Escolar Documentos
Profissional Documentos
Cultura Documentos
DESIGN CONTROLS
FDA
Regulations
CBER
Biologics
21 CFR 600/601/610
Blood
21CFR 606
21CFR 1270, 1271
(tissue)
21 CFR 58 (GLP)
21CFR 11 (electronic
records)
CDRH
Devices
CDER
Drugs
21 CFR 56 (IRBs)
21 CFR 56 (IRBs)
21 CFR 58 (GLP)
21 CFR 58 (GLP)
21CFR 11 (Electronic
records)
21 CFRR 800-1050
(devices)
21 CFR 807 (510(k))
21 CFR 812 (IDE)
21 CFR 814 (PMA)
21CFR 11
(Electronic records)
21 CFR 210, 211
(Drug GMPs)
21 CFR 312 (IND)
21 CFR 314 (NDA)
FDA review
Design and Development
Design Controls
Good Lab Practices
Document Controls
Electronic Records
Recalls
Complaints
Medical Device Reporting
510(k) Clearance
PMA
Document Controls
Obsolescence
Record
Retention
12 CFR 820.30
Requirements
Intended use
Product Class
Examples
Quality System
A Medical Device Quality System is
designed to assure that products are
Safe and Effective for their Intended
Use
and
Consistently meet the specifications
as defined by results of clinical and/or
detailed technical design and validation
Design Planning
Design Input (Requirements)
Design Output (Specifications)
Design Reviews (Technical)
Design Verification (Meets
Specifications)
Design Validation (Meets clinical needs)
Design Transfer (Moves from Design to
Manufacturing)
Design Changes (Formal Process)
Design History File (DHF)
10
Stage-Gate Method
No
Feasibility and
planning
OK
Design Review
OK
Design and
development
OK
Design Review
OK
Verification and
Validation
OK
Design Review
OK
Transfer to
manufacturing
11
Design Controls
General Stage-Gate Process
12
Design Planning
Feasibility Studies
Risk Assessments
Project Plan Defines Interfaces with
Others
Stage-Gate Methodology
Constantly Changing
13
Design Input-Feasibility
Where
What
Customers
Technical Papers
Medical experts
Service people
Intended Use
Technical Requirements
Safety Issues
How
Documented
Approved
Filed
Formal Change Control System
14
Risk Assessment
15
Risk Assessment
Feasibility
Clinical Risk
Summary
Design Input
Preliminary
Design
Specification Trace Matrix:
(links between)
Specification
Risk Analysis
Fault Table
Test Plan
Preliminary Risk
Assessment:
Mitigations:
Final Risk
Assessment:
Risk Management
Document, Approvals
16
ISO 14971
Risk Assessment
Example
Example of a Hypothetical Risk
Assessment for a Electronic
System to Monitor Patient Core
Body Temperatures
17
Definitions
Severity
Occurrence
Detection
Risk Quadrants
Current Controls
Corrective Actions
1- 10
Scale
1-3 Scale
1- Risk, None to
Little
None required
None required
2- Risk, Minimal
to Moderate
Recommended
Recommended
Required
Required if no
existing
controls.
(ALARP)
Redesign *
Redesign *
3- Risk,
Significant
4- Risk, Serious
19
Rating
Effect
SEVERITY TABLE
Description of Rating
None
Very Minor
Minor
Very Low
Low
Moderate
High
Very High
Hazardous -
10
Hazardous
Irreversi
ble
Example
Negligible
Marginal
Critical
Needle stick
Exposure to
blood
borne
pathogens
Catastrophic
20
Occurrence
Rating
Probability of
Failure
Description of Rating
DFMEA
Failure Rate
PFMEA
Improbable
Failure is unlikely.
1 in 1,500,000
(~ 0.000067%)
Remote
1 in 150,000
(~ 0.00067%)
1 in 15,000
(~ 0.0067%)
1 in 2000
(~ 0.05%)
1 in 80
(~1.25%)
1 in 8
(~ 12.5%)
3
4
Occasional
Occasional failures.
5
6
Probable
Repeated failures.
7
8
Frequent
1 in 400
(~ 0.25%)
1 in 20
(~ 5%)
1 in 3
(~ 33 %)
10
1 in 2 (
50%)
21
Detection
Rating
Probability of
Detecti
on
Description of Rating
DFMEA
PFMEA
Almost
Certain
Very High
High
Moderate
Low
Remote
Absolute
Uncertai
nty
22
Quadrant Map
Occur
rence
10
9
Quad 4
8
7
Quad 3
6
5
Quad 2
4
3
2
Quad 1
1
1
10
Severity
23
CRA 01
CRA 02
CRA 03
CRA 04
CRA 05
CRA 06
CRA 07
Possible
effects
Potential
causes
Initial State
S
Of effect
Of cause or
failure
Controlling Action's)/
Design Mitigations
Post Mitigation
State
SpecRef
Of effect
Of cause or
failure
Of cause or
failure
18
Q3
CDS-015
18
Q3
CDS-019
Score
Score
(Quad)
Patient Core
Temperature
exceeds
physiological limits
Patient Core
Temperature
exceeds
physiological limits
Patient Core
Temperature
exceeds
physiological limits
Severe
Hyperthermia
(Seizure, Death,
Brain Damage)
Severe
Hyperthermia
(Seizure, Death,
Brain Damage)
Severe
Hyperthermia
(Seizure, Death,
Brain Damage)
Probe has a
9
intermittent or
noisy signal due
to EMI in area
Probe is loose or 9
disconnected
54
54
Probe not in
9
calibration window
Wrong Temp
Probe used
63
18
Q3
CDS-002
Patient Core
Temperature
exceeds
physiological limits
Patient Core
temperature
exceeds
physiological limits
Patient Core
temperature lower
than physiological
limits
Patient Core
temperature lower
than physiological
limits
Severe
Hyperthermia
(Seizure, Death,
Brain Damage)
Severe
Hyperthermia
(Seizure, Death,
Brain Damage)
Patient enters
Hypothermia
Infection, Drug
reaction, disease
state
36
18
Q3
CDS-012
45
18
Q3
CDS-015
Probe has a
9
intermittent or
noisy signal due
to EMI in area
Probe is loose or 9
disconnected
36
18
Q3
CDS-016
54
18
Q3
CDS-018
Patient enters
Hypothermia
24
Design Output
Quantitative
Documented
Approved
Design Reviews
Formal Process
Required for Phase Approval
Checklists
Minutes
Attendees- one not associated with items
reviewed
Areas covered
Action items/open issues
Open items closed for final release
Formal design review prior to release for
manufacture and distribution
26
System
ValidationTest
Plangenerated
SoftwareRequirements
Specificationgenerated
andapproved
No
SoftwareValidationand
VerificationPlandrafted
Yes
SoftwareDevelopment
Plan
approved?
Plan
approved?
Detaileddesign
No
Systemintegration
completed
Yes
Planexecuted
Yes
No
PilotRuncompleted
SoftwareV&
Vacceptable?
SystemValidation
andVerification
TestPlanexecuted
SoftwareValidation
andVerificationTest
Reportgenerated
No
SystemV&V
testingOK?
Yes
SystemValidationand
VerificationTest
Reportgenerated
FinalDesignReview
29
SDS
Software Verification
Testing
30
Design Transfer
31
Design Changes
32
33
Rx Medical
Intended
Use Device Labeling
Indications for Use
Contraindications for Use
Warnings, Cautions
Description of the Device
User Instructions
Specifications
Corrective Actions
(Troubleshooting)
34
Labeling Controls
35
Labeling Verification
36
Record of the
Development Process
Plans
Specifications
V&V Test Results
Design Reviews
Changes to the Design
37
Class Exercise-Design
Controls
Dr. Bright and Dr. Idea have found a novel way to produce a
machine to determine if a heart attack patient has additional
blockage in the coronary arteries that may be caused by the
surgical bypass procedure (CABG). The machine non-invasively
measures arterial flow by using Doppler sonar to determine if
the arteries are blocked. It can be used in a patients home, by
itself, on post heart attack patients who may be at risk for
additional heart attacks. It transfers the data to a monitoring
station at a EMS facility for 24/7 monitoring.
They have formed a company (The Bright-Idea Company), built
a prototype and tested it in the lab on sheep and pigs. It
worked great. Now they want to begin marketing it for use on
humans.
1.
2.
3.
38
Questions
39