Transcript Lecture 22 - Rice University

BIOE 301
Lecture Twenty-Two
Schedule
• Today, April 10
– Lecture 22: FDA Device Regulation & Research
Funding
• Thursday, April 12
– Lecture 23: Future of Bioengineering in World Health
& Review for Final
• Tuesday, April 17
– No class!
• Thursday, April 19
– Exam 3, Lectures 16-23
• Tuesday, April 24
– Project Presentations
• Final Exam (see syllabus for details)
Reading Assignment for Thursday
• Financial Anatomy of Biomedical Research,
JAMA. 2005, Sep 21;294(11):1333-42
• Application of Microchip Assay System for the
Measurement of C-reactive Protein in Human
Saliva, Lab Chip. 2005, 5, 261-269
• An exam question will draw from these
articles
After Today’s Lecture…
• Appreciate why it costs so much in the US
(time & money) to develop devices and get
them to market
• Speculate on what this means for
developing countries that depend on 1st
world research
• Understand the importance and magnitude
of research funded by the government
U. S. Department of Health & Human Services
The
Secretary
Deputy Secretary
Administration for
Children and Families
(ACF)
Administration on
Aging
(AoA)
Food and Drug
Administration
(FDA)
Health Resources
and Services
Administration
(HRSA)
Centers for Medicare
And Medicaid Services
(CMS)
Agency for Healthcare
Research and Quality
(AHRQ)
Indian Health
Services
(IHS)
National Institutes
of Health
(NIH)
Centers for
Disease Control
and Prevention
(CDC)
Agency for Toxic
Substances and
Disease Registry
(ATSDR)
Substance Abuse and
Mental Health Services
Administration
(SAMHSA)
Program Support
Center
(PSC)
NIBIB Grantsmanship Program
U of H, Oct. 31, 2006
http://www.fda.gov/oc/orgcharts/fda.pdf
Workings of the FDA
•
•
•
•
Responsibility to protect the public and dealing with
technological changes
Regulates anything for diagnosis, cure, mitigation, or
prevention of disease as well as anything intended to affect
structure/function of the human body
3 Branches
– Drugs
– Devices
– Biologics
– Combination products overseen by panel from three
areas
Requires the expertise of many
- Engineers (including biomedical
electrical, and materials)
- Biologists and microbiologists
- Physcians and other clinicians
- Chemists, biochemists, and toxicologists
- Medical technologists
- Statisticians
- Consumer safety officers and field
investigators
- Human factors specialists
Role of Center for Devices and Radiological
Health (CDRH)
• Ensure that products coming to market have
more benefit than risk
• Ensure that products are labeled so that
practitioners and patients know what to expect
from their use
• Regulates 1,700 types of devices
• 23,000 registered manufacturers
• In 1996 received 20,236 device related
submissions
Regulation of Medical Devices
• FDA did not regulate devices before 1938
• 1938:
– FDA could only challenge sale of products it believed were unsafe
– Could only remove them from the market after patient injuries
• 1960s:
– Rapid innovation in medical technology
– Tried to regulate many as drugs, i.e. contact lenses, IUDs
– Catastrophic failures of heart valves and pacemakers
• 1970s:
– Broad recognition that different rules were needed to regulate devices
– No single policy would work for all devices
• Tongue depressor
• Artificial heart
• Review commission determined that more than 700 deaths
and 10,000 injuries were associated with medical devices
Medical Device Act (1976)
• Amendments to FD&C act allowed for classification
of medical devices, device listing, establishment
registration, adherence to Good Manufacturing
Practices (GMP), and extensive control over market
introduction of medical devices
• Major amendments again in ’90, ’97, and ’02
• However, CDRH can not specifically regulate
biomaterials; biomaterials are indirectly regulated
according to intended use
Class Activity (~5 min)
• Break up into groups of 3 students representing
– Policy Maker
– Manufacturer
– Consumer
• Discuss what you would want to see in a device
approval process from each perspective
• Report back
Basic Regulatory Requirements
• Premarket notification 510(k) or
Premarket approval (PMA)
• Establishment registration on form FDA2891
• Medical device listing on form FDA-2892
• Quality system (QS) regulation
• Labeling requirements
• Medical device reporting (MDR)
http://www.fda.gov/cdrh/devadvice/overview.html
Device Approval Process
• Device + intended use considered together
• Manufacturer submits request for marketing
approval
• Advisory panel
– One consumer representative (non-voting)
– One industry representative (non-voting)
– Physicians and scientists
• FDA not required to follow recommendations
of panel, although they usually do
Steps in Device Approval Process
• Device, drug, biologic, combo?
• If device, Class I, II, or III?
• 510(k) or PMA pathway?
• If PMA passes, get IDE
• 2 phases of clinical trials
• If efficacy shown, submit pre-market notification
• Post-market surveillance
Classes of Devices according to CDRH
• Class I
–
–
–
–
–
Pose least risk to patient
Not life sustaining
GMP, proper record keeping required
30% of devices
X-ray film, tongue depressors, stethoscopes
• Class II
– Not life sustaining, but must meet performance standards
– Blood pressure monitors, Catheter guide wires
– 60% of devices
• Class III
–
–
–
–
–
Pose greatest risk to patient
For use in supporting or sustaining human life
10% of devices
Stents, heart valves, LVADs
Require GMP, failure modes analysis, animal tests, human
clinical studies under IDE
510(k) vs PMA
• Substantially equivalent to a legally • Most Class III required
marketed product
– Before May 28th, 1976
• Requires submission of clinical
– Determined by FDA
data
• Most Class I exempt, most Class II • Actual approval process of device
required
by FDA
• For description of device
classification and database access,
visit
http://www.fda.gov/cdrh/devadvice/
313.html
• 3rd Party review process now
available
510(k) Determination Flow Chart
http://www.fda.gov/cdrh/ode/dd510kse.pdf
Premarket Approval (PMA)
•
•
•
•
•
•
•
Device and company name
Indications
Device description and schematics
Description of alternate practices
Contraindications
Potential adverse affects
Summary of all pre-clinical studies
Pre-clinical studies
• Physical and chemical analysis
• Biological testing
–
–
–
–
–
Pyrogenicity (LAL assay)
Blood compatibility
Acute/chronic toxicity
Mutagenicity
Validation of sterility
• Animal studies
–
–
–
–
Inflammatory/immune response
Degradation
Particulate migration
Performance
• How can one know how to perform all these tests? STANDARDS!
Standards
• Tripartite Agreement on Biocompatibility: FDA guidelines
regarding techniques for pre-clinical testing
• ASTM Committee F-04 on Medical and Surgical Materials and
Devices
• Standards for
– Test methods: specimen prep, conditions, number of samples, data
analysis
– Materials: chemical and physical properties
– Devices: schematics, dimensions, tolerances
– Procedures: how to do something besides a test, i.e. sterilization,
• FDA accepts standards such that one can write, “I did X
according to Y standard”
• Shift in perspective towards worldwide harmonized system
– ISO 10993 document
– At least 16 parts describing globally recognized standards for
•
•
•
•
Biocompatibility screens
Evaluation for ethylene oxide residues
Toxicity studies (i.e., cyto, systemic, & kinetics)
Many more
IDE and Clinical Trials
• Investigational Device Exemption
– Enables experimental use of high risk device
– Must have positive engineering and animal data
• Clinical Trials
– First give approval for feasibility studies with small
number of patients
– Then proceed to multi-center trials
– Larger data sets frequently show results from small
sample sets are not true
Humanitarian Use Exemption
• Device designed to treat or diagnose
condition that affects <4,000 patients/year
• Device would not otherwise be available
without exemption
• No comparable device is available
• Patients will not be exposed to
unreasonable or significant risk of injury or
illness by device
Medical Device Reporting
• System to detect device related problems
in a timely manner
• Serious injuries or deaths that may have
been caused by or related to a a medical
device must be reported to the
manufacturer of the device within 10 days
• Must be reported to the FDA within 10
days
Steps in Device Approval Process
• Device, drug, biologic, combo?
• If device, Class I, II, or III?
• 510(k) or PMA pathway?
• If PMA passes, get IDE
• 2 phases of clinical trials
• If efficacy shown, submit pre-market notification
• Post-market surveillance
Recently Approved Devices
• http://www.accessdata.fda.gov/scripts/cdrh
/cfdocs/cfTopic/MDA/mda-list.cfm?list=1
Device Development Costs $$$
• Who funds development?
• What is the typical government grant
process?
R&D Funding for Biomedical Research
• Federal government
– Funds ~ 35% of all medical research in US
• Mostly funded through NIH
– Current NIH budget: ~$28 billion/year
– NIH budget doubled from 1998-2003
– Last year 0% increase
– Focus is on basic research
NIH Congressional Appropriations
FY1997- FY2006
Dollars in billions
$30.0
$27.1
$25.0
$28.0 $28.6 $28.7
$23.3
$20.0
$20.5
$17.8
$15.0
$15.6
$12.7 $13.7
$10.0
$5.0
$0.0
FY FY FY FY FY FY FY FY FY FY
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
NIBIB Grantsmanship Program
U of H, Oct. 31, 2006
Total Research Expenditures at Rice
$80,000,000
$70,000,000
$60,000,000
$50,000,000
$40,000,000
Rice
$30,000,000
$20,000,000
$10,000,000
$0
1999
2001
2003
2005
The NIH Organization
OD
NIA
NIAAA
NIAID
NIAMS
NIBIB
NICHD
NIDCD
NIDCR
NIDDK
NIDA
NIEHS
NIGMS
NIMH
NINDS
NINR
NCI
NEI
NCCAM
NCMHD
NCRR
NHGRI
NHLBI
NLM
FIC
CC
CSR
CIT
NIBIB Grantsmanship Program
U of H, Oct. 31, 2006
NIH
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
National Cancer Institute
National Eye Institute
National Heart, Lung, and Blood Institute
National Human Genome Research Institute
National Institute on Aging
National Institute on Alcohol Abuse and Alcoholism
National Institute of Allergy and Infectious Diseases
National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institute of Biomedical Imaging and Bioengineering
National Institute of Child Health and Human Development
National Institute on Deafness and Other Communication Disorders
National Institute of Dental and Craniofacial Research
National Institute of Diabetes and Digestive and Kidney Diseases
National Institute on Drug Abuse
National Institute of Environmental Health Sciences
National Institute of General Medical Sciences
National Institute of Neurological Disorders and Stroke
National Institute of Nursing Research
National Library of Medicine
The NIBIB Vision
To profoundly change health
care by pushing the frontiers of
technology to make the
possible a reality.
NIBIB Grantsmanship Program
U of H, Oct. 31, 2006
A big challenge for the NIBIB is
promoting multidisciplinary research
•
Clinicians, biologists
and engineers speak in
different languages
•
Clinicians and
biologists may not
know what is
technically possible;
engineers may not
know the biomedical
problems
•
Continued, ongoing
collaboration essential
NIBIB Grantsmanship Program
U of H, Oct. 31, 2006
Current NIBIB Grant Portfolio Areas
•
•
•
•
•
•
•
•
•
•
•
•
•
Biosensors
Biomaterials
Biomechanics
Biomedical Informatics
Computational Biology
Drug & Gene Delivery Systems
Lab-on-a-Chip
Devices/Microsystems
Medical Devices & Implant
Science
Nanotechnology
Rehabilitation Engineering
Surgical Tools & Techniques
Telemedicine
Tissue Engineering
• Imaging Agents & Molecular
Probes
• Image Displays
• Image Guided Therapies &
Interventions
• Image Perception
• Image Processing
• Magnetic, Biomagnetic &
Bioelectric Devices
• Magnetic Resonance Imaging &
Spectroscopy
• Nuclear Medicine
• Optical Imaging & Spectroscopy
• Ultrasound and Acoustics
• X ray, Electron & Ion Beam
NIBIB Grantsmanship Program
U of H, Oct. 31, 2006
NIH Granting Process
My Application
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxx
PI / Institution submits application
Center for Scientific Review
Division of Receipt and Referral
Integrated Review Group (in CSR)
or Review Office (in Awarding IC)
Evaluates Scientific Merit
Revision / Resubmission
Awarding Institute or Center
Evaluates Relevance
Advisory Council
Conduct
Research
$$$
$$$
Recommends Action
Allocates Funds
http://www.csr.nih.gov/video/video.asp
Institute Director
NIBIB Grantsmanship Program
U of H, Oct. 31, 2006
Scores and Funding Level
• ~1/3 go unscored (triaged)
• ~2/3 are scored
– 100 best score
– 500 worst score
– Typically need score of 100-170 to be funded
– Approximately 10-15% of submitted proposals
are funded
For More Information, See the Following
Sources
• http://www.fda.gov/cdrh/devadvice/overview.html
• Biomaterials Science: An Introduction to
Materials in Medicine, 2nd Ed. Chap 10. Elsevier
Academic Press. Editors: Ratner, Hoffman,
Schoen, Lemons.
• Materials from NIBIB Grantsmanship Program,
University of Houston, Oct. 31, 2006
Index Cards
• What was the muddiest point of this
lecture?
• What was the clearest point in this
lecture?
HHMI survey, see you on Thursday!
Design Control Guidance
http://www.fda.gov/cdrh/comp/designgd.html
Types of Universities
• Carnegie Classification
– Taxonomy of colleges and universities
• Doctorate-Granting Institutions
– Research Universities /Very High Research Activity
– Research Universities/ High Research Activity
– Doctoral/Research Universities
• Master’s Colleges & Universities
• Baccalaureate Colleges
– http://www.carnegieclassificationpreview.org/index.aspx
Rice