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

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

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

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

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

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

LEARN

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FDA News: Acting Commissioner, Harmonized Benefit/Risk Assessments, Precision Medicine Innovation

FDA News: Week of January 23, 2017


Meet Stephen Ostroff, M.D., Acting FDA Commissioner 

Stephen Ostroff, M.D., Chief Scientist

Stephen Ostroff, M.D., is the acting Commissioner of Food and Drugs

Prior FDA Appointments

  •  Deputy Commissioner for Foods and Veterinary Medicine
  • Acting FDA Commissioner
  • Chief Scientist
  • Chief Medical Officer

Dr. Ostroff graduated from the University of Pennsylvania School of Medicine in 1981 and completed residencies in internal medicine at the University of Colorado Health Sciences Center and preventive medicine at CDC.

READ


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2 comprehensive benefit-risk frameworks for Medical Devices and Drugs, respectively

Similarities:

  • Structured decision-support tools, quantitative and qualitative assessments
  • Consider nature and severity of the condition, magnitude of effect, strength of evidence, other available therapies, applicability ot broader population, postmarket data collection

Differences:

  • Ways in which uncertainty and patient perspectives are assessed

Considerations for Harmonized Framework:

  • Greater consistency in benefit/risk assessment
  • Reduce variability in decision making; promote transparent regulatory flexibility
  • Promote stakeholder understanding of FDA judgments based on scientific, clinical, and public health considerations
  • Foster increased alignment between FDA and external stakeholders

READ


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FDA Guidances: Abuse Potential of Drugs, Human Subject Protection

FDA BRIEF: Week of January 16, 2017fda guidances


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Abuse Potential assessment of CNS active drugs

  • Under Controlled Substances Act (CSA) : Schedules I, II, III, IV and V (I being most controlled)
  • Placement determined on relative abuse potential and psychological or physical dependence
  • FDA along with DEA (Control Substances Staff) and NIDA involved in review that includes preparation of 8 Factor Analysis (8FA)

OVERVIEW

Assessing Abuse Potential

  • Key Decision Points and Recommended Studies
  • When Abuse-Related Studies Should Be Conducted
  • Preparing NDA Submission
  • NDA Review and Product Labeling Related to Abuse Potentia
  • Drug Scheduling Process.

Abuse-Related Data  form Chemistry and Nonclinical Studies

  • Chemistry and Manufacturing
  • Screening with Receptor-Ligand Binding Studies
  • Use of Nonclinical Pharmacokinetic Data in Animal Abuse-Related Studies
  • Animal Abuse-Related Behavioral Pharmacology Studies

Abuse-Related Data from Clinical Studies

  • Use of Clinical Pharmacokinetic Data in Human Abuse-Related Studies
  • Abuse-Related Adverse Events in Clinical Safety and Efficacy Studies.
  • Human Abuse Potential Study in Recreational Drug Users
  • Clinical Studies That Evaluate Cognition and Performance
  • Clinical Evaluation of Physical Dependence

Post-Marketing Illicit Drug Abuse data

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Final rule on Protection of Human Subjects enhances protections for research participants, modernizes oversight system

IMPORTANT ELEMENTS

  • Informed Consent to provide better understanding of scope, risks and benefits
  • Use single institutional review board (IRB) for multi-institutional research studies
  • For studies on stored identifiable data or identifiable biospecimens, alternative to seek Consent waiver
  • New exempt categories of research based on risk level
  • Consent for certain federally funded clinical trials be posted on public website

READ


 

 

 

FDA Voice: IMEDS, CRISPR & Genome Edited Products, Advisory Committees, Oncology Center of Excellence, Opioid Misuse

FDA BRIEF: Week of January 16, 2017

Voice

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By : Robert M. Califf, M.D., Former FDA Commissioner 


Introducing IMEDS, a Public-Private Resource for Evidence Generation

Home

  • Nonprofit public-private partnership by the Reagan-Udall Foundation for FDA
  • FDA Sentinel System’s distributed data, scientific methods and tools available to entities outside of FDA for medical product research

Access to:

  • Database on privacy-protected information from millions of patients
  • Data quality checked and formatted according to FDA standards
  • Modular programs with FDA’s epidemiologic methods and software templates
  • Collective experience with drug safety analyses
  • Transparency with detailed descriptions of analytic decisions and results
  • IMEDS@reaganudall.org for additional information..

FDA’s Science-based Approach to Genome Edited Products

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Genome editing technologies used to introduce, remove, or substitute one or more specific nucleotides at a specific site in genome

  • Most recent discovery – CRISPR/Cas9
  • Treat HIV, cancer or rare diseases by genetically altering specific types of cells
  • Control or alter organisms that carry infectious diseases
  • Improve health and welfare of food producing animals, alter food plants or fungi

Maintaining product-specific, risk-based regulation

  • Relevant to three main FDA-regulated product classes- Medical Products, Foods derived from Plants, Animals
  • Medical products reviewed under CBER program and policies, NIH Recombinant DNA Advisory Committee (RAC)

Other Initiatives

  • Collaborating with Federal agencies : White House Office of Science and Technology Policy (OSTP), FDA,  EPA and  U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (APHIS)
  • Scientific engagement and horizon-scanning: Co-sponsoring 2 studies on innovative technology
  • Working with international partners: e.g. International Pharmaceutical Regulators’ Forum (and its Gene Therapy working group)

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FDA Advisory Committees: Independent, Informed, Essential, and Evolving

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Need to improve FDA’s Advisory Committees (ACs) function

  • impartiality, transparency, affect FDA decision-making
  • system seen as overburdened with unnecessary paperwork by Academia
  • “imputed interest” of significant academic leaders and conflicts relating to grants

FDA taking steps

  • Process improvement evaluation using Lean concepts
  • Evaluate current policies and modernize evaluation of conflicts of interest
  • Develop criteria for disqualifying members
  • Discuss best ways for FDA to get advice

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Oncology Center of Excellence

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

  • Coordinated clinical review of drugs, biologics and devices across FDA’s three medical product centers
  • Overarching effort to better address the needs of cancer patients
  • Uniting experts to collaborate on clinical review of oncology products
  • Advance oncology-related regulatory science, streamline stakeholder engagement.

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Working Together to Reduce the Devastating Effects of Opioid Misuse

Medicine Bottle with Hydrocodone Label and Tablets

Critical Issue of opioid misuse, addiction and overdose

FDA actions

  • Improved product labeling
  • Prescriber education
  • Abuse-deterrent formulations
  • New intranasal and auto-injector forms of naloxone — reversal agent
  • Partnerships with CDC to understand prescription use

FDA Priorities

  1. Encouraging appropriate prescribing by healthcare practitioners
  1. Considering the family as well as the patient
  1. Finding better ways to treat pain with new medications and holistic pain management
  1. Improving how companies, professional societies and academics communicate
  1. Finding new ways to curb diversion and misuse
  1. Increasing pragmatic research for appropriate pain therapy
  1. Treating addiction as a disease, not as criminal behavior

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Is It Really ‘FDA Approved?’

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Clarification of   “FDA approved!” claim

DOES approve:

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

DOES NOT approve :

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

Misuse of FDA’s logo may violate federal law

LEARN

EvGen- Evidence Generation

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

LEARN

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

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22 Case Studies with Divergent Phase 2/Phase 3 Results

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

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

Why?

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

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FDA Views on Medical Product Communication

FDA BRIEF: Week of January 16, 2017

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FDA Views on Medical Product Communication to Payors and to Public

Statement from FDA Commissioner Robert Califf, M.D.

  • Addressing high level of interest regarding FDA’s views on medical product communications
  • Ongoing dialogue with industry and other stakeholders
  • Providing guidance to clarify the agency’s thinking

Drug and Device Manufacturer Communications with Payors, Formulary Committees, and Similar Entities – Questions and Answers

SCOPE

  • Payors seek information on effectiveness, safety, cost-effectiveness for coverage and reimbursement
  • Information can differ from submissions provided for FDA review
  • Health Care Economic Information (HCEI) to payors – Economic consequences related to the clinical outcomes of treating /diagnosing/preventing disease
  • Should be based on Competent and Reliable Scientific Evidence (CARSE)
  •  Should be related to an approved indication – so not ‘false or misleading’

Q/A

  • Communication of HCEI by Firms to Payors Regarding Approved Drugs
  • Communications by Firms to Payors Regarding Investigational Drugs and Devices

Medical Product Communications that are Consistent with the FDA-required Labeling – Questions and Answers

SCOPE: FDA-required labeling

  • Primary FDA tool to communicate essential information for safe and effective use
  • Premarket Approval products: labeling reviewed and approved by FDA
  • Premarket Notification products: also includes labeling to provide adequate directions for use and other important information

FACTORS to consider:

  1. Comparison to conditions of use in FDA-required labeling: Indication, Patient Population, Limitations and Directions for Handling/Use, Dosing/Administration
  2. Potential for harm to health relative to FDA-required labeling: Alter Benefit/Risk, Abuse/Misuse
  3. Represent directions for use provided in FDA-required labeling:  To enable safe and effective product use

Q/A:

  • Evidentiary support
  • Recommendations for communicators
  • Examples of consistency and inconsistency

Reopening Public Comment  PeriodPublic Health Interests and First Amendment Considerations Related to Manufacturer Communications Regarding Unapproved Uses of Approved or Cleared Medical Products

SCOPE:

  • Reexamination of FDA rules and policies on communications on unapproved uses
  • Integration of significant information
  • Incorporation of input from two-day public hearing on November, 2016

CONSIDERATIONS:

Advancement of Public or Individual Health Interests:

  • Motivating Development of Robust Scientific Data on Safety and Efficacy
  • Preventing Public Harm- Fraud, Misrepresentation, Bias, Ineffective Treatments
  • Ensuring Required Labeling is Accurate and Informative
  • Protecting Integrity and Reliability of Promotional Information
  • Protecting Human Subjects Receiving Experimental Treatments
  • Protecting Innovation Incentives, Statutory Grants of Exclusivity
  • Promoting Development of Products for Underserved Patients

How Communications on Unapproved Uses Can Advance Public or Individual Health Interests

  • Supporting Informed Decision-Making for Patient Treatment
  • Furthering Scientific Understanding and Research

Ensuring Policy to Maximize Public Good and Appropriate Consideration of First Amendment

  • Evidence of “Intended Use”
  • Commercial Speech under Central Hudson
  • Content- and Speaker-Based Restrictions
  • Alternative Approaches

Summary of Statutory and Regulatory Authorities: Human and Animal Drugs, Devices

Examples where Commonly Accepted Unapproved Uses have Led to Patient Harm: Erythropoiesis Stimulating Agents, Atypical Antipsychotics, Premarin/Prempro, Tambocor and Enkaid,

Examples of Products Marketed for Unapproved Uses that Caused Harm: Aranesp (Amgen), Seprafilm (Genzyme), Depakote (Abbott), Neurontin (Warner-Lambert), Atypical Antipsychotics (Eli Lilly, Bristol-Myers Squibb, Pfizer, AstraZeneca, Boehringer Ingelheim Vetmedica)

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FDA Classification Orders: HEM-AVERT, APAS compact, CIPHEROX

FDA BRIEF: Week of January 9, 2016


Hem-Avert Perianal Stabilizer, Stetrix, Inc., Oakland, TN, USA

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INDICATION FOR USE:  Providing counter-pressure to the anus during vaginal childbirth, applied at 8-10 cm of dilation, to help reduce the likelihood of cesarean delivery

REG PATHWAY: De Novo Request

  • Regulation Number: 21 CFR 884.5210
  • Regulation Name: Pressure wedge for the reduction of cesarean delivery
  • Regulatory Classification: Class II
  • Product Code: PNU

GENERIC DEVICE TYPE: Pressure wedge for the reduction of cesarean delivery

  • Prescription device that provides external mechanical support to the perianal region during the labor and vaginal delivery process. External mechanical support of the perianal region is intended to help reduce the occurrence of cesarean delivery

IDENTIFIED RISKS AND MITIGATIONS:

  • Skin/tissue trauma: Nonclinical performance data, Clinical performance data, Labeling
  • Device failure (breakage, slippage): Nonclinical performance data, Labeling
  • Infection: Sterilization validation, Shelf life testing, Labeling
  • Adverse tissue reaction: Biocompatibility evaluation
  • Pain: Labeling
  • Use error: Labeling

CLASSIFICATION ORDER


APAS Compact, Clever Culture Systems, Bäch, Switzerland

INDICATION FOR USE: The APAS Compact is an in vitro diagnostic system comprised of an instrument for automated imaging of agar culture plates and a software analysis module for the following use:

The APAS Compact, when using its urine analysis module, automates urine culture plate imaging and interpretation to detect the presence or absence of microbial growth on sheep blood and MacConkey agar culture plates that are inoculated with a 1µL sample volume. The APAS Compact, when using its urine analysis module, provides a semi-quantitative assessment of colony counts that are used as an aid in the diagnosis of urinary tract infection. All urine culture plates that are identified as positive for growth by the APAS Compact, when using its urine analysis module, must be reviewed by a trained microbiologist.

REG. PATHWAY: De Novo Request

  • Regulation Number: 21 CFR 866.2190
  • Regulation Name: Automated image assessment system for microbial colonies on solid culture media
  • Regulatory Classification: Class II
  • Product Code: PPU

GENERIC DEVICE TYPE: Automated image assessment system for microbial colonies on solid culture media

System that is intended to assess the presence or absence of microbial colonies on solid microbiological culture medium, and to interpret their number, phenotypic and morphologic characteristics through analysis of two dimensional digital images as an aid in diagnosis of infectious disease.

IDENTIFIED RISKS & MITIGATIONS:

  • False positive results (i.e., incorrect designation of plates for “Review” or as “Positive”):  General controls and special controls
  • False negative results (i.e., failure to detect growth and incorrect designation of plates as “Negative”): General controls and special controls

CLASSIFICATION ORDER


CipherOx CRI Tablet, Flashback Technologies, Boulder, CO, USA

INDICATION FOR USE: For continuous noninvasive monitoring of functional oxygen saturation of arterial hemoglobin (SpO2), pulse rate (measured by an SpO2 sensor), and the Compensatory Reserve Index (CRI), which trends changes in intravascular volume relative to the individual patient’s response to hypovolemia.

For patients with a finger thickness of 0.3” to 1” in hospital and pre-hospital settings

CRI trends with changes in intravascular volume relative to the individual patient’s response to hypovolemia, and should only be used by qualified medical providers as an adjunct to rather than as a replacement for traditional hemodynamic measures.

CRI is indicated for adults (19-36 years old) in the supine position under non-motion conditions and without cardiovascular disease. CRI has not been studied in trauma patients.

REG PATHWAY:De Novo Request

  • Regulation Number: 21 CFR 870.2200
  • Regulation Name: Adjunctive cardiovascular status indicator
  • Regulatory Classification: Class II Product Code: PPW

GENERIC DEVICE TYPE: Adjunctive cardiovascular status indicator

  • Prescription device based on sensor technology for the measurement of a physical parameter(s). This device is intended for adjunctive use with other physical vital sign parameters and patient information and is not intended to independently direct therapy.

IDENTIFIED RISKS & MITIGATIONS:

  • Delayed or incorrect treatment due to erroneous output as a result of software malfunction or algorithm error: Software verification, validation, and hazard analysis Non-clinical performance testing, Clinical performance testing, Labeling
  • Delayed or incorrect treatment due to user misinterpretation: Usability assessment, Labeling

CLASSIFICATION ORDER


FDA NEWS: Diversity in Clinical Trials, Humanity Award for FDA Invention, Health Equity Journey

FDA BRIEF: Week of January 9, 2016

FDA Encourages More Participation, Diversity in Clinical Trials

FDA relies on data from clinical these trials to safety and effectiveness of medical products. Participation low for certain populations: age >75, certain racial and ethnic groups

Diversity important

  • Full picture of the risk/benefit
  • Certain populations can be more at risk for certain diseases
  • Differences in response among diverse groups
  • Information in product labeling to help treatment decisions

FDA initiatives to encourage diversity

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FDA-Patented Invention Earns 2016 Patents for Humanity Award for Impact on Global Public Health

By: Carolyn A. Wilson, Ph.D., Associate Director for Research, CBER & Alice Welch, Ph.D., Director, Technology Transfer Program

  • Dr. Robert Lee and Dr. Carl E. Frasch, enabled the production of inexpensive and highly effective vaccine, earning 2016 Patents for Humanity Award from the U.S. Patent and Trademark Office.
  • In 2003, the CBER scientists  developed a pivotal step in manufacture of MenAfriVac vaccine
  • Vaccine  has since protected > 235 million lives against recurring meningitis outbreaks in sub-Saharan Africa
  • By 2020 the vaccine is expected to have protected > 400 million people, preventing 100 million cases of meningitis A, 150,000 deaths, and 250,000 cases of severe disability

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Martin Luther King and the Journey Towards Health Equity

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“Of all the forms of inequality, injustice in health is the most shocking and the most inhuman because it often results in physical death.”

  • Minority communities and lower rungs socio-economically remain disproportionately burdened by chronic disease
  • FDA Office of Minority Health (OMH) dedicated to strengthening FDA’s ability to respond to minority health concerns

Let’s create a world where health equity is a reality for all. 

www.FDA.gov/MinorityHealth / @FDAOMH


 

 

Drug Safety Priorities, 2015-2016

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Drug Safety Oversight Across the Product Lifecycle

Advancing Drug Safety Science

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

Improving Operations and Management in Support of Drug Safety

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

 Communicating Drug Safety: A Global Public Interface

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

LEARN

2016 Novel Drug Summary

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22 NOVEL DRUGS

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

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

SUMMARY

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

LEARN

Laboratory Developed Tests

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

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

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

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

LEARN

 

FDA Guidances: CDER’s 2017 List, Multiple Endpoints Trial, IDE Benefit-Risk

FDA BRIEF: Week of January 9, 2017

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OVERVIEW: >100 documents, list reflects draft and revised draft guidances under development at the time of this release

CATEGORIES: Advertising, Biopharmaceutics, Biosimilarity, Clinical/Antimicrobial, Clinical/Medical, Clinical Pharmacology, Clinical/Statistical, Drug Safety, Electronic Submissions, Generics, Labeling, Pharmaceutical Quality/CMC,  Pharmaceutical Quality/Manufacturing Standards, Pharmacology/Toxicology, Procedural, User Fee

READ


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OVERVIEW:  Problems with analysis and interpretation of results of study with multiple endpoints & management of problems of false conclusions if no adjustment for multiplicity

GENERAL PRINCIPLES:

  • Hierarchy of Families of Endpoints
  • Type II Error Rate and Multiple Endpoints.
  • Types of Multiple Endpoints.
  • Individual Components of Composite and Other Multi-Component Endpoints

STATISTICAL METHODS:

  • Type I Error Rate for a Family of Endpoints and Conclusions on Individual Endpoints
  •  When the Type I Error Rate Is Not Inflated or When the Multiplicity Problem Is Addressed Without Statistical Adjustment or by Other Methods
  • Common Statistical Methods for Addressing Multiple Endpoint-Related Multiplicity Problems

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OVERVIEW: Clarity regarding principal factors that FDA considers when assessing the benefits and risks of IDE applications for human clinical studies; to run trials in an efficient and cost-effective manner, while maintaining appropriate patient and research participant protections

SCOPE:

  • Informed Consent and IDE decisions
  • IDE application assessment in the context of device development pathway
  • Assessing benefits and risks for IDE applications
  • Recommended General Framework for benefit-risk assessment
  • Hypothetical examples of summary benefit-risk assessment
  • Reference guide
  • Risk management terms

READ


 

FDA Guidances: Post-Market Cybersecurity, Benefit-Risk in Device Availability, Accessories Classification, Bone Anchor 510(k), Botanical Drug Development

FDA BRIEF: Week of December 26th, 2016 and January 2nd, 2017

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SCOPE

  • FDA recommendations for managing postmarket cybersecurity vulnerabilities
  • Emphasis on monitor, identify, and address cybersecurity vulnerabilities
  • Establishes risk-based framework for assessing when changes to medical devices for cybersecurity vulnerabilities require FDA reporting

GENERAL PRINCIPLES

  •  Premarket considerations
  • Postmarket considerations
  • Maintaining safety and essential performance

MEDICAL DEVICE CYBERSECURITY RISK MANAGEMENT

  • Assessing explolitability of cybersecurity vulnerability
  • Assessing severity of patient harm
  • Evaluation of patient harm

REMEDIATING AND REPORTING CYBERSECURITY VULNERABILITIES

  • Controlled risk of patient harm
  • Uncontrolled risk to safety and essential performance

RECOMMENDED CONTENT TO INCLUDE IN PMA PERIODIC REPORTS

CRITERIA FOR DEFINING ACTIVE PARTICIPATION BY A MANUFACTURER IN AN ISAO

ELEMENTS OF AN EFFECTIVE POSTMARKET CYBERSECURITY PROGRAM

  • Identify
  • Maintaining safety and essential performance
  • Protect/Detect
  • Vulnerability characterization and assessment
  • Analysis of threat sources
  • Incorporation of threat detection capabilities
  • Im[act assessment of all devices
  • Protect/Respond/Recover
  • Risk mitigation of safety and essential performance

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SCOPE:

Benefit and risk factors, including reliable patient input, for prioritizing resources for product availability, compliance and enforcement efforts  and for informed and science-based decisions

DESCRIPTION OF FACTORS

  • Assessment of Benefits
  • Assessment of Risks
  • Additional Factors to Consider

PATIENT FOCUS IN BENEFIT-RISK ASSESSMENT

EXAMPLES

  • Product Availability Decisions
  • Compliance and Enforcement Decisions.

OTHER

  • Intersection with ISO 14971
  • Worksheets for Benefit Assessments
  • Worksheets for Risk Assessments
  • Worksheet for assessing potential decisions based on the Benefit-Risk Assessment Outcome

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SCOPE: Risk- and Regulatory control-based Classification of accessories and  use of the De Novo classification process.

ACCESSORY:  A finished device that is intended to support, supplement, and/or augment the performance of one or more parent devices. Includes Software

TRADITIONAL CLASSIFICATION APPROACH: Same as parent device OR Unique, separate classification

NEW REGULATIONS PER 21ST CENTURY CURES ACT: classify an accessory . . . based on the intended use of the accessory, notwithstanding the classification of any other device with which such accessory is intended to be used

DE NOVO PATHWAY ENCOURAGED: For new types of accessories

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SCOPE: Current thinking on relevant bench testing methods for bone anchor devices including nitinol and absorbable polymeric bone anchors

  • Classified under:21 CFR 888.3030, CFR 888.3040
  • Product Codes: MAI, MBI

510(K) SUBMISSION RECOMMENDATIONS

  • Device Description: General Suture,  Anchors,  Nitinol Suture Anchors,  Polymeric Absorbable Suture Anchors
  • Predicate Comparison
  • Biocompatibility
  • Sterility
  • Reprocessing
  • Shelf-Life and Packaging
  • Magnetic Resonance Compatibility
  • Non-Clinical Performance testing: Suture Characterization, Insertion Testing, Pullout Testing, Component Interconnection Testing,  Fatigue Testing, Corrosion (Nitinol), Degradation Testing
  • Clinical Performance Testing
  • Labeling
  • Modifications

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SCOPE: Unique nature of botanical drugs leading to different regulatory policiesfor nonbotanical drugs

  • Pre-IND, end-of-phase 1, end-of-phase 2 and 2A, pre-phase 3, and pre-NDA consultations strongly encouraged

IND FOR PHASE 1 AND PHASE 2 CLINICAL STUDIES

  • Description of Product and Documentation of Prior Human Experience
  • Chemistry, Manufacturing, and Controls
  • Nonclinical Pharmacology/Toxicology
  • Clinical Pharmacology
  • Clinical Considerations

IND FOR PHASE 3 CLINICAL STUDIES

  • General Regulatory Considerations in Late-Phase Development
  • Description of Product and Documentation of Prior Human Experience
  • Chemistry, Manufacturing, and Controls
  • Nonclinical Safety Assessment
  •  Clinical Pharmacology
  • Clinical Considerations
  • Applicability of Combination Drug Regulations.

NDA FOR BOTANICAL DRUG PRODUCTS

  • Description of Product and Documentation of Prior Human Experience
  • Quality Control
  • Nonclinical Safety Assessment
  • Clinical Pharmacology
  • Clinical Evidence of Efficacy and Safety
  • Evidence To Ensure Therapeutic Consistency
  • Postmarketing Considerations

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Medical Device Recalls, Database & OpenFDA API

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

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

WHO: Company (voluntarily) or by FDA

HOW: FDA notifies public
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Searchable Database

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

LINK


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

LINK


 

FDA VOICE: CDER 2016 Approvals, Medical Device Cybersecurity

FDA BRIEF: Week of December 26th, 2016 and January 2nd, 2017

Voice



A Review of CDER’s Novel Drug Approvals for 2016

By: John Jenkins, M.D., Director of the Office of New Drugs, CDER 

Approved 22 novel drugs

  • FIRST: Spinal muscular atrophy, Duchenne muscular dystrophy
  • NEW: Hallucinations/delusions in Parkinson’s disease, Primary biliary cirrhosis, Hepatitis C
  • NEW ONCOLOGY: Ovarian cancer, Bladder cancer, Soft tissue sarcoma, Chronic lymphocytic leukemia
  • NEW DIAGNOSTIC AGENTS: Detecting certain forms of cancer

Expedited drug development and review

  • Fast Track designation, Breakthrough Therapy designation, priority review designation, accelerated approval
  • 73%

Met PDUFA goals

  •  95%  “first cycle”
  • 86% first approved in US

However, lower approval rate vs. 2015

  • 22 vs. 45
  • 5 novel drugs approved in in 2015 with 2016 PDUFA dates
  • 14 Complete Response Letters (non-approval) 2016, higher than in recent years

Details in  annual Novel Drugs summary

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Managing Medical Device Cybersecurity in the Postmarket: At the Crossroads of Cyber-safety and Advancing Technology

suzanne-schwartz-new-dec-2016

By:  Suzanne B. Schwartz, M.D., M.B.A., Associate Director, Science and Strategic Partnerships, CDRH

Medical device Cybersecurity FDA guidances covering early product development and extending throughout the product’s lifespan

  • FDA has issued final guidance on postmarket cybersecurity
  • Premarket cybersecurity guidance issued in 2014

Importance to medical device community

  • Breaches can affect device’s performance and functionality
  • Need for continuous quality improvement to ensure safety and effectiveness

Recommended steps

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FDA Classification Orders/Approvals: ULTRAVISION, CLEANCISION, SPINRAZA

FDA BRIEF: Week of December 26th, 2016 and January 2nd, 2017

class


ULTRAVISION™ Visual Field Clearing System

Alesi Surgical, Cardiff, UK

Image result for Ultravision™ Visual Field Clearing System

INDICATION FOR USE:  Clearance of smoke and other particulate matter that is created during laparoscopic surgery.

REG PATHWAY: De Novo Request

  • Regulation Number: 21 CFR 878.5050
  • Regulation Name: Surgical smoke precipitator
  • Regulatory Classification: Class II
  • Product Code: PQM

GENERIC DEVICE TYPE: Surgical smoke precipitator

  • Prescription device intended for clearance of the visual field by precipitation of surgical smoke and other aerosolized particulate matter created during laparoscopic surgery.

IDENTIFIED RISKS & MITIGATION:

  • Electrical shock:  Electrical safety testing. Labeling
  • Electromagnetic interference: Electromagnetic compatibility testing, Labeling
  • Infection Sterilization validation : Shelf-life validation, Labeling
  • Adverse tissue reaction:  Biocompatibility evaluation
  • Tissue injury:  Animal testing, Software verification, validation, and hazard analysis, Labeling

CLASSIFICATION ORDER


CLEANCISION Wound Retraction and Protection System

Prescient Surgical, San Carlos, CA, USA

surgery room

INDICATION FOR USE: For use by a surgeon during abdominal surgery to retract the surgical incision, provide access to the abdominal cavity, and irrigate the surgical wound edge. The device may aid in the prevention of wound edge contamination. This device is intended to deliver a sterile irrigant solution and serve as a conduit for fluid removal from the surgical wound edge.

 REG PATHWAY: De Novo request

  • Regulation Number: 21 CFR 878.4371
  • Regulation Name: Irrigating Wound Retractor Device
  • Regulatory Classification: Class II
  • Product Code: PQI

GENERIC DEVICE TYPE: Irrigating Wound Retractor Device

  • An irrigating wound retractor device is a prescription device intended to be used by a surgeon to retract the surgical incision, to provide access to the surgical wound, to protect and irrigate the surgical wound, and to serve as a conduit for removal of fluid from the surgical wound.

IDENTIFIED RISKS & MITIGATION:

  • Adverse Tissue Reaction: Biocompatibility Evaluation
  • Tissue or Wound Damage:  Non-clinical Performance Testing, Shelf Life Testing, Labeling
  • Infection: Sterilization Validation, Non-clinical Performance Testing, Shelf Life Testing, Labeling

CLASSIFICATION ORDER


FDA approved


 SPINRAZA  (nusinersen) injection, for intrathecal use 

Biogen Inc. Cambridge, MA, USA

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INDICATION: Treatment of spinal muscular atrophy (SMA) in pediatric and adult patients

UNMET NEED:

  • SMA is hereditary, causes weakness and muscle wasting
  • Wide variability in age of onset, symptoms and rate of progression
  • Long-standing need for a treatment

REG PATHWAY: NDA. Fast track designation, Priority Review, Orphan Drug Designation, Rare Pediatric Disease priority review voucher

MECHANISM OF ACTION:  Antisense oligonucleotide (ASO) designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency.

EFFICACY:

  • Multicenter, randomized, double-blind, sham-procedure controlled, n =121,  symptomatic infants ≤ 7 months, SPINRAZA vs.  sham injection
  • Primary endpoint (interim analysis): Responders with improvement in motor milestones according to Section 2 of the Hammersmith Infant Neurologic Exam (HINE)
  • Interim Analysis:  21 (40%) vs. 0 (0%),  p<0.0001

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SAFETY:

  • Most common side effects: Upper respiratory infection, lower respiratory infection and constipation
  • Warnings and Precautions: Low blood platelet count, renal toxicity, neurotoxicity

LABEL


 

FDA -CDRH FY2017 Proposed Guidances

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

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

HOW:  3 lists

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

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