FDA Clearance, Classification: EMBRACE MRI, QUANTX

FDA BRIEF: Week of July 24, 2017

EMBRACE Neonatal MRI System

Aspect Imaging Ltd.


Used on neonates with a head circumference up to 38 centimeters and weight between 1 and 4.5 kilograms. The system has a temperature-controlled incubator placed directly into the MRI system, minimizing movement of the baby. If urgent access to the baby is necessary during the imaging process, the baby can typically be removed from the system in less than 30 seconds.


  • First magnetic resonance imaging (MRI) device specifically for neonatal brain and head imaging in neonatal intensive care units (NICU)
  • No need to take babies out of the NICU
  • Safer imaging


  • Device Classification Name: Nuclear MRI System
  • Regulation Number: 892.100
  • Classification Product Code: LNH
  • Subsequent Product Code: MOS


  • Does not require a safety zone or a radiofrequency shielded room
  • Fully enclosed, medical device implants in close proximity to the system are not required to be “MR Conditional” or “MR Safe.”
  • Contraindicated for patients weighing more than 4.5 kilograms or with a head circumference of more than 38 centimeters
  • Contraindicated for all infants with metallic or electronically active implants since the MRI may cause tissue near the implant to heat or the implant to malfunction


  • Efficacy: Non-clinical testing including images of phantoms simulating an infant brain- of sufficient quality for use by an independent board-certified radiologist
  • Safety: Performance testing – electrical and mechanical safety measures


Quantitative Insights, Inc


Computer-aided diagnosis (CADx) software device used to assist radiologists in the assessment and characterization of breast abnormalities using MR image data. The software automatically registers images, and segments and analyzes user-selected regions of interest (ROI). QuantX extracts image data from the ROI to provide volumetric analysis and computer analytics based on morphological and enhancement characteristics. These imaging (or radiomic) features are then synthesized by an artificial intelligence algorithm into a single value, the QI score, which is analyzed relative to a database of reference abnormalities with known ground truth.

QuantX is indicated for evaluation of patients presenting for high-risk screening, diagnostic imaging workup, or evaluation of extent of known disease. Extent of known disease refers to both the assessment of the boundary of a particular abnormality as well as the assessment of the total disease burden in a particular patient. In cases where multiple abnormalities are present, QuantX can be used to assess each abnormality independently.

This device provides information that may be useful in the characterization of breast abnormalities during image interpretation. For the QI score and component radiomic features, the QuantX device provides comparative analysis to lesions with known outcomes using an image atlas and histogram display format.

QuantX may also be used as an image viewer of multi-modality digital images, including ultrasound and mammography. The software also includes tools that allow  users to measure and document images, and output in a structured report.

Limitations: QuantX is not intended for primary interpretation of digital mammography images.

REG PATHWAY: De Novo request

  • Regulation Number: 21 CFR 892.2060
  • Regulation Name: Radiological computer-assisted diagnostic (CADx) software for lesions suspicious for cancer
  • Regulatory Class: Class II
  • Product Code: POK

GENERIC DEVICE TYPE: Radiological computer-assisted diagnostic (CADx) software for lesions suspicious for cancer.

  •  image processing device intended to aid in the characterization of lesions as suspicious for cancer identified on acquired medical images such as magnetic resonance, mammography, radiography, or computed tomography
  • characterizes lesions based on features or information extracted from the images and provides information about the lesion(s) to the user
  • diagnostic and patient management decisions are made by the clinical user


  • Incorrect lesion(s) characterization leading to false positive results
  • Incorrect lesion(s) characterization leading to false negative results
  • Misused to analyze images from an unintended patient population or on images acquired with incompatible imaging hardware
  • Device failure could lead to the absence of results, delay of results or incorrect results


  • General Controls and Special Controls

Image Credits: Aspect Imaging, Quantitative Insights


FDA News and Views: Patient Engagement Advisory Committee, Generic Drug Competition, Advancing Digital Healthcare, Supply Chain Security Toolkit, OTC Drugs & Dietary Supplements Misbranding

FDA BRIEF: Week of July 24, 2017

Meeting Image

FDA Sets Inaugural Meeting of First-Ever Patient Engagement Advisory Committee

New Patient Engagement Advisory Committee (PEAC)

  • PEAC is a forum for the voice of patients
  • Inaugural Meeting: On Oct. 11-12, 2017
  • Topic: Challenges of clinical trial design, conduct, and reporting identified by patients

Committee Members

  • Nine core voting members, chair and consumer representative
  • All have direct experience as a patient or as a care-partner for a patient
  • American Association of Kidney Patients
  • Consumer Representative – Retired from the University of Pittsburgh
  • National Mammography Quality Assurance
  •  Health Motivations
  • Emory Alzheimer’s Disease Research Center
  • Veterans Administration
  • Diabetes association
  • American Cancer Society and the Cancer Action Network
  • Arthritis Foundation


generic medications

Opening Remarks by Dr. Gottlieb for Public Meeting on Generic Drug Competition

FDA doesn’t have a direct role in how drugs are priced but play a  role in the eventual cost of medicines

  • impact on cost of drug development
  • impact on drug pricing
  • cost of scientific and regulatory risk, time for development and approval, failures
  • can impact drug costs by encouraging competition with focus on generic drugs

Concern with branded companies “gaming” FDA system

  • taking advantage of rules to deliberately forestall generic entry
  • making it hard for generic drug makers to purchase branded drug  for testing
  • raising scientific objections timed to delay approval of ANDA
  • gratuitous price increases on niche products

FDA wants to hear from the public

  • ways to benefiting consumers
  • ways to balance access and innovation
  • market-based incentives to attract entrepreneurship to support new innovation

FDA undertaken “Drug Competition Action Plan” with 3 major elements

  • Identify sources of ‘gaming’ and change rules e.g. REMS
  • Identify scientific and regulatory obstacles to generic entry of generic medicines e.g. improve regulatory framework
  • Focus on the efficiency and throughput of overall generic drug program e.g. review efficiencies, improve scientific knowledge, enhance communication

GDUFA II proposal, currently pending before Congress

  • designed to reduce the number of ANDA review cycles
  • expand frequency and scope of communications between FDA and ANDA filers,  more opportunities to cure deficiencies,  get quick approvals
  • create pre-ANDA program, with a special focus on complex generics
  • issue “Good ANDA Assessment Practices” MAPP for internal policies
  • issue  “Good ANDA Submission Practices” guidance

Continued efforts on Drug Competition Action Plan and ongoing implementation of the Hatch-Waxman Amendments


Classifying Over-the-Counter Drugs as Generally Recognized as Safe and Effective and Not Misbranded

Additional criteria and procedures for classifying over-the-counter (OTC) drugs as generally recognized as safe and effective (GRASE) and not misbranded

  • OTC drug products without any US marketing experience can be evaluated under the monograph process if active ingredients meet certain “time and extent” criteria
  • If eligible, parties can submit safety and effectiveness information

FDA inviting comments on

  • Necessity of proposed collection of information for proper FDA performance
  • Accuracy of FDA’s estimate of burden of  proposed collection of information
  • Ways to enhance quality, utility, and clarity of information to be collected
  • Ways to minimize burden of collection of information on respondents


APEC Toolkit diagramKeeping the U.S. Prescription Drug Supply Chain Among the Safest in the World

By: Ilisa Bernstein, Pharm.D., J.D. Deputy Director,  Office of Compliance, CDER

Challenging yo keep U.S. prescription drug supply safest in the world

  • 4 billion prescriptions filled last year
  • moving through the U.S. supply chain
  • large percentage made outside of US
  • substandard and falsified drugs are global problems
Supply Chain Security Toolkit for Medical Products


  • Information and resources related to track and trace, internet sales, detection technology, and much more
  • Can be used by industry stakeholders and global regulators
  • PREVENT, DETECT, and RESPOND to medical products that threaten patient health and safety


dietary supplements, bottles image

Dietary supplement concerns? Tell the FTC and FDA

By: Mary Engle, FTC, and Steven Tave, FDA

Federal Trade Commission (FTC) and FDA have enforcement programs to protect consumers from false and misleading claims
  • Oversee Labeling Claims, Content, Purity, Safety
  • Monitor truth and accuracy of advertising claims
  • Monitor claims made on websites or in other online marketing
  • Inform FDA, FTC if false advertising or safety concerns

Safety Reporting Portal

FDA Guidance: IRB Waiver, Alteration of Informed Consent


  • IRB waiving or altering informed consent requirements for certain minimal risk
    clinical investigations
  • no objection to a sponsor initiating, or an investigator conducting, a minimal risk clinical investigation for which an IRB waives or alters informed consent requirements
  • in accordance with 21st Century Cures Act

Waiver: Current Rule

  • life-threatening situations
  • emergency research
  • ‘where it is not feasible or it is contrary to the best interest of such human

Waiver Revisions: Based on 21st Century Cures Act

  • clinical investigation involves minimal risk (21 CFR 50.3(k), or 56.102(i))
  • will not adversely affect the rights and welfare of the subjects
  • clinical investigation could not practicably be carried out without the waiver
  • subjects will be provided with additional pertinent information after participation


Image credit: FDA

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

FDA News and Views: 2017 Reauthorization Act, FDA Workforce, STEM Education, Grapefruit Interaction, Medical Device Standard Recognition

FDA BRIEF: Week of July 17, 2017

The Committee on Energy and Commerce extended user-fee programs for prescription drugs, medical devices, generic drugs, and biosimilar biological products


  • new user fees for de novo medical device classification requests
  • pilot program to audit and certify laboratories for device conformance testing
  • flexibility to better assess device types most appropriate for third-party review
  • all device submissions in electronic format by 1 October 2021
  • risk-based inspection of medical device establishments
  • establish standards to improve predictability for scheduled inspections
  • process for issuance of foreign export certificates
  • regulations to establish category of over-the-counter hearing aids
  • ensure  quality, safety and effectiveness of services devices
  • voluntary pilot program for device manufacturers for postmarket study requirements using active surveillance
  • classification of medical device accessories based on intended use
  • approval of imaging device with use of contrast agent

Prescription Drugs

  • raises penalties for counterfeit and illegally diverting drugs
  • engage with Congress to lower the cost of prescription drugs
  • recognize foreign government auditors to improve international inspection
  • clarify qualifying criteria for neglected tropical diseases priority review voucher
  • reauthorize critical path public-private partnership for five years

FDA Authorization Act of 2017

Audience Participating in Scientific Professional Development Lecture

Building a Strong FDA Workforce to Bring Scientific Advances to Patients

By: Scott Gottlieb, M.D., Commissioner 

FDA staff must remain current with dramatic advances in science and medicine

  • need for diverse, talented, and dedicated professional workforce
  • requested comprehensive evaluation of  hiring practices and procedures
  • critical to modernize process for recruiting personnel

Piloting new hiring procedures headed by Melanie Keller, Office of Management, CDER

  • align administrative hiring procedures and scientific staffing objectives
  • reflect scientific objectives of review programs in recruitment and hiring
  • prioritize hiring into positions supported by PDUFA commitments


Dr. Rick Pazdur and Members of Summer Scholars

Leveraging FDA Resources to Encourage Students to Pursue STEM Careers

By: Richard Pazdur, M.D., Director, FDA Oncology Center of Excellence

Oncology Center of Excellence recently launched pilot Summer Scholars Program

  • to introduce high-school students to oncology drug development
  • 11 Washington, D.C., area HS students to FDA’s Silver Spring campus for six weeks
  • curriculum: basic and translational science, drug manufacturing, clinical trials, regulatory review, patient advocacy, and marketing

The OCE Summer Scholars Program could be expanded next year to high school students nationally


Grapefruit Juice Drug Overdose Info-graphic (800x237)

Grapefruit Juice Drug Under-dose Info-graphic (800x237)

Grapefruit Juice and Some Drugs Don’t Mix

Grapefruit juice interacts with some drugs:

  • statin drugs to lower cholesterol: Zocor (simvastatin), Lipitor (atorvastatin)
  • to treat high blood pressure: Procardia and Adalat CC (both nifedipine)
  • organ-transplant rejection drugs: Sandimmune and Neoral (both cyclosporine)
  • anti-anxiety drugs: buspirone
  • corticosteroids to treat Crohn’s disease or ulcerative colitis: Entocort EC and Uceris (both budesonide)
  • to treat abnormal heart rhythms: Pacerone and Nexterone (both amiodarone)
  • antihistamines: Allegra (fexofenadine)

Severity of the interaction dependent on the person, the drug, and the amount of grapefruit juice


Recognition of a Medical Device Standard

The 21st Century Cures Act of 2016 clarifies how FDA will process requests for recognition of voluntary consensus standards:

  • 60-day timeframe for FDA response to recognition requests
  • FDA response in writing
  • FDA publication of rationale for recognition of all, part, or none of standard


Image Credit: FDA



FDA Brief: Week of July 17, 2017

FDA approved

TREMFYA (guselkumab) injection

Janssen Biotech, Inc.

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


  • Required Pediatric Assessments: PK, Safety and Efficacy Study in pediatric subjects
    6 years to < 18 years with moderate to severe plaque psoriasis
  • Postmarketing requirements: Registry-based observational exposure cohort study on maternal, fetal, and infant outcomes of exposed pregnant women, claims or electronic medical record data or a case control study to assess adverse pregnancy outcomes

MECHANISM OF ACTION: Human monoclonal IgG1λ antibody, selectively binds to p19 subunit of interleukin 23 (IL-23), inhibits its interaction with the IL-23 receptor – inhibits release of proinflammatory cytokines and chemokines


  • Three multicenter, randomized, double-blind trials, n=1443 + 268, moderate-to-severe plaque psoriasis eligible for systemic therapy or phototherapy, TREMFYA vs. placebo or adalimumab, 16 weeks
  • Study 1 &2: Co-primary endpoints- Achievement of (i) Investigator’s Global Assessment (IGA) score of 0 (“cleared”) or 1 (“minimal”) and (ii) at least a 90% reduction from baseline in Psoriasis Area and Severity Index (PASI) composite score
  • 70%-80% vs. <10% response rate, maintained and durable for 48 weeks, greater improvements on Patient Reported Outcome based on Psoriasis Symptoms and Signs Diary (PSSD)
  • Study 3: TREMFYA vs. ustekinumab treatment; greater response with TREMFYA


  • Warnings and Precautions: Infections,  Tuberculosis (TB) – Evaluate for TB prior to initiating treatment
  • Most common (≥1%) adverse reactions:  Upper respiratory infections, headache, injection site reactions, arthralgia, diarrhea, gastroenteritis, tinea infections, herpes simplex infections


NERLYNX (neratinib maleate) Tablets

Puma Biotechnology, Inc.

INDICATION:  Extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab based therapy

ADDRESSING UNMET NEED: Personalized medicine


  • Postmarketing Requirements: Physiologically-based pharmacokinetic  modeling/simulation study on effect of repeat doses of a moderate CYP3A4 inhibitor, 2-year carcinogenicity study in the rat

MECHANISM OF ACTION: Irreversibly binds to Epidermal Growth Factor Receptor  (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4, inhibited activity of EGFR, HER2 and HER4


  • Single multicenter, randomized, double-blind, placebo-controlled trial,  n=2,840, early-stage HER2-positive breast cancer, NERLYNX vs. placebo, one year
  • Major efficacy outcome measure: Invasive disease-free survival (iDFS)  with 2 years and 28 days of follow-up; 94.2% vs. 91.9%  (HR 0.66; 95% CI: 0.49, 0.90, p=0.008)


  • Common adverse reaction leading to discontinuation: Diarrhea, Hepatotoxicity or increases in liver transaminases
  • Most common adverse reactions: Diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection


VOSEVI (sofosbuvir, velpatasvir, and voxilaprevir) tablet

Gilead Sciences, Inc.

INDICATION: Treatment of adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have:

  • genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV
  • regimen containing an NS5A inhibitor
  • genotype 1a or 3 infection and have previously been treated with an HCV regimen
    containing sofosbuvir without an NS5A inhibitor
  • Additional benefit of VOSEVI over sofosbuvir/velpatasvir (SOF/VEL)was not shown in adults with genotype 1b, 2, 4, 5, or 6 infection previously treated with sofosbuvir
    without an NS5A inhibitor


  • Estimated 2.7 to 3.9 million people in US with chronic HCV; may lead to liver cancer and death
  • At least six genetically distinct HCV genotypes or strain; 75% (genotype 1); 20-25% (genotypes 2 or 3), small number (genotypes 4, 5, 6)
  • First treatment approved for patients who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A


  • Fixed-dose, combination tablet with two previously approved drugs – sofosbuvir and velpatasvir – and a new drug, voxilaprevir
  • Required Pediatric Assessments:  PK, safety and treatment response  in pediatric subjects 12 -18 years with chronic HCV genotype 1- 6
  • Postmarketing Requirement:  Assess signals of serious risk due to treatment-emergent resistance substitutions

MECHANISM OF ACTION: Combination of 3 drugs that are direct-acting antiviral (DAA) agents against the hepatitis


  • two trials in DAA-experienced subjects with genotype 1, 2, 3, 4, 5, or 6 HCV infection without cirrhosis or with compensated cirrhosis
  • VOSEVI vs Placebo or VOSEVI vs. SOF/VEL
  • Serum HCV RNA values measured using COBAS AmpliPrep/ COBAS Taqman HCV test,  lower limit of quantification (LLOQ) of 15 IU/mL
  • Primary Endpoint: Sustained virologic response (SVR12) – HCV RNA < LLOQ at 12 weeks; Relapse- HCV RNA >LLOQ; Virologic Failure- breakthrough, rebound, or non-response
  • 90-100% vs 0%  achievement of SVR12 in VOSEVI vs. placebo
  • 96% vs 85% achievement of SVR12 in VOSEVI vs. SOF/VEL


  • Most common adverse reactions: Headache, fatigue, diarrhea and nausea
  • Contraindication: Rifampin
  • Hepatitis B virus (HBV) reactivation: Need for screening


D2 Dressing (QuikClot+)

Z-Medica, LLC

INDICATION FOR USE: For temporary control of internal organ space bleeding for patients displaying class III or class IV bleeding. It may also be used for control of severely bleeding wounds such as surgical wounds and traumatic injuries

REG PATHWAY: De Novo request

  • Regulatory Classification: Class II
  • Product Code: POD
  • Non-absorbable, hemostatic gauze for temporary internal use
  • Intended to be placed temporarily for control of severely bleeding wounds such as surgical wounds and traumatic injuries. The gauze is coated or impregnated with a hemostatic material which may enhance hemostasis by physical means. The device is intended to be removed once the patient is stabilized.


  • Biocompatibility, performance bench, performance animal testing, clinical data on a previous formulation of the device (D1 Dressing)


  • Infection: Shelf Life Testing, Sterilization Validation, Labeling
  • Bleeding (Hemostasis Failure, Bleeding Recurrence): Animal Performance Testing, Technological Specifications
  • Vascular Obstruction (Ischemiam, Emboli Formation): Animal Performance Testing, Labeling
  • Adhesion Formation: Animal Performance Testing, Labeling
  • Adverse Tissue Reaction: Animal Performance Testing. Biocompatibility Evaluation
  • Device Retained in Body Leading to ReOperation: Animal Performance Testing, Non-Clinical Performance Testing, Labeling

Image Credits: Janssen, Puma, Gilead, Z-Medica

FDA News and Views: Addressing Opioid Epidemic, NASEM Report on Opioid Abuse, Precision Medicine Approvals, Clinical Trials in India, Class II Device Exemptions

FDA BRIEF: Week of July 10, 2017

 Marshaling FDA Benefit-Risk Expertise to Address the Current Opioid Abuse Epidemic

By: Scott Gottlieb, MD, Commissioner & Janet Woodcock, MD, Director, CDER

Addressing the opioid crisis is a national priority and role of prescription opioids is critical FDA focus 

  • Need to consider both benefits of opioids for severe and chronic pain, as well as the multiple adverse effects
  • FDA assesses diverse risks and benefits to ensure that it is considering the full public health implications of any decisions
  • Sought market withdrawal of Opana ER over concerns about illicit use
  • Placed specific restrictions on certain prescription fentanyl formulations to prevent life-threatening respiratory depression
  • Placed limits on prescribing of sodium oxybate to prevent abuse
  • Continuing efforts to support development of abuse-deterrent opioids
  • Commissioned study from National Academies of Sciences, Engineering, and Medicine (NASEM) to identify additional actions FDA should consider to address opioid crisis


 National Academies of Sciences, Engineering, and Medicine (NASEM) report on pain management and prescription opioid abuse

By Scott Gottlieb, MD, Commissioner

NASEM Report on prescription opioid abuse, misuse and pain management
  • Opioid approval and removal decisions made within a benefit-risk framework evaluating outcomes when used as prescribed as well as public health effects of inappropriate use
  • Reducing rate of new addictions by ensuring only appropriately indicated patients are prescribed, for durations and doses matching clinical reason
  • Securing the critical data needed to better understand the impact of opioid medications

 Will require coordinated effort including federal, state, and local partners to properly address its continued destruction of individual lives and families


Two Recent Scientific Advances Underscore an Encouraging Future for Precision Medicine at FDA

By: Janet Woodcock, MD, Director, CDER

Two recent FDA drug approvals point to an encouraging future for “precision medicine”

  • Involve diseases resulting from particular genetic characteristics identified by laboratory testing
  • KALYDECO (ivacaftor) indicated for 33 Cystic Fibrosis  mutations
  • KEYTRUDA (pembrolizumab) to treat cancers having specific genetic feature (instead of location)

FDA has also approved “targeted therapies”

  • 25 new drugs that benefit patients with specific genetic characteristics
  • New uses for marketed drugs based on specific genetic characteristics e.g. rare genetic disorders


Leslie Ball, M.D., FDA Assistant Commissioner of International Programs and Elizabeth Wiley, M.D., J.D., M.P.H., AAAS Science and Technology Policy Fellow

FDA Collaborates to Promote Safety, Quality in Clinical Trials Done in India

 By: Leslie Ball, MD, Assistant Commissioner for International Programs, Letitia Robinson, PhD, RN, FDA India Office, Elizabeth Wiley, MD, JD, MPH, Office for International Programs

India holds vast potential for clinical research and has become a global leader in generic drugs

  • FDA’s Office of International Programs (OIP) and India Foreign Office adopted strategic engagement approach- inspections, targeted engagements, training, collection and use of data- to inform FDA decision-making

Joint training workshop for Indian regulators, academic representatives, and drug industry on scientific and ethical standards for clinical trials

  • Identifying general concepts in inspections of clinical investigators, clinical trial sites, ethics committees, and bioanalytical study sites
  • Identifying techniques for maintaining data integrity in clinical trials
  • Reviewing inspections to develop evidence and determining appropriate observations to include in inspection reports

Effort to promote data integrity, credible and accurate results, and protection of subjects in clinical trials


Class II Device Exemptions from Premarket Notification 

Federal Register announced 1,003 class II exempt device types sufficiently well understood and do not present risks

  • To decrease regulatory burden
  • To reduce private costs and expenditures
  • Follows streamlined procedures established by the 21st Century Cures Act
  • Some device types are partially exempt from premarket requirements
  • New product codes issued


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




FDA BRIEF: Week of July 3, 2017

FDA approved

DIGNICAP Cooling System

 Dignitana Inc.

EXPANDED INDICATION FOR USE: To reduce the frequency and severity of hair loss during chemotherapy in solid tumor cancer patients in which alopecia-inducing chemotherapeutic agents and doses are used

ADDRESSING UNMET NEED: First cooling cap cleared for use in cancer patients with solid tumors

REG PATHWAY:  510(k)

  • First clearance via De Novo pathway (2015) – For use in patients with breast cancer
  • Classification Name: Scalp Cooling System
  • Regulation Number: 878.4360
  • Regulation Name: PMC


  • Computer-controlled system – cap is worn on the head and circulates liquid to a cap to cool the scalp during chemotherapy treatment
  • Cap is covered by a second cap made from neoprene to hold cooling cap in place and act as an insulation cover
  • Cooling intended to constrict scalp blood vessels to reduce amount of chemotherapy reaching hair follicles
  • Cold temperature also decreases hair follicles activities, slows cell division, making them less affected by chemotherapy
  • Combined actions thought to reduce the effect chemotherapy has on the cells, which may reduce hair loss


De Novo Indication for use in breast cancer:

  • Stage I and Stage II breast cancer undergoing chemotherapy associated with hair loss (n=122)
  • Primary endpoint: Self-assessment of hair loss using standardized photographs
  • 66% reported losing less than half their hair

510(k) for expanded indication for use in solid tumors

  • Evidence from published, peer-reviewed articles analyzing DigniCap use in cancer patients with solid tumors in other areas of the body besides the breast
  • These studies provided valid scientific evidence to support expanded indication


  • Contraindicated for pediatric patients, patients with certain cancers and patient undergoing specific chemotherapy treatments
  • Not appropriate for patients with cold sensitivity or susceptibility to cold-related injuries
  • Most common side effects: Cold-induced headaches, neck and shoulder discomfort, chills and pain associated with extended use
  • Long-term effects of scalp-cooling and risk of scalp metastasis have not been fully studied

Scalp Cooling System

Image result for sickle cell

ENDARI (L-glutamine) oral powder 

Emmaus Medical Inc

INDICATION: To reduce the acute complications of sickle cell disease (SCD) in adult and pediatric patients 5 years of age and older


  • SCD is an inherited blood disorder with red blood cells (RBC) abnormally sickle shaped
  • Restricts blood flow leading to severe pain and organ damage
  • 100,000 US patients; mostly in African-Americans, Latinos, other minority groups

REG PATHWAY: NDA, Standard Review, Orphan Drug Designation

  • Postmarketing commitment: Dose-finding trial in adult and pediatric SCD patients with body weight less than or equal to 65 kg

MECHANISM OF ACTION: L-glutamine may improve the NAD redox potential in sickle RBCs through increasing the availability of reduced glutathione

  • Randomized, double-blind, placebo-controlled, multi-center clinical trial (n=230)
  • Efficacy: Reduction in number of sickle cell crises through Week 48 and prior to start of tapering among patients


  • Common side effects: Constipation, nausea, headache, abdominal pain, cough, pain in the extremities, back pain and chest pain


PRAXIS Extended RAS Panel


INTENDED USE: Qualitative in vitro diagnostic test using targeted high throughput parallel sequencing for the detection of 56 specific mutations in RAS genes [KRAS (exons 2, 3, and 4) and NRAS (exons 2, 3, and 4)] in DNA extracted from formalin‐fixed, paraffin‐embedded (FFPE) colorectal cancer (CRC) tissue samples.

The Praxis™ Extended RAS Panel is indicated to aid in the identification of patients with colorectal cancer for treatment with Vectibix® (panitumumab) based on a no mutation detected test result. The test is intended to be used on the Illumina MiSeqDx® instrument

ADDRESSING UNMET NEED: First FDA-approved NGS test that can detect multiple RAS gene mutations for colorectal cancer in a single test


  • Product Code: PQP


  • Qualify DNA sample that can be used for the test
  • Manually prepare samples for sequencing – library preparation – Hybridization, Extension‐Ligation, PCR Amplification, and Library Normalization
  • Sequence prepared sample using SBS (sequencing by synthesis) chemistry on the MiSeqDx


  • Studied retrospectively using available specimens from mCRC patients enrolled in  multi-center clinical trial with Vectibix plus FOLFOX to FOLFOX alone
  • Progression-free survival and overall survival in wild-type RAS patients demonstrated that the efficacy of panitumumab in patients whose tumors do not have a KRAS or NRAS mutation is supported
  • Analytical validation demonstrated that the panel performs consistently and accurately in the detection of the select KRAS and NRAS mutations in mCRC patients.


Vectibix Label


FDA News: Biomarker for Acute Pancreatic Injury, Innovation Initiative and Cures Act, Nail Care Products

FDA BRIEF: Week of July 3, 2017

Spotlight on CDER Science

Lab Tests in Rodents Suggest Potential New Biomarker for Acute Pancreatic Injury

Biomarkers are measurable indicators that can signify presence/severity of disease 

  • FDA prioritizes identification of new, reliable and sensitive biomarkers

Acute pancreatic injury requires sensitive biomarkers

  • Numerous drugs, including those to treat type-2 diabetes, linked to pancreatic injury
  • Not evident in pre-approval, non-clinical safety and clinical trials with traditional pancreatic injury biomarkers, serum amylase and lipase
  • Thus more sensitive and specific biomarkers required to detect /monitor pancreatic injury potential of new drugs

Division of Applied Regulatory Science research suggest microRNAs (miRNAs) may be good biomarker candidates

  • Have a key role in the regulation of genes by repressing gene expression
  • Can increase rapidly after tissue injury
  • miR-216a, miR-217, miR-216b, miR-375, miR-148a able to detect pancreatic injury earlier and were more specific to pancreatic injury in rats and mice. These miRNAs also found in humans.
  • Additional data needed to determine utility in patients


Dr. Scott Gottlieb

Innovation Initiative: How FDA Plans to Help Consumers Capitalize on Advances in Science

FDA will soon unveil a comprehensive Innovation Initiative
  • Modern and efficient regulatory processes
  • Efficient and science-based regulatory principles
  • Remove regulatory barriers to beneficial new medical innovations
  • Help facilitate access to new innovations after FDA approval
  • Help maintain costs and hence, pricing, of new medical innovations

Detailed work plan to implement different aspects of Cures Act. Examples-

  • CDER: Modeling and simulation to predict clinical outcomes, inform clinical trial designs, support evidence of effectiveness, optimize dosing, predict product safety, and evaluate potential adverse event mechanisms
  • CDRH: In silico regulatory models for product design and evaluation, digital library of models, family of “virtual patients” for device testing
  • CBER: Implementing the Regenerative Medicine Advanced Therapy designation,


How to Safely Use Nail Care Products

Cosmetic Nail Care Products: Ingredients and Warnings

  • Do not need FDA approval for marketing
  • But required to be safe when used as intended
  • Must include instructions or warnings needed for safe use
  • Consumers must read label prior to use
  •  FDA’s nail care products webpage

Nail Drying and Curing Lamps—and UV Exposure

  • Viewed as low risk when used as directed by the label
  • FDA has not received any reports of burns or skin cancer

Report Problems with Nail Care Products

  • FDA Consumer Complaint Coordinator
  • Medwatch


Image credit: FDA 

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


FDA News: eMDR Enhancements, Enhance Generic Drug Development, Compounded Drug Safety, Antibiotic Misuse/Resistance

FDA BRIEF: Week of June 26, 2017

eMDR System Enhancements and HL7 Individual Case Safety Reporting

Electronic Medical Device Reporting (eMDR) program’s system update

  • Mandatory medical device reports from Manufacturers, Importers, Device User Facilities
  • Updates available for public access, download, and review
  • Specific changes being implemented outlined

 Health Level 7 (HL7) Individual Case Safety Reporting (ICSR)

  • Standard for capture of information needed to support submission of MDR reportable events
  • Files have also been updated for review

eMDR System Enhancements

Health Level 7 (HL7) Individual Case Safety Reporting (ICSR) Files

Generics have the same quality as brand name drugsGeneric Drug Development and Access Enhancements


Safety of Compounded Drugs by Drug Quality and Security Act (DQSA)

Need for robust oversight over human drug compounding, dispensing prescription and strong coordination with state regulatory partners to protect public health

  • Enactment of DQSA in 2013
  • Oversight of compounding and implementing compounding provisions of the law
  • > 400 inspections, including 109 inspections of outsourcing facilities
  • > 150 warning letters issued
  • > 50 letters referring inspectional findings to state regulatory agencies
  • > 125 recalls involving compounded drugs
  • 21 draft guidances, 10 final guidances, 3 proposed rules, a final rule, a draft memorandum of understandin
  • Taking risk-based approach to maximize public health purpose



Antibiotic Misuse and Resistance

Dr. Woodcock discusses the issues surrounding the use and misuse of antibiotic medicines, as well as the emergence of antibiotic-resistant bacteria and how the issues are related.


Image credit: FDA




FDA BRIEF: Week of June 26, 2017

FDA approved

Image result for bevyxxa logo

BEVYXXA (betrixaban) capsules

Portola Pharmaceuticals, Inc.

INDICATION:  For the prophylaxis of venous thromboembolism (VTE) in adult patients  hospitalized for an acute medical illness who are at risk for thromboembolic complications due to moderate or severe restricted mobility and other risk factors for  VTE


  • Required Pediatric assessments

MECHANISM OF ACTION: Oral FXa inhibitor, selectively blocks active site of FXa, decreases thrombin generation


  • Single randomized, double-blind, multinational study, n=7,513, patients hospitalized for acute medical illness, moderate or severe immobility, additional VTE risk
    factors, extended duration BEVYXXA vs. short duration enoxaparin
  • Composite Efficacy Endpoint: Asymptomatic proximal Deep Vein Thrombosis (DVT), Symptomatic proximal or distal DVT, Non-fatal Pulmonary Embolism (PE), VTE-related death
  • Composite Outcome, n(%) : 165 (4.4) vs. 223 (6.0)


  • Most common adverse reactions (≥5%): Related to bleeding (betrixaban vs enoxaparin)
    • at least one adverse reaction: 54% vs. 52%
    • serious adverse reactions: 18% vs. 17%
    •  incidence rate for all bleeding episodes: 2.4% vs. 1.2%
    • major bleeding episodes: 0.67% vs. 0.57%


Related image


Beckman Coulter, Inc.

INTENDED USE: Authorized test for use with flow cytometry to aid in the detection of  several leukemias and lymphomas, including chronic leukemia, acute leukemia, non-Hodgkin lymphoma, myeloma, myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN)


  • First FDA authorized test for use with flow cytometry to aid in the detection of several leukemias and lymphomas
  • For laboratories and health care professionals to have an FDA-validated test that provides consistent results to aid in the diagnoses of these serious cancers
  • Regulation Number: 21 CFR 864.7010
  • Regulatory Classification: Class II
  • Product Code: PWD


  • Study designed to demonstrate the test’s performance, n=279 samples at 4 independent clinical sites
  • Study compared the test’s results to alternative detection methods
  • Results of test aligned with the study site’s final diagnosis 93.4% of time
  • Correctly detected cancer presence 84.2% of time
  • Device:  Flow Cytometric Test System For Hematopoietic Neoplasms
  • Definition:  Reagents intended for in vitro diagnostic use as a panel for qualitative identification of cell populations by multiparameter immunophenotyping on a flow cytometer.These reagents are used as an aid in the differential diagnosis of hematologically abnormal patients having, or suspected of having the following hematopoietic neoplasms: chronic leukemia, acute leukemia, non-hodgkin’s lymphoma, myeloma, myelodysplastic syndrome (mds), and/or myeloproliferative neoplasms (mpn)


BioSphere Medical, S.A. (Merit Medical)

INDICATION FOR USE: embolization of arteriovenous malformations, hypervascular tumors, including symptomatic uterine fibroids, and prostatic arteries for symptomatic benign prostatic hyperplasia (BPH)


  • Regulation Number: 21 CFR 876.5550
  • Regulation Name: Prostatic artery embolization device
  • Regulatory Classification: Class II
  • Product Code: NOY

GENERIC DEVICE TYPE: Intravascular implant intended to occlude the prostatic arteries to prevent blood flow to the targeted area of the prostate, resulting in a reduction of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH). This does not include cyanoacrylates and other embolic agents which act by in situ polymerization or precipitation, or embolization devices used in neurovascular applications


  • Adverse tissue reaction: Biocompatibility evaluation
  • Infection: Sterilization validation, Shelf-life validation, Non-clinical performance testing, Labeling
  • Non-target ischemia: Clinical data, Non-clinical performance testing, Labeling
  • Urinary retention: Labeling
  • Post-prostatic artery embolization syndrome (nausea, vomiting, regional pain, non-infectious fever, minor hematuria or hematochezia): Labeling


Image credits: Portola, Beckman Coulter, Merit