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



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

St. Jude’s Medical (Abbott)

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


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


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


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


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


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

Fact Sheet


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



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

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

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

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


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

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

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

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


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


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


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


  • N/A. Non-prescription product


CaptureTROGARZO™ (ibalizumab-uiyk) injection

TaiMed Biologics USA Corp.

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


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

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


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


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


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




Imugen Babesia microtiArrayed Fluorescent Immunoassay (AFIA)

Oxford Immunotec


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

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


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


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

CBER Infectious disease tests


SkinPen Precision System

Bellus Medical, LLC

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

GENERIC DEVICE TYPE: Microneedling device for aesthetic use

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


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


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


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


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


GUDID Analytics


Global Unique Device Identification Database (GUDID)

  • Serves as reference catalog for every device with an identifier
  • Labeler of each medical device labeled with UDI must submit information concerning device to GUDID, unless subject to an exception or alternative
  • Open to public AccessGUDID


Image credit: FDA

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



 Predicting Stem Cell Activity to Ensure Safe and Effective Therapies

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

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

FDA scientists developing ways to improve predictability

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


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

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

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

FDA Steps

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

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

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

Patient Decision Checklist



 CDER: Regulatory Science

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

Image credit: FDA






Aug 13-14: Public Meeting – Pediatric Medical Device Development. Identify strategies that enhance medical device ecosystem toward development and innovation of devices that serve the complex needs of children. INFORMATION


⊕ May 10: Endocrinologic and Metabolic Drugs Advisory Committee Meeting. Discuss NDA for volanesoren solution for subcutaneous injection, Akcea Therapeutics, Inc, for use as an adjunct to diet for the treatment of patients with familial chylomicronemia syndrome. INFORMATION

May 18: MDIC workshop on Patient-Centered Clinical Trial Design. Method for incorporating patient preference information to set significance levels in clinical trial design. Focus on Parkinson’s disease; may be generalizable to other diseases.  In collaboratorion with FDA (CDRH), MIT, RTI Health Solutions and Michael J. Fox Foundation. INFORMATION

May 22-23: Accreditation Scheme for Conformity Assessment (ASCA) of Medical Devices to Food and Drug Administration-Recognized Standards; Public Workshop.  Discuss draft design of pilot program, including goals and scope, framework, requirements, and streamline standards. INFORMATION

May 24: FY 2018 Generic Drug Research Public Workshop.  Provide overview of regulatory science initiatives for generic drugs and public input on research priorities INFORMATION


Apr 3: Public workshop: CDER and You: Keys to Effective Engagement. Share information with stakeholders including patients, patient advocates, academic and medical researchers, health care professionals, drug developers. Share unique perspectives on drug development and safety. INFORMATION

Apr 6: US FDA and Health Canada: Joint Regional Consultation on the ICH. To provide information and receive comments on the current ICH activities as well as the upcoming meetings in Kobe, Japan INFORMATION

⊕ Apr 11-12: CDER Small Business and Industry Assistance Regulatory Education for Industry (REdI): Generic Drugs Forum. Interact with FDA subject matter experts  on Generic Drug Review Program, program progress, current initiatives. INFORMATION

Apr 16: Evaluating Inclusion and Exclusion Criteria in Clinical Trials; Public Meeting. Discuss topics related to eligibility criteria in clinical trials and their potential impact on patient access to investigational drugs, and how to facilitate the enrollment of a diverse patient population. INFORMATION

⊕ Apr 16-18: 2018 AAPS Workshop on Drug Transporters in ADME: From Bench to Bedside. Present next generation of transporters and transport mechanisms that may contribute to ADME properties of drugs in disease states considered in drug discovery and development. INFORMATION 

Apr 17: Public Meeting on Patient-Focused Drug Development for Opioid Use Disorder (OUD). To learn patients’ perspectives on OUD, effects on health and well-being, experience using prescription medical treatments and other treatments, challenges or barriers to accessing medical treatments for OUD. INFORMATION

⊕ Apr 19: Peripheral and Central Nervous System Drugs Advisory Committee Meeting . Discuss NDA for cannabidiol oral solution, GW Pharmaceuticals, for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older. INFORMATION

⊕ Apr 20: FDA/OCE Public Meeting on Relevant Molecular Targets in Pediatric Cancers: Applicability to Therapeutic Investigation FDARA 2017. Discuss provisional list of molecular targets for adult cancer indications but also relevant to cancer in children thereby providing a rationale for early pediatric evaluation. INFORMATION

Apr 21: Public Meeting on Electronic Submissions and Data Standards. Discuss current status of electronic submissions and data standards initiatives to improve predictability and consistency of electronic submissions process in support of human drug review program. INFORMATION

Apr 23-25: 12th Annual FDA/DIA Biostatistics Industry and Regulator Forum. Discuss relevant statistical issues associated with the development and review of therapeutic drugs and biologics. INFORMATION

Apr 30Public Workshop – Orthopaedic Sensing, Measuring, and Advanced Reporting Technology (SMART) Devices. Enhance engagement with stakeholders to facilitate device development and to discuss scientific and regulatory challenges associated with Orthopaedic SMART Devices.   INFORMATION


Mar 1: Vaccines and Related Biological Products Advisory Committee Meeting. Hear  research program in the Laboratory of Mucosal Pathogens and Cellular Immunology (LMPCI), Division of Bacterial, Parasitic and Allergenic Products (DBPAP), Office of Vaccines Research and Review (OVRR), and discuss selection of strains to for vaccines for the 2018-2019 influenza season INFORMATION

Mar 1: 21st US-Japan Cellular and Gene Therapy Conference. Exchange ideas on cutting edge and diverse areas of biomedical research, and enhance opportunities for collaborations among scientists from the US and Japan.  INFORMATION

Mar 1: Neurological Devices Panel  Advisory Committee Meeting. Discuss safety and effectiveness of intracranial aneurysm treatment devices and factors affecting clinical outcomes such as aneurysm morphology, size, and location in the neurovasculature. INFORMATION

Mar 1-2: IASLC-FDA Lung Cancer Neoadjuvant Meeting.Discuss standardization and validation of endpoints in neoadjuvant lung cancer trials. INFORMATION

Mar 4-6: FDA-PhUSE Computational Science Symposium. Review progress on topics such as data standards, best-practices-driven analytical tool development, business processes for information systems, evaluation of current tools. INFORMATION

Mar 5: Risk Communication Advisory Committee Meeting. Committee will discuss  impact of pregnancy and lactation labeling information in prescription drug and biological products as modified under the Pregnancy and Lactation Labeling Rule.  INFORMATION

Mar 8: FDA Grand Rounds:  Stem cell-based cellular therapies. Use of stem cell-based products is new and characterizing the product still faces hurdles.  FDA conducting research into identifying cell therapy product characteristics that will predict the reliably of the performance of cell-based therapies in humans. INFORMATION

 Mar 8: Gastrointestinal Drugs Advisory Committee Meeting. Discuss sNDA for XELJANZ (tofacitinib) proposed for the treatment of adult patients with moderately to severely active ulcerative colitis. INFORMATION

Mar 8: Public Workshop: Safety Assessment for Investigational New Drug Safety Reporting. Engage external stakeholders in discussions related to finalizing the draft guidance entitled “Safety Assessment for IND Safety Reporting.” INFORMATION

Mar 15: Oncology Center of Excellence Listening Session; Solicit comments regarding what stakeholders desire of the OCE in terms of structure, function, regulatory purview, and activity. INFORMATION

Mar 20: Promoting the Use of Complex Innovative Designs (CID) in Clinical Trials. March 20, 2018. Discuss use of CID in drug development and regulatory decision making, CID pilot program. INFORMATION

Mar 21-22: Joint Meeting of the Blood Products Advisory Committee and the Microbiology Devices Panel. Discuss reclassification from Class III to Class II of nucleic acid and serology-based point-of-care and laboratory-based in vitro diagnostic devices indicated for use as aids in the diagnosis of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection.⊕ INFORMATION

⊕ Mar 22: Webinar – Duodenoscope Sampling and Culturing. FDA, CDC, ASM and other endoscope culturing experts will review the voluntary duodenoscope surveillance sampling and culturing protocols to monitor quality of reprocessing procedures.  INFORMATION

Mar 22:  Patient Engagement in the National Evaluation System for health Technology (NEST): Lessons Learned and Best Practices Workshop.  Gather lessons learned and best practices for patient engagement in evidence generation (planning, collection of data and information, analysis, and dissemination). INFORMATION

Mar 22: Pediatric Advisory Committee and Endocrinologic and Metabolic Drugs Advisory Committee Meeting. To discuss major objectives of Phase 3 drug development program for treatment of children with achondroplasia (ACH) submitted by BioMarin Pharmaceutical Inc. INFORMATION

Mar 23: Advisory Committee Meeting: Pediatric. Discuss the following products for CDER – BANZEL, INTUNIV, LEXAPRO and CDRH – FLOURISH, ACTIVA, LIPOSORBER, IMPELLA RP SYSTEM. INFORMATION

⊕ Mar 26-28: Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics for Alcoholic Hepatitis and Alcohol Associated Liver Disease and Pediatric Irritable Bowel Syndrome and Pediatric Functional Constipation Workshop, Facilitate dialogue among industry, academia, and other stakeholders on common data elements needed to be included in clinical trials, clinical trial designs, potential surrogate and clinical benefit endpoints, and practical issues with managing clinical trials.  INFORMATION

⊕ Mar 27: Meeting of the Psychopharmacologic Drugs Advisory Committee. Discuss  NDA for  lofexidine hydrochloride, US WorldMeds, LLC, for mitigation of symptoms associated with opioid withdrawal and facilitation of completion of opioid discontinuation treatment. INFORMATION

Mar 28: Promoting the Use of Complex Innovative Designs in Clinical Trials
Inform development of guidance document and CID pilot program. INFORMATION


Feb 1: FDA-ISoP Public Workshop: Model Informed Drug Development (MIDD) for Oncology Products. Discuss integrating human pharmacokinetic, pharmacodynamic, efficacy, safety data into models, use of  novel imaging techniques, diagnostic, predictive biomarkers, shift from traditional endpoints,  regulatory implications.  INFORMATION

Feb 7-8: 10th Annual Sentinel Initiative Public Workshop.  Bring stakeholder community together to discuss a variety of topics on active medical product surveillance. INFORMATION

Feb 14-15:  Joint Drugs Advisory Committee Meeting: Anesthetic and Analgesic Products and Drug Safety and Risk Management. Discuss NDA for HYDEXOR, for the short-term management of acute pain severe enough to require an opioid analgesic while preventing and reducing opioid-induced nausea and vomiting. Also discuss sNDA  for EXPAREL (bupivacaine liposomal injectable suspension) to produce local analgesia and as a nerve block to produce regional analgesia. INFORMATION

Feb 22-23: FDA-AACR-ASTRO Regulatory Science and Policy Workshop – Clinical Development of Drug-radiotherapy Combinations. Address the lack of drug development for products intended specifically for use with radiation therapy.   INFORMATION

Feb 27:  Webinar – Custom Device Annual Reporting. Custom Device Exemption allows manufacturers to market medical devices designed to treat a unique pathology or physiological condition without premarket approval. Webinar to discuss custom device annual report requirement. INFORMATION

Feb 28: Public Meeting: Enhanced Drug Distribution Security under the Drug Supply Chain Security Act.Provide members of the drug distribution supply chain and other interested stakeholders an opportunity to discuss strategies and issues related to the enhanced drug distribution security provisions of the Act. INFORMATION


Jan 8: CLIA Waiver Applications Draft Guidance Documents. Discuss draft guidances on CLIA waiver applications and Dual 510(k) and CLIA waivers INFORMATION

Jan 9:  Webinar – Pediatric Information for X-ray Imaging Device Premarket Notifications:  Discuss final guidance on radiation safety of pediatric populations in the design of X-ray imaging devices. INFORMATION

Jan 10:  Webinar – Technical Considerations for Additive Manufactured Medical Devices. Technical aspects associated with AM processes, recommendations for device design, manufacturing, testing considerations. INFORMATION

Jan 11: Public Workshop – Self-Collection Devices for Pap Test. Obtain feedback on feasibility, benefits, risks for self-collection cervical sampling devices for cervical cancer screening by Pap testing INFORMATION

Jan 11:  Safety Assessment for IND Safety Reporting.Convened by the Duke-Robert J. Margolis Center for Health Policy at Duke University and FDA; to bring stakeholder community together to discuss IND safety topics INFORMATION

Jan 11: FDA Grand Rounds. Marker of brain injury increased in African Americans with Alzheimer’sBetter understanding of ethnicity and gender differences involved in the cause and progression of Alzheimer’s Disease could contribute to better drugs–and other types of interventions–to slow Alzheimer’s progression INFORMATION

Jan 16:  Webinar – FDA Categorization of Investigational Device Exemption (IDE) Devices to Assist the Centers for Medicare and Medicaid Services (CMS) with Coverage Decisions. Discuss final guidance on FDA categorization of IDE devices that is used by CMS to determine whether an IDE device, and certain related services, may be covered by CMS. INFORMATION

Jan 26: Evaluating Nicotine Replacement Therapies. Public comments on FDA’s approach to evaluating the safety and efficacy of nicotine replacement therapy (NRT) products, including how they should be used and labeled. INFORMATION

Jan 29: Weighing the Evidence: Variant Classification and Interpretation in Precision Oncology. To discuss how genetic sequencing data is best implemented in patient management to advance innovative regulatory strategies to support development of safe and effective precision-based drugs and devices. INFORMATION

Jan 30: Opioid Policy Steering CommitteePrescribing Information  Receive stakeholder input on how FDA REMS authority, might improve the safe use of opioid analgesics by curbing over-prescribing to decrease the occurrence of new addictions and limit misuse and abuse INFORMATION

Jan 30-31: Fostering Digital Health Innovation. Developing the Software Precertification Program. Discuss progress of pilot precertification program and seek input on ongoing development of the Software Precertification Program. INFORMATION

Image credit: FDA

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

FDA BRIEF: Week of February 26, 2018

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

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

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

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

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


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

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

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

FDA incentives, approvals, trends

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

Modernization and new initiatives

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

New Website



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

Working to determine the root causes

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

Looking ahead to 2018-2019 flu season

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


Capture.JPGDuodenoscope surveillance sampling and culturing

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

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

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

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


Image credit: FDA, CDC


Novel Materials and Manufacturing Research Program


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

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

Novel Materials and Manufacturing Research Program elucidates 

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


Image credit: FDA

Market Authorizations: IMFINZI, VERZENIO


 IMFINZI (durvalumab) injection


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


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


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



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


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


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


Capture.JPGVERZENIO (abemaciclib) tablets

Eli Lilly

EXPANDED INDICATION:  In combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative  advanced or metastatic breast cancer

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


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


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



  • No Medicare coverage
  • Obtained through specialty pharmacies


Image credit: AstraZeneca, Eli Lilly 

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

CapturePublic Warning and Notification of Recalls

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

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

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

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

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

Public Notification of Recalls: Weekly FDA Enforcement Report

FDA 101: Product Recalls



Acceptance of Clinical Data to Support Medical Device Applications and Submissions

FDA regulations on data acceptance from clinical investigations conducted outside US

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

Conformity with GCP

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

Supporting Information, Waivers, Records



Refuse to Accept Policy for 510(k)

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

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

Refuse to Accept Principles

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

Checklist provided


Image credit: FDA