FDA Brief: Week of Feb 22, 2016

FDA approved



GAZYVA (obinutuzumab) Injection

 Genentech, Inc, San Francisco, CA, USA

Indication: In combination with bendamustine followed by GAZYVA monotherapy, for the treatment of patients with follicular lymphoma (FL) who relapsed after, or are refractory to, a rituximab-containing regimen

Reg. Pathway: Supplemental BLA, (previously approved for chronic lymphocytic leukemia), Priority Review


  • Single open-label, multicenter, randomized study (n=321); patients with FL who had no response to or have progressed during or within 6 months of rituximab or a rituximab-containing regimen; GAZYVA plus bendamustine vs. bendamustine alone
  • 6 cycles of Gazyva plus bendamustine followed by continued Gazyva monotherapy for up to 2 years with 6 cycles of bendamustine therapy
  • Primary Endpoint: Progression Free Survival (PFS) by independent review. Median PFS 13.8 months  for bendamustine alone vs . not reached in the Gazyva plus bendamustine, p-value < 0.0001
  • Median Overall Survival not yet reached in either arm




  • Serious adverse reactions:  Febrile neutropenia, neutropenia, infusion related reactions, sepsis, pneumonia and pyrexia
  • Most common adverse reactions:  Infusion reactions, neutropenia, nausea, fatigue, cough, diarrhea, constipation, pyrexia, thrombocytopenia, vomiting, upper respiratory tract infection, decreased appetite, arthralgia, sinusitis, anemia, asthenia and urinary tract infection.



AFINITOR ( everolimus) Tablet

Novartis, East Hanover, NJ, USA

Indication: Treatment of adult patients with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin with unresectable, locally advanced or metastatic disease

Reg Pathway:  Supplemental NDA (previously approved for breast cancer and several other cancer indications)


  • Single, multicenter, randomized (2:1), n=302,  patients with unresectable, locally advanced or metastatic, well differentiated (low or intermediate grade), non-functional (no current or prior history of carcinoid symptoms), neuroendocrine tumors (NET) of gastrointestinal or lung origin
  • Afinitor plus best supportive care (BSC)  vs.  placebo plus BSC
  • Primary Endpoint : Improvement in progression-free survival (PFS)
  • Median PFS : 11 mo. vs. 3.9 mo., p <0.001
  • Overall Response Rates: 2% vs. 1%
  • Overall Survival: No statistically significant difference



  • Serious adverse reactions: In  42% of Afinitor-treated patients and included 3 fatal events (cardiac failure, respiratory failure, and septic shock
  • Most common adverse reactions: Stomatitis, infections, diarrhea, peripheral edema, fatigue and rash
  • Most common laboratory abnormalities: anemia, hypercholesterolemia, lymphopenia, elevated aspartate transaminase and fasting hyperglycemia


Expediting Medical Device Regulatory Review and Reimbursement

FDA Brief: Week of Feb 22, 2016



Proposal for Joint FDA-Coverage Organization Meeting to discuss Evidentiary Standards for Regulatory Review and Reimbursement



  • 2011-2015: FDA-CMS Pilot Initiative for parallel discussion and review of device premarket clearance (by FDA) and National Coverage Determination (by CMS)
  • 2016:  FDA intends to provide a mechanism to get early payer input on evidentiary needs to streamline process from FDA Approval  to Payer Coverage
  • Use CDRH’s Pre-Submission program as a forum for joint discussion between Sponsor, FDA and Coverage organization


Debrief: Small Business Vendor Fair

Small Business Outreach Vendor fair

White Oak Campus

Feb 24, 2016




FDA and DHHS Presentations

  • Office of Info. Management (OIMT, FDA)
  • Office of Acquisitions and grants (OAGS, FDA)
    • Get DUNS#, SAM registration, NAICS Code
    • Become a subcontractor to get experience
    • FedBizzOps http://www.fbo.gov
  • Office of Small and Disadv. Business Utilization (OSDBU, DHHS)
    • Women owned small bizz (WOSB) encouraged
    • Core capability and FDA experience
    • Templates for Capability Statement and Business Cards

Key FDA Technology Initiative for potential contracts:

Scientific Computing.



Debrief: Medical Device Interoperability



About MDIC

Topic & Presenters

  • Introduction: Dawn Bardot, PhD, MDIC
  • FDA Draft Guidance on Interoperable Medical Devices: Bakul Patel, FDA CDRH
  • Safe Medical Device Interoperability to Enable Healthcare Transformation: Julian Goldman, MD, Massachusetts General Hospital
  • Center for Medical Interoperability Review: Ed Cantwell, Center4M


FDA Presentation


Draft guidance focuses on:

  • Design for interoperability
  • Anticipate interoperable scenarios
  • Manage and minimize risks
  • Create transparent or standards based medical device interface

FDA Slides

FDA’s position summarized in this blog

interop guidance

FDA Draft Guidance


Take the MDIC Poll to help discussions on this topic


Debrief: Human Factors & Usability Engineering

FDA Webinar Debrief

February 19, 2016



CDRH, Human Factors Team

  • Shannon Hoste, M.S., Human Factors Pre-Market Evaluation Team Member
  • Xin Feng, Ph.D., Human Factors Pre-Market Evaluation Team Member
  • Hanniebey Wiyor, Ph.D., Human Factors Pre-Market Evaluation Team Member

Presentation Overview

  • Relevant regulations and standards
  • FDA’s Human Factors guidance
  • List of highest priority devices for human factors review – draft guidance


Human Factors/Usability Engineering

Focuses on interactions between people and devices. The critical element is the device user interface, depicted as the red zone in Figure below

.user interface.JPG

FDA Human Factors Page

FDA 2016 Guidances

Clarify expectations around when to submit a HF report with a premarket submission

HFE3human factors

Summarized previously in this blog

Key Takehomes

  • Human Factors testing is a part of a robust design control subsystem
  • Submit data in premarket submissions if risk analysis indicates user error could result in serious harm
  • Consult FDA early using Q-Sub process to discuss and align on development plan and labeling implications






FDA Strengthening Regulatory Relationships in India

FDA Brief: Week of Feb 22, 2016


FDA Voice

Strengthening Regulatory Relationships in India

By:  Mathew T. Thomas, Director,  and Dean Rugnetta, Deputy Director, FDA’s India Office, New Delhi, India

  •  India is one of the largest suppliers of drug products to US
  • FDA India office established in 2008 to promote govt. -to-govt. interactions
  • Working with counterparts in Indian government to ensure manufactured medical products meet FDA’s safety and quality requirements
  • Meeting of India and US offices held in Nov. 2015 to learn respective regulatory perspectives
  • Continue leveraging knowledge and strengths to ensure patient safety in India and product quality of FDA-regulated pharmaceuticals.




Senate Confirmaton of Dr. Robert Califf as FDA Commissioner

FDA Brief: Week of Feb 22, 2016


  • Served as FDA’s Deputy Commissioner for Medical Products and Tobacco
  • Professor of Medicine & Vice Chancellor Clinical and Translational Research, Duke University
  • Director of the Duke Translational Medicine Institute
  • Founding director of  Duke Clinical Research Institute
  • Served on Institute of Medicine committees
  • Served on Board of Scientific Counselors for  NIH and NLM
  • Served on several Advisory Committees

Congratulations and Regards to Dr. Califf- we had the good fortune of working with him.


MDUFA IV Reauthorization Meeting Summaries

FDA Brief: Week of Feb 22, 2016


KEY DISCUSSIONS : FDA’s and Industry’s proposal packages for MDUFA IV reauthorization

FDA Proposal: Cost Estimate of Industry 2015 Proposals

Industry Proposals:

  • Process Improvement and Independent Assessment
  • Review Summaries Proposal
  • Pre-Submission Proposal
  • PMA Proposal
  • De Novo Proposal
  • CLIA Proposal




Integrated Infrastructure Proposal

  • Managerial Retention and Oversight: Implement effective recruitment and hiring
  • Quality Management: Establish a Quality Management team
  • IT Modernization: myDevices Portal and eSubmitter

Integrated Process Improvements Proposal

  • Integrated Review Process: Shift compliance and surveillance activities into ODE
  • Device Coordinators: Ensure consistency in process, feedback through reg lifespan
  • Review Summaries Proposal: Revised for 510(k) review summaries

Integrated Performance Proposals

  • Q-Submissions: Revised proposals to improve success and timeliness
  • De Novo: Steadily improve performance target to a decision within 120 days
  • Third Party 510(k) Review: Proposal to strengthen program via analysis and training
  • CLIA Waiver: Steadily increasing performance target to a decision within 180 days

Integrated Innovation Proposals

  • Digital Health: Consistent review of software and issues related to digital health
  • Device-Specific Guidance: Streamline guidance development and updates
  • Leveraging Standards: Accreditation scheme for conformity assessment
  • Real World Evidence: Enable reviewers to use evidence for decision-making
  • Patient Input: Useful for  benefit/risk evaluation




FDA Formal Dispute Resolution


WHAT: Formal Review of scientific and/or medical disputes. Related to applications for user fee products.  To quickly and impartially investigate complaints and resolve disputes between CDER and CDER-regulated industry, health care practitioners, and consumers by offering an informal, confidential, and neutral environment

HOW: Process codified in Code of Federal Regulations (CFR) and  CDER/CBER Guidance for Industry

WHO:  FDA contacts:

  • CDER Formal Dispute Resolution Project Manager
  • Ombudsman







Drug development is a time-consuming and expensive process. There is tremendous sense of urgency for the pharmaceutical industry to develop new tools to accelerate the drug development process and to reduce attrition rate on drug candidates.

Microdosing is a tool in the early drug development. The term Phase 0 is therefore often used to refer to such studies. Dose needs to administer in microdosing study is less than 1/100 of the test substance calculated to yield a pharmacologic effect, with a maximum dose of 100 μg.

The FDA in 2006 issued a guidance document on exploratory Investigative New Drug detailing the regulatory process for microdosing clinical studies (FDA Guidance ). These studies helps to understand the bioavailability and pharmacokinetic profiles of test compounds in human, to evaluate the metabolic profiles in human or to obtain the information on the tissue distribution of test compounds in human by using molecular imaging technology.

Microdosing can be useful in the discovery of endogenous biomarkers, which would assist in the quantitative evaluation of the in vivo effects of drugs. Since the dose is sub-therapeutic level, the potential for adverse side effect to a human subject in the clinical study is considered to be minimal. The preclinical toxicology required to support microdosing is minimal. Furthermore, if human screening of compounds is done earlier in the drug development process, fewer animal studies are required before Phase I clinical trials. Therefore, animal studies can be avoided with compounds having unsuitable pharmacokinetic (PK) profiles. Hence these studies can be used as a candidate selection tool to effectively eliminate drug candidates that show sub-optimal human PK before spending time and effort in the kind of extensive toxicology that is required prior to conventional Phase 1. Ultrasensitive bioanalytical equipment and techniques are obviously required, but the substantial cost and time savings from early elimination of unviable compounds may more than justify the investment. When the drug discovery process yielded a single molecule, microdosing can still be useful in such circumstance. It can quickly establish if it is worth taking the molecule forward prior to committing large-scale resources to a full Phase I study. Sometimes a metabolic pathway is identified in human hepatocytes or liver microsomes, which is not seen in animals. Microdosing may be used to establish if the metabolic pathway occurs in vivo.

 The fundamental strengths of microdosing, improved safety, reduced cost, and time to developmental decisions, are likely to get only stronger. The concept has been widened from a purely pharmacokinetic predictive method towards addressing other questions, such as drug-drug interactions, polymorphism and looking at whether a drug is likely to reach its site of action. Microdosing study data with modelling may lead to much more reliable predictions for drug candidate selection.

There are limitations in microdosing technique. At therapeutic dose level drug may exhibit limited solubility, and absorption becomes dependent on the rate and extent of dissolution, which cannot be predicted at microdose levels since drug candidate could dissolve readily at microdose, yielding good PK. Also this study may not be able to predict nonlinear pharmacokinetic characteristics of the drug at therapeutic dose level. Microdosing study needs very sensitive analytical methods to measure circulating drug levels in blood as a function of time.


FDA Guidance

FDA Databases: Noncompliance Letters, Medication Guides

FDA Brief: Week of Feb 15, 2016



noncompliance table.JPG

Non-Compliance Letters Listing

WHAT: Identifies drug and biologic products for which the sponsor has received a pediatric research Equity Act (PREA) Non-Compliance letter

WHY: Sponsors required to submit pediatric assessments required by PREA as part of drug approval

HOW:  Provides links to the PREA Non-Compliance letter and sponsor response. When the sponsor fulfills, FDA will add the date to the last column of the table




Medication Guide Database

WHAT: Paper handouts provided with certain prescription medicines. Contain information to avoid serious adverse events

WHY : FDA requires  Medication Guides be issued when  Agency determines that certain information is necessary to prevent serious adverse effects

HOW:  Inform Patient decision-making  by information about known serious side effect, or patient adherence to directions for the use



FDA CE Course on ‘Biosimilars’

FDA Brief: Week of Feb 15, 2016


WHAT: Continuing Education Course for health care professionals  to strengthen knowledge and understanding of biosimilars and interchangeable products – which are not generic products

WHY: Growing interest in biosimilars and interchangeable products in the pharmaceutical industry

HOW: Will inform about the development process, approval pathways, and  relationships between biosimilars and interchangeable products.


FDA Approvals: Briviact, Ibrance

FDA Brief: Week of Feb 15, 2016

FDA approved


BRIVIACT® (brivaracetam) tablets

UCB, Inc. Smyrna, Georgia

Indication : Add-on treatment to other medications to treat partial onset seizures in patients age 16 years and older with epilepsy.

Unmet Need:

  • Approximately 5.1 million people in the United States have a history of epilepsy and approximately 2.9 million people in the United States have active epilepsy
  • Brain disorder that causes people to have recurring seizures
  • Need for new treatment option

Reg Pathway: NDA, standard review

Mechanism of Action: Binding to the ubiquitous synaptic vesicle glycoprotein 2A


  • 3 randomized, double-blind, fixed-dose, multi-center studies (n=1,550); 8-week baseline period followed by a 12-week treatment period, patients with uncontrolled partial onset seizures despite concomitant antepileptic therapy; Briviact vs Placebo
  • Effective in reducing the frequency of seizures.with Briviact vs placebo


  • Serious risks: Suicide thoughts / attempts,  depression, aggression, panic attacks, allergic reaction
  • Must be dispensed with Medication Guide
  • Most common side effects: Drowsiness, dizziness, fatigue, nausea and vomiting


palbo structure

IBRANCE® (palbociclib) capsules

Pfizer, Inc., NY

Indication: Treatment of HR-positive, HER2-negative advanced or metastatic breast cancer in combination with:

  • letrozole as initial endocrine based therapy in postmenopausal women, or
  • fulvestrant in women with disease progression following endocrine therapy.

Reg Pathway:  

  • Accelerated approval in 2015 for combination treatment with letrozole for the treatment of HR-positive, HER2-negative advanced breast cancer as initial endocrine based therapy in postmenopausal women
  • This approval based on study showing profression free survival (PFS); Prior Approval sNDA, , Priority Review, Breakthrough designation


  • Single international, randomized, double-blind, parallel group, multicenter study (n=521); IBRANCE plus fulvestrant vs. placebo plus fulvestrant (n=521;  women with HR-positive, HER2-negative advanced breast cancer
  • Major efficacy outcome: Investigator-assessed PFS evaluated according to RECIST 1.1: 41.8% vs 65.5% , p p<0.0001
  • Median PFS was 9.5 versus 4.6 months



  • Most common adverse reactions: Neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, thrombocytopenia, constipation, vomiting, alopecia, rash, decreased appetite, and pyrexia


New Drug Guidances: Anthrax Prophylactic, Safety Data Collection

FDA Brief: Week of Feb 15, 2016


  • Assist sponsors in the development of drugs for prophylaxis of inhalational anthrax
    • inhaled aerosolized Bacillus 21 anthracis spores but who have not yet manifested clinical evidence of disease
    • probable imminent exposure to anthracis spores
  • Consider approved antibacterial drugs for other indications marketed for many years, and have safety information from millions of patients before approval for inhalational anthrax
  • Approval based on Animal Rule regulations as definitive human efficacy studies cannot be conducted; Rely on evidence from animal studies to provide substantial evidence of effectiveness


safety data.JPG

  • Help sponsors determine amount and type of safety data to collect during late-stage premarket and postapproval clinical investigations
  • Selective approach based on known drug safety profile
  • Balance eliminating data collection that will not be useful vs. collecting sufficient data to allow adequate characterization of safety profile
  • Consult with the relevant FDA review division on appropriate strategy



Device Notifications: Dignicap-Class II, Hip Joint Systems-Class III

FDA Brief: Week of Feb 15, 2016



Final Order for Dignicap  Classification Order

  • Target Health, Inc. (on behalf of Dignitana AB)submitted a request for classification for class II
  • FDA approved Class II with the establishment of special controls for reasonable assurance of effectiveness and safety
  • Final order requires any firm submitting 510(k) for a similar device will need to comply with the special controls identified in the Order
  • Identified Risks : Thermal Tissue Damage, Electromagnetic Interference/Electrical Shock, Adverse Tissue Reaction, Increased Risk of Scalp Metastases, Use Error, Scalp Pain, Headache, and Chills
  • Special Controls: Non-clinical Performance Testing, Software Verification, Hazard Analysis, Electromagnetic Compatibility, Electrical testing, Biocompatibilty and Labeling





FR Order fpor hip implants

Premarket Approval (PMA) Required for Hip Joint Systems

  • For hip joint metal/metal semi-constrained with (1) cemented acetabular component or (2) semi-constrained with an uncemented acetabular component.
  • Remain Class III (higher risk) devices
  • Rationale : Insufficient evidence and information to conclude that general controls in combination with special controls would provide reasonable assurance of the safety and effectiveness of these devices.

FDA based decision based on following activities:

  • Working with the manufacturers
  • Supporting technology to improve image quality around metal implants
  • Encouraging metal ion test labs in trace element proficiency testing program
  • Continuing review of published literature, Medical Device Reports
  • Launching collaborative International Consortium of Orthopaedic Registries (ICOR)
  • Requesting and reviewing device retrieval analyses from manufacturers
  • Pursuing global collaborations to fully understand postmarket performance
  • Issued Safety Communication to patients and health care providers
  • Issued proposed order to submit premarket approval (PMA) applications.
  • Convened Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory Committee to seek expert scientific and clinical opinion



FDA Approval of Sernivo

FDA Brief: Week of Feb 8, 2016


FDA approved





Sernivo (betamethasone dipropionate) Spray, 0.05%

Promuis Pharma,  Princeton, New Jersey, USA

Indication: treatment of mild to moderate plaque psoriasis in patients 18 years of age or older.

Reg Pathway: 505 (b)(2)

Mechanism of Action: Steroid. Precise mechanism of action of spray in psoriasis is unknown.


  • 2 multi-center, randomized, double-blind; moderate plaque psoriasis; 28 days; Sernivo vs. Vehicle
  • Primary Endpoint: Investigator Global Assessment (IGA) score of  0 or 1 [clear or almost clear] and at least a 2-scale reduction from baseline
  • Treatment success of 42.7% and 34.5% vs. 11.7% and 13.6%, respectively (p<0.001).


  • Warnings/Precautions: Reversible HPA axis suppression, Cushing’s syndrome, hyperglycemia and unmasking of latent diabetes mellitus
  • Most common adverse reactions : Application site reactions, including pruritus, burning and/or stinging, pain, and atrophy




FDA Views on 2017 Budget, Interoperability, Proprietary Names, Biomarkers

FDA Brief: Week of Feb 8, 2016



FDA Voice


FDA seeks $5.1 billion total for FY 2017, including funds to implement food safety law, improve medical product safety and quality

  • Total budget of $5.1 billion to protect and promote the public health
  •  Several key areas related to Drug and Medical Devices
  • Improving the Safety and Quality of Medical Products
    • Precision medicine tools to “personalize” the diagnosis and treatment
    • Safety of compounded drugs through inspection and enforcement activities
    • Policies for antimicrobial drug use in animals to protect antibiotic effectiveness
    • Prevent prescription opioid abuse, speeding generic drug access, reducing drug shortages.
  • Supporting the National Cancer Moonshot Initiative
    • Oncology Center of Excellence with regulatory scientists and reviewers
    •  Integrated approach for prevention, screening, diagnosis, and treatment
    • Companion diagnostic tests
    • Combinations of drugs, biologics and devices
    • Precision Medicine science.
  • Investing in the FDA’s Infrastructure


Building a case for medical device interoperability: FDA’s Call to Action

by Bakul Patel, M.S., M.B.A., is associate director for digital health in FDA’s Center for Devices and Radiological Health

  • Interoperability : Smart and safe interaction among medical devices and information systems
  • Medical Device Interoperability: Improve patient care, reduce errors and adverse events, lower costs. Critical safety factor
  • FDA collaborating with stakeholders (e.g. hospitals, health care providers, manufacturers, standards-development organizations) to promote medical device interoperability to help patients
  • Key Activities:
    • Summit on Medical Device Interoperability (2012)
    • Manufacturing standards (2013)
    • Finalize Guidance on medical device data systems-MDDS ( 2015)
    • Draft Guidance on Design Considerations and Pre-market Submission Recommendations for Interoperable Medical Devices (2016)


Working to prevent proprietary drug name confusion

by Lubna Merchant, M.S., Pharm.D., Deputy Director, DMEPA,  

About medication errors: Preventable event leading to inappropriate medication use or patient harm

Drug name confusion can cause medication errors : Shared strength or dose between products, drugs with similar names, confirmation bias (tendency to search for, interpret, or recall information in a way that confirms one’s beliefs or hypotheses)

Efforts to avoid drug name confusion before approval: Safety review,  look for error-prone naming attributes (spelling, pronunciation, appearance), prescription simulation studies, use FDA’s Phonetic and Orthographic Computer Analysis (POCA) program to identify similar looking or sounding names, analyze using failure modes and effects analysis (FMEA) for failures

Reporting medication errors to FDA: Evaluate reports from companies, health care professionals, patients and other sources (e.g Institute for Safe Medication Practices). Apply  “lessons learned” to improve drug name review process

Addressing name confusion errors and informing the public: Drug safety communications, consumer updates, or scientific literature

Help combat drug name confusion errors: Build awareness amongst health care professionals, pharmacists, nurses, patients

Draft Guidance (2015):  “Best Practices in Developing Proprietary Names for Drugs.”


Clarifying What We Mean When We Talk About Biomarkers: An NIH/FDA Joint Leadership Council Success

by Melissa A. Robb, B.S.N., M.S. (RegSci), is FDA’s Associate Director for Regulatory Affairs, Office of Medical Policy, CDER Robert M. Califf, M.D., is FDA’s Deputy Commissioner for Medical Products and Tobacco

  • Biomarkers, Endpoints, and other Tools (BEST) Resource : FDA + NIH collaboration
  • Harmonizing definitions and use of key terms e.g. biomarkers, surrogates, clinical outcome assessments
  • Requesting public feedback on glossary BEST (Biomarkers, EndpointS, and other Tools) Resource.





FDA Guidances on Rhinitis, Diagnostic Radiology, Orthopedic Devices

FDA Brief: Week of Feb  8, 2016

fda guidances




  • Developing drug products for the treatment of nonallergic rhinitis (NAR) in children and adults
  • Definition of a clinical phenotype, trial design, efficacy, and safety
  • Development programs for the treatment of vasomotor rhinitis, a subtype of NAR



  • Developing drug products for treatment of seasonal allergic rhinitis (SAR) in children and adult
  • Trial design, effectiveness, and safety for SAR and perennial allergic rhinitis (PAR)
  • Based on assessment of :
    • Prior allergic rhinitis clinical trials
    • Agency’s current understanding of SAR and PAR mechanisms, pathophysiology



display devices

  • Based on current technologies – to assist premarket notification submissions for display devices intended for use in diagnostic radiology
  • Class II devices intended  for controlled viewing conditions to display and view digital images for primary image interpretation
  • Application should include:
    • Device description & Indications for Use
    • Electrical Safety
    • Firmware and Software Documentation
    • Physical Laboratory Testing
    • Labeling




  • Orthopedic devices using ultrahigh molecular weight polyethylene (UHMWPE) – Conventional, Highly crosslinked, Vit E highly crosslinked, Non-conventional
  • Determining appropriate information and testing for 510(k), de novo requests, PMA, HDE and IDE
  • Characterization of material (e.g.material description, sterility, biocompatibility, mechanical properties, and chemical properties), Biocompatibility and Shelf life






FDA Databases for Post-Approval Requirements




WHAT: Database for  oversight and tracking Studies, Requirements and Commitments postapproval.

WHY: Need for oversight. Drug studies, mandated as condition of approval (accelerated approval) or for improving prescribing and use, quality and consistency. Device studies mandated as condition of approval (PMA, PDP. HDE)  and to ensure well-designed post-approval studies conducted effectively and efficiently..

HOW: Publicly accessible database. Updated regularly

LINK for Drugs


LINK for Devices

FDA Guidances: UDI, Human Factors Evaluation

FDA Brief: Week of Feb 1, 2016


fda guidances


  • Medical devices eligible for reimbursement labeled with an 11-digit reimbursement number – National Health Related Item Code (NHRIC) or National Drug Code (NDC) number
  • The Unique Device Identification System final rule (UDI Rule) includes provision that rescinds any NHRIC or NDC number
  • Draft guidance communicates
    • Intent not to enforce before September 24, 2021
    • Continued use of FDA labeler codes until September 24, 2018



human factors

  • Guidance on appropriate human factors and usability engineering processes for safe and effective use – users, uses, use environment
  • Improve device design to minimize potential use errors and resulting harm
  • Risk Management by eliminating or reducing design-related problems

Guidance describes :

  • Device Users, Use Environments and User Interface
  • Preliminary Analyses and Evaluations
  • Elimination or Reduction of Use-Related Hazards
  • Human Factors Validation Testing
  • Documentation





  • Requirement of human factors data in premarket submissions based on potential for serious harm due to use error
  • LISTED (for PMA, 510(k)) : Ablation generators, Anesthesia machines, Artificial pancreas systems,  Auto injectors,  Automated external defibrillators,  Duodenoscopes,  Gastroenterology-urology endoscopic ultrasound systems, Hemodialysis and peritoneal dialysis systems, Infusion pumps, Insulin delivery systems, Negative-pressure wound therapy, Robotic catheter manipulation systems, Robotic surgery devices, Ventilators,  Ventricular assist devices
  • NOT LISTED (for PMA, De Novo): Risk assessment on case-by-case basis; include criteria such as User interface modification, Different users, Recalls, adverse events, and problem reports, Device modifications



FDA Voice: Opioid Policy, Pharmaceutical Manufacturing Modernization

FDA Brief: Week of Feb 1, 2016


FDA Voice


Sweeping Review of Agency Opioids Policies

 Dr. Robert Califf, Deputy Commissioner for Medical Products and Tobacco

To addres opioid abuse epidemic:

  • Develop policies to reverse epidemic while providing access to effective relief
  • Re-examine the risk-benefit paradigm to consider wider public health effects
  • Convene Advisory Committee prior to non abuse-deterrent opioid approval
  • Consult with Pediatric Advisory Committee on labeling
  • Include additional warnings and safety information to existing labeling
  • Update REMS requirements
  • Expand access to abuse-deterrent products
  • Improve access to naloxone for use disorders
  • Support alternative pain management options

Complements U.S. Health and Human Services initiative focusing on 3 priority areas:

  1. Providing training and educational resources,updated prescriber guidelines
  2. Increasing use of naloxone to reduce overdose deaths
  3. Expanding use of Medication-Assisted Treatment for substance use disorders




Modernizing Pharmaceutical Manufacturing to Improve Drug Quality: Ensuring a Safe and Adequate Supply of Drugs

Michael Kopcha, Ph.D., R.Ph. Director, Office of Pharmaceutical Quality, CDER

To avoid drug shortages, FDA proposing and adopting  novel technologies to produce quality medicines that are safe and effective

  • Expedite review of ANDAs when potential shortage issues arise with approved drugs
  • Embrace advanced manufacturing technologies that improve quality, increase efficiency, reduce product failures
  • Modernize pharmaceutical manufacturing by encouraging new technologies
  • Guide and Approve emerging technology

Accomplishments thus far:

  1.  First 3D printed pill Spritam (levetiracetam) approved
  2. Emerging Technology Team to assist industry identify and resolve technology issues
  3. Draft Guidance Advancement of Emerging Technology Applications to Modernize the Pharmaceutical Manufacturing Base.




FDA Metric: FDA TRACK and MDUFA III Independent Assessment


FDA Track

WHAT: Agency-wide performance management system

HOW: Monitors FDA programs through key performance measures and projects

WHEN: Quarterly





WHAT: independent assessment of CDRH’s premarket review program

WHO: Booz/Allen/Hamilton

HOW: Process improvements to promote predictable, efficient, and consistent premarket reviews (Phase 1), FDA’s implementation Phase 1 recommendations (Phase 2)




Debrief: Collaborative Approaches to Medical Device Cybersecurity

FDA Meeting Debrief

Moving Forward: Collaborative Approaches to Medical Device Cybersecurity

FDA White Oak Campus

Jan 20-21, 2016


  • FDA – CDRH
  • Chair:  Suzanne Schwartz, MD, MBA, Associate Director for Science and Strategic Partnerships


  • National Health Information Sharing Analysis Center
  • Dept. of Health and Human Services
  • Dept. of Homeland Security

Panelists: FDA, Industry, Academia, Profit & Nonprofit Cybersecurity Alliances,  National Health Information Centers, Healthcare Systems

Issue: Medical device vulnerabilities can serve as access points for entry into hospital and health care facility networks leading to compromise of data confidentiality, integrity, and availability

Objective: Engage diverse stakeholders across medical device ecosystem to discuss and identify approaches to address unresolved gaps and challenges that have hampered progress in advancing medical device cybersecurity. The attention should be on ‘total product life cycle’ – from design to obsolescence

Meeting Discussions:


Has issued 2 guidances and has evaluated information contained in premarket submissions.

  • Premarket Cybersecurity Guidance (finalized 2014) emphasizes (a) shared responsibility between stakeholders, including health care facilities, patients, providers, and manufacturers (b) addressing cybersecurity during the design and development (c) establishing cybersecurity design inputs,  vulnerability and management approach as part of software validation and risk analysis
  • Observation of Premarket submissions (2014-2015) indicated deficiencies in cybersecurity information as defined by the guidance
  • Postmarket Cybersecurity Guidance (draft issued 1/2015) emphasizes (a) collaborative approach to information sharing and risk assessment (b) manufacturer responsibilities by leveraging existing Quality System Regulation (c) alignment with Presidential Executive Orders and NIST Framework (d) Incentivizing the “right” behavior (e) using risk-based approach to addressing public health risks

Panel and Breakout Sessions

Panel experience and best practice sharing across several topics

Cyber threat landscape, implementation of NIST, Information Sharing and Analysis Organization (ISAO), Postmarket vulnerability handling and disclosure, manufacturing challenges, addressing gaps and challenges to strengthening cybersecurity, current activities in healthcare and public health sector, risk assessment tools, adapting and implementing medical device cybersecurity

Breakout sessions involving 400 attendees to share opinions and proposals for ISAOs, Coordinated vulnerability disclosure, gaps and action plan

Key Takehomes:

  • Cybersecurity is critical for total product lifecycle and is a collaborative effort across multiple stakeholders. Recognition of hackers ‘from hoodies to business suits’
  • There should be information sharing (profit/nonprofit organization) and collaborative discussion of setting of cybersecurity standards, conformity assessments and certifications across all stakeholders to strengthen the ecosystem; consideration of centralized listing
  • Experience from other sectors (eg banking, homeland security) can be leveraged; however, medical device approach needs to be grounded in context of patient safety and effectiveness
  • Device manufacturers should follow the principles of Premarket Cybersecurity Guidance

ACTION : All stakeholders to review and comment on the draft Postmarket Cybersecurity Guidance by April 21, 2016

 Graphic Memorialization:

By Stephanie Brown @stephscribes



postmarket  Premarket






Premarket Cybersecurity Guidance

Postmarket Cybersecurity Guidance

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