FDA News: Sickle Cell Research, Office of Orphan Products Development (OOPD), Biomarker Qualification Case Study, Generic Drug Access, Bodybuilding Products

FDA BRIEF: Week of June 19, 2017

group picture of ethnically diverse patients

Celebrate World Sickle Cell Day by Learning About Clinical Trials

Sickle Cell Disease is most common inherited blood disorder in US

  • Chronic condition with no cure
  • Can cause severe pain, organ damage, stroke
  • One way to help advance scientific discovery is through clinical trials

Learn more about clinical trials in videos

  • Brings awareness to importance of having diverse participants in clinical trials
  • Help ensure medical products are safe and effective for everyone


Office of Orphan Products Development (OOPD)

To promote the development of products for the treatment, diagnosis, and prevention of rare diseases and conditions

  • Drugs, Devices, Biologics, Medical Foods

Designation Programs

  • Orphan Drug Designation
  • Rare Pediatric Disease Designation
  • Humanitarian Use Device Designation

Grant Programs

  • Orphan Products Grants
  • Orphan Products Natural History Grants
  • Pediatric Device Consortia Grants

Medical Device Humanitarian Use Device (HUD) and Humanitarian Device Exemption (HDE) programs


FDA Case Study 1

Case Study for Biomarker Qualification Program

CDER Biomarker Qualification Program works with external stakeholders to develop biomarkers for drug development process

  • Fictional case studies part of an educational series on qualifying biomarkers
  • Intended to help patients, patient advocacy groups, health professionals, small businesses, and pharmaceutical and clinical innovators learn more
  • Provide “real-world” examples

Case Study on fictional biomarker of drug-induced kidney injury in rats

  • Understand role of biomarker qualification in drug development
  • Understand validation studies necessary to support qualification
  • Understand collaborative efforts in qualification for a specific context of use


Think it's easy becoming a generic drug in America? Think againFDA Working to Lift Barriers to Generic Drug Competition

By: Scott Gottlieb, M.D., FDA Commissioner, @SGottliebFDA

FDA doesn’t have direct role in drug pricing – but taking steps to help address access

  • Expediting approval of lower-cost, generic medicines.
  • Facilitating increased competition for prescription drugs

Drug Competition Action Plan Federal Register

  • Understand ‘gaming’ of FDA’s rules to create obstacles to generic access
  • Blocking availability of branded products for comparative testing
  • Misusing REMS by having single shared program to delay generic entry

Policy and programmatic changes to address issues

  • Using FDA authorities more forcefully
  • Collaborate with sister agencies
  • Coordinate with Federal Trade Commission in identifying and publicizing anti-competitive practices
  • Simultaneously strike a careful balance between pharmaceutical innovation and access to lower cost generic products



FDA issues warning about body-building products labeled to contain steroid and steroid-like substances

Illegally marketed products labeled to contain steroid and steroid-like substances and promoted to increase muscle mass and strength

Illegally marketed as dietary supplements 

  • Unapproved drugs without FDA review of safety and effectiveness
  • Safety assessment based on more than seven years of adverse event reports
  • Risk of serious liver injury and other adverse health consequences including kidney injury, increased risk of heart attack and stroke, shrinkage of testes, male infertility





FDA BRIEF: Week of June 19, 2017

FDA approved

Image result for baxdela logo

BAXDELA (delafloxacin) Tablets and Injection 

Melinta Therapeutics

INDICATION: Treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following:

Gram-positive organisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillinsusceptible [MSSA] isolates), Staphylococcus haemolyticus, taphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), Streptococcus pyogenes, and Enterococcus faecalis.

Gram-negative organisms: Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

ADDRESSING UNMET NEED: Antibacterial product treating serious or life-threatening infections


  • Qualified infectious disease product (QIDP)  under Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act
  • Fast Track Designation, Priority Review
  • Postmarketing Requirements: Surveillance for resistance, tissue distribution

MECHANISM OF ACTION: Fluoroquinolone class of antibacterial drugs,  antibacterial activity due to inhibition of both bacterial topoisomerase IV and DNA gyrase
(topoisomerase II) enzymes for DNA replication, transcription, repair, recombination.


  • 2 multicenter, multinational, double-blind, double-dummy, non-inferiority trials. (n=1510), adults with ABSSSI, BAXDELA vs. comparator (intravenous combination of vancomycin and aztreonam)
  • Objective Clinical Response: 20% or greater decrease in lesion size determined by digital planimetry of the leading edge of erythema 48 to 72 hr post initiation.
  • Investigator Assessment of response was made at Follow-up (Day 14 ± 1)
  • Positive Clinical Response and Investigator Assessments in both trials


  • Boxed Warning:  Increased risk of disabling and potentially irreversible serious adverse reactions that have occurred together including tendinitis and tendon rupture, peripheral neuropathy, and central nervous system effects.
  • Contraindication: Hyersensitivity to fluoroquinolones
  • Adverse reactions: Nausea, diarrhea, headache, transaminase elevations (an enzyme that is an indicator of liver injury) and vomiting


Image result for haegarda logo

HAEGARDA (C1 Esterase Inhibitor Subcutaneous [Human])

CSL Behring 

INDICATION:  Plasma-derived concentrate of C1 Esterase Inhibitor (Human) (C1-INH)  indicated for routine prophylaxis to prevent Hereditary Angioedema (HAE) attacks in adolescent and adult patients.


  • HAE patients have absence or low levels of endogenous or functional C1-INH
  • HAEGARDA replaces missing or malfunctioning C1-INH protein
  • First C1-INH for subcutaneous  administration for rare genetic disease


  • Orphan Drug Designation

DESCRIPTION: Human plasma-derived, purified, pasteurized, lyophilized (freeze-dried) concentrate prepared from large pools of human plasma from U.S. donors.


  • A multicenter, randomized, double-blind, placebo-controlled, crossover study (n=90), 16-week treatment period, HAEGARDA (2 doses) vs placebo
  • Efficacy Endpoint: Time-normalized number of HAE attacks (the rate of attacks) relative to placebo
  • Significant decreases with both doses (p<0.001); median reduction 89%, 95%
  • Responders (95% CI) with a ≥50% reduction vs placebo was 83% (73%, 90%)
  • Significant decrease in time-normalized number of uses of rescue medication


  • Most common side effects: Injection site reactions, hypersensitivity reactions, nasopharyngitis and dizziness


RITUXAN HYCELA (rituximab and hyaluronidase human) injection


INDICATION: For the treatment of Follicular Lymphoma (FL),  diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL)

Indicated for the following previously approved indications for Rituxan:

  • Relapsed or refractory FL as a single agent
  • Previously untreated FL in combination with first line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy.
  • Non-progressing (including stable disease), FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.
  • Previously untreated DLBCL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens.
  • Previously untreated and previously treated CLL in combination with fludarabine and cyclophosphamide (FC).


  • Subcutaneous route of administration that shortens administration time to 5 to 7 minutes vs. several hours for intravenous infusion
  • Provides for flat dosing.



  • Rituximab is monoclonal antibody targeting CD20 antigen and mediates B-cell lysis
  • Hyaluronidase increases permeability of the subcutaneous tissue by temporarily depolymerizing hyaluronan


  • Based on Pharmacokinetic (PK) results
  • Non-inferior rituximab trough concentrations (Ctrough) levels for Rituxan Hycela 1,400 mg/23,400 Units compared to a intravenous rituximab 375 mg/m2
  • NBon-inferior rituximab Ctrough levels for Rituxan Hycela 1,600 mg/26,800 Units compared to intravenous rituximab 500 mg/m2
  • Comparable Overall Response, Progression Free Survival, Overall Survival Rates of Rituxan vs, Rituxan Hycela


  • Boxed Warning: Severe mucocutaneous reactions, Hep B Virus reactivation, progressive multifocal leukoencephalopathy
  • Most common adverse events: FL- infections, neutropenia, nausea, constipation, cough, and fatigue, DLBCL-infections, neutropenia, alopecia, nausea, and anemia, CLL- infections, neutropenia, nausea, thrombocytopenia, pyrexia, vomiting, and injection site erythema


Image Credits: Melinta, CSL Behring, Genentech

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


FDA News: FDA Science, Digital Health Devices, Abuse-Deterrent Opioids, Creative FDA Regulation

FDA BRIEF: Week of June 12, 2017

2017 FDA Science Forum

FDA Science: Working at the Speed of Emerging Technologies

By: Luciana Borio, M.D.,  Acting Chief Scientist

Innovation is happening extraordinarily fast in biomedical sciences and at FDA

  • FDA’s 11,000 scientists play essential role in advancing biomedical innovations
  • Scientific research presented at Science Forum at FDA
  • Research concentrates on developing knowledge to ensure medical products are safe and effective

2017 Science Forum topics

  1. Identification and Evaluation of New Biomarkers
  2. FDA Response to Urgent Public Health Needs
  3. Microbiome and Human Health
  4. Advanced Manufacturing and 3D Printing
  5. Omics Technologies at FDA
  6. Patient and Consumer Engagement and Communication
  7. Computational Modeling and Simulation at FDA
  8. Current Progress in Nanotechnology Research at FDA

Mobile communications also included

  • Healthy Citizen @FDA to collaborate and communicate with citizens on public health outcomes


Everyone at FDA is committed to focusing on all aspects of the opioid epidemic

New policy steps

  • Steering committee formation to examine regulatory and policy action
  • Evaluate efforts to reduce number of new addiction cases

Abuse-deterrent opioid formulations and public health effect assessment

  • Formulations intended to deter abuse
  • However, effect in a real-world, meaningful decrease of opioid misuse/abuse unknown
  • Public meeting on opioid medications with abuse-deterrent properties to discuss impact of these products in the real world
  • Publicly available issues paper outlining existing regulatory and public health challenges


Sapien 3

By: Jeffrey Shuren, M.D., J.D., and Bram Zuckerman, M.D.

FDA was first to approve Sapien 3 valve interatin to treat high-risk patients with transcatheter valve replacement (TAVR)

  • For high-risk patients with worn out aortic or mitral bioprosthetic valves; Sapien 3 slips into these valves – “valve-in-valve” option
  • FDA Heart Valve Review Team streamlined FDA’s nonclinical testing expectations
  • More consistent, predictable, and transparent about clinical study expectations
  • Industry collaboration on creative clinical trial designs and use of other sources of clinical evidence

Use of real-world evidence for approval

  • Based on Transcatheter Valve Therapy (TVT) Registry, partnership of American College of Cardiology and Society of Thoracic Surgeons
  • Collection of clinical data on TAVR performance both on-label and off-label uses
  • 100,000 TAVR patients since 2011 first approval; >600 patients for off-label, valve-in-valve uses
  • Reliance on real-world evidence to evaluate the benefits and risks of off-label use

FDA working to broaden and improve the opportunities to leverage real-world evidence

  • Establishment of National Evaluation System for health Technology (NEST)
  • Integrate data from clinical registries, electronic health records, and medical billing claims


Image credits: FDA

FDA Approvals: SYMJEPI

FDA BRIEF: Week of June 12, 2017

FDA approved

SYMJEPI (epinephrine injection)

Adamis Pharmaceuticals Corporation


Emergency treatment of allergic reactions (Type I) including anaphylaxis  to stinging insects (e.g., order Hymenoptera, which include bees, wasps, hornets, yellow jackets and fire ants) and biting insects (e.g., triatoma, mosquitoes), allergen immunotherapy, foods, drugs, diagnostic testing substances (e.g., radiocontrast media) and other allergens, as well as idiopathic anaphylaxis or exercise-induced anaphylaxis.

For immediate administration in patients who are determined to be at increased risk for anaphylaxis, including individuals with a history of anaphylactic reactions.

Anaphylactic reactions may occur within minutes after exposure and consist of flushing, apprehension, syncope, tachycardia, thready or unobtainable pulse associated with a fall in blood pressure, convulsions, vomiting, diarrhea and abdominal cramps, involuntary voiding, wheezing, dyspnea due to laryngeal spasm, pruritus, rashes, urticaria or angioedema.

For immediate administration as emergency supportive therapy only and is not a
substitute for immediate medical care.

ADDRESSING UNMET NEED: New drug alternative to EpiPen


  • 505(b)(2) pathway
  • Postmarketing Commitment: Fault Tree Analysis and quantification to support device reliability specification

MECHANISM OF ACTION: Acts on both alpha and beta-adrenergic receptors

EFFICACY & SAFETY: Established based on initial approval in 1939


Image credit: Adamis

FDA Guidances: Drug Development Tools, Clinical Consultative Review, Certifications, Reusable Medical Devices, QT/QTc Prolongation

fda guidances

Updated Process for Qualification of Drug Development Tools (DDT) Under New FD&C Act Section 507

DDT Qualification to follow updated, multi-stage process under 21stCentury Cures Act 

  • 3 submission milestones: Letter of Intent (LOI), Qualification Plan (QP), Full Qualification Package (FQP)2
  • Transparency provisions and public posting of information by FDA
  • To transition from legacy qualification program process to new section 507 DDT Qualification Process


Good Review Practice: Clinical Consultative Review of Drugs Regulated with OND

Describes  clinical consultative review process in the CDER Office of New Drugs (OND)  for INDs, NDAs, BLAs, and supplemental NDAs and BLAs

  • To gather expertise of second review division because of familiarity with drug for other uses, expertise in another aspect of disease or organ system


Form FDA 3674 – Certifications To Accompany Drug, Biological Product, and Device Applications/Submissions

Form 3674: All Drug, Biologic, Device Submissions require certification that all applicable requirements have been met (implemented in 2007)

  • Form FDA 3674 can be obtained at LINK
  • Requires submitter to confirm compliance with all applicable requirements of Title VIII, including applicable implementing regulations, e.g., the requirement to register applicable clinical trials
  • Guidance to provide clarifications and additional details


Validated Instructions for Use and Validation Data Requirements for Resuable Medical Devices


List of reusable medical devices for which the FDA will require for premarket submissions:

  • validated instructions for use
  • validation data regarding cleaning, disinfection, and sterilization
  • in accordance with the requirements of 21st Century Cures Act
  • facilitates 510(k) reviews


E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs — Questions and Answers (R3)

ICH E14 guidance Clinical Evaluation of QT/QTc Interval Prolongation finalized in 2005

  • This guidance for clarifying key issues
  • Sex Differences, Incorporating New Technologies, Concentration-Response Relationships, Combination Products, Large Targeted Proteins and Monoclonal Antibodies, and Special Cases, Use of Concentration Response Modeling


  • Electrocardiograms Methodology
  • Gender
  • Positive Control
  • Study Design
  • Concentration Response Modeling
  • Special Cases
  • Electrocardiograms monitoring in late stage clinical trial



FDA Approvals, Classifications: SAPIEN 3, SENTINEL System, GLEOLAN, TRUVADA generic

Week of June 5, 2017

FDA approved

EXPANDED INDICATION FOR USE: Indicated for patients with symptomatic heart disease due to failure (stenosed, insufficient, or combined) of a surgical bioprosthetic aortic or mitral valve who are judged by a heart team, including a cardiac surgeon, to be at high or greater risk for open surgical therapy (i.e., predicted risk of surgical mortality ≥ 8% at 30 days, based on the STS risk score and other clinical co-morbidities unmeasured by the STS risk calculator).

 REG PATHWAY: PMA supplement

  • Priority Review status because device availability is in the best interest of patients
  • Device Generic Name: Aortic or mitral valve, prosthesis, percutaneously
  • Device Procode: NPT, NPU
  • Original PMA approved in 2015
  • Current supplement to expand to include patients with failed bioprosthetic heart valve in the aortic or mitral position


  • Analysis of real-world off-label use data captured in Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry (n=314)
  • Valve Performance:  Clinically significant improvements;  mean aortic valve pressure gradient decreased from 39.3 ± 15.8 mmHg to 21.5 ± 11.3 mmHg at 30 d
  • NYHA: 85.4% of the patients had an improved NYHA class at the 30-day visi
  • Quality of Life (QoL) – KCCQ clinical summary score: Improved from 39.4 at baseline to 75.3 at 30 d


  • Did not include specific information
  • Patients/physicians likely to prefer due to less invasive approach (FDA belief)
  • High off-label use supports this belief


  • All-cause death: 4.5% and 6.8% at 30 days in aortic and mitral valve-in-valve patients, respectively
  • Aortic valve-in-valve patients: Stroke and reintervention – 1.0%, 0.3 %
  • Mitral valve-in-valve patients: Stroke, heart failure-related readmission – 0.7%,  0.8%, 0.4%



SENTINEL Cerebral Protection System

Claret Medical

INDICATION FOR USE:  For use as an embolic protection device to capture and remove thrombus/debris while performing transcatheter aortic valve replacement procedures. The diameters of the arteries at the site of filter placement should be between 9 – 15 mm for the brachiocephalic and 6.5 – 10 mm in the left common carotid.

REG PATHWAY: De Novo request

  • Regulation Number: 21 CFR 870.1251
  • Regulation Name: Temporary catheter for embolic protection during transcatheter  intracardiac procedures
  • Regulatory Classification: Class II
  • Product Code: PUM

GENERIC DEVICE TYPE:  Temporary catheter for embolic protection during transcatheter intracardiac procedures

  • Single use percutaneous catheter system that has (a) blood filter(s) at the distal end. This device is indicated for use while performing transcatheter intracardiac procedures. The device is used to filter blood in a manner that may prevent embolic material (thrombus/debris) from the transcatheter intracardiac procedure from  traveling towards the cerebral circulation.


  • Device failure leading to debris embolization and stroke or death: Non-clinical Performance Testing, Animal Testing, Clinical Performance Testing
  • Impeded or disrupted blood flow leading to peripheral ischemia: Non-clinical Performance Testing, Animal Testing, Clinical Performance Testing, Labeling
  • Device incompatibility with transcatheter intracardiac procedure device leading to prolonged treatment time or device failure: Non-clinical Performance Testing, Animal Testing, Clinical Performance Testing, Labeling
  • Adverse tissue reaction:  Biocompatibility Evaluation
  • Vascular Injury due to device delivery, deployment, placement, or retrieval:  Non-clinical Performance Testing, Animal Testing, Clinical Performance Testing, Labeling



GLEOLAN (aminolevulinic acid hydrochloride, ALA HCl)

NX Development Corp.

INDICATION:  In patients with glioma [suspected World Health Organization (WHO) Grades III or IV on preoperative imaging] as an adjunct for the visualization of malignant tissue during surgery


  • Orphan designation, Priority Review

MECHANISM OF ACTION:  ALA occurs endogenously as a metabolite; accumulation of ALA metabolite PpIX in tumor cells. Gleolan used with an operating microscope adapted with a blue emitting light source allows tumor tissue to be visualized as red fluorescence. Tissue lacking sufficient PpIX concentrations appears blue


  • 3 clinical studies (n=527), patients with preoperative MRI compatible with high-grade glioma (WHO Grade III or IV) undergoing surgical resection
  • Presence of fluorescence (positive/negative) was compared to tumor status (true/false) using histopathology as reference standard
  • High predictive value for visualization of malignant tissue


  • Phototoxic reactions, hypersensitivity reactions, and interpretation errors (false negatives and false positives)
  • Increase in extent of resection might increase risk of serious neurologic deficits
  • Adverse reactions: Pyrexia, hypotension, nausea, and vomiting


Image result for truvada logoTRUVADA (Emtricitabine and tenofovir disoproxil fumarate) generic

Teva Pharmaceuticals

INDICATION: For the treatment of HIV-1, in combination with other antiretroviral agents, and for pre-exposure prophylaxis (PrEP) in combination with safer sex practices to prevent sexually-acquired HIV infection in adults at high risk

REG PATHWAY: ANDA, Therapeutic Equivalence Code- AB

SAFETY: Diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash



Image credits: FDA, Claret Medical, NX Corp, Gilead

FDA News: UDI for Class I Devices, HUD IRB Policy, Opana ER Removal, Dermal Fillers Information, Outsmart Poison Ivy

FDA BRIEF: Week of June 5, 2017

UDI Compliance Dates for Class I and Unclassified Devices

Unique Device Identification (UDI) system established in 2013  to adequately identify devices though distribution and use

Extending  compliance dates for lower-risk medical devices

  • For class I and unclassified devices
  • Not applicable to class I/unclassified implantable, life-supporting or life-sustaining devices – should already be compliant
  • Guidance to provide enforcement discretion policy for labeling, data submission, standard date formatting, and direct mark requirements


Humanitarian Use Devices; 21st Century Cures Act; Technical Amendment

The 21st Century Cures Act removed local Institutional Review Board (IRB) review

  • Rely on a central IRB
  • Investigational Device Exemption (IDE) studies
  • Humanitarian Device Exemption (HDE) devices
  • Same measures and policies to protect patients who are involved in clinical research or are treated with Human Device Exemption (HDE) for HUD


Wrinkle Filler

Dermal fillers are FDA approved medical device implants

  • to create smoother and/or fuller facial appearance including nasolabial folds, cheeks and lips
  • increasing volume of back of hand

NOT approved for breast, buttock augmentation, increase fullness of the feet, implant into bone, tendon, ligament, or muscle

Risks and Serious Adverse Events reported with use

Information for Healthcare Providers and Patients

Approved Dermal Fillers


Endo Pharmaceuticals

FDA Requests Removal of Opana ER for Abuse-Related Risks

FDA requested Endo Pharmaceuticals removal of reformulated injectable Opana ER

  • concern that benefits may no longer outweigh its risks
  • public health consequences of abuse.
  • first time to remove marketed opioid pain medication from sale

FDA decision based on

  • review of all available postmarketing data
  • significant shift in route of abuse (nasal to injection) after product reformulation
  • injection abuse associated with serious HIV and hepatitis outbreaks, cases of  serious blood disorder (thrombotic microangiopathy)
  • March 2017 FDA advisory committee voted that benefits no longer outweigh risks

FDA will continue to examine risk-benefit profile of all approved opioid analgesic products in response to public health crisis



Outsmarting Poison Ivy and Other Poisonous Plants






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

FDA Approvals: ZYKADIA Supplemental Indication, STRATTERA first time generics

Week of May 29, 2017

FDA approved

Brand logo alt

ZYKADIA (ceritinib)


SUPPLEMENTAL INDICATION:  treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.


  • Original  accelerated approval (2014) for patients with ALK-positive metastatic NSCLC whose disease has progressed or who are intolerant to crizotinib


  • Open-label, randomized, active-controlled, multicenter study, LK-positive NSCLC patients with no prior systemic therapy (n=376),   ZYKADIA vs chemotherapy plus maintenance chemotherapy
  • Major efficacy outcome: Progression-free survival (PFS) determined by blinded independent review committee (BIRC) according to RECIST v1.1
  • Additional efficacy outcomes: Overall survival (OS), overall response rate (ORR),  duration of response (DOR) determined by BIRC, overall intracranial response rate (OIRR), duration of intracranial response (DOIR), and patient reported outcomes (PRO)
  • PFS: 16.6 mo. vs. 8.1 mo., p-value <0.0001
  • Confirmed ORR: 73% vs. 27%, Median DOR: 23.9 mo. vs. 11.1 mo., OSS: immature
  • Overall OIRR: 57% vs,  22%, DOIR: 16.6 mo. vs. not estimable
  • PRO Exploratory analyses: Delay in time to development/worsening of

    shortness of breath with ZYKADIA


  • Most common adverse reactions: Diarrhea, nausea, vomiting, fatigue, abdominal pain, decreased appetite, and cough
  • Serious adverse reactions in 38%, discontinuation occurred in 12%, dose interruption due to adverse reactions 77%, dose reductions in 66%.


First Time Generic

First generic versions of STRATTERA (atomoxetine) 

Apotex Inc., Teva Pharmaceuticals, Aurobindo Pharma,  Glenmark Pharmaceuticals


INDICATON: Treat attention-deficit/hyperactivity disorder (ADHD) in pediatric and adult patients



  • Most common side effects ( children and adolescents,): Upset stomach, decreased appetite, nausea or vomiting, dizziness, tiredness, and mood swings
  • Most common side effects (adults): Constipation, dry mouth, nausea, decreased appetite, dizziness, sexual side effects, and problems passing urine.
  • Boxed Warning : Increased risk of suicidal ideation


Image credits: Novartis, 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

FDA News: Commissioner Remarks, Supply Chain Security Toolkit, Measuring Cancer Patient Benefit, Fighting Misleading Ads

FDA BRIEF: Week of May 29, 2017

Image result for fda science forum

FDA Commissioner Remarks to the 2017 FDA Science Forum

FDA’s work environment encourages creativity, efficiency, and superior science

  • Address challenges  in promoting and protecting the public health
  • Ability to use tools of science to meet public health challenges

Volume and complexity of regulated products increasing

  • More novel drugs and medical devices
  • New technologies such as gene therapy, gene editing, regenerative medicine

Broader societal challenges

  • Addiction to opioids and the abuse of opioid drugs, tobacco products
  • Address health care costs without sacrificing medical innovation

Science at FDA

  • CDRH developing novel methods to create models of virtual patient outcomes
  • Massive longitudinal study on Population Assessment of Tobacco and Health
  • Progress in nanotechnology, 3D printing, computational modeling and simulation
  • GenomeTrakr network
  • Human organ systems in miniature, micro-engineered chips to evaluate toxicity


drug supply chain

FDA Leads Effort to Create a Supply Chain Security Toolkit for Medical Products

Medical Product Security Toolkit covers entire supply chain and lifecycle- from raw materials to use by patients

  • Developed in collaboration with Asia Pacific Economic Cooperation (APEC)
  • Processes, procedures, and tools to enhance quality and supply chain security
  • Help support global sourcing and manufacturing of medical products

Addresses areas of vulnerability in the medical product supply chain

  • Prevent, detect substandard/falsified medical products prior to reaching consumer
  • Respond to incidents
  • Tools and training for 10 categories covering supply chain


Rick Pazdur

In cancer treatment, there’s more than one way to measure patient benefit

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

Randomized controlled study demonstrating improvement in overall survival (OS) is gold standard for new cancer therapies 

Not viable for:

  • Slow growing tumors
  • Targeting specific mutations
  • Comparison with standard therapy with modest benefit (loss of equipoise)

Alternative endpoints:

  • Progression-free survival (PFS)
  • Overall response rate (ORR)
  • Supported by patient and advisory committee feedback
  • Several approvals – renal cell carcinoma, Merkel cell carcinoma, medullary thyroid cancer, gastrointestinal stromal tumor, metastatic basal cell carcinoma, pancreatic neuroendocrine tumor, multiple myeloma, chronic myelogenous leukemia, chronic lymphocytic leukemia, certain types of lung cancer

Approval based on meaningful difference for patients and their loved ones:

  • Incorporate patient’s experience and quality of life in benefit-risk assessments
  • Evaluate post-approval real-world use; inform labeling


#IAmHHS: Fighting Misleading Prescription Drug Ad Claims

  • Develop policies for advertising and promotion of prescription drugs
  • Truthful and not misleading
  • Ensure pharmaceutical industry understand the rules of the road


Image credits: 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