Fraudulent COVID-19 Products


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


Image credit: FDA

COVID-19 FDA Guidances


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



Increased availability of NIOSH approved respirators to healthcare personnel


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

Clinical Trial of Remdesivir to Treat COVID-19


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)


Image credit: FDA and NIAID

Potential Nitrosamines in Medication


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


Image credit: FDA

e-cigarettes: Enforcement policy on unauthorized flavored cartridges


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


Image credit: FDA

Medicines and Driving


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


Image credit: FDA

CURE ID crowdsourcing App for novel uses of existing medicines


 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


Image credit: FDA

Vaping Illnesses


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.


image credit: FDA

Biosimilars Basics


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


Image credit: FDA

2019 FDA Science Forum


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.


Image credit: FDA

FDA’s New History Exhibit


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



Image credit: FDA on Flickr




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


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


Image credit: FDA

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,


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


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



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



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


  • 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



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



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



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



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


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


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




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


Image credit: FDA

Remove the Risk- Opioid Disposal Campaign


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.


image: FDA

Fact or Fiction: Smoking Cessation and Medications



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




Youth Tobacco Prevention Plan


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


Image credit: FDA

Obesity Prevention Game


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!


Image credit: FDA

Framework for Safety and Performance Based Pathway


Framework for the Safety and Performance Based Pathway

Modernized pathway to facilitate 510(k) Submissions

Safety and Performance Based Pathway when: 

  • New device has indications for use and technological characteristics that do not raise different questions of safety and effectiveness than identified predicate
  • Predicate is within  scope of list of eligible device types
  • Performance criteria align with performance of predicate
  • New device meets all the FDA-identified performance criteria.


  • Use pathway instead of conducting direct comparison testing to predicate despite technological differences
  • Will still need to identify a predicate for certain aspects of substantial equivalence, when appropriate.



2018 New Drug Approvals


2018 New Drug Approvals

  • Rare Diseases: 34 novel approvals including treatments for of rickets, Fabry disease, phenylketonuria
  • Infectious Diseases: Notables include treatments for smallpox, malaria, HIV-1, nontuberculous mycobacterial lung disease
  • Neurological Disorders: Notables include treatment for seizures in Lennox-Gastaut syndrome and Dravet syndrome, migraine, polyneuropathy in hereditary transthyretin-mediated amyloidosis, multiple sclerosis in children
  • Heart, Lung, and Circulatory Diseases: Notable include treatment of hereditary angioedema
  • Women’s Health:  First new treatment for endometriosis pain,  first vaginal ring contraceptive for use for an entire year
  • Cancer and Blood Disorders: New advances for breast cancer, prostate cancer, lung cancer, melanoma, cancer in pancreas or gastrointestinal tract, first treatment  for pheochromocytoma or paraganglioma, new cancer therapy to treat any tumor with specific genetic marker, acute myeloid leukemia, classical Hodgkin lymphoma, acute lymphoblastic leukemia, mycosis fungoides or Sézary syndrome,  thrombocytopenia
  • Other: Non-opioid drug product  for opioid withdrawal symptoms, non-opioid nerve block therapy,  ulcerative colitis, neurotrophic keratitis, seven new biosimilars




Patients Matter and Patient Engagement

Patient Engagement

Individual patient

  • experience diseases and therapies differently
  • has unique perspective about treatments or diagnostic procedures

Opportunities for patients and caregivers to get involved with FDA

  • Evolution of Patient Engagement at FDA
  • Patient Engagement Collaborative
  • FDA and European Medicines Agency Patient Engagement Cluster
  • FDA Patient Council
  • MOU with the National Organization of Rare Disorders
  • FDA Patient Representative Program
  • Food and Drug Administration Safety and Innovation Act (FDASIA) Section 1137
  • Patient Reported Outcomes
  • Patient Focused Drug Development Initiative
  • Device Patient Preference Initiative
  • Devices Patient Engagement Advisory Committee
  • Additional Patient Resources


Video credit: FDA

Bisimilars Learning Toolkit


Biosimilar Development Process

Biological products that are demonstrated to be biosimilar to or interchangeable with an FDA-approved biological product

  • Abbreviated pathway to provide more treatment options, increase access, lower costs
  • Rigorous approval standards for  safety and effectiveness
  • Ten biosmilars approved to date

Learning toolkit to help promote understanding of biosimilars and interchangeable products


Image credit: FDA

Digital Health Software Precertification (Pre-Cert) Program


Digital Health Software Precertification (Pre-Cert) Program


  • Develop tailored and pragmatic regulatory oversight
  • Trust organizations with demonstrated culture of quality and organizational excellence
  • Leverage transparency of organization’s excellence and product performance across entire lifecycle
  • Streamline premarket review to verify the continued safety, effectiveness, and performance


  • Leverage information from all available sources to be more efficient and streamlined without compromising safety and effectiveness
  • Enable modern and tailored approach to allow timely software iterations and changes
  • Ensure high-quality by enabling companies to demonstrate their embedded culture of quality and organizational excellence
  • Learn, adapt, adjust key elements based on program effectiveness



Image credit: FDA

Spectrum of Disease Conditions

Spectrum of Disease Conditions


Help FDA improve MedWatch System

CaptureHelp FDA Improve FDA MedWatch Forms

MedWatch is FDA gateway for clinically important safety information and reporting serious problems with human medical products

  • Physicians and Consumers can report unexpected side effects, adverse events, or other problems through MedWatch program
  • Report adverse events, product problems, errors with use,  evidence of therapeutic failure is suspected or identified

FDA is seeking comments to help improve adverse event information collection

  • Forms 3500, 3500A and 3500B

Image credit: FDA

CDRH Device Evaluation Intern Program


Device Evaluation Intern Program

Challenging and rewarding experience for individuals interested in pursuing careers in the fields of science, engineering, and/or medicine

  • Test educational interests in practical work environment
  • Gain professional “real work” experience
  • Work alongside Agency’s top healthcare authorities, establish professional contacts


Image credit: FDA


Benefit-Risk Assessment in Drug Regulatory Decision-Making : 2018-2022


Benefit-Risk Assessment in Drug Regulatory Decision-Making

Under FDARA 2017, FDA committed to furthering implementation of structured benefit-risk assessment into drug review

Commitments on Enhancing Benefit-Risk Assessment

  • Continue implementation of the Benefit-Risk Framework
  • Participate in stakeholder meetings
  • Draft guidance on benefit-risk assessment
  • Revise relevant MAPPs and SOPPs
  • Conduct second evaluation of Benefit-Risk Framework

Additional Opportunities to Enhance FDA’s Benefit-Risk Assessment

  • Improving accessibility for approved products
  • Use to support Advisory Committee meetings
  • Exploring additional tools to support assessment


Image credit: FDA

Novel Materials and Manufacturing Research Program


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

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

Novel Materials and Manufacturing Research Program elucidates 

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


Image credit: FDA

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

CapturePublic Warning and Notification of Recalls

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

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

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

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

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

Public Notification of Recalls: Weekly FDA Enforcement Report

FDA 101: Product Recalls



Acceptance of Clinical Data to Support Medical Device Applications and Submissions

FDA regulations on data acceptance from clinical investigations conducted outside US

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

Conformity with GCP

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

Supporting Information, Waivers, Records



Refuse to Accept Policy for 510(k)

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

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

Refuse to Accept Principles

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

Checklist provided


Image credit: FDA

FDA Soundcast: KYMRIAH, first CAR-T cell immunotherapy


KYMRIAH, CAR-T cell immunotherapy- an entirely new treatment approach for patients with cancer FDA Approvals: KYMRIAH, MYLOTARG, VABOMERE, Benznidazole

  • Produced by taking patient’s blood sample, isolating T lymphocytes, and genetically engineering those T-cells to express a new chimeric receptor that recognizes CD19 on their leukemia and normal B-cells
  • Engineered T-cell should recognize and kill B-cells, including the malignant cells


Image credit: FDA

FDA Drug Databases

Drug Approvals and Databases



Transparency at FDA

New platforms for analyzing and visualizing large, complex datasets

  • Harness data to advance the safe and efficient development of new therapies
  • Tailor clinical care to individual patient characteristics and preferences
  • Communicate information supporting regulatory decision-making to engender greater public confidence

Advance transparency without reducing incentives to innovate

  • FDA’s Data Dashboard: publicly available datasets, data visualization tools 
  • openFDA
    • APIs and full sets of downloadable FDA data files for adverse events, drug product labeling, recall enforcement reports
    • supports open source user community, sharing of source code and techniques for use through GitHub, Twitter, and StackExchange

New Steps to filter information and harness it into more usable knowledge

  • Greater transparency and efficiency in NDA and BLA reviews
  • Track product development in clinical trials posted on the
  • Pilot (9 applications) to disclose key portions of Clinical Study Reports to decipher  key clinical evidence for approval decision
  • Add special identifier number to clinical trials registered through  and link to FDA communications (e.g. labeling, advisory committee materials)
  • Explore possibility – under existing statutory authority- to release Complete Response Letters (CRLs) information directly relevant to patients

Technology, no matter how powerful, is always just a tool

  • Commitment to transparent, responsible, and science-based use to save and improve lives

FDA Commissioner Statement

Blueprint for FDA transparency


FDA Marketing Authorizations: FLUARIX, LYNPARZA, GILOTRIF, REMOVE System

Image result for fluarix logoFLUARIX QUADRIVALENT (Influenza Vaccine) Suspension for Intramuscular Injection


INDICATION: Active immunization for the prevention of disease caused by influenza A subtype viruses and type B viruses contained in the vaccine. Approved for use in persons aged 3 years and older


  • Randomized, double-blind, active-controlled, safety, immunogenicity, and noninferiority trial, FLUARIX QUADRIVALENT (n = 791) vs. comparator trivalent influenza vaccine (FLUARIX, TIV-1, n = 819 or TIV-2, 426 n = 801), age 3-17 years
  • Endpoint: % achieving seroconversion.  Non-Inferiority achieved


  • Injection site adverse reactions:  pain, redness, swelling
  • Systemic adverse events: drowsiness, irritability, loss of appetite, fatigue, muscle aches, headache, arthralgia, gastrointestinal symptoms


  • Initial approval in 2012
  • Extended to age range to include children 6 to 35 months of age


  • Vaccine product codes as well as some common administration codes associated with immunization



LYNPARZA (olaparib) tablet

AstraZeneca Pharmaceuticals

SUPPLEMENTAL INDICATION: Indicated in patients with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer, who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic


  • Approximately 20-25% patients with hereditary breast cancers and 5-10%  have a BRCA mutation
  • First treatment for breast cancer with a certain inherited gBRCAm HER2-negative metastatic breast cancer
  • Patients selected for treatment based on an FDA-approved genetic test – BRACAnalysis CDx.

MECHANISM OF ACTION:  Poly (ADP-ribose) polymerase (PARP) inhibitor


  • Open-label study (n=302) patients with gBRCAm HER2-negative metastatic breast cancer, LYNPARZA vs. healthcare provider’s choice of chemotherapy. Tested with the BRACAnalysis CDX to confirm deleterious or suspected deleterious gBRCAm status
  • Major efficacy outcome measure: Progression Free Survival (PFS)  assessed by blinded independent central review using RECIST version 1.1
  • PFS Number of events: 163 (80%) vs. 71 (73%), p=0.0009


  • Common side effects: Anemia), neutropenia, leukopenia, nausea, fatigue, vomiting, nasopharyngitis, respiratory tract infection, influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation and inflammation and sores in the mouth
  • Severe side effects:  Myelodysplastic syndrome/acute myeloid leukemia, pneumonitis
  • Cause harm to a developing fetus and newborn baby


  • Priority Review
  • First approved in 2014 to treat certain patients with ovarian cancer


  • No Medicare coverage for previously approved indication (specialty product); high copay



GILOTRIF (afatinib) tablets

Boehringer Ingelheim Pharmaceutical

SUPPLEMENTAL INDICATION:  First-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test.
Limitation of Use: Safety and efficacy have not been established in patients whose tumors have resistant EGFR mutations

MECHANISM OF ACTION: Covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling


  • In NSCLC patients harboring non-resistant EGFR mutations (S768I, L861Q, and/or G719X) other than exon 19 deletions or exon 21 L858R substitutions enrolled in one of three clinical trials – pooled analysis
  • Non-resistant EGFR mutations identified using either Sanger sequencing or by  therascreen EGFR RGQ PCR Kit.
  • Confirmed overall response rate: 66% .
  • Among the 21 responders, 52% had response duration of ≥12 months and 33% had response duration  ≥18 months


  • Most common adverse reactions: Diarrhea, rash/acneiform dermatitis, stomatitis, paronychia, dry skin, decreased appetite, nausea, vomiting, pruritis


  • Priority Review and Orphan Drug Designation
  • Initial approval in 2013 for treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations
  • This approval broadens the patient population


  • 100% of Medicare Part D and Medicare Advantage plan coverage; Tier 5 (non-preferred brand-name drugs)
  • Restrictions: Quantity limits, Prior Authorization




Ovesco Endoscopy AG


The remOVE System consists of the DC Impulse and the DC Cutter Set.
The remOVE DC Impulse is a medical electrical device for fragmentation of OTSC® (endoscopic device for effective treatment of hemorrhage and acute or chronic wall defects in the GI tract) and FTRD® (endoscopic device for full-thickness resection of colorectal wall lesions) clips made by Ovesco Endoscopy AG for the digestive tract.
The remOVE DC Cutter Set is a set of instruments for use in flexible endoscopy. It consists of a bipolar DC instrument for the fragmentation of OTSC (endoscopic device for effective treatment of hemorrhage and acute or chronic wall defects in the GI tract) and FTRD (endoscopic device for full thickness resection of colorectal wall lesion) clips from Ovesco Endoscopy AG, a pair of forceps and a cap for removal of these fragmented clips.

GENERIC DEVICE TYPE: Endoscopic electrosurgical clip cutting system

Prescription device that applies electrical energy to fragment metallic clips, which are devices placed in the digestive tract to close gastrointestinal perforations, hemorrhages, or perform resection.
The system includes instruments that are then used to remove the fragmented clips from the digestive tract.


  • Unintended tissue damage (burns, perforations, bleeding):  Animal performance testing, Non-clinical performance testing, Electrical and thermal safety testing, Usability testing, Labeling
  • Electromagnetic interference / Electrical shock: Electromagnetic compatibility testing, Electrical safety testing, Labeling
  • Adverse tissue reaction: Biocompatibility evaluation
  • Infection: Sterilization validation, Shelf life testing, Labeling


  • Regulation Number: 21 CFR 876.4310
  • Regulation Name: Endoscopic electrosurgical clip cutting system
  • Regulatory Class: Class II
  • Product Code: QAG




Image credits: GSK, AstraZeneca, Boehringer Ingelheim, Ovesco

List of Off-Patent, Off-Exclusivity Drugs without an Approved Generic


List of Off-Patent, Off-Exclusivity Drugs without an Approved Generic

  • To improve transparency and encourage the development and submission of  ANDAs in markets with limited competition
  • Part I of the list identifies those drug products for which FDA could immediately accept an ANDA without prior discussion
  • Part II identifies drug products for which ANDA development or approval may raise potential legal, regulatory, or scientific issues that should be addressed with the Agency prior to considering submission of an ANDA


Image credit: FDA

Patent Certifications and Suitability Petitions


Patent Certifications and Suitability Petitions

To continually improve its pre-ANDA interactions with applicants for generic drugs 

Paragraph IV Patent Certifications

  • Generic applicant provides “paragraph IV certification”  challenging brand product patent listed in FDA’s Orange Book
  • Must notify brand product sponsor/patent holder of ANDA submission and patent challenge
  • If approved, eligible for exclusive right to market generic drug for 180 days

Paragraph IV Certifications List

  • To assist generic drug applicants, FDA publishes list of drug products for which ANDA received containing Paragraph IV patent certification

Suitability Petitions

  • Generic application may petition FDA for ANDA for drug product different from Orange Book listing (e.g. route of administration, dosage form, strength, or active ingredient)


Image credit: FDA

CDRH FY 2018 Proposed Guidance Development & Retrospective Review

fda guidancesCDRH Fiscal Year 2018 (FY 2018) Proposed Guidance Development and Focused Retrospective Review of Final Guidance

Three lists:

  1. A-List:  fully intends to publish
  2.  B-List: intends to publish as resources permit
  3. Focused retrospective review: guidances issued in 2008, 1998, 1988, and 1978


Final Guidance Topics

  • Medical Device Accessories: Describing Accessories and Classification Pathway for New Accessory Types (revision)
  • Unique Device Identification: Policy Regarding Compliance Dates of Class I and Unclassified Devices
  • Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical Devices
  • Considerations for Design, Development, and Analytical Validation of Next Generation Sequencing (NGS)-Based In Vitro Diagnostics (IVDs) Intended to Aid in the Diagnosis of Suspected Germline Diseases
  • Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics

Draft Guidance Topics

  • Export Certificates
  • Multifunctional Device Products: Policy and Considerations
  • The Least Burdensome Provisions: Concept and Principles
  • Humanitarian Devices Exemption (HDE) Program
  • 510(k) Third Party Review Program
  • Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program
  • Expansion of the Abbreviated 510(k) Program: Demonstrating Substantial Equivalence through Performance Criteria
  • The Application of Acceptable Uncertainty to Support Marketing Authorization Decisions for Medical Devices
  • Principles and Procedures for the Recognition and/or Withdrawal of Voluntary Consensus Standards
  • Validation of Automated Process Equipment Software



Updated Orange Book, Patent/Exclusivity FAQs

Orange Book 2.0  New Look, New Features

Orange Book

identifies drug products approved on the basis of safety and effectiveness by the FDA under the Federal Food, Drug, and Cosmetic Act (FD&C Act) and related patent and exclusivity information.  LEARN

Patent Submission Date

date on which FDA receives patent information from NDA holder (21 C.F.R. 314.53(d)(ii)(5) LEARN

Orange Book Update

search results and drug listings now show patent submission dates where available;  may help generic drug manufacturers determine earliest date for marketing LEARN

Patent vs. Exclusivity

Patent– granted by US Patent and Trademark Office anytime during drug development;  encompass a wide range of claims.

Exclusivity– granted per FD&C Act. delays and prohibitions on approval of competitor drugs; for NDA and ANDA holders;  promote balance between new drug innovation and  generic drug competition LEARN

Image credit: FDA

Influenza Virus Vaccine: 2017-2018 Season


Influenza Virus Vaccine: 2017-2018 Season

  • Trivalent vaccines contain the following:
    • an A/Michigan/45/2015 (H1N1) pdm09-like virus
    • an A/Hong Kong /4801/2014 (H3N2)-like virus
    • a B/Brisbane/60/2008-like virus (B/Victoria lineage).
  •  Quadrivalent vaccines contain additional B/Phuket/3073/2013-like virus (B/Yamagata lineage)
  • Flu vaccine lots that have been released and available for distribution by manufacturers


Image credit: FDA



  • A searchable catalogue of nearly 500 profiles on research consortia. Learn more about their work – including mission, structure, data sharing, partners, and more – and connect with them
  • framework report that presents a series of questions for those seeking to create new collaborative efforts, expand existing ones, or re-orient early-stage programs
  • 2013 landscape analysis in Science Translational Medicine analyzing characteristics of 369 consortia around the world
  • Highlighted by CDER-FDA  as a comprehensive public resource for researchers seeking partners with similar interests and objectives






2017 FDA Science Forum


2017 FDA Science Forum

  • Presentation of unique scientific research and collaborative efforts of 11,000 FDA scientists
  • Investigation and application of new science and emerging technologies to inform FDA’s regulatory decision-making and foster safe innovation
  • Concentrating on creating test methods and developing process knowledge to ensure safety and efficacy of products
  • FDA science is critical to product quality and safety


Image credit: FDA

FDA CDER Presentations Library


FDA CDER Presentations Library

  • CDER professionals participate in several meetings, conferences and workshops throughout the year
  • Topics can range from users fees, to drug advertising and marketing, to genomics, to over-the-counter products
  • Materials and overviews from some of those meetings are listed in the presentations library


Image credit: FDA

NextGen Collaboration Portal


NextGen Collaboration Portal

New technology platform to allow industry to request FDA pre-ANDA meetings for complex generic drug products

  • initiate requests by uploading meeting request package
  • submit supporting documents e.g. presentation materials, additional information responses, post-meeting comments
  • minimize manual data entry
  • support GDUFA II performance goals.


Image credit: FDA

CLIA and Waiver by Application


 CLIA  and Waiver by Application

CLIA: Clinical Laboratory Improvement Amendments

  • Regulate laboratory testing and require clinical laboratories certification prior to in vitro diagnostic (IVD) testing
  • Multiple types of CLIA certificates, based on  complexity of diagnostic tests
  • Responsible federal agencies: FDA, CMC, CDC

CLIA  IVD Categorization:

  • By degree of complexity: waived, moderate complexity, and high complexity

CLIA Waiver by Application:

  • For moderate complexity may test
  • Manufacturer may request categorization of the test as waived
  • Provides evidence to FDA that test meets CLIA statutory criteria for waiver


Image credit: FDA

FDA Sentinel System

SentinelFDA Sentinel System

Sentinel is used by the FDA-CDER to assess the safety of prescription drugs, including biological therapeutics and generic drugs

  • Managed in CDER’s Office of Surveillance and Epidemiology
  • Important component of CDER’s postmarketing safety system
  • Used to proactively assess drug safety, under real-world conditions, that more closely reflect patient care
  • Sentinel assessments make use of the automated surveillance tools


Image credit: Sentinel/FDA


FDA/CMS Hurricane Relief Efforts

Hurricanes Irma and Jose

Support of the Hurricane Relief Effort

Harvey, Irma, and Maria


Address safety and shortages

  • Ensuring safety of regulated products including medicines, medical devices, food, and the blood supply
  • Priority Actions : Recommendations on food and medical products handling, assess damage and impact to industry facilities, avoid food and crop loss, identify solutions to prevent shortages of life-saving therapies



Gain access to health coverage immediately 

  • Medicare special enrollment period:  Enroll, dis-enroll or switch Medicare health or prescription drug plans
  • Federal Health Insurance Exchange special enrollment period: For individuals  unable to complete application, plan selection, and enrollment process


Image credit: FDA

FDA Adverse Events Reporting System (FAERS) Public Dashboard


FDA Adverse Events Reporting System (FAERS) Public Dashboard

Highly interactive web-based tool for FAERS data

  • Human adverse events reported to the FDA by the pharmaceutical industry, healthcare providers and consumers
  • Expand access of FAERS data to general public
  • Some limitations : Incomplete reports, uncertain causation, unverified information, unknown rates of occurrence



Image credit: FDA

FDA Opioid Action Plan

Opioids and FDA Opioid Action Plan

To address  growing epidemic of opioid abuse, dependence and overdose in the US

  • Expand use of advisory committees
  • Develop warnings and safety information for immediate-release (IR) opioid labeling
  • Strengthen postmarket requirements
  • Update Risk Evaluation and Mitigation Strategy (REMS) Program
  • Expand access to abuse-deterrent formulations (ADFs) to discourage abuse
  • Support better treatment.
  • Reassess the risk-benefit approval framework for opioid use


Image credit: FDA

Medical Device and Hurricane Emergencies

Hurricanes Irma and Jose

Medical Device and Hurricane Emergencies

During natural disasters medical devices may be exposed to fluctuating power, contaminants, or unusual levels of heat or humidity.

FDA provides information on using medical devices during and following emergency situations

  • Re-Use of Devices
  • Disposal of Contaminated Devices
  • Reopening Dialysis Clinics
  • Medical Devices Requiring Refrigeration
  • Medical Devices Exposed to Heat and Humidity
  • Blood Glucose Meters
  • Mammography Facilities


Image credit: FDA

Digital Health Entrepreneur-in-Residence Program


Entrepreneur-in-Residence in CDRH Digital Health team 

  • To support and help develop our Software Precertification (PreCert) Pilot Program —a critical piece of CDRH’s Digital Health Innovation Action Plan
  • Need to have experience in digital health and passionate about developing innovative solutions to complex challenges
  • Help FDA establish the most appropriate criteria for standing up a firm-based precertification program



FDARA & User Fees


FDARA and FDA User Fee Programs

President signed into law the Food and Drug Administration Reauthorization Act (FDARA)

  • Revises and extends FDA’s user-fee programs for prescription drugs (PDUFA), medical devices (MDUFA), generic drugs (GDUFA) and biosimilar (BsUFA) products
  • Provides FDA resources for increasing regulatory efficiency and expedite availability of innovative, safe and effective medical products
  • Read how FDARA is making a difference

Drug User Fees


Medical Device User Fees





Expanded Access Navigator

Expanded Access Navigator launched by Reagan-Udall Foundation in collaboration with patient advocacy groups, pharmaceutical industry, FDA, and Federal government

  • online tool to guide patients, caregiver, physicians, through process for requesting single-patient expanded access for unapproved investigational drugs
  • for patient who has serious or immediately life-threatening disease or condition for which there is no FDA-approved treatment
  • permits the product’s manufacturer, with FDA authorization, to provide investigational drug for patient
  • physician submits Single Patient Expanded Access request


Image Credit: Reagan-Udall Foundation for the FDA 

Digital Health Innovation Action Plan

FDA announced the Digital Health Innovation Action Plan 

  • integrated approach to digital health technology and the implementation of the 21st Century Cures Act
  • recognize the unique characteristics of digital health technology and the marketplace
  • promote innovation of high-quality, safe, and effective digital health devices
  • Software Pre-Cert Pilot Program a key component of this plan

Additional information can be found on the Digital Health Webpage


Image Credit: FDA

Digital Health Software Precertification (PreCert) Program

FDA reimagining oversight of digital health technology

 “Software Precertification (PreCert) Pilot Program.” – new pilot program

  • looking first at the software developer and/or digital health technology developer, rather than primarily at the product


  • modern approach to software iterations and changes
  • high quality medical product software throughout the life of the product
  • adjust key elements and measure based on program effectiveness


Image Credit: FDA

Purple Book Updates

The Purple Book - med

Purple Book Updates

“Purple Book” lists biological products, including any biosimilar and interchangeable biological products



Cures Web Page

images of FDA-regulated innovative products

Cures Web Page

The 21st Century Cures Act (Cures Act) signed into law on December 13, 2016

  • Help accelerate medical product development
  • Bring new innovations to patients faster and more efficiently
  • Incorporate patient perspectives into the development of medical products
  • Modernize clinical trial designs and clinical outcome assessments

Newly created webpage details FDA plans and progress 


Image credit: FDA


Humanitarian Device Exemption Updates

Humanitarian Use Device (HUD) 

Humanitarian Device Exemption (HDE)

  • Marketing Application for an HUD;  exempt from the effectiveness requirements and is subject to certain profit and use restriction

Learn about

  • Definitions: HUD & HDE
  • Prohibition on Profit
  • Annual Distribution Number


Class of 2017 Commissioner’s Fellowship Program

Commissioner's Fellows

FDA Accepting Applications for Class of 2017 Commissioner’s Fellowship Program 

For health care professionals, scientists, and engineers

For regulatory science training, conduct cutting edge research on targeted scientific, policy, or regulatory issues under FDA senior scientist mentorship

Application deadline:  July 7, 5 pm EST

Image credit: FDA

ORA Program Alignment

ORA: Aligning for the Future

  • FDA Program Alignment: Modernize and strengthen workforce to keep pace with acceleration of scientific innovation, global expansion, new programmatic mandates
  • Office of Regulatory Affairs (ORA): Implement program-based management to align staff by FDA-regulated product – enhance communication effectiveness, processes, ability to keep pace with scientific innovation and protect public health


Image credit: FDA

National Drug Code (NDC) App

NDC Express mobile application

Section 510 of the Federal Food, Drug, and Cosmetic Act (Act) (21 U.S.C. (1972)

  • Requires registered drug establishments to list of  drugs manufactured, prepared, propagated, compounded, or processed for commercial distribution
  • Drug products have unique, three-segment number- National Drug Code (NDC)
  • Published in NDC Directory which is updated daily

New Mobile NDC App for quick directory searches 


Image credit: FDA

Drug, Cosmetic or Both?


Product’s Intended Use determines regulation as Drug, Cosmetic, or Both 

  • Drugs:  Diagnosis, cure, mitigation, treatment, or prevention of disease and affect structure/function of body
  • Cosmetics: Rubbed, poured, sprinkled, sprayed on, introduced into, applied to human body for cleansing, beautifying, promoting attractiveness, or altering the appearance
  • Drug + Cosmetic:  Example – antidandruff shampoo
  • FDA does not recognize the term “cosmeceutical”


FDA Research on Health Disparities

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

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

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

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


VIBERZI Drug Safety Podcast

FDA Logo, hands holding pills

Viberzi (eluxadoline) Safety Podcast

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

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




FDA BRIEF: Week of March 27, 2017

FDA approved

Image result for zejula

ZEJULA (niraparib) capsules

Tesaro, Waltham, MA, USA 

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


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


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

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


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


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


Image result for Regeneron

DUPIXENT (dupilumab) injection

Regeneron Pharmaceuticals,  Tarrytown, NY, USA

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


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


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

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


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

Image result for ocrevus


OCREVUS (ocrelizumab) intravenous infusion

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

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


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


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

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


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



Brain Sentinel Monitoring and Alerting System

Brain Sentinel, San Antonio, TX, USA

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

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

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

REG PATHWAY: De Novo request

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

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


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



CDER Oncology Fellowships

Students participating in the Commissioner's Fellowship Program

Oncology Genomics Fellowship – CDER

Oncology Bioinformatics Fellowship – CDER

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

Oncology Genomics Fellowship – CDER

Oncology Bioinformatics Fellowship – CDER

FDA – Office of Translational Sciences

Whats new in regulatory science

Office of Translational Sciences (OTS) – CDER

Promotes and Protects Public Health by:

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


Office of Biostatistics

Office of Computational Science

Office of Clinical Pharmacology

Office of Study and Integrity and Surveillance


FDA Patient Representative Program

FDA Patient Representative Programpatient

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

FDA Patient Representatives

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


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



Biomarkers Used as Outcomes


Biomarkers In Development of FDA-Approved Therapeutics

October 2007- December 2015


  • used as clinical trial outcome
  • accepted as basis for drug and biologic approvals
  • consult with FDA review division as early as possible in drug development regarding the use of a particular biomarker in clinical trials
  • examples of approved biomarkers below


Anesthesiology T1*; magnitude of T4/T1* ratio by acceleromyography
Cardiology Blood pressure
Serum low-density lipoprotein (LDL-C)
Hematology Hemoglobin
Platelet count
Ecarin clotting time; activated partial thromboplastin time; thrombin time; activated clotting time; plasma diluted thrombin time
Serum ferritin
Infectious Disease Hepatitis C virus (HCV) RNA*
Human immunodeficiency virus (HIV)-1 RNA
Sputum culture conversion to negative
Parasite count resolution
Inborn Errors of Metabolism White blood cell count; neutrophil count; red blood cell count; mean corpuscular volume
Growth in height or weight
Serum LDL-C
Blood phenylalanine
Forced vital capacity (FVC)
Plasma ammonia; plasma glutamine; and plasma citrulline
Splenic volume by magnetic resonance imaging (MRI)
Metabolism and Endocrinology Body weight
Bone mineral density by DEXA* scan
Hemoglobin A1c*
Serum calcium; oral calcium supplements; oral vitamin D supplements
Serum LDL-C
Urinary free cortisol (UFC)
Vertebral fractures by X-ray
Visceral adipose tissue (VAT) by computed tomography (CT) scan
Nephrology Hemoglobin
Serum sodium
Oncology CD34 positive cell count
Complete blood count (e.g., absolute neutrophil count)
Tumor burden by Bcr-Abl* (Philadelphia chromosome)
Tumor burden by Philadelphia chromosome positive cells
Plasma methotrexate
Splenic volume
Serum asparaginase
Serum testosterone
Tumor burden by imaging (using criteria such as RECIST* or EBMT*)
Ophthalmology Anterior chamber cells
Intraocular pressure (IOP)
Vitreomacular adhesion (VMA) by optical coherency tomography
Pulmonology Forced expiratory volume in one second (FEV1)
Respiratory distress syndrome (RDS) by chest X-ray and fraction of inspired oxygen (FiO2)
Rheumatology Joint angle
Uric acid
Transplant Biopsy-proven acute rejection (BPAR)

Medical Imaging Qualitative assessment of cerebral distribution of radioactive signal
Qualitative assessment of radioactive uptake (such as lymph node or tumor detection)
Qualitative regional assessment of localized radiographic signal intensity
Quantitation of arterial narrowing
Radioactive uptake in myocardial segments
Semi-quantitative lesion characteristics (such as internal morphology; contrast enhancement; border delineation)
Ultrasonographic signal intensity


Office of Manufacturing Quality Presentations



RAT (Regenerative Advanced Therapy Designation) & OTAT (Office of Tissues and Advanced Therapies)


WHAT: Resource for seeking designation as Regenerative Advanced Therapy – RAT

  • Cell therapy, therapeutic tissue engineering product, human cell and tissue product, any combination

WHY: Described in Section 3033 of the 21st Century Cures Act

WHEN: Either concurrently with IND submission or as an IND amendment

WHO: CBER, Office of Tissues and Advanced Therapies (OTAT)


Is It Really ‘FDA Approved?’


Clarification of   “FDA approved!” claim

DOES approve:

  • New Drugs and Biologics – by determining e benefits of the product outweigh the known risks for the intended use
  • Medical Devices – use risk-based, tiered approach
  • Human Cells and Tissues – use risk-based approach
  • Food and Color additives – for safety

DOES NOT approve :

  • Companies – health care facilities, laboratories, or manufacturers; can inspect
  • Compounded drugs
  • Tobacco products – regulated based on public health standard
  • Cosmetics – except color additives
  • Medical foods – for dietary management
  • Infant formula
  • Dietary Supplements
  • Food Label, including the Nutrition Facts panel
  • Structure-Function claims on dietary supplements and other foods

Misuse of FDA’s logo may violate federal law


EvGen- Evidence Generation


WHAT:  National Medical Evidence Generation Collaborative (EvGen) for high quality scientific evidence to support medical product development and decision making
WHY: Leverage previously isolated data systems to utilize available information collected during healthcare-related activities (e.g., medical research, medical product development, clinical care)
HOW: Combining insights, expertise, and technologies from across the spectrum of federal and private health sectors


22 FDA Case Studies with Divergent Phase 2/Phase 3 Results

Image result for FDA Logo

22 Case Studies with Divergent Phase 2/Phase 3 Results

22 case studies of drugs, vaccines and medical devices since 1999 – No confirmation of:

  • 14: effectiveness
  • 1 : safety
  • 7: safety and effectiveness


  • Unexpected Results with Large Randomized Controlled Studies
  • Presumed Mechanism of Action Does Not Automatically Predict Clinical Effects
  • Biomarkers Do Not Reliably Predict Clinical Outcomes

summary 1.JPGsummary 2.JPGLEARN

Drug Safety Priorities, 2015-2016


Drug Safety Oversight Across the Product Lifecycle

Advancing Drug Safety Science

  •  JumpStart – Enhancing Pre-Market Drug Review with Digital Tools
  • Postmarketing Safety Surveillance and Oversight
  • Improving Drug Safety through Research
  • Advancing Drug Safety Science through Public-Private Partnerships

Improving Operations and Management in Support of Drug Safety

  • 2015 GAO Report: A Call To Improve Data on Safety Issues
  • Opioid Addiction and Abuse: Addressing a National Crisis
  • Safe Use Initiative
  • Working to Ensure Drug Product Quality
  • Compounded Drugs and Drug Supply Chain Security

 Communicating Drug Safety: A Global Public Interface

  • Expert Responses to Public Queries
  • Social Media and Online Tools
  • Drug Safety Communications.
  • Safety Labeling Changes
  • Risk Communications Research


2016 Novel Drug Summary



Innovative products that serve unmet medical needs/significantly advance patient care. Have chemical structures that have never been approved before.

Adlyxin,  Anthim,  Axumin,  Briviact,  Cinqair, Defitelio, Epclusa, Eucrisa, Exondys 51, Lartruvo, Netspot, Nuplazid, Ocaliva, Rubraca, Spinraza, Taltz, Tecentriq, Venclexta, Xiidra, Zepatier, Zinbryta, Zinplava


  • Impact: Public health, First-in-class,  Rare diseases
  • Innovation: Breakthrough, Fast Track, Pirority Review, Accelerated Approva
  • Predictability: Met PDUFA goal date
  • Access: First cycle approval, First approval in US


Laboratory Developed Tests

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WHAT: Laboratory developed test (LDT) is in vitro diagnostic test designed, manufactured and used within a single laboratory

WHY: To measure or detect analytes in sample taken from a human body

WHO:  Individual labs. However, diagnostic devices not considered to to be LDTs if they are designed or manufactured completely, or partly, outside of the laboratory that offers and uses them.

HOW: FDA does not enforce premarket review as tests are relatively simple. However, FDA concern with some high-risk LDTs (e.g. cancer detection)  with unsubstantiated claims, erroneous results, data falsification. Discussion paper issued in Jan 2017



Medical Device Recalls, Database & OpenFDA API

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Medical Device Recalls
WHAT: Manufacturer takes a correction or removal action for medical device problem. FDA reviews strategy, assesses health hazard, violatiion of law, assigns classification
  • Class I: Reasonable chance to cause serious health problems or death
  • Class II: May cause temporary/reversible health problem
  • Class III: Not likely to cause health problem or injury

  • Inspecting for problems
  • Repairing device
  • Adjusting settings
  • Re-labeling
  • Destroying
  • Notifying patients of problem
  • Monitoring patients for health issues

WHO: Company (voluntarily) or by FDA

HOW: FDA notifies public
recall database.JPG

Searchable Database

  • Recalls since Nov 2002
  • Beginning Jan 2017, includes correction or removal actions prior to recall classification


Downloads [/device/recall]
  • OpenFDA is Elasticsearch-based API that serves public FDA data
  • Zipped JSON files
  • Records in same format as API calls to endpoint



FDA -CDRH FY2017 Proposed Guidances

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WHAT: Guidance documents that CDRH intends to publish in FY2017 & previously-issued final guidances for which CDRH is interested in receiving external feedback regarding whether these final guidances should be revised or withdrawn.

WHY: Per MDUFA III negotiations, to help get safe and effective medical devices to market more quickly

HOW:  3 lists

  • A List: To be published
  • B List: To be published  as resources permit
  • Retrospective review of 2007, 1997, 1987, 1977 documents



Patient-Reported Outcomes with LASIK (PROWL)

Patient-Reported Outcomes with LASIK (PROWL)

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WHAT:  Patient experiences, not health care provider, to measure impact symptoms directly had on performing usual activities.

HOW: Pilot, PROWL-1 and PROWL-2 studies

  • Evaluate new scales to measure visual symptoms, patient satisfaction, and expectations for and following LASIK surgery


  • Difficulty driving at night, severely impacted a patient’s daily living
  • Debilitating vision symptoms and severe dry eye
  • <1% experienced difficulty performing their usual activities following LASIK surgery


MATx App for Opioid Use Disorder

WHAT: Free App to  support practitioners who provide medication-assisted treatment (MAT), as well as those who plan to do so in the future.

WHY: 80% of Americans with opioid use disorder do not receive treatment


  • Information on FDA approved treatment approaches and medications
  • Buprenorphine prescribing guide
  • Clinical support tools – treatment guidelines, ICD-10 coding, working with special populations
  • Access to critical helplines and SAMHSA’s treatment locators.


LASIK Quality of Life Collaboration Project

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WHAT:  LASIK Quality of Life Collaboration Project (LQOLCP) to understand potential risk of severe problems from LASIK

WHY: Develop tool to assess patients with difficulties with usual activities and identify predictors

WHO:  FDA, National Eye Institute and Department of Defense

HOW: Patient-Reported Outcomes with LASIK (PROWL) studies

  • visual symptoms before and after their LASIK surgery
  • impact of symptoms on performing usual activities



FDA News: Orphan Disease R&D, Mouse Model for Zika, FDA-CMS Shared Responsibility

FDA BRIEF: Week of Nov. 14, 2016

FDA Voice

Orphan Disease R & D Has a Home at FDA

John J. Whyte, MD, MPH, Director, Professional Affairs and Stakeholder Engagement, FDA

Gayatri Rao, MD, JD, Director, Office of Orphan Products Development, FDA


FDA Research on Zika Virus Vaccines and Therapeutics

Neonatal mouse model provides a new platform for Zika virus research

  • New mouse model developed by FDA for exploring activity of Zika vaccines/therapeutics
  • C57BL/6 mouse strain susceptible to Zika, develops neurological symptoms and eventually recover from disease

PLoS Publication


  • Acknowledges ‘ fragmentation’: FDA approval/clearance vs. approval for coverage and payment
  • States shared sources of evidence for both Agencies while still applying the most appropriate criteria to their decision making
  • Clarified differing FDA and CMS standards:
    • FDA: Product approval or clearance, based on  “substantial evidence”
    • CMS: Coverage approval based on  “reasonable and necessary”
  • Recommends early involvement of health systems and payers to help to understand and address the kinds of evidence needed to incorporate the new product into practice
  • Highlights several FDA-CMS initiatives to facilitate gathering adequate evidence for both Agencies
  • Provides perspectives on ‘personalized medicine’



Regulatory Pharmaceutical Fellowship

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WHAT: 2-year fellowship – Rotations with FDA’s CDER and Industry

WHY: Train selected candidates in one of three tracks focused on the medical and regulatory aspects of drug information dissemination, drug advertising and promotion, or medication safety

WHO: Jointly Sponsored by: FDA, Purdue University, Eli Lilly and Company, Janssen Scientific Affairs, LLC, and Johnson and Johnson

WHEN: Available Positions for 2017 – 2019


Reporting Allegations of Regulatory Misconduct

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WHAT:  FDA reporting  of allegation of regulatory misconduct of medical device manufacturer or individuals marketing medical devices

WHY: Help FDA identify potential risks to patients, determine whether further investigation is warranted, and identify steps needed to address or correct violation

WHO: Anyone may file a complaint; identity or contact information will not be shared publicly


HOW: Allegations of Regulatory Misconduct Form, by email, or by regular mail.




FDA-EMA Patient Engagement Cluster

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WHAT: Cluster to share best practices involving patients along drug and biologic regulatory lifecycles

WHY: Broadened approach to advance and strengthen international collaboration

WHO: FDA and European Medicines Agency (EMA)

HOW:  Meet up to four times per year

  • Learn how their respective patients are engaged and involved
  • Develop common goals of expanding future patient engagement activities