FDA News and Views: Essure Sales Halt, Biomarkers and Surrogate Markers, Mobile Medical Apps Listing

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Manufacturer announcement to halt Essure sales in the U.S- 

Statement from FDA Commissioner

FDA notified by Bayer that Essure permanent birth control device will no longer be sold or distributed after December 31, 2018

Steps taken by FDA based on increased reporting to MAUDE database

  • September 2015: Input from expert panel on abdominal pain, abnormal uterine bleeding, device migration
  • February 2016: Ordered Bayer to conduct a postmarket study on safety profile
  • October 2016: FDA final Guidance on device and updated labeling with boxed warning and Patient Decision Checklist
  • February 2018: FDA meeting with women implanted with Essure and patient advocates
  • March 2018:FDA report on rise in safety reporitng with >90%  on device removal
  • April 2018: FDA restriction on sale and distribution

FDA will remain vigilant in protecting patients with implanted device

  • Restriction on sale and distribution will remain in place
  • Postmarket study, will continue to enroll new participants
  • Each study participant will be followed for a total of three years
  • Bayer will continue to submit reports on study’s progress and results

READ

WATCH: The Bleeding Edge


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Biomarkers and Surrogate Markers

Biomarker is objective measure of normal biological processes, pathologic processes, responses to exposure or therapeutic intervention

  • May be used for identifying patients for clinical trial enrollment, monitoring safety and effectiveness

Surrogate endpoints (SEs) are  small subclass of biomarkers

  • Clearly predicts beneficial effect through appropriate studies
  • More efficient drug development programs

FDA steps to enhance SE use in drug development

READ


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Examples of Pre-Market Submissions that Include Mobile Medical Apps (MMAs)  Cleared or Approved by FDA

Mobile apps are software programs run on smartphones and other mobile communication devices

  • Are medical devices if meet definition of medical device or accessory to regulated medical device or transform mobile platform into regulated medical device
  • Consumers can use both mobile medical apps and mobile apps to manage health and wellness

FDA providing listing of MMAs cleared or approved since 1997

READ


Image credits: Bayer, FDA

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MRI Safety Posters

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MRI Safety Posters

Series of posters addressing MRI safety key aspects for MR technologists and other site personnel

  • MRI Burn Prevention poster
  • Scanning patients with implants
  • How to interpret MRI safety labeling

All three posters are available for free download

LEARN


Image credit: FDA

 

Market Authorizations: TIBSOVO + REALTIME ASSAY, KISQALI, TPOXX, XTANDI, FRENCH FREEZE DRIED PLASMA

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TIBSOVO (ivosidenib) tablets

Agios Pharmaceuticals

 RealTime IDH1 Assay  

Abbott Laboratories

INDICATION:  Treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test

ADDRESSING UNMET NEED:

  • AML is rapidly progressing cancer;  ~19,520 people will be diagnosed with ~10,670 deaths in 2018
  • Targeted therapy  for patients with relapsed or refractory AML who have an IDH1 mutation

MECHANISM OF ACTION: Targets mutant isocitrate dehydrogenase 1 (IDH1) enzyme;  decreases abnormal production of the oncometabolite 2-hydroxyglutarate (2-HG), leading to differentiation of malignant cells.

EFFICACY:

  • Open-label, single-arm, multicenter clinical trial, n=174 adult patients with relapsed or refractory AML with IDH1 mutation  confirmed using Abbott RealTime TM IDH1 Assay
  • Endpoints:  Rate of complete remission (CR) plus complete remission with partial hematologic recovery (CRh), the duration of CR+CRh, rate of conversion from transfusion dependence to transfusion independence
  • 32.8 % experienced a CR orCRh lasting median 8.2 months
  • 37% went at least 56 days without requiring transfusion

SAFETY:

  • Common side effects: Fatigue, increase in white blood cells, joint pain, diarrhea, shortness of breath, swelling in the arms or legs, nausea, pain or sores in the mouth or throat, irregular heartbeat (QT prolongation), rash, fever, cough and constipation
  • Boxed warning: Differentiation syndrome can occur and can be fatal if not treated
  • Other serious warnings: QT prolongation, Guillain-Barré syndrome

REGULATORY PATHWAY: NDA

  • Fast Track and Priority Review designations, Orphan Drug designation
  • Exempt from pediatric requirements
  • Postmarketing requirements:  long-term safety, PK/PD assessments

LABEL


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KISQALI (ribociclib) tablets

Novartis

EXPANDED INDICATION:  KISQALI in combination with:

  • an aromatase inhibitor for the treatment of pre/perimenopausal or postmenopausal women, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, as initial endocrine-based therapy

or

  • fulvestrant for the treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer, as initial endocrine based therapy or following disease progression on endocrine therapy

ADDRESSING UNMET NEED: 

  • First cancer drug approval through new oncology review pilot that enables greater development efficiency
  • Aim to make development and review of cancer drugs more efficient, while improving FDA’s rigorous standard for evaluating efficacy and safety
  • FDA start evaluating clinical data as soon as trial results become available, enabling FDA to be ready to approve the new indication upon filing of a formal application

EFFICACY AND SAFETY:

  • In combination with an AI for pre/perimenopausal women:  Clinical trial, n=495, Progression Free Survival (PFS) was longer for patients taking Kisqali plus an AI (median PFS of 27.5 months) compared to placebo plus an AI (median PFS of 13.8 months)
  • In combination with fulvestrant:  Clinical trial, n=726, PFS longer for patients taking Kisqali plus fulvestrant (median PFS of 20.5 months) compared to placebo plus fulvestrant (median PFS of 12.8 months)
  • Common side effects: Infections, neutropenia, leukopenia, headache, cough, nausea, fatigue, diarrhea, vomiting, constipation, hair loss and rash
  • Warnings: QT prolongation, serious liver problems, low white blood cell counts that may result in infections that may be severe, and fetal harm

REGULATORY PATHWAY: Prior Approval Supplement utilizing two new pilot programs

  • Real-Time Oncology Review (RTOR): Early submission of data that are the most relevant to assessing safety and effectiveness of the product. Then, when the sponsor submits the application with the FDA, the review team will already be familiar with the data and in a better position to conduct a more efficient, timely, and thorough review.
  • Assessment Aid to organize submission into structured format to facilitate review
  • Priority Review and Breakthrough Therapy designation

Updated LABEL not available at this time


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TPOXX (tecovirimat) capsules

Siga Technologies 

Developed in conjunction with U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA)

INDICATION:  Treatment of human smallpox disease caused by variola virus in adults and pediatric patients weighing at least 13 kg

ADDRESSING UNMET NEED:

  • First drug with an indication for treatment of smallpox
  • Addressing the risk of bioterrorism

MECHANISM OF ACTION:  Antiviral drug against variola (smallpox) virus

EFFICACY:

  • Has not been determined in humans because adequate and well-controlled field trials have not been feasible, and inducing smallpox disease in humans to study the drug’s efficacy is not ethical
  • Effectiveness based on results of adequate and well-controlled animal efficacy studies of non-human primates and rabbits infected with non-variola orthopoxviruses
  • Primary efficacy endpoint: Survival
  • Statistically significant improvement in survival relative to placebo

SAFETY:

  • Evaluated in 359 healthy human volunteers without smallpox infection
  • Most frequently reported side effects: Headache, nausea and abdominal pain

REGULATORY PATHWAY: NDA, approved under the FDA’s Animal Rule

  • Fast Track and Priority Review designations, Orphan Drug designation
  • Awarded Material Threat Medical Countermeasure priority review voucher

LABEL


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XTANDI (enzalutamide) capsules

Astellas 

SUPPLEMENTAL INDICATION:  Treatment of patients with castration-resistant prostate cancer (CRPC)

ADDRESSING UNMET NEED:   Broadens indicated patient population to include patients with non-metastatic CRPC (NM-CRPC) in addition to previously approved metastatic CRPC

EFFICACY:

  • Randomized, multicenter clinical trial, n= 1,401 patients. XTANDI vs. placebo; patients continued on gonadotropin-releasing hormone (GnRH) therapy or had prior bilateral orchiectomy
  • Major efficacy outcome: Metastasis-free survival (MFS)
  • Statistically significant improvement:  Median MFS of 36.6 vs. 14.7 months (HR 0.29; 95% CI: 0.24, 0.35; p<0.0001).

SAFETY:

  • Most common adverse reactions:  Asthenia/fatigue, hot flush, hypertension, dizziness, nausea, and fall

REGULATORY PATHWAY: sNDA

  • Postmarket requirements: Collect and analyze all cases of new (non-prostate) malignancies identified in treated patients on an annual basis

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Capture.JPGCentre de Transfusion Sanguine des Armées Freeze Dried Plasma (French FDP)

U.S. Department of Defense (DoD)

USE: Treatment of hemorrhage or coagulopathy during an emergency involving agents of military combat when plasma is not available or when use of plasma is not practical

ADDRESSING UNMET NEED: 

  • Importance of access to freeze-dried plasma in initial efforts to control hemorrhage from battlefield trauma
  • Collaborative program with DoD to expedite development and availability of safe and effective, priority medical products for military service members

DESCRIPTION: 

  • Lyophilized, leukocyte-depleted, pathogen-reduced (Intercept-treated), pooled
    apheresis Fresh Frozen Plasma product collected from volunteer donors and manufactured by the Centre de Transfusion Sanguine des Armées
  • Following reconstitution with water for injection, it can be administered intravenously

DATA COLLECTION: Intended to support the safety of the use of French FDP in combat settings

  • Patient survival until transfer of care
  • Patient survival at Day 30 following treatment with French FDP
  • Adverse events related to French FDP administration until transfer of care

REGULATORY PATHWAY: Emergency Use Authorization

  • DoD request and declaration by Secretary of the Department of Health and Human Services

FACT SHEET

DECLARATION


Image credits: Agios, Novartis, Siga, Astellas, FDA

News and Views: Biosimilars Action Plan, Treatment of Opioid Use Disorder, Medical Countermeasures Mission, Nonprescription Drugs Access, Generic Opioids with Abuse-Deterrent Formulations

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Biosimilars Action Plan (BAP)

Focus on four key areas

  • Improving efficiency of biosimilar and interchangeable product development and approval process
  • Maximizing scientific and regulatory clarity for biosimilar product development community;
  • Developing effective communications to improve understanding of biosimilars among patients, clinicians, and payors
  • Supporting market competition by reducing gaming of FDA requirements or other attempts to unfairly delay competition

Actions will help create competitive market, provide incentives for sponsors

Commissioner Gottlieb’s remarksDynamic Regulation: Key to Maintaining Balance Between Biosimilars Innovation and Competition” at Brookings Institution about BAP

READ


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CDER Conversation: Treatment for Opioid Use Disorder

Medication assisted treatment (MAT) is key to combating opioid use disorder (OUD)

  • Evidence-based, FDA approved medication (methadone, buprenorphine,  naltrexone) combined with counseling and psychosocial support
  • Decrease cravings,  relieve withdrawal symptoms; none cause euphoria or “high”

Use Information

  • Can be administered through different routes depending on specific drug; however,  many clinicians are not assessing and treating patients with OUD
  • Potential for drug-drug interactions
  • Recommended for pregnant women with substance use disorder
  • SAMHSA’s treatment locator service can be helpful in finding a nearby treatment program

READ


CaptureProtecting and Promoting Public Health: Advancing the FDA’s Medical Countermeasures Mission 

Role in national security by facilitating development and availability of safe and effective medical countermeasures

  • Animal Rule: Efficacy data obtained solely from animals when studies in humans are not ethical or feasible
  • New guidances: eg smallpox
  • Emergency Use Authorizations: Facilitating availability and use of MCMs needed during public health emergencies
  • FDA and DoD joint program for development of medical oroducts intended to save  American military personnel
  • FDA’s Medical Countermeasures Initiative (MCMi) established in 2010

READ


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New efforts to empower consumers by advancing access to nonprescription drugs

Increase access to broader selection of nonprescription drug products  empowering consumers to self-treat common conditions and potentially some chronic conditions

  • lower costs for health care system overall
  • provide greater efficiency and empowerment for consumers
  •  access to resources to help patients determine if medicine is right for them

Use of innovative technologies

  • Mobile Medical App with a set of questions to help someone determine (self-select) appropriateness of drug for them
  • Sponsors could develop approaches for self-selection and accurate use of their prescription product in the nonprescription setting

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CaptureAgency’s efforts to encourage the development of and broaden access to generic versions of opioid analgesics that are formulated to deter abuse

Encouraging development of opioids with abuse-deterrent formulations (ADFs) intended to make certain types of abuse, e.g. crushing, dissolving, more difficult or less rewarding

  • New 43 product-specific guidances related to the development of generic drug products
  • In vivo and in vitro study considerations for abuse deterrence evaluations
  • Final guidance  on development of generic versions of approved ADF opioids

READ


Image credits: FDA

News and Views: Budget and Real World Evidence, Inclusion/Exclusion in Clinical Trials, Gene Therapies, Balancing Opioid Access, Information and Usage Labeling, Mobile Medical Apps Regulation, Drug Shortages Task Force

CaptureFDA Budget Matters: A Cross-Cutting Data Enterprise for Real World Evidence 

FDA committed to new tools to collect data from routine medical care and develop valid scientific evidence  appropriate for regulatory decision making

  • Leverage “real world data” relating to patient health status and/or the delivery of health care obtained at the point of care
  • Enable more efficient medical product development by integrating safety and benefit information from clinical care
  • Can overcome limitations of traditional randomized clinical trials with defined inclusion and exclusion criteria

FDA’s Sentinel System and the National Evaluation System for health Technology (NEST) analyzes real world data for ‘real world evidence’

  • Need to govern responsible use of data and provide timely access through creation of national resource
  • Maintain strict data security and privacy of personal information
  • $100M medical data enterprise proposal budget for modern system for electronic health records from about 10 million lives

Current initiatives

  • Post-Market Data Sources: Claims Data vs. EHRs and access to clinical medical information in de-identified electronic health records and real-time information
  • Establishing a System that can Leverage All Data Sources by full interoperability
  • Improving Clinical Trials by using real world data for efficient recruitment, integration across clinical care settings, innovative statistical approaches to reduce  size and duration
  • Investing in Tools to More Wisely Use Data to Improve Health for data standards and data quality

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Evaluating Inclusion and Exclusion Criteria in Clinical Trials

Eligibility criteria define patient population under investigation

  • Inclusion criteria identify population in which it is expected that the effect of the drug can be shown
  • Exclusion criteria specify characteristics that disqualify patients from participation
  • Both exclude patient subgroups who may eventually receive drug once approved

Strategies to Support Better Development of Eligibility Criteria and Increase Enrollment

  • Improving transparency and increasing patient involvement in clinical trial design
  • Re-examining exclusion and inclusion Practices
  • Increasing the use of innovative and alternative trial designs and methods to support inclusion

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FDA’s Efforts to Advance Development of Gene Therapies

For novel technologies like gene therapy, FDA tailoring regulatory path for assuring safety and efficacy

  • Six scientific guidance documents for modern, comprehensive framework
  • Clear recommendations to support innovation

Disease Specific Gene Therapy Guidances

Human Gene Therapy for Rare Diseases

Guidances on Manufacturing Gene Therapies

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Balancing access to appropriate treatment for patients with chronic and end-of-life pain with need to take steps to stem misuse and abuse of opioids

New policy to strike right balance between

  • reducing new addiction rate by decreasing exposure to opioids prescribing  – and –
  • make sure that patients with pain have access to appropriate, evidence-based care
  • Mostly, opioid treatment for acute pain and prescribed for short durations
  • Patient-Focused Drug Development meeting  for additional patient viewpoints

New steps to aggressively confront the addiction epidemic

  • Revised Blueprint for opioid drug manufacturers required to make available to prescribers
  • Required training on non-opioid alternatives
  • Develop evidence-based guidelines on appropriate prescribing
  • lnnovation challenge to spur development of medical devices ‒ including digital health and diagnostics – to provide novel solutions to treating pain
  • New series of guidance documents on development of new drugs targeted to the treatment of various types of pain
  • Collaboration with NIH public-private partnership to advance pharmacological treatments for pain and addiction

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Steps to encourage more informative labeling on prescription drug and biological products’ indications and usage

General Principle: To enable health care practitioners to readily identify appropriate therapies for patients by clearly communicating drug’s approved indication(s)

  • Scope of an Indication Relative to Population Studied
  • Age Groups in Indication
  • Distribution of Information Among Labeling Sections

Content and Format

  • Indication: Disease, Condition, or Manifestation Being Treated, Prevented, Mitigated, Cured, or Diagnosed
  • Other Information Necessary To Describe the Approved Indication
  • Limitations of Use : Appropriate and Inappropriate situations

Other considerations

  • Identification of Outcomes, Endpoints, and Benefit(s)
  • Accelerated Approval
  • Required or Recommended Language
  • Preferred Wording and Wording Generally To avoid

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FDA Regulation of Mobile Medical Apps

Efficient regulation of mobile medical apps – Software as Medical Device (SaMD) – tailored to potential benefits and risks

  • Traditional FDA regulatory framework can stifle the development/access
  • New framework being developed to  recognize distinctive aspects of digital health technology, clinical benefit, unique user interface, and compressed commercial cycles

FDA initiatives

  • Working with International Medical Device Regulators Forum (IMDRF) on internationally harmonized regulatory framework
  • Digital Health Innovation Action Plan to implement the software provisions of the Cures Act
  • Precertification program to qualify for a more streamlined premarket review process
  • New guidance on Mobile Medical Apps

Firm-based approach based on culture of excellence and leveraging

  • Postmarket data collection
  • Clinical data from device registries, EHRs
  • Other electronic health information sources through the National Evaluation System for health Technology (NEST)

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Formation of a new drug shortages task force and FDA’s efforts to advance long-term solutions to prevent shortages

New Drug Shortages Task Force – including CMS and VA

  • Understand root causes – e.g. low margins with low incentives, reimbursement issues, limited manufacturing capacity
  • Consider regulations coupled with financial incentives to market critical access drugs
  • Conduct a risk assessment and mitigation plans  to proactively address shortage
  • Emerging technology program  to prevent shortages and new quality metrics initiatives

READ


Image credits: FDA, HHS

Market Authorizations: EPIDIOLEX, ZEPHYR Endobronchial Valve, ELLIPSYS System, EVERLINQ System, DreaMed decision-support software, EVERSENSE CGM system

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EPIDIOLEX  (cannabidiol) oral solution

GW Pharmaceuticals

INDICATION:  Treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients 2 years of age and older

ADDRESSING UNMET NEED:

  • Treatment of rare genetic conditions in pediatric population
  • First botanical marijuana product to be FDA approved

MECHANISM OF ACTION: Precise mechanisms of anticonvulsant effect unknown; does not appear to exert its anticonvulsant effects through interaction with cannabinoid receptors

EFFICACY:

  • Three randomized, double-blind, placebo-controlled clinical trials, n=516 patients with either Lennox-Gastaut syndrome or Dravet syndrome, Epidiolex + other medications vs. placebo, 14-week treatment period
  • Primary efficacy measure: %change from baseline in the frequency (per 28
    days) of drop seizures (atonic, tonic, or tonic-clonic seizures)
  • Significant decrease in seizures vs placebo; p≤0.01

SAFETY:

  • Most serious risks: Thoughts about suicide, attempts to commit suicide, feelings of agitation, new or worsening depression, aggression and panic attacks
  • Also caused liver injury, generally mild, but raising the possibility of rare, but more severe injury
  • Most common side effects:  Sleepiness, sedation and lethargy; elevated liver enzymes; decreased appetite; diarrhea; rash; fatigue, malaise and weakness; insomnia, sleep disorder and poor quality sleep; and infections
  • Must be dispensed with a patient Medication Guide

REGULATORY PATHWAY:

FDA

  • Orphan designation, Fast Track, Priority Review, Priority Review Voucher
  • Postmarketing requirements: Embryofetal development study, juvenile toxicology, carcinogenicity,  potential for chronic liver injury, pregnancy outcomes study, risk of drug-drug interactions or QT interval prolongation.

DEA

  • Currently controlled in Schedule I under the Controlled Substances Act
  • FDA scheduling recommendation has been transmitted to DEA
  • Final DEA scheduling decision pending

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ZEPHYR Endobronchial Valve (Zephyr Valve)

Pulmonx

INTENDED USE: Treat breathing difficulty associated with severe emphysema

ADDRESSING UNMET NEED:  Less invasive treatment that expands the options available to emphysema patients

DEVICE DESCRIPTION:

  • Flexible bronchoscope to place Zephyr Valves, similar in size to pencil erasers, into diseased areas of lung airways
  • Device design intended to prevent air from entering damaged parts of lung and allow trapped air and fluids to escape
  • During inhalation, valves close, preventing air from entering damaged part of lung
  • During exhalation, valves open, letting out trapped air, which is intended to relieve pressure

EFFECTIVENESS: 

  • Study, n=190 emphysema patients, Zephyr Valves + medical management (medications and pulmonary rehabilitation) vs. Control group received medical management only, one year treatment
  • Primary endpoint: % with at least a 15% improvement in pulmonary function scores (the volume of air that can forcibly be blown out in one second after full inhalation)
  • 47.7 % with Zephyr Valves  vs. 16.8% in control group

SAFETY:

  • Adverse events: Death, air leak (pneumothorax), pneumonia, worsening of emphysema, coughing up blood, shortness of breath and chest pain
  • Contraindication: Active lung infections; those who are allergic to nitinol, nickel, titanium or silicone; active smokers and those who are not able to tolerate the bronchoscopic procedure

REGULATORY PATHWAY: PMA

  • Breakthrough designation

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Ellipsys Vascular Access System 

Avenu Medical

INDICATION FOR USE:  Creation of a proximal radial artery to perforating vein  anastomosis via a retrograde venous access approach in patients with a minimum vessel diameter of 2.0mm and less than 1.5mm of separation between the artery and vein at the fistula creation site who have chronic kidney disease requiring dialysis

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EVERLINQ endoAVF System 

TVA Medical

INDICATION OF USE: Creation of an arteriovenous fistula (AVF) using the ulnar artery and ulnar vein in patients with minimum artery and vein diameters of 2.0 mm and less than 2.0 mm separation between the artery and vein at the fistula creation site who have chronic kidney disease and need hemodialysis

………………..

ADDRESSING UNMET NEED: Additional, less-invasive vascular access options for patients who will require hemodialysis

DEVICE TYPE: Percutaneous catheter for creation of an arteriovenous fistula for hemodialysis access

  • Single use percutaneous catheter system that creates an arteriovenous fistula (AVF) in the arm of patients with chronic kidney disease who need hemodialysis

CLINICAL PERFORMANCE:

  • Safely deliver, deploy, and remove the device
  • Create an arteriovenous fistula
  • Attain blood flow rate and diameter suitable for hemodialysis
  • Use fistula for vascular access for hemodialysis
  • Patency of the fistula

RISKS: 

  • Unintended vascular or tissue injury
  • Adverse hemodynamic effects
  • Failure to create a durable fistula that is usable for hemodialysis
  • Use of the device adversely impacts future vascular access sites
  • Adverse tissue reaction
  • Infection
  • Electrical malfunction or interference leading to electrical shock, device failure, or inappropriate activation
  • Software malfunction leading to device failure or inappropriate activation

REGULATORY PATHWAY: De Novo request

  • Regulation Number: 21 CFR 870.1252
  • Regulation Name: Percutaneous catheter for creation of an arteriovenous fistula for hemodialysis access
  • Regulatory Class: Class II
  • Product Code: PQK

CLASSIFICATION ORDER (Ellipsys)

CLASSIFICATION ORDER (everlinQ)


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DreaMed Advisor Pro decision-support software

DreaMed Diabetes, Ltd

INDICATION FOR USE:  Decision-support software intended for assisting healthcare professionals in the management of patients with Type 1 diabetes who:

  • use insulin pumps as their insulin delivery therapy
  • monitor their glucose levels using either of the following: CGM, or o CGM and self-management blood glucose meter
  • Are above the age of 6 and under 65 years old
  • Use rapid acting U-100 insulin analogs in their pump

Use by healthcare professionals when analyzing continuous glucose monitoring (CGM), self-monitoring blood glucose (SMBG) and pump data to generate recommendations for optimizing a patient’s insulin pump settings for basal rate, carbohydrate ratio (CR), and correction factor (CF); without considering the full clinical status of a particular patient.

DreaMed Advisor Pro does not replace clinical judgment

DEVICE TYPE: Insulin Therapy Adjustment Device

  • Incorporate biological inputs, including glucose measurement data from a CGM to recommend insulin therapy adjustments as an aid in optimizing insulin therapy regimens for patients with diabetes mellitus

DESIGN VERIFICATION & VALIDATION:

  • Required data inputs, including timeframe over which data inputs must be collected and number of data points required
  • Types of device outputs and insulin therapy adjustment recommendations, including how the recommendations are generated
  • Clinical validity of the device outputs and insulin therapy recommendations
  • Input data specifications, including accuracy requirements for CGM  and other devices generating data inputs
  • Clinical justification for each specification
  • Ensure secure and reliable means of data transmission to and from device, data integrity checks, accuracy checks, reliability checks, security measures
  • Users can understand and appropriately interpret recommendations
  • Mitigation strategy to minimize dosing recommendation errors

RISKS:

  • Erroneous or extreme changes in insulin dosing recommendations may cause hypoglycemia or hyperglycemia
  • Incorrect interpretation of results may lead to inappropriate clinical decision making
  • Incorrect understanding of appropriate device use may lead to inappropriate treatment decisions
  • Patient harm due to insecure transmission of data
  • Data corruption may lead to inappropriate treatment recommendations

REGULATORY PATHWAY: De Novo request

  • 21 CFR 862.1358
  • Regulation Name: Insulin Therapy Adjustment Device
  • Regulatory Class: Class II
  • Product Code: QCC

CLASSIFICATION ORDER


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EVERSENSE Continuous Glucose Monitoring (CGM) system

Senseonics

INDICATION FOR USE: For continually measuring glucose levels in adults (18 years and older) with diabetes for up to 90 days.The system is intended to:

  1. Provide real-time glucose readings
  2. Provide glucose trend information
  3. Provide alerts for the detection and prediction of episodes of low blood glucose (hypoglycemia) and high blood glucose (hyperglycemia)

The system is a prescription device. Historical data from the system can be interpreted to aid in providing therapy adjustments. These adjustments should be based on patterns seen over time.The system is indicated for use as an adjunctive device to complement, not replace, information obtained from standard home blood glucose monitoring devices.

ADDRESSING UNMET NEED: 

  • More seamless digital system giving patients ability to effectively manage diabetes
  • Modern regulatory approach for products that’s carefully adapted to the unique characteristics of these opportunities

DESCRIPTION: Continuous Glucose Monitor, Implanted, Adjunctive Use

EFFECTIVENESS & SAFETY: 

  • Clinical study, n=1254 diabetes patients, comparing readings by Eversense CGM vs.  laboratory-based glucose analyzer
  • Safety based on procedure used to implant; <1% experiences serious adverse event
  • Potential adverse effects: Related to insertion, removal and wear of the sensor include allergic reaction to adhesives, bleeding, bruising, infection, pain or discomfort, scarring or skin discoloration, sensor fracture during removal, skin inflammation, thinning, discoloration or redness
  • Other risks: Hypoglycemia or hyperglycemia in cases where information provided by the device is inaccurate or where alerts are missed

REGULATORY PATHWAY: PMA

  • Advisory Committee meeting:  8 to 0 vote, committee recommended that benefits outweigh the risks for patients with diabetes

PMA Listing


Image credit: GW, Pulmonx, Avenu, TVA, DreaMed, Senseonics

FDA News: Marijuana Research, Inhaled Antibiotics, Quality Metrics for Drugs, Compounded Drugs Enforcement

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Importance of conducting proper research to prove safe and effective medical uses for the active chemicals in marijuana and its components

Marijuana is a Schedule I compound with known risks

  • Safety and effectiveness in treatment of medical disorders held to the same standard as other drug compounds
  • FDA approved purified form of drug cannabidiol (CBD) to treat seizures with rare, severe forms of epilepsy
  • Approval based on well-controlled clinical trials, reliable  dosage form, through  reproducible route of delivery to ensure anticipated benefits

Path for other marijuana-derived products 

  • Robust clinical development program, purity and  manufacturing controls
  • FDA Botanicals Team with expertise on botanical issues
  • Involvement of other federal agencies- National Institute on Drug Abuse, Drug Enforcement Administration
  • Continued vigilance of illegal marketing of unapproved CBD-containing products with unproven medical claims

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Development of Inhaled Antibacterial Drugs for Cystic Fibrosis and Non-Cystic Fibrosis Bronchiectasis

Summary:

Public workshop held on “Development of Inhaled Antibacterial Drugs for Cystic Fibrosis and Non-Cystic Fibrosis Bronchiectasis.”

Purpose:

Discuss the clinical trial design challenges and future considerations for inhaled antibacterial products to treat cystic fibrosis (CF) and non-CF bronchiectasis.

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Quality Metrics for Drug Manufacturing

Quality metrics

  • Used throughout drugs and biologics industry to monitor quality control
  • Foundation for continual improvement of product and process quality
  • Element of companies’ commitment to quality culture

Two new programs on use of quality metrics to modernize pharmaceutical quality systems and advance innovation

  1. Quality Metrics Feedback Program: New drugs, generics, pharmaceutical ingredients (API) establishments, contract manufacturing organizations (CMOs), OTC products
  2. Quality Metrics Site Visit Program:  Experiential and firsthand learning opportunities to FDA staff i

Provide an opportunity for FDA to continue learning about the advantages and challenges companies have experienced in implementing Quality Systems

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Continued efforts relating to compounded drugs for patients who cannot use an FDA-approved drug

Compounded drugs are not FDA-approved

  • Quality of products important
  • Developing policies and conducting oversight to minimize risks to patients
  • Taking actions to protect patients and enforce existing laws

Fraud enforcement actions 

  • Billing reimbursors for medically unnecessary compounded drugs
  • Examples: topical pain creams comprised of multiple ingredients to increase billing amount, include non-topical products such as antidepressants, anticonvulsants, antivirals, narcotics
  • Clinicians and patients not aware of potential safety risks, lack of effectiveness

FDA Actions:

  • Draft guidance on evaluation of  clinical need
  • Inspection of compounding facilities
  • Prescription requirement

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