, including credit card fraud, identity theft and computer viruses

azmedicinalshop.com and thedonrx.net

Stem Cell Clinics

Warning letter for

  • Manufacturing unapproved umbilical cord blood products
  • Violation of current good manufacturing practice (CGMP) requirements, including failing to validate processes to prevent bacterial contamination, raising potential significant safety concerns that put patients at risk

Cord for Life


Image credit: FDA

Device Authorizations: OSIRIX software for device development, EARLYBIRD bleed monitor, CLEARMATE ventilator, MITRACLIP for mitral regurgitation

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OSIRIX CDE SOFTWARE MODULE (Medical Device Development Tool)

TBI Endpoints Initiative, Unv. of California, San Francisco

CONTEXT OF USE: Contusions, as assessed by an expert rater from MRI using OsiriX CDE Software Module MDDT, may be used for enrichment of clinical trials for therapeutic medical devices intended to improve outcomes at 3 months for patients aged between 18-65 years with acute non-penetrating head trauma and Glasgow Coma Scale (GCS) 13-15 who have undergone acute head CT (e.g., as part of standard clinical care) at a U.S. Level 1 trauma center

ADDRESSING UNMET NEED:

  • First biomarker test tool type
  • Tool for more efficient development of devices in traumatic brain injury (TBI) treatment

TOOL DESCRIPTION AND OPERATION:

  • Software module that provides standardized way to mark boundaries and classify brain contusions (bruises) using Common Data Element (CDE) criteria
  • Information can be used to label abnormalities on MR images for enriching enrollment in clinical trials for therapeutic medical devices intended to improve outcomes of mild Traumatic Brain Injury (TBI) patients
  • Detection of a medical device effect (if present) is more likely than it would be in an unselected population
  • Can be used by medical device developers to identify and enroll patients into TBI studies.

EVIDENCE TO SUPPORT QUALIFICATION:

  • Clinical study evaluate the association between contusions and diffuse axonal injury with 3-month Glasgow Outcome Scale  and Interrater reliability
  • Previous investigations and pilot studies on level of risk associated with MDDT use,  possible advantages/disadvantages

REGULATORY PATHWAY: Qualification through MDDT pathway

  • Program to qualify tools that medical device sponsors can use in the development and evaluation of medical devices
  • ‘Qualification’ means FDA has evaluated the tool and concurs with available supporting evidence that the tool produces scientifically and clinically meaningful measurements within the authorized context of use
  • Qualified tools serve as a resource that can be referenced by any medical device sponsor
  • When used consistent with the qualified Context of Use: Results support regulatory decision-making, eliminates sponsor burden to demonstrate validation, reduces workload of FDA staff e

QUALIFICATION SUMMARY


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EARLY BIRD Bleed Monitoring System

Saranas, Inc

INDICATION FOR USE: For the introduction of catheters, catheter balloons, and other diagnostic and interventional devices into the femoral artery or femoral vein while maintaining hemostasis during diagnostic and interventional endovascular procedures.
The Early Bird provides physicians with an early indication of a potential internal bleeding complication by initial detection and monitoring of extravascular fluid accumulation.

GENERIC TYPE OF DEVICE: Intravascular bleed monitor.

Probe, catheter, or catheter introducer that measures changes in bioimpedance and uses an algorithm to detect or monitor progression of potential internal bleeding complications.

RISKS & MITIGATIONS: 

  • Adverse tissue reaction: Biocompatibility evaluation
  • Infection: Sterilization validation, Pyrogenicity testing, Shelf-life testing, Labeling
  • Blood loss, bleeding, hematoma: Human factors testing, Labeling, Animal performance testing, Non-clinical performance testing
  • Embolization (micro or macro) with ischemia: Human factors testing, Labeling
    Animal performance testing, Non-clinical performance testing
  • Vascular trauma: Human factors testing, Labeling, Animal performance testing, Non-clinical performance testing
  • Electrical shock: Electrical safety testing
  • Device failure due to interference with other devices: Electromagnetic compatibility (EMC) testing, Electrical safety testing
  • Device failure due to software malfunction: Software verification, validation, hazard analysis

REGULATORY PATHWAY: De Novo classification

  • Regulation Number: 21 CFR 870.1345
  • Regulation Name: Intravascular bleed monitor
  • Regulatory Class: Class II
  • Product Code: QFJ

CLASSIFICATION ORDER


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CLEARMATE ventilation device

Thornhill Research, Inc.

INDICATION FOR USE: To be used by emergency department medical professionals as an adjunctive treatment for patients suffering from carbon monoxide poisoning. The use of ClearMate enables accelerated elimination of carbon monoxide from the body by allowing isocapnic hyperventilation through simulated partial rebreathing

ADDRESSING UNMET NEED: 

  • Carbon monoxide poisoning affects thousands of people each year
  • Hyperbaric treatment, necessary for severe poisoning, has low accessibility; only 60 US medical centers with hyperbaric units
  • New device provides access to lifesaving device

DEVICE DESCRIPTION:

  • Gas mixer, valves, meters, breathing circuits, oxygen reservoir, mask and hoses
  • Speeds up elimination of carbon monoxide from body
  • Delivers both 100 % oxygen to patient, as well as a mixture of oxygen and carbon dioxide, to breathe faster
  • Increased breathing accelerates rate of elimination of carbon monoxide in body

GENERIC DEVICE TYPE: Isocapnic ventilation device

Prescription device used to administer a blend of carbon dioxide and oxygen gases to a patient to induce hyperventilation. This device may be labeled for use with breathing circuits made of reservoir bags (21 CFR 868.5320), oxygen cannulas (21 CFR 868.5340), masks (21 CFR 868.5550), valves (21 CFR 868.5870), resuscitation bags (21 CFR 868.5915), and/or tubing (21 CFR 868.5925).

EFFECTIVENESS AND SAFETY:

  • Data from multiple clinical studies for efficacy and safety, n=100
  • Effective at eliminating carbon monoxide; combination of oxygen and carbon dioxide resulted in faster elimination of carbon monoxide but not faster than hyperbaric oxygen therapy
  • Patients did not experience any device-related complications

RISKS & MITIGATIONS:

  • Hypocapnia (lacking CO2): Non-clinical performance testing, Labeling
  • Hypercapnia (excess CO2): Non-clinical performance testing, Labeling
  • Hypoxemia (lacking O2): Non-clinical performance testing, Labeling
  • High airway pressure (e.g., barotrauma): Non-clinical performance testing
    Labeling
  • Adverse tissue reaction: Biocompatibility evaluation

REGULATORY PATHWAY: De Novo classification

  • Regulation Number: 21 CFR 868.5480
  • Regulation Name: Isocapnic ventilation device
  • Regulatory Class: Class II
  • Product Code: QFB

CLASSIFICATION ORDER


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 MITRACLIP NT Clip Delivery System and MITRACLIP NTR/XTR Clip Delivery System

Abbott Vascular

EXPANDED INDICATION:  To include secondary (or functional) mitral regurgitation (MR), when MR is caused by a dysfunctional left ventricle, not by degeneration of the mitral valve itself

ORIGINAL INDICATION (2013): For the percutaneous reduction of significant symptomatic mitral regurgitation (MR ≥ 3+) due to primary abnormality of the mitral apparatus [degenerative MR] in patients who have been determined to be at prohibitive risk for mitral valve surgery by a heart team, which includes a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease, and in whom existing comorbidities would not preclude the expected benefit from reduction of the mitral regurgitation.

ADDRESSING UNMET NEED: 

  • 6.5 million American adults live with chronic heart failure
  • Small percentage also have moderate-to-severe or severe secondary mitral regurgitation, increasing risks and complicating heart failure treatment
  • This small percentage of patients could be candidates for the new indication

DESCRIPTION:

  • MitraClip device repairs MR without open-heart surgery and is delivered to the heart through a small incision in the leg
  • Clips portions of the leaflets, or flaps, of the mitral valve together to reduce the backflow of blood, restoring the heart’s ability to pump oxygenated blood more efficiently

EFFECTIVENESS & SAFETY:

  • Patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation, n=614,  transcatheter mitral-valve repair plus medical therapy (device group)  vs. medical therapy alone (control group)
  • Primary effectiveness end point: All hospitalizations for heart failure within 24 months of follow-up
    • 35.8% per patient-year in device group vs. 67.9% per patient-year in control group, P<0.001
  • Primary safety end point: Freedom from device-related complications at 12 months vs. performance goal of 88.0%
    • 96.6%  vs. 88% performance goal, P<0.001
    • Death from any cause: 29.1% in device group vs. 46.1% in control, P<0.001
  • Potential adverse events: Death, stroke, major bleeding, and atrial fibrillation

CONSUMER INFORMATION


Image Credit: UCSF, Saranas, Thornhill, Abbott 

Drug Authorizations: SPRAVATO for treatment-resistant depression, CABLIVI for thrombotic thrombocytopenic purpura, EGATEN for fascioliasis

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SPRAVATO™ (esketamine) nasal spray, CIII

 Janssen Pharmaceuticals, Inc.

INDICATION: In conjunction with an oral antidepressant, for the treatment of treatment-resistant depression (TRD) in adults
Limitations of Use: Not approved as an anesthetic agent

ADDRESSING UNMET NEED:

  •  Long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition
  • FDA review of safety and efficacy along with robust discussion with external advisory committee

MECHANISM OF ACTION: Esketamine, the S-enantiomer of racemic ketamine, is a non-selective, noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor; mechanism of antidepressant effect is unknown

EFFICACY:

  • Three short-term (four-week) clinical trials and one longer-term maintenance-of-effect trial; Spravato vs. placebo nasal spray – all patients on new oral antidepressant (AD) from time of randomization
  • Primary endpoint: Change in baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score
  • SPRAVATO plus AD demonstrated statistical superiority vs. placebo
  • Timecourse: SPRAVATO’s treatment difference observed at 24 hrs; both arms continued to improve to Day 28.
  • In the longer-term maintenance-of-effect trial: SPRAVATO + AD experienced a statistically significantly longer time to relapse of depressive symptoms vs, placebo

SAFETY:

  • Boxed Warning: Risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug
  • REMS with Patient Enrollment Form and patient Medication Guide; self-administration of nasal spray under supervision of health care provider in certified doctor’s office or clinic; spray cannot be taken home
  • Most common side effects: Disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk.

REG PATHWAY: NDA

  • The FDA approved ketamine (Ketalar) in 1970. This is the first FDA approval of esketamine for any use
  • Fast Track and Breakthrough Therapy designations
  • Postmarketing requirements: Long-term effects esketamine on cognitive function and urinary symptoms, further characterize potential risk of increasing thyroid stimulating hormone levels

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 CABLIVI (caplacizumab-yhdp) 

Ablynx N.V.  and Genzyme (Sanofi)

INDICATION: Treatment of adult patients with acquired thrombotic thrombocytopenic purpura (aTTP), in combination with plasma exchange and immunosuppressive therapy

ADDRESSING UNMET NEED: Treatment option for a Rare disease

MECHANISM OF ACTION: Targets A1-domain of von Willebrand factor (vWF) and inhibits the interaction between vWF and platelets, thereby reducing both vWF-mediated platelet adhesion and platelet consumption

EFFICACY & SAFETY:
  • Clinical study, n=145 patients with aTTP stratified per Glasgow Coma Scale score, CABLIVI vs placebo,  median treatment duration of 35 days
  • Endpoint: Time to platelet count response (platelet count ≥150,000/µL followed by cessation of daily plasma exchange within 5 days
  • Time to platelet count response shorter with CABLIVI vs. placebo, lower number of  TTP-related deaths (0 vs. 3) and TTP recurrence (3 vs. 28)
  • Recurrence of TTP in overall study period lower with CABLIVI vs placebo (28/73 patients [38%]; p<0.001)
  • Most common adverse reactions:  Epistaxis, headache, and gingival bleeding.

REG.PATHWAY:  BLA

  • Priority review and orphan product designation
  • Postapproval commitments on manufacturing and testing
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EGATEN™ (triclabendazole) tablets, for oral use

Novartis

INDICATION:  Treatment of fascioliasis in patients 6 years of age and older.
ADDRESSING UNMET NEED:
  • WHO estimates ~ 2.4 million infected people infected in > 70 countries worldwide
  • Treatment option for global markets

MECHANISM OF ACTION: Anthelmintic against Fasciola species

EFFICACY: 

  • Open label, randomized trial, in Vietnam, n=100 children, EGATEN vs. artesunate, 3 months treatment
  • No clinical symptoms in  92% EGATEN vs in 76% placebo, p = 0.035
  • Six nonrandomized, open label studies in Cuba, Bolivia, Peru, Chile, Iran, n=245 adult and pediatric patients with stool-confirmed fascioliasis
  • Cure defined as absence of Fasciola eggs in stool based on Kato-Katz method. Day 60
  • Dose response seen in all studies

SAFETY:

  • Most common adverse reactions: Abdominal pain, hyperhidrosis, nausea, decreased appetite, headache, urticaria, diarrhea, vomiting, musculoskeletal chest pain, pruritus

REG PATHWAY: NDA

  • Fast Track and Orphan Drug designations
  • Tropical Disease Priority Review Voucher to encourage development of products for certain tropical diseases
  • Postmarketing requirements: QT/QTc trial, additional dose evaluation,
Image credits: Janssen, Sanofi, Novartis

 

News & Vews: Farewell Commissioner Gottlieb, Patient participation in cancer clinical trials, CDRH reorganization, Request to Connect for patients, Implanted Brain-Computer Interface devices, Safe Use alerts

Capture.JPGFarewell Commissioner Gottlieb

Sincere gratitude for your leadership and exemplary work during your current FDA tenure. You have been an inspiration.Capture.JPGEXIT INTERVIEW


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New steps to broaden patient participation in cancer clinical trials

FDA issued new recommendations for broadening cancer trial eligibility criteria

  • More representative of patient population
  • Maximize the generalizability of the trial results
  • Maximize understanding of therapy’s benefit-risk profile across the patient population likely to receive the drug in clinical practice

Broadening eligibility criteria to include:  Pediatric patients, Patients with HIV, Hepatitis B and Hepatitis C Virus infections, Patients with brain metastases, organ dysfunction and prior or concurrent malignancies

New Guidances

READ


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Reorganization of CDRH

CDRH reorganization to implement efficiencies to integrate CDRH’s premarket and postmarket program functions

  • Reviewers, compliance officers and other experts would work in teams responsible for device oversight throughout the product’s development and commercialization
  • More integrated approach to device safety throughout the Total Product Life Cycle (TPLC) – already in pilot testing
  • Timeline: March 18, 2019 (begin) – September 30, 2019 (full implementation)

New Offices 

  • Office of Product Evaluation and Quality (OPEQ) :  Combines Office of Compliance, Office of Device Evaluation, Office of Surveillance and Biometrics, and  Office of In Vitro Diagnostics
  • Office of Policy – Two teams, the Guidance, Legislation and Special Projects Team and the Regulatory Documents and Special Projects Team
  • Office of Strategic Partnerships and Technological Innovation – Combines Science & Strategic Partnerships, Digital Health, Health Informatics and Innovation teams

READ


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“Request to Connect” – A New Way for Patients to Connect with FDA

“Request to Connect” portal is live
  • Gives patients and caregivers a single entry point to the Agency for questions and meeting requests
  • Co-developed by Patient Affairs Staff and the medical product centers
  • Will route inquiries to appropriate medical product center or office for responses in effective and efficient manner
  • Opportunity for FDA to better understand patient perspective and advance science of patient input

Implanted Brain-Computer Interface (BCI) Devices for Patients with
Paralysis or Amputation – Non-clinical Testing and Clinical
Considerations

Implanted BCI devices increase ability to interact with environment and provide independence to patients with paralysis or amputation

  • Interface with nervous system to restore motor and/or sensory capabilities
  • Recommendations for non-clinical testing and study design considerations for IDE feasibility and pivotal clinical studies

Non-Clinical Bench Testing Considerations: Risk analysis, Electrodes, Leads and Connectors, Implanted casing and electronics, Output simulation measurements, Output simulation safety, Programmers/control unit, Radiofrequency transmitter and receiver, System level testing, factors for determining and design of animal studies

Clinical Study Considerations: Patient population, Home-Use, Duration and follow-up schedule, Inclusion/Exclusion criteria, Demographics, Treatment parameters, Endpoints including patient input (patient engagement. patient preference information, patient reported outcome measures)

READ


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SAFE USE ALERTS: Surgical Staplers and Staples, Contact Lenses

Surgical Staplers and Staples:

  • Increased number of adverse events reported to the FDA since 2011: 366 deaths, > 9,000 serious injuries, > 32,000 malfunctions
  • FDA Actions:
    • Letter to Healthcare Providers
    • Issue draft guidance on recommendations to manufacturers
    • Hold public meeting of  General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee  to reclassify as Class II (from Class I)
    • Require premarket notification and establish mandatory special controls to help mitigate known risks 

Contact lenses 

  • Risk of several serious conditions including eye infections and corneal ulcers
  • Can develop very quickly, be serious and can cause blindness
  • Video on safe and effective use

Image credits: FDA

News & Views: Flu vaccine supply, Rare Disease Day, Childhood Cancer Advocacy Forum, Heart Devices, Physiologically Based Pharmacokinetic (PBPK) Modeling

Capture.JPGEnsuring Supply of Influenza Vaccine

Starts well before the current flu season ends – a year-round initiative

  1. Vaccine composition changes every year as flu viruses are constantly evolving
  2. Collaboration of FDA, WHO, CDC to evaluate global circulating strains and disease trends
  3. FDA advisory committee recommend 3-4 strains to include in trivalent and quadrivalent influenza vaccines
  4. Manufacturers begin manufacturing process to include the newly selected flu strains and seek FDA approval for lot release – quality control tests, including testing for sterility

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CaptureObservation of Rare Disease Day

Created to raise awareness about the 7,000 known rare diseases with theme of Bridging Health and Social Care

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CaptureOncology Center of Excellence Childhood Cancer Advocacy Forum

Topics for Discussion:

  • FDA’s External Engagement and Patient Advocacy: A Dialogue to Better Inform FDA of Patient Needs and Priorities
  • Avoiding Pitfalls in Drug Development
  • Approved Cancer Drugs in Children
  • BPCA/WR Study Results
  • Expanded Access to Investigational Drugs
  • FDARA Implementation
  • Pediatric PROs: Are they feasible?

Register here for in-person or online attendance


CaptureHeart Devices regulated by FDA

  • Automated external defibrillators (AEDs): Portable and automatic,  to restore normal heart rhythm
  • Cardiac ablation catheters: Long, thin flexible tubes.  to treat abnormally rapid heartbeats
  • Cardiovascular angioplasty devices: Long, thin, flexible tubes threaded into  heart vessel to open narrowed or blocked areas
  • Cardiac pacemakers: Small, battery-powered, implanted permanently, monitor heart’s electrical impulses. deliver electrical stimulation if bradycardia
  • Implantable cardioverter defibrillators (ICDs): Monitor heart rhythms and deliver shocks if dangerous tachycardia
  • Prosthetic (artificial) heart valves: Replacing diseased or dysfunctional heart valves,
  • Stents: Small, lattice-shaped, metal tubes, some with drugs,  to improve blood flow
  • Ventricular assist devices (VADs): Mechanical pumps for short-term or long term use

Warning signs and symptoms of a heart attack 


CaptureSupporting Drug Development Through Physiologically Based Pharmacokinetic (PBPK) Modeling

PBPK Models to Mechanistically Predict Drug Pharmacokinetics

  • Grounded in human physiology – describe time course of absorption, distribution, metabolism, and elimination of one or more drugs
  • Includes anatomical or physiological parameters such as blood flow, tissue composition, enzyme abundance, drug-specific values, such as tissue-to-plasma concentration ratios, metabolism and clearance
  • Make predictions on drug concentrations achieved in the absence of clinical data
  • Focus to improve accuracy of predictions and incoporate PBPK models in drug development

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image credit: FDA

News & Views: 2019 Opioid Agenda, Quality for Continuous Manufacturing, Task Force for Public Health Emergencies, Brain Computer Interface devices, Quantifying Oncology Patient Experience

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2019 policy and regulatory agenda for continued action to forcefully address the tragic epidemic of opioid abuse

New actions to build on 2018 efforts and also adapt to changing nature of threat

  • Reducing Misuse and Abuse of Opioid Drugs: Appropriately prescription, dose, quantity, treatment duration, disposal, REMS effectiveness
  • Support Addiction Recovery and Reduce Overdose Deaths:  OTC naloxone with model Drug Facts Labels with easy directions for use
  • Research and Innovation in Non-Addictive Pain Treatments: Non-opioid drugs, abuse-deterrent features
  • Strengthen Enforcement Against Illicit Opioids: Partnership with U.S. Customs and Border Protection

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CaptureQuality Considerations for Continuous Manufacturing

Continuous technology is foundation for improving  overall quality of products and availability to patients

  • Integrated process with fewer steps , shorter processing times, smaller equipment footprint, enhanced development approach e.g., quality by design (QbD) and use of process analytical technology (PAT)

Quality considerations

  • Key Concepts: Process dynamics, Defining batches for continuous manufacturing processes
  • Control Strategy: Input material, Process monitoring, Material diversion, Real Time Release, Specification, Equipment, System integration, Data processing, and Management
  • Process Validation: Stage 1 – Process  Design, Stage 2 – Process  Qualification, Stage 3 – Continued Process Verification
  • Additional Pharmaceutical Quality System Considerations: Scale-Up,  Stability, Bridging existing batch to Continuous Manufacturing
FDA requesting comments on
  • data storage and handling from process analytical technology systems
  • potential approaches for situations where direct attribute measurement is not possible (e.g., low dose compounds)
  • contract manufacturers employing continuous manufacturing
  • risk-based reporting of routine model maintenance and updates
  • statistical approaches using large samples (e.g., Large N)

DRAFT GUIDANCE


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FDA, CDC, and CMS launch task force to help facilitate rapid availability of diagnostic tests during public health emergencies

The Tri-Agency Task Force for Emergency Diagnostics (TTFED)ompsed of FDA + CDC + CMS

  • Collaborate on future emergency diagnostic response needs
  • Convene, provide timely recommendations to laboratories for rapid implementation of FDA’s Emergency Use Authorization (EUA) assays

Focus to

  • establish efficient communication channels between TTFED members
  • formalize and document interagency process for rapid implementation of EUA IVD assays in public health emergency
  • provide timely recommendations during emergencies

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Implanted Brain-Computer Interface (BCI) Devices for Patients with Paralysis or Amputation – Non-clinical Testing and Clinical Considerations

Implanted BCI devices have potential to bring benefit to people with severe disabilities by increasing their ability to interact with their environment, and consequently, providing new independence in daily life

  • Implanted BCI devices are neuroprostheses that interfaces with central or peripheral nervous system to restore lost motor and/or sensory capabilities in patients with paralysis or amputation

Pre-Submission/IDE recommendations:

  • Device description
  • Software
  • Biocompatibility
  • Sterility
  • Pyrogenicity
  • Shelf life and packaging
  • Electrical safety and Electromagnetic compatibility
  • Wireless technology
  • Magnetic resonance compatibility
  • Non-clinical bench testing
  • Risk analysis
  • Electrodes
  • Leads and connectors
  • Implanted casing and electronics
  • Output simulation measurements
  • Output stimulation safety
  • Programmrrs/control unit
  • Radiofrequency transmitter and receiver
  • System level testing
  • Referencing Master Files
  • Animal testing scope
  • Clinical study considerations

READANNOUNCEMENT


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Oncology Center of Excellence — Quantifying the Patient Experience

Collaboration between FDA Centers and external stakeholders involved in patient outcomes research in cancer populations

  • Actively engaging with patients and advocacy groups
  • Fostering research into measurement of the patient experience
  • Generating science-based recommendations for regulatory policy

Goals to assess patient experience that complement existing survival and tumor information

  • Learning from Patient Experiences
  • Collaborating with Patients, Public and Private Sectors
  • Fostering Continued Engagement

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Image credit: CMS, FDA

News and Views: Voluntary Consensus Standards, Stopping Illicit Opioids, Device Inspection Nonbinding Feedback, Ebola Virus Pathogenesis

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Voluntary Consensus Standards to promote the adoption of innovations in drug manufacturing that can improve quality and lower drug costs

Recognizing “voluntary consensus standards” based on nationally and internationally accepted standards for drug quality

  • New draft guidance  to propose pharmaceutical quality standards for potential recognition by the FDA, providing industry with additional options for pharmaceutical development and manufacturing
  • Promote and expedite  development, streamline FDA review of drug product applications
  • Provide list of recognized standards on website; reduce regulatory uncertainty

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Efforts to stop the spread of illicit opioids, further secure the U.S. drug supply chain and forcefully confront opioid epidemic

Efforts to stopping spread of illicit opioids and  securing all aspects of supply chain

  • Enforcement and interdiction of illegal shipment through US Postal Services
  • Work closely with U.S. Customs and Border Protection and U.S. Department of Justice
  • Warning Letters for illegal online marketing
  • Online Opioid Summit with appropriate stakeholders for stronger action
  • Warning letter under the Drug Supply Chain Security Act (DSCSA) McKesson Corp
  • New guidances
    • Risk/benefit framework to opioid analgesics including illicit use risks
    • Modernize development pathway for non-opioid analgesics for specific clinical conditions
    • Packaging requirements to limit number with single prescription
  • Continue work in accordance with Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act

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Nonbinding Feedback after Certain FDA Inspections of Device Establishments

Standardized method for communicating and submitting requests for nonbinding feedback and describes how FDA evaluates and responds to such requests

  • Request for nonbinding feedback submitted by device establishment to FDA regarding firm’s proposed actions to address Form 483 inspectional observations

Firm’s proposals for addressing Inspectional Observations related to

  • release of violative product that may cause death or serious injury
  • production of nonconforming, violative, and/or defective finished devices
  • release of devices likely to cause 196 death or serious injury

FDA informal feedback on whether proposals

  • address inspectional observations
  • partially adequate or inadequate with explanation
  • recommend what may be needed to be adequate

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Capture.JPGNew approach for understanding Ebola Virus Pathogenesis

Contract with Broad Institute to conduct the largest Ebola virus and host gene expression (i.e., transcriptomics) study

  • Assess how Ebola virus evolves and spreads within the body
  • Identify mechanisms and biological pathways altered in immune cells and tissues during infection
  • Inform natural history of Ebola virus disease in humans
  • Characterize nonclinical models necessary for testing
  • Utilize fordeveloping medical countermeasures (MCMs) to prevent and treat Ebola virus disease

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Image credit: FDA

Youth Tobacco Prevention Plan

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FDA’s Youth Tobacco Prevention Plan—a key component of the agency’s Comprehensive Plan for Tobacco and Nicotine Regulation—to stop youth use of tobacco products, especially e-cigarettes

  • Preventing youth access to tobacco products
  • Curbing marketing of tobacco products aimed at youth; and
  • Educating teens about the dangers of using any tobacco product, including e-cigarettes, as well as educating retailers about their key role in protecting youth

LEARN


Image credit: FDA

News & Views: Patients First, Least Burdensome Provisions, Drug Supply Chain security, 510(K) exemptions

Capture.JPGFDA’s Patient Affairs Staff (PAS)-  FDA Puts Patients First

PAS works with patients, caregivers, and advocates in 2019
  • Understanding patient experience and incorporating patient feedback into FDA’s work

PAS launched several initiatives to support and connect with patients


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The Least Burdensome Provisions: Concept and Principles

Final guidance on use of least burdensome approach to medical device regulation
  • Support timely patient access to high quality, safe and effective medical devices
  • Remove or reduce unnecessary burdens throughout total product lifecycle
  • Maintaining statutory requirements for clearance and approval
  • Principles are based on sound science, intent of the law, use of alternative approaches, efficient use of resources to effectively address regulatory issues

Guiding principles

  • FDA to request minimum information necessary to adequately address regulatory question or issue at hand
  • Industry should submit material, including premarket submissions, that are least burdensome for FDA to review
  • FDA to use most efficient means to resolve regulatory questions and issues
  • Right information provided at right time (e.g., just-in-time data collection) to address right questions
  • Regulatory approaches designed to fit technology, taking into account unique innovation cycles, evidence generation needs, timely patient access
  • FDA to leverage outside US data to the extent appropriate and feasible

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Improving security of Drug Supply Chain through innovations that improve tracking and tracing of medicines

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Intent to Exempt Certain Unclassified Medical Devices from Premarket Notification Requirements

Intent to exempt certain unclassified medical devices from premarket notification requirements

  • Devices are sufficiently well understood
  • Do not require premarket notification (510(k)) to assure their safety and effectiveness.

Device categories

  • Ear, Nose, and Throat
  • Gastroenterology-Urology
  • General and Plastic Surgical
  • Neurological
  • Obstetrical and Gynecological Devices
  • Physical Medicine Devices

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Image credit: FDA


Obesity Prevention Game

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Obesity Prevention Game Challenge

  • 2 out of every 3 women overweight or with obesity problems in US
  • 1 in 3 girls (2-19 years old) overweight or with obesity problems
  • Create engaging web- or mobile-based game that helps women or girls build healthier exercise and eating habits to prevent obesity
  • Chance to win up to $77,000 in prize money!

LEARN


Image credit: FDA

Market Authorizations: ULTOMIRIS for paroxysmal nocturnal hemoglobinuria, Personal Genome Service (PGS) for Cervical Cancer screening

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ULTOMIRIS (ravulizumab-cwvz) injection

Alexion Pharmaceuticals
INDICATION: Treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH)
ADDRESSING UNMET NEED:
  • PNH is a rare acquired disorder that leads to the rupture or destruction of red blood cells (hemolysis)
  • Prior to this approval, treatment required every two weeks, which can be burdensome for patients and families
  • Novel formulation so patients only need treatment every eight weeks, without compromising efficacy

MECHANISM OF ACTION: Terminal complement inhibitor specifically binds to complement protein C5 with high affinity; inhibits terminal complement-mediated intravascular hemolysis in patients with PNH

EFFICACY & SAFETY:
  • First randomized clinical trial, n=246 PNH patients (treatment naïve), Ultomiris vs. eculizumab, current standard of care for PNH
  • Non-inferiority on endpoints: Transfusion avoidance and hemolysis directly measured by normalization of LDH levels
  • Second randomized trial, n=195 PNH patients clinically stable after eculizumab treatment, Ultomiris vs. continue eculizumab
  • Similarity on several clinical measures including hemolysis and avoiding transfusion
  • Common side effects: Headache, upper respiratory infection
  • Boxed Warning: Risk of life-threatening meningococcal infections and sepsis
REGULATORY PATHWAY: BLA
  • Priority Review designation, Orphan Drug designation
  • Postmarketing commitments: Data from clinical trials in patients with paroxysmal nocturnal hemoglobinuria (ALXN1210-PNH-301 and ALXN1210-PNH-302) to include the extension period of up to 2 years of follow-up

Personal Genome Service (PGS) Genetic Health Risk Report for
MUTYH-Associated Polyposis for Cervical Cancer screening

23andMe

INTENDED USE: PGS uses qualitative genotyping to detect select clinically relevant variants in genomic DNA isolated from human saliva collected from individuals ≥18 years for the purpose of reporting and interpreting genetic health risks, including the 23andMe PGS Genetic Health Risk Report for MUTYH-Associated Polyposis (MAP)

INDICATION FOR USE: The 23andMe PGS Genetic Health Risk Report for MUTYHAssociated Polyposis is indicated for reporting of the Y179C and the G396D variants in the MUTYH gene. The report describes if a person is at increased risk of developing colorectal cancer. The two variants included in this report are most common and best studied in people of Northern European descent and may not represent the majority of the MUTYH variants found in people of other ethnicities. 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.

DESCRIPTION:

  • The core components of the PGS are unchanged from the de novo authorization for the predicate device, the PGS Genetic Health Risk Report for BRCA1/BRCA2 and also the additional de novo Authorizations of the PGS for Carrier Screening Tests for Bloom Syndrome and PGS Genetic Health Risk Reports including saliva collection kit, reagents and beadchip, instrumentation, software, test processes, procedures
  • Novel components: (a) specific variants to be reported (b) qualitative reporting of risk for MAP, as opposed to the BRCA related cancer risks

REGULATORY PATHWAY: Traditional 510(k)

  • Trade/Device Name: MUTYH-Associated Polyposis (MAP)
  • Regulation Number: 21 CFR 866.6090
  • Regulation Name: Cancer Predisposition Risk Assessment System
  • Regulatory Class: Class II
  • Product Code: QAZ

SUMMARY


Image credits: Alexion, 23andMe

News & Views: FDA opens, CDRH record-setting year, New Drug Class for Migraines

FDA Opens

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Capture.JPGCapture.JPGCDRH-Record Year for Device Innovation

Success in advancing device innovation and approval/clearance novel, safe and effective technologies

  • Approval of 106 novel devices, surpassing the 40-year record we set in 2017 of 99
  • Granted 112 Breakthrough Device Designation requests;  9 approved/cleared

Examples of innovative products

  • Automated insulin dosing system – including for those as young as age 7
  • World’s smallest heart valve for newborns
  • First blood test in the world to evaluate mild traumatic brain injury
  • First mobile medical app to help treat substance abuse disorders\
  • Artificial Intelligence to detect diabetic retinopathy in adults
  • Artificial Intelligence to detect wrist fractures
  • First artificial iris

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captureNew Drug Class Employs Novel Mechanism for Migraine Treatment and Prevention

Recently approved drug class targeting  calcitonin gene-related peptide (CGRP) – elevated in blood serum during migraine attacks

  • New migraine drugs block effects of CGRP
  • Specialized monoclonal antibodies cloned subclasses of immunoglobulin G (IgG)
  • Designed to have low potential to interact with other drugs
  • Metabolized differently with fewer adverse reactions
  • Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), Emgality (galcanezumab-gnlm)

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Image credit: FDA